A compound of Formula I or II or a pharmaceutically acceptable salt thereof, is described, where the substituents are as defined herein. Pharmaceutical compositions comprising the same and method of using the same are also described.
C07D 471/02 - Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups in which the condensed system contains two hetero rings
A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
A61P 25/00 - Drugs for disorders of the nervous system
A61P 37/00 - Drugs for immunological or allergic disorders
2.
SPIROINDOLINONE COMPOUNDS AS Kv1.3 POTASSIUM SHAKER CHANNEL BLOCKERS
A compound of Formula (I) or a pharmaceutically-acceptable salt thereof, is described, wherein the substituents are as defined herein. Pharmaceutical compositions comprising the same and method of using the same are also described.
A compound of Formula (I) or a pharmaceutically-acceptable salt thereof, is described, wherein the substituents are as defined herein. Pharmaceutical compositions comprising the same and method of using the same are also described.
A61K 31/407 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with heterocyclic ring systems, e.g. ketorolac, physostigmine
A61K 31/4155 - 1,2-Diazoles not condensed and containing further heterocyclic rings
A compound of Formula I
A compound of Formula I
A compound of Formula I
or a pharmaceutically-acceptable salt thereof, is described, wherein the substituents are as defined herein. Pharmaceutical compositions comprising the same and method of using the same are also described.
C07D 207/09 - Radicals substituted by nitrogen atoms not forming part of a nitro radical
A61K 31/40 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
A61K 31/4025 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil not condensed and containing further heterocyclic rings, e.g. cromakalim
A61K 31/427 - Thiazoles not condensed and containing further heterocyclic rings
A61K 31/4439 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/444 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. amrinone
A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
A61K 31/4725 - Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61K 31/53 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
C07D 401/06 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
C07D 403/06 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
C07D 403/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
C07D 405/04 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
C07D 409/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 413/06 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
4.
Joint Generation of a Molecular Graph and Three-Dimensional Geometry
A machine-learning approach jointly generates molecular graphs and corresponding three-dimensional geometries, for example, for searching a chemical space of potential molecules with desired chemical properties. In some examples, molecules are generated incrementally by repeatedly adding atoms to a molecular graph as well as determining geometric (e.g., location) information for the added atoms until a complete molecule is generated. This incremental process can be stochastic enabling random sampling from a chemical space.
The present disclosure relates to novel compounds and pharmaceutical compositions thereof, and methods for inhibiting the activity of PI3K-α enzymes with the compounds and compositions of the disclosure. The present disclosure further relates to, but is not limited to, methods for treating disorders associated with PI3K-α signaling with the compounds and compositions of the disclosure.
A61K 31/4155 - 1,2-Diazoles not condensed and containing further heterocyclic rings
A61K 31/416 - 1,2-Diazoles condensed with carbocyclic ring systems, e.g. indazole
A61K 31/428 - Thiazoles condensed with carbocyclic rings
A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
A61K 31/4375 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring hetero atom, e.g. quinolizines, naphthyridines, berberine, vincamine
A61K 31/4545 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
A61K 31/472 - Non-condensed isoquinolines, e.g. papaverine
A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 31/536 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and at least one oxygen as the ring hetero atoms, e.g. 1,2-oxazines ortho- or peri-condensed with carbocyclic ring systems
C07D 239/82 - Oxygen atoms with an aryl radical attached in position 4
C07D 265/18 - 1,3-OxazinesHydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring with hetero atoms directly attached in position 2
C07D 275/06 - Heterocyclic compounds containing 1, 2-thiazole or hydrogenated 1,2-thiazole rings condensed with carbocyclic rings or ring systems with hetero atoms directly attached to the ring sulfur atom
C07D 401/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 403/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 403/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 405/06 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
C07D 409/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 409/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
C07D 417/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
A compound of Formula (I) or a pharmaceutically acceptable salt thereof, is described, wherein the substituents are as defined herein. Pharmaceutical compositions comprising the same and method of using the same are also described.
Improvements in a molecular-dynamic simulator provide ways to save energy during computation and reduce die area consumed on an integrated circuit. Examples of such improvements include different interaction modules for different ranges, the use of streaming along rows while multicasting along columns in an array of interaction modules, the selection of computation units based on balancing computational costs and communication costs, the use of fences in networks that connect computation units, and the use of bond calculators to carry out specialized bond calculations.
A compound of Formula (I), or a pharmaceutically acceptable salt thereof, is described, where the substituents are as defined herein. Pharmaceutical compositions including the same and method of using the same are also described.
A compound of Formula (I), or a pharmaceutically acceptable salt thereof, is described, where the substituents are as defined herein. Pharmaceutical compositions including the same and method of using the same are also described.
C07D 401/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 403/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 405/04 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 207/27 - 2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
C07D 403/06 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
C07D 417/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 413/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring- member bond
A compound of Formula (I) or a pharmaceutically acceptable salt thereof, is described, wherein the substituents are as defined herein. Pharmaceutical compositions comprising the same arid method of using the same for treatment of medical conditions, including pain, a skin disorder, a respiratory disease, a fibrotic disease, an inner ear disorder, fever or another disorder of thermoregulation, are also described.
A61K 31/4412 - Non-condensed pyridinesHydrogenated derivatives thereof having oxo groups directly attached to the heterocyclic ring
A61K 31/443 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with oxygen as a ring hetero atom
A61K 31/4439 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61K 31/513 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
The present disclosure relates to novel compounds and pharmaceutical compositions thereof, and methods for inhibiting the activity of PI3K-α enzymes with the compounds and compositions of the disclosure. The present disclosure further relates to, but is not limited to, methods for treating disorders associated with PI3K-α signaling with the compounds and compositions of the disclosure.
A compound of Formula (I) or a pharmaceutically acceptable salt thereof, is described, wherein the substituents are as defined herein. Pharmaceutical compositions comprising the same and method of using the same are also described.
A61K 31/34 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
A61K 31/435 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
A compound of Formula (I) or a pharmaceutically acceptable salt thereof, is described, wherein the substituents are as defined herein. Pharmaceutical compositions comprising the same and method of using the same are also described.
