Provided herein are solid forms, for example polymorphs, of 2 -(3 - ((7 R, 8a S) -7 -fl uo ro h exa hyd ro pyrro Io [ 1, 2-a ] pyra zi n - 2 (1 H) - yl) - 1- (5- methyl - 2 - ((I - methy l-lH-pyrazol-4-yl)amino)pyrimidin-4- yl)azetidin-3-yl)acetonitrile, which are useful for treating kinase- related diseases or disorders. The solid forms, and compositions thereof, are useful for treating diseases, including, without limitation, eye disease, such as glaucoma, ocular hypertension, ocular wound repair, neurodegenerative ocular diseases, retinal detachment, and non-ocular diseases such as neuronal damage, or skin wound repair, or inflammatory diseases, among others, in a subject. (Compound 1)
Described are improved processes for the syntheses of isoquinoline- based compounds that are kinase inhibitors or useful pharmaceutical intermediates thereof, and, pharmaceutical compositions including these compounds, and methods of using these compounds and compositions for treating diseases, including, without limitation, eye disease, such as glaucoma, ocular hypertension, ocular wound repair, neurodegenerative ocular diseases, retinal detachment, and non¬ ocular diseases such as neuronal damage, or skin wound repair, or inflammatory diseases, among others, in a subject.
C07D 205/06 - Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
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 403/14 - 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 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 403/14 - 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 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID]
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 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
4.
SYNTHETIC INTERMEDIATES AND IMPROVED PROCESSES FOR PREPARING ROCK INHIBITORS
Provided herein are methods of synthesizing netarsudil, and intermediates thereof, in high yield and at large commercial scale. A key intermediate in this synthesis is the preparation of piperidinium (S)-3-((tert-butoxycarbonyl)amino)-2-(4-(((2,4-dimethylbenzoyl)oxy)methyl)phenyl)propanoate, a salt that has been found to be easily purified by recrystallization.
C07C 271/22 - Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
C07D 295/027 - 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 containing only hydrogen and carbon atoms in addition to the ring hetero elements containing only one hetero ring
C07D 217/02 - Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ringAlkylene-bis-isoquinolines
5.
OPHTHALMIC PHARMACEUTICAL COMPOSITIONS AND USES THEREOF
A61K 31/167 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen atom of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
A61K 47/44 - Oils, fats or waxes according to two or more groups of Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
Provided herein are ophthalmic pharmaceutical compositions comprising (1