The present disclosure relates to novel compounds including formula (X) and pharmaceutical compositions thereof, and methods for inhibiting the activity of SHP2 phosphatase with the compounds and compositions of the disclosure. The present disclosure further relates to, but is not limited to, methods for treating disorders associated with SHP2 deregulation with the compounds and compositions of the disclosure.
The present disclosure relates to novel compounds including formula (X) and pharmaceutical compositions thereof, and methods for inhibiting the activity of SHP2 phosphatase with the compounds and compositions of the disclosure. The present disclosure further relates to, but is not limited to, methods for treating disorders associated with SHP2 deregulation with the compounds and compositions of the disclosure.
C07D 401/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 417/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 417/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
C07D 491/107 - Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
A compound of Formula (I), or a pharmaceutically acceptable salt thereof, is described, wherein the substituents are as defined herein. Pharmaceutical compositions comprising the same and method of using the same are also described.
A compound of Formula (I), or a pharmaceutically acceptable salt thereof, is described, wherein the substituents are as defined herein. Pharmaceutical compositions comprising the same and method of using the same are also described.
C07D 213/73 - Unsubstituted amino or imino radicals
C07C 215/50 - Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by hydroxy groups with amino groups and the six-membered aromatic ring, or the condensed ring system containing that ring, bound to the same carbon atom of the carbon chain
C07D 213/38 - Radicals substituted by singly-bound nitrogen atoms having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
C07D 231/12 - Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
C07C 237/30 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having the nitrogen atom of the carboxamide group bound to hydrogen atoms or to acyclic carbon atoms
C07D 213/64 - One oxygen atom attached in position 2 or 6
C07D 209/08 - IndolesHydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
C07D 241/12 - Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
C07D 205/04 - Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
C07D 211/60 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
C07C 235/08 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
C07D 211/62 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals attached in position 4
C07D 265/30 - 1,4-OxazinesHydrogenated 1,4-oxazines not condensed with other rings
C07D 207/16 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
The present disclosure relates to novel compounds and pharmaceutical compositions thereof, and methods for inhibiting the activity of FGFR enzymes with the compounds and compositions of the disclosure. The present disclosure further relates to, but is not limited to, methods for treating disorders associated with FGFR signaling with the compounds and compositions of the disclosure.
C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
C07D 491/048 - Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
C07D 498/22 - Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains four or more hetero rings
C07D 498/02 - Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
C07D 487/22 - Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups in which the condensed system contains four or more hetero rings
16.
JOINT GENERATION OF A MOLECULAR GRAPH AND THREE-DIMENSIONAL GEOMETRY
A machine-learning approach jointly generates molecular graphs and corresponding three-dimensional geometries, for example, for searching a chemical space of potential molecules with desired chemical properties. In some examples, molecules are generated incrementally by repeatedly adding atoms to a molecular graph as well as determining geometric (e.g., location) information for the added atoms until a complete molecule is generated. This incremental process can be stochastic enabling random sampling from a chemical space.
The present disclosure relates to novel compounds and pharmaceutical compositions thereof, and methods for inhibiting the activity of PI3Kα enzymes with the compounds and compositions of the disclosure. The present disclosure further relates to, but is not limited to, methods for treating disorders associated with PI3Kα signaling with the compounds and compositions of the disclosure.
A compound of Formula (I), or a pharmaceutically acceptable salt thereof, is described, where the substituents are as defined herein. Pharmaceutical compositions including the same and method of using the same are also described.
A compound of Formula (I), or a pharmaceutically acceptable salt thereof, is described, where the substituents are as defined herein. Pharmaceutical compositions including the same and method of using the same are also described.
C07D 401/02 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
C07D 405/02 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
C07D 413/02 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
A compound of Formula (I), or a pharmaceutically acceptable salt thereof, is described, where the substituents are as defined herein. Pharmaceutical compositions including the same and method of using the same are also described.
A compound of Formula (I), or a pharmaceutically acceptable salt thereof, is described, where the substituents are as defined herein. Pharmaceutical compositions including the same and method of using the same are also described.
A compound of Formula (I), or a pharmaceutically-acceptable salt thereof, is described, wherein the substituents are as defined herein. Pharmaceutical compositions comprising the same and method of using the same are also described.
A compound of Formula (I), or a pharmaceutically-acceptable salt thereof, is described, wherein the substituents are as defined herein. Pharmaceutical compositions comprising the same and method of using the same are also described.
C07D 211/34 - Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
C07D 211/22 - Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulfur atoms by oxygen atoms
C07D 295/096 - Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
C07D 205/04 - Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
C07D 243/08 - Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 not condensed with other rings
C07D 211/52 - Oxygen atoms attached in position 4 having an aryl radical as the second substituent in position 4
C07D 451/02 - Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.02,4] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamineCyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.02,4] nonane ring systems, e.g. tropaneCyclic acetals thereof
C07D 207/08 - Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
C07D 223/04 - Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings with only hydrogen atoms, halogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
C07D 211/28 - Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by nitrogen atoms to which a second hetero atom is attached
C07D 211/26 - Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by nitrogen atoms
C07D 211/32 - Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by doubly bound oxygen or sulfur atoms or by two oxygen or sulfur atoms singly bound to the same carbon atom by oxygen atoms
C07D 241/04 - Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
C07D 211/60 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
C07D 211/70 - Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
C07D 211/58 - Nitrogen atoms attached in position 4
C07D 211/42 - Oxygen atoms attached in position 3 or 5
C07D 401/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 401/06 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 413/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 405/12 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 403/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
21.
ARYLMETHYLENE HETEROCYCLIC COMPOUNDS AS KV1.3 POTASSIUM SHAKER CHANNEL BLOCKERS
A compound of Formula (I) or a pharmaceutically acceptable salt thereof is described, wherein the substituents are as defined herein. Pharmaceutical compositions comprising the same and method of using the same are also described.
A compound of Formula (I) or a pharmaceutically acceptable salt thereof is described, wherein the substituents are as defined herein. Pharmaceutical compositions comprising the same and method of using the same are also described.
C07D 211/12 - Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with only hydrogen atoms attached to the ring nitrogen atom
C07D 401/06 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 405/04 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 413/06 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
C07D 401/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 413/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 409/06 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
C07D 205/04 - Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
C07D 207/06 - Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with radicals, containing only hydrogen and carbon atoms, attached to ring carbon atoms
C07D 223/04 - Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings with only hydrogen atoms, halogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
C07D 453/02 - Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems
C07D 417/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond
22.
ARYLMETHYLENE HETEROCYCLIC COMPOUNDS AS KV1.3 POTASSIUM SHAKER CHANNEL BLOCKERS
A compound of Formula (I), or a pharmaceutically acceptable salt thereof, is described, wherein the substituents are as defined herein. Pharmaceutical compositions comprising the same and method of using the same are also described.
A compound of Formula (I), or a pharmaceutically acceptable salt thereof, is described, wherein the substituents are as defined herein. Pharmaceutical compositions comprising the same and method of using the same are also described.
C07D 207/06 - Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with radicals, containing only hydrogen and carbon atoms, attached to ring carbon atoms
C07D 491/107 - Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
C07D 223/04 - Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings with only hydrogen atoms, halogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
C07D 205/04 - Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
C07D 491/113 - Spiro-condensed systems with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring
C07D 401/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 401/06 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
C07D 413/06 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
C07D 405/04 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
A compound of Formula (I) or a pharmaceutically-acceptable salt thereof, is described, wherein the substituents are as defined herein. Pharmaceutical compositions comprising the same and method of using the same are also described.
A61K 31/407 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with heterocyclic ring systems, e.g. ketorolac, physostigmine
A61K 31/438 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring being spiro-condensed with carbocyclic or heterocyclic ring systems
A compound of Formula (I) or a pharmaceutically-acceptable salt thereof, is described, wherein the substituents are as defined herein. Pharmaceutical compositions comprising the same and method of using the same are also described.
A61K 31/407 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with heterocyclic ring systems, e.g. ketorolac, physostigmine
A61K 31/438 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring being spiro-condensed with carbocyclic or heterocyclic ring systems
A compound of Formula (I), (I'), (II), (II'), (III), or (IV) or a pharmaceutically-acceptable salt thereof, is described, wherein the substituents are as defined herein. Pharmaceutical compositions comprising the same and method of using the same are also described.
C07D 207/08 - Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
A61K 31/40 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
A61K 31/4025 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil not condensed and containing further heterocyclic rings, e.g. cromakalim
A61K 31/4155 - 1,2-Diazoles not condensed and containing further heterocyclic rings
A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
C07D 401/06 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
C07D 403/06 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
26.
ARYL HETEROCYCLIC COMPOUNDS AS Kv1.3 POTASSIUM SHAKER CHANNEL BLOCKERS
A compound of Formula (I), (I'), (II), (II'), (III), or (IV) or a pharmaceutically-acceptable salt thereof, is described, wherein the substituents are as defined herein. Pharmaceutical compositions comprising the same and method of using the same are also described.
C07D 213/75 - Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Improvements in a molecular-dynamic simulator provide ways to save energy during computation and reduce die area consumed on an integrated circuit. Examples of such improvements include different interaction modules for different ranges, the use of streaming along rows while multicasting along columns in an array of interaction modules, the selection of computation units based on balancing computational costs and communication costs, the use of fences in networks that connect computation units, and the use of bond calculators to carry out specialized bond calculations.
G16C 10/00 - Computational theoretical chemistry, i.e. ICT specially adapted for theoretical aspects of quantum chemistry, molecular mechanics, molecular dynamics or the like
G06F 9/50 - Allocation of resources, e.g. of the central processing unit [CPU]
G06F 30/25 - Design optimisation, verification or simulation using particle-based methods
Discovering molecules (which may be known or may never have been cataloged or ever synthesized) that have desired characteristics is addressed using a machine learning approach. As compared to a brute-force search of a database of known molecules, which may not be computationally feasible, the present machine learning approach renders identification of both known and unknown molecules computationally tractable. Furthermore, the computational effort is largely shifted to training of the machine learning system using a database of known molecules, and the generation of molecules to match any particular characteristics requires relatively little computation. The molecules using the present approach may be further studied, for example, with computer-based simulation or after physical synthesis using biological experimentation to ultimately yield useful chemical compounds.
The present invention relates to compounds and methods useful for inhibiting non-receptor tyrosine-protein kinase Src ("Src"). The invention also provides pharmaceutically acceptable compositions comprising compounds of the present invention and methods of using said compositions in the treatment of various disorders.
A compound of Formula (I) or a pharmaceutically acceptable salt thereof is described, wherein the substituents are as defined herein. Pharmaceutical compositions comprising the same and method of using the same are also described.
A compound of Formula (I) or a pharmaceutically acceptable salt thereof is described, wherein the substituents are as defined herein. Pharmaceutical compositions comprising the same and method of using the same are also described.
A compound of Formula (I), or a pharmaceutically acceptable salt thereof, is described, where the substituents are as defined herein. Pharmaceutical compositions including the same and method of using the same are also described.
A61K 31/4015 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
A61K 31/4025 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil not condensed and containing further heterocyclic rings, e.g. cromakalim
A61K 31/4155 - 1,2-Diazoles not condensed and containing further heterocyclic rings
A61K 31/4178 - 1,3-Diazoles not condensed and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
A61K 31/421 - 1,3-Oxazoles, e.g. pemoline, trimethadione
A61K 31/422 - Oxazoles not condensed and containing further heterocyclic rings
A61K 31/427 - Thiazoles not condensed and containing further heterocyclic rings
A61K 31/4439 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
C07D 263/24 - Oxygen atoms attached in position 2 with hydrocarbon radicals, substituted by oxygen atoms, attached to other ring carbon atoms
C07D 265/32 - 1,4-OxazinesHydrogenated 1,4-oxazines not condensed with other rings with oxygen atoms directly attached to ring carbon atoms
C07D 401/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 403/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 403/06 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
C07D 405/04 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 405/06 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
C07D 413/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 417/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond
32.
LACTAM COMPOUNDS AS Kv1.3 POTASSIUM SHAKER CHANNEL BLOCKERS
A compound of Formula (I), or a pharmaceutically acceptable salt thereof, is described, where the substituents are as defined herein. Pharmaceutical compositions including the same and method of using the same are also described.
A61K 31/40 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
A61K 31/4015 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
C07D 207/263 - 2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms
The present disclosure relates to novel compounds and pharmaceutical compositions thereof, and methods for inhibiting the activity of PI3K-? enzymes with the compounds and compositions of the disclosure. The present disclosure further relates to, but is not limited to, methods for treating disorders associated with PI3K-? signaling with the compounds and compositions of the disclosure.
The present disclosure relates to novel compounds and pharmaceutical compositions thereof, and methods for inhibiting the activity of PI3K-α enzymes with the compounds and compositions of the disclosure. The present disclosure further relates to, but is not limited to, methods for treating disorders associated with PI3K-α signaling with the compounds and compositions of the disclosure.
A compound of Formula Ior a pharmaceutically acceptable salt thereof, wherein the substituents are as defined herein. Pharmaceutical compositions comprising the same and methods of using the same as a Kv1.3 channel blocker are also described. Such compounds can be used in therapy, e.g. in the treatment of cancer, immunological disorders, Central Nerve System (CNS) disorders, inflammatory disorders, gastroenterological disorders, metabolic disorders, cardiovascular disorders, and kidney disease.
C07D 211/22 - Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulfur atoms by oxygen atoms
A61K 31/397 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having four-membered rings, e.g. azetidine
A61K 31/40 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
A61K 31/403 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
A61K 31/438 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring being spiro-condensed with carbocyclic or heterocyclic ring systems
A61K 31/445 - Non-condensed piperidines, e.g. piperocaine
A61K 31/4523 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
A61K 31/453 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with oxygen as a ring hetero atom
A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
A61K 31/495 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
A61P 1/00 - Drugs for disorders of the alimentary tract or the digestive system
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
A61P 13/12 - Drugs for disorders of the urinary system of the kidneys
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
A61P 37/06 - Immunosuppressants, e.g. drugs for graft rejection
C07D 205/04 - Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
C07D 207/08 - Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
C07D 209/02 - Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
C07D 211/26 - Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by nitrogen atoms
C07D 211/48 - Oxygen atoms attached in position 4 having an acyclic carbon atom attached in position 4
C07D 211/58 - Nitrogen atoms attached in position 4
C07D 211/60 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
C07D 223/04 - Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings with only hydrogen atoms, halogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
C07D 241/04 - Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
C07D 265/30 - 1,4-OxazinesHydrogenated 1,4-oxazines not condensed with other rings
C07D 295/185 - Radicals derived from carboxylic acids from aliphatic carboxylic acids
C07D 403/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 405/04 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
A compound of Formula (I), or a pharmaceutically acceptable salt thereof, is described, where the substituents are as defined herein. Pharmaceutical compositions including the same and method of using the same are also described.
C07D 213/75 - Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
37.
ARYLMETHYLENE AROMATIC COMPOUNDS AS KV1.3 POTASSIUM SHAKER CHANNEL BLOCKERS
A compound of Formula (I), or a pharmaceutically acceptable salt thereof, is described, wherein the substituents are as defined herein. Pharmaceutical compositions comprising the same and method of using the same are also described.
A compound of Formula (I), or a pharmaceutically acceptable salt thereof, is described, where the substituents are as defined herein. Pharmaceutical compositions including the same and method of using the same are also described.
C07D 213/75 - Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
39.
ARYL HETEROBICYCLIC COMPOUNDS AS KV1.3 POTASSIUM SHAKER CHANNEL BLOCKERS
A compound of Formula (I), or a pharmaceutically acceptable salt thereof, is described, where the substituents are as defined herein. Pharmaceutical compositions including the same and method of using the same are also described.
A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
A61K 31/53 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
A61K 31/551 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogens as ring hetero atoms, e.g. clozapine, dilazep
A61P 1/00 - Drugs for disorders of the alimentary tract or the digestive system
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
A61P 13/12 - Drugs for disorders of the urinary system of the kidneys
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
A compound of Formula (I), or a pharmaceutically acceptable salt thereof, is described, where the substituents are as defined herein. Pharmaceutical compositions including the same and method of using the same are also described.
A61K 31/407 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with heterocyclic ring systems, e.g. ketorolac, physostigmine
A61K 31/4188 - 1,3-Diazoles condensed with heterocyclic ring systems, e.g. biotin, sorbinil
A61K 31/424 - Oxazoles condensed with heterocyclic ring systems, e.g. clavulanic acid
A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61K 31/5365 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and at least one oxygen as the ring hetero atoms, e.g. 1,2-oxazines ortho- or peri-condensed with heterocyclic ring systems
A61K 31/5383 - 1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with heterocyclic ring systems
A61K 31/551 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogens as ring hetero atoms, e.g. clozapine, dilazep
A61P 1/00 - Drugs for disorders of the alimentary tract or the digestive system
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
A61P 13/12 - Drugs for disorders of the urinary system of the kidneys
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
A compound of Formula (I), or a pharmaceutically acceptable salt thereof, is described, wherein the substituents are as defined herein. Pharmaceutical compositions comprising the same and method of using the same are also described.
A61K 31/135 - Amines, e.g. amantadine having aromatic rings, e.g. methadone
A61K 31/277 - NitrilesIsonitriles having a ring, e.g. verapamil
A61K 31/397 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having four-membered rings, e.g. azetidine
A61K 31/40 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
A61K 31/4409 - Non-condensed pyridinesHydrogenated derivatives thereof only substituted in position 4, e.g. isoniazid, iproniazid
A61K 31/4427 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems
A61K 31/4439 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/445 - Non-condensed piperidines, e.g. piperocaine
A61K 31/4465 - Non-condensed piperidines, e.g. piperocaine only substituted in position 4
C07C 215/50 - Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by hydroxy groups with amino groups and the six-membered aromatic ring, or the condensed ring system containing that ring, bound to the same carbon atom of the carbon chain
C07C 235/06 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
C07C 237/30 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having the nitrogen atom of the carboxamide group bound to hydrogen atoms or to acyclic carbon atoms
C07C 255/50 - Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton to carbon atoms of non-condensed six-membered aromatic rings
C07D 205/04 - Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
C07D 207/16 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
C07D 209/08 - IndolesHydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
C07D 211/60 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
C07D 213/38 - Radicals substituted by singly-bound nitrogen atoms having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
C07D 231/12 - Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
C07D 239/26 - Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
C07D 241/12 - Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
C07D 265/30 - 1,4-OxazinesHydrogenated 1,4-oxazines not condensed with other rings
C07D 401/06 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
42.
ARYL HETEROCYCLIC COMPOUNDS AS KV1.3 POTASSIUM SHAKER CHANNEL BLOCKERS
A compound of Formula (I), or a pharmaceutically-acceptable salt thereof, is described, wherein the substituents are as defined herein. Pharmaceutical compositions comprising the same and method of using the same are also described.
C07D 213/75 - Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
43.
ARYLMETHYLENE HETEROCYCLIC COMPOUNDS AS KV1.3 POTASSIUM SHAKER CHANNEL BLOCKERS
A compound of Formula (I) or a pharmaceutically acceptable salt thereof is described, wherein the substituents are as defined herein. Pharmaceutical compositions comprising the same and method of using the same are also described.
A compound of Formula (I), or a pharmaceutically acceptable salt thereof, is described, wherein the substituents are as defined herein. Pharmaceutical compositions comprising the same and method of using the same are also described.
The present disclosure relates to novel compounds and pharmaceutical compositions thereof, and methods for inhibiting the activity of SHP2 phosphatase with the compounds and compositions of the disclosure. The present disclosure further relates to methods for treating disorders associated with SHP2 deregulation with the compounds and compositions of the disclosure.
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
46.
MOLECULAR GRAPH GENERATION FROM STRUCTURAL FEATURES USING AN ARTIFICIAL NEURAL NETWORK
Discovering molecules (which may be known or may never have been cataloged or ever synthesized) that have desired characteristics is addressed using a machine learning approach. As compared to a brute-force search of a database of known molecules, which may not be computationally feasible, the present machine learning approach renders identification of both known and unknown molecules computationally tractable. Furthermore, the computational effort is largely shifted to training of the machine learning system using a database of known molecules, and the generation of molecules to match any particular characteristics requires relatively little computation. The molecules using the present approach may be further studied, for example, with computer-based simulation or after physical synthesis using biological experimentation to ultimately yield useful chemical compounds.
The present disclosure relates to novel compounds and pharmaceutical compositions thereof, and methods for inhibiting the activity of FGFR enzymes with the compounds and compositions of the disclosure. The present disclosure further relates to, but is not limited to, methods for treating disorders associated with FGFR signaling with the compounds and compositions of the disclosure.
The present disclosure relates to novel compounds and pharmaceutical compositions thereof, and methods for inhibiting the activity of FGFR enzymes with the compounds and compositions of the disclosure. The present disclosure further relates to, but is not limited to, methods for treating disorders associated with FGFR signaling with the compounds and compositions of the disclosure.
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
A61K 31/5386 - 1,4-Oxazines, e.g. morpholine spiro-condensed or forming part of bridged ring systems
A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
A61K 31/553 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and at least one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
C07D 471/22 - Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups in which the condensed systems contains four or more hetero rings
C07D 498/22 - Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains four or more hetero rings
C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
49.
HETEROCYCLIC COMPOUNDS AND THEIR USE IN THE TREATMENT OF AMYLOID-RELATED DISEASES
A compound of Formula (I) or a pharmaceutically acceptable salt thereof is described, wherein the substituents are as defined herein. Pharmaceutical compositions comprising the same and method of using the same are also described.
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Cellular biological activities are tightly controlled by intracellular signaling processes initiated by extracellular signals. Protein tyrosine phosphatases, which remove phosphate groups from tyrosine phosphorylated signaling molecules, play equally important tyrosine roles as protein kinases in signal transduction. SHP-2, a cytoplasmic SH2 domain containing protein tyrosine phosphatase, is involved in the signaling pathways of a variety of growth factors and cytokines. Recent studies have clearly demonstrated that this phosphatase plays an important role in transducing signal relay from the cell surface to the nucleus, and is a critical intracellular regulator in mediating cell proliferation and differentiation.
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
51.
Substituted pyrazolo[3,4-b]pyrazines as SHP2 phosphatase inhibitors
The present disclosure relates to compounds of formula (I) and pharmaceutical compositions thereof and methods for inhibiting the activity of SHP2 phosphatase with the compounds and compositions of the disclosure. The present disclosure further relates to, but is not limited to, methods for treating disorders associated with SHP2 deregulation with the compounds and compositions of the disclosure.
C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
52.
SHP2 phosphatase inhibitors and methods of use thereof
The present invention relates to novel compounds and pharmaceutical compositions thereof, and methods for inhibiting the activity of SHP2 phosphatase with the compounds and compositions of the invention. The present invention further relates to, but is not limited to, methods for treating disorders associated with SHP2 deregulation with the compounds ad compositions of the invention.
C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
A method for managing flow of particles into an array of pairwise-point-interaction-module includes receiving a first set of particles into a first queue. The first set is a proper subset of a second set of particles that comprises all particles that are to be passed into an array of pairwise-point-interaction-modules during a current time period. Prior to having received all particles from the second set, particles from the first set are allowed to pass from the first queue into the array.
G16C 10/00 - Computational theoretical chemistry, i.e. ICT specially adapted for theoretical aspects of quantum chemistry, molecular mechanics, molecular dynamics or the like
The present invention relates to novel compounds having the general formula:
and pharmaceutical compositions thereof, and methods for inhibiting the activity of SHP2 phosphatase with the compounds and compositions of the invention. The present invention further relates to, but is not limited to, methods for suppressing tumor cell growth, ameliorating the pathogenesis of systemic lupus erythematosus, and the treatment of various other disorders, including Noonan syndrome, diabetes, neutropenia, neuroblastoma, melanoma, juvenile leukemia, juvenile myelomonocytic leukemia, chronic myelomonocytic leukemia, acute myeloid leukemia, and other cancers associated with SHP2 deregulation with the compounds and compositions of the invention, alone or in combination with other treatments. Other cancers associated with SHP2 deregulation include HER2-positive breast cancer, triple-negative breast cancer, ductal carcinoma of the breast, invasive ductal carcinoma of the breast, non-small cell lung cancer, esophageal cancer, gastric cancer, squamous-cell carcinoma of the head and neck (SCCHN), and colon cancer.
A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
The present disclosure relates to novel compounds and pharmaceutical compositions thereof, and methods for inhibiting the activity of SHP2 phosphatase with the compounds and compositions of the disclosure. The present disclosure further relates to methods for treating disorders associated with SHP2 deregulation with the compounds and compositions of the disclosure.
C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
A61P 43/00 - Drugs for specific purposes, not provided for in groups
A61P 7/00 - Drugs for disorders of the blood or the extracellular fluid
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
The present disclosure relates to novel compounds including formula (X) and pharmaceutical compositions thereof, and methods for inhibiting the activity of SHP2 phosphatase with the compounds and compositions of the disclosure. The present disclosure further relates to, but is not limited to, methods for treating disorders associated with SHP2 deregulation with the compounds and compositions of the disclosure.
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
C07D 401/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 401/06 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 417/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 417/06 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
The present disclosure relates to novel compounds and pharmaceutical compositions thereof, and methods for inhibiting the activity of SHP2 phosphatase with the compounds and compositions of the disclosure. The present disclosure further relates to, but is not limited to, methods for treating disorders associated with SHP2 deregulation with the compounds and compositions of the disclosure.
C07D 417/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 417/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 417/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
A61K 31/41 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which is nitrogen, e.g. tetrazole
A61K 31/4188 - 1,3-Diazoles condensed with heterocyclic ring systems, e.g. biotin, sorbinil
A61K 31/427 - Thiazoles not condensed and containing further heterocyclic rings
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
Disclosed herein are novel compounds of formula (I) and pharmaceutical compositions thereof, and methods for inhibiting the activity of SHP2 phosphatase with the compounds and compositions of the disclosure. The present disclosure further relates to, but is not limited to, methods for treating disorders associated with SHP2 deregulation with the compounds ad compositions of the disclosure.
A61P 7/00 - Drugs for disorders of the blood or the extracellular fluid
A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
A method comprising causing a simulation machine for molecular dynamic simulation to determine that a topological distance that separates two particles is less than a threshold. The simulation machine includes nodes connected by a network. The nodes collectively representing a volume with each node corresponding to a portion of the simulation space. A topological relationship between the nodes corresponds to spatial relationship thereof in the simulation space. The simulation volume is occupied by particles that interact with each other. The two particles are among these particles. The simulation volume includes node boxes, each of which is handled by one of the nodes. Each of the nodes is implemented as an application specific integrated circuit that includes a combination of first and second hardware elements. The first hardware elements are especially designed to perform pairwise interactions. The second hardware elements operate to provide potentially interacting particles to the first hardware elements.
G16C 10/00 - Computational theoretical chemistry, i.e. ICT specially adapted for theoretical aspects of quantum chemistry, molecular mechanics, molecular dynamics or the like
A compound of Formula (Ia) or (Ib), or a pharmaceutically acceptable salt thereof is described, wherein the substituents are as defined herein. Pharmaceutical compositions comprising the same and method of using the same are also described.
A61K 31/4152 - 1,2-Diazoles having oxo groups directly attached to the heterocyclic ring, e.g. antipyrine, phenylbutazone, sulfinpyrazone
C07D 231/08 - Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with oxygen or sulfur atoms directly attached to ring carbon atoms
61.
PYRAZOLO[3,4-B]PYRAZINE DERIVATIVES AS SHP2 PHOSPHATASE INHIBITORS
The present disclosure relates to compounds of formula (I) and pharmaceutical compositions thereof, and methods for inhibiting the activity of SHP2 phosphatase with the compounds and compositions of the disclosure. The present disclosure further relates to, but is not limited to, methods for treating disorders associated with SHP2 deregulation with the compounds and compositions of the disclosure
C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
The present invention relates to novel compounds and pharmaceutical compositions thereof, and methods for inhibiting the activity of SHP2 phosphatase with the compounds and compositions of the invention. The present invention further relates to, but is not limited to, methods for treating disorders associated with SHP2 deregulation with the compounds ad compositions of the invention.
C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
The present invention relates to novel compounds and pharmaceutical compositions thereof, and methods for inhibiting the activity of SHP2 phosphatase with the compounds and compositions of the invention. The present invention further relates to, but is not limited to, methods for suppressing tumor cell growth, ameliorating the pathogenesis of systemic lupus erythematosus, and the treatment of various other disorders, including Noonan syndrome, diabetes, neutropenia, neuroblastoma, melanoma, juvenile leukemia, juvenile myelomonocytic leukemia, chronic myelomonocytic leukemia, acute myeloid leukemia, and other cancers associated with SHP2 deregulation with the compounds and compositions of the invention, alone or in combination with other treatments. Other cancers associated with SHP2 deregulation include HER2-positive breast cancer, triple-negative breast cancer, ductal carcinoma of the breast, invasive ductal carcinoma of the breast, non-small cell lung cancer, esophageal cancer, gastric cancer, squamous-cell carcinoma of the head and neck (SCCHN), and colon cancer.
A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
A method for treating neurodegenerative disease in a subject in need thereof by administering to the subject an effective amount of a Nedd4 activator as described herein.
A61K 31/53 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
In one aspect, the invention relates to a method for identifying a compound which modulates the activity of a voltage-gated protein. In certain embodiments, the voltage gate protein is a voltage-gated ion channel. In certain embodiments, the voltage-gated protein is a voltage sensitive phosphatase. In certain embodiments, the voltage-gated protein used in conjunction with the methods of the invention is modified to altered permeability or voltage sensitivity.
G06F 19/00 - Digital computing or data processing equipment or methods, specially adapted for specific applications (specially adapted for specific functions G06F 17/00;data processing systems or methods specially adapted for administrative, commercial, financial, managerial, supervisory or forecasting purposes G06Q;healthcare informatics G16H)
A data communication apparatus includes a router, first and second packet producers, and a penalizer. The router is directly connected to the first and second producers. The penalizer assesses penalties against each producer whenever that producer is serviced. The penalty value depends at least in part on an expected extent to which the first producer requires service. The penalizer then accumulates penalties against each producer.
Atomic or molecular models of the autoinhibitory interaction between JAK domains are provided along with methods using the atomic models for identifying agents that restore the autoinhibitory interaction between JAK domains.
In one aspect, the invention relates to a method for identifying a compound which modulates the activity of a voltage-gated protein. In certain embodiments, the voltage gate protein is a voltage-gated ion channel. In certain embodiments, the voltage-gated protein is a voltage sensitive phosphatase. In certain embodiments, the voltage-gated protein used in conjunction with the methods of the invention is modified to altered permeability or voltage sensitivity.
An apparatus for high-performance parallel computation, includes plural computation nodes, each having dispatch units, memories in communication with the dispatch units, and processors, each of which is in communication with the memories and the dispatch units. Each dispatch unit is configured to recognize, as ready for execution, one or more computational tasks that have become ready for execution as a result of counted remote writes into the memories. Each of the dispatch units is configured to receive a dispatch request from a processor and to determine whether there exist one or more computational tasks that are both ready and available for execution by the processor.
D.E. SHAW RESEARCH INDIA TECHNOLOGY PRIVATE LIMITED (India)
Inventor
Jensen, Morten, Ostergaard
Borhani, David
Jogini, Vishwanath
Abstract
In one aspect, the invention relates to a method for identifying a compound which modulates the activity of a voltage-gated protein. In certain embodiments, the voltage gate protein is a voltage gated ion channel. In certain embodiments, the voltage gated protein is a voltage sensitive phosphatase. In certain embodiments, the voltage gated protein used in conjunction with the methods of the invention is modified to altered permeability or voltage sensitivity.
A parallel processing system for computing particle interactions includes a plurality of computation nodes arranged according to a geometric partitioning of a simulation volume. Each computation node has storage for particle data. This particle data is associated with particles in a region of the geometrically partitioned simulation volume. The parallel processing system also includes a communication system having links interconnecting the computation nodes. Each of the computation nodes includes a processor subsystem. These processor subsystems cooperate to coordinate computation of the particle interactions in a distributed manner.
G06F 7/60 - Methods or arrangements for performing computations using a digital non-denominational number representation, i.e. number representation without radixComputing devices using combinations of denominational and non-denominational quantity representations
G06F 9/30 - Arrangements for executing machine instructions, e.g. instruction decode
G06F 19/00 - Digital computing or data processing equipment or methods, specially adapted for specific applications (specially adapted for specific functions G06F 17/00;data processing systems or methods specially adapted for administrative, commercial, financial, managerial, supervisory or forecasting purposes G06Q;healthcare informatics G16H)
G06F 15/76 - Architectures of general purpose stored program computers
G06F 19/16 - for molecular structure, e.g. structure alignment, structural or functional relations, protein folding, domain topologies, drug targeting using structure data, involving two-dimensional or three-dimensional structures
73.
Parallel computer architecture for computation of particle interactions
A computation system for computing interactions in a multiple-body simulation includes an array of processing modules arranged into one or more serially interconnected processing groups of the processing modules. Each of the processing modules includes storage for data elements and includes circuitry for performing pairwise computations between data elements each associated with a spatial location. Each of the pairwise computations makes use of a data element from the storage of the processing module and a data element passing through the serially interconnected processing modules. Each of the processing modules includes circuitry for selecting the pairs of data elements according to separations between spatial locations associated with the data elements.
G06F 9/30 - Arrangements for executing machine instructions, e.g. instruction decode
G06F 19/00 - Digital computing or data processing equipment or methods, specially adapted for specific applications (specially adapted for specific functions G06F 17/00;data processing systems or methods specially adapted for administrative, commercial, financial, managerial, supervisory or forecasting purposes G06Q;healthcare informatics G16H)
G06F 15/76 - Architectures of general purpose stored program computers
G06F 19/16 - for molecular structure, e.g. structure alignment, structural or functional relations, protein folding, domain topologies, drug targeting using structure data, involving two-dimensional or three-dimensional structures
74.
Zonal methods for computation of particle interactions
A method for performing computations associated with bodies located in a computation region includes, for each subset of multiple subsets of the computations, performing the computations in that subset of computations, including accepting data of bodies located in each of a plurality of import regions associated with the subset of the computations, the import regions being parts of the computation region; for each combination of a predetermined plurality of combinations of multiple of the import regions, performing computations associated with sets of bodies, wherein for each of the sets of bodies, at least one body of the set is located in each import region of the combination.
G06F 9/30 - Arrangements for executing machine instructions, e.g. instruction decode
G16C 10/00 - Computational theoretical chemistry, i.e. ICT specially adapted for theoretical aspects of quantum chemistry, molecular mechanics, molecular dynamics or the like
G06F 15/76 - Architectures of general purpose stored program computers
G16B 15/00 - ICT specially adapted for analysing two-dimensional or three-dimensional molecular structures, e.g. structural or functional relations or structure alignment
75.
Selection-based criteria for computation of multiple body interactions
Distributed computation of multiple body interactions in a region uses multiple processing modules, where each of the processing modules is associated with a respective corresponding portion of the region. In some examples, the approach includes establishing multiple coordinate frames of reference, each processing module corresponding to one the coordinate frames of reference. In some examples, efficient techniques are used for selecting elements for computation of interactions according at least in part to a separation-based criterion.
An approach to data communication makes use of a protocol for encoding data on a serial link that provides both a run length limiting function and a frame marking function, while minimizing communication overhead over the data bearing portions of the signal, and while limiting latency introduced into the communication. In some examples, a single bit is added as a frame marker in such a way that a single bit frame marker also limits run length.
An approach to introducing adaptive routing into a communication approach for passing messages between nodes over links between the nodes includes forming virtual channels over the links of the system and defining a deterministic routing function over the virtual channels such that the deterministic routing function is deadlock free. Adaptive routing is then permitted at nodes using the existing virtual channels by introducing a constraint on the available virtual channels used to forward communication that arrives at a node for a particular destination. The constraint on the virtual channels is such that the adaptive system is also deadlock free.
A computer-implemented method for determining computational units for computing interactions among sets of bodies located in a computation region includes, for each computation associated with one of the sets of bodies, determining, according to an assignment rule that provides a mapping from a location of each of the bodies to a determined computation unit from the plurality of computation units, a computation unit from a plurality of computation units for performing the computation.
G06F 15/16 - Combinations of two or more digital computers each having at least an arithmetic unit, a program unit and a register, e.g. for a simultaneous processing of several programs
G06F 7/60 - Methods or arrangements for performing computations using a digital non-denominational number representation, i.e. number representation without radixComputing devices using combinations of denominational and non-denominational quantity representations
G06G 7/48 - Analogue computers for specific processes, systems, or devices, e.g. simulators
Distributed computation of multiple body interactions in a region uses multiple processing modules, where each of the processing modules is associated with a respective corresponding portion of the region. In some examples, the approach includes establishing multiple coordinate frames of reference, each processing module corresponding to one the coordinate frames of reference. In some examples, efficient techniques are used for selecting elements for computation of interactions according at least in part to a separation-based criterion.
G06F 19/00 - Digital computing or data processing equipment or methods, specially adapted for specific applications (specially adapted for specific functions G06F 17/00;data processing systems or methods specially adapted for administrative, commercial, financial, managerial, supervisory or forecasting purposes G06Q;healthcare informatics G16H)
80.
Distributed computation of multiple-body interactions using local-coordinate reference frames
Distributed computation of multiple body interactions in a region uses multiple processing modules, where each of the processing modules is associated with a respective corresponding portion of the region. In some examples, the approach includes establishing multiple coordinate frames of reference, each processing module corresponding to one the coordinate frames of reference. In some examples, efficient techniques are used for selecting elements for computation of interactions according at least in part to a separation-based criterion.
G06G 7/48 - Analogue computers for specific processes, systems, or devices, e.g. simulators
G06F 19/00 - Digital computing or data processing equipment or methods, specially adapted for specific applications (specially adapted for specific functions G06F 17/00;data processing systems or methods specially adapted for administrative, commercial, financial, managerial, supervisory or forecasting purposes G06Q;healthcare informatics G16H)
A method for dynamics simulation involves maintaining quantities according to a floating point binary format quantized to a first precision lower than the precision supported by the floating point format. For example, although an IEEE floating point number can represent numbers with a precision of one part in 2^24, the quantities are quantized to a lower precision, such as one part in 2^22. Operations are applied to sets of the quantities by quantizing the intermediate results of the operations to the lower precision than the precision supported by the floating point format.
An inter-processor communication approach is applicable to a message passing pattern called iterative exchange. In such patterns, two processors exchange messages, then perform a computation, and then this process is repeated. If two sets of send and receive buffers are used, then it is possible to guarantee that a receive buffer on the receiver's side is always available to receive the message. A message passing system controls which buffers are used for sending and receiving. These buffers are registered beforehand, thereby avoiding repeated registration at the time messages are sent. The sender is initially informed of all the possible receive buffers that the receiver will use, and the sender then uses these receive buffers alternately. Examples of this approach can avoid the use of multiple-step rendezvous protocols, memory copies, and memory registrations when a message needs to be sent.
G06F 3/00 - Input arrangements for transferring data to be processed into a form capable of being handled by the computerOutput arrangements for transferring data from processing unit to output unit, e.g. interface arrangements
G06F 9/44 - Arrangements for executing specific programs
An improved constraint approach reduces the energy drift rate to acceptable levels. In an embodiment of this approach, massively parallel constrained velocity Verlet NVE (constant particle number, constant volume, constant energy) MD simulations can be run using single precision arithmetic with very low energy drift (e.g., ˜1 Kelvin per microsecond simulated time) using large timesteps (e.g., 2.5 fs) for typical systems and MD force fields.
An architecture for computation of particle interactions makes use various forms of parallelism. In one implementation, the parallelism involves using multiple computation nodes arranged according to a geometric partitioning of a simulation volume. These computation nodes together, in a distributed manner, coordinate computation of the particle interactions. Nodes each include a group of subsystems, including a processor subsystem, a computation subsystem, and a memory subsystem, as well as a communication subsystem linking the subsystems of the group of subsystems and providing at least part of a link between subsystems of the node and subsystems of other processing nodes of the processing system. The computation system includes an array of processing modules arranged into one or more serially interconnected processing groups of the processing modules. Each of the processing module includes a storage for data elements and includes circuitry for performing pairwise computations between data elements, each of the pairwise computations making use a data element from the storage of the processing module and a data element passing through the serially interconnected processing modules.
A generalized approach to particle interaction can confer advantages over previously described method in terms of one or more of communications bandwidth and latency and memory access characteristics. These generalizations can involve one or more of at least spatial decomposition, import region rounding, and multiple zone communication scheduling. In a parallel implementation, the generalized approach can have the advantage that the communication bandwidth required by several instances of the approach come close or achieve an approximate lower bound for communication bandwidth. In a serial processing implementation, effective cache utilization can substantially reduce memory latency in processing.
A method and a corresponding software and a system for processing a charge distribution according to a spreading function and a predefined operation are described.
G06F 7/60 - Methods or arrangements for performing computations using a digital non-denominational number representation, i.e. number representation without radixComputing devices using combinations of denominational and non-denominational quantity representations
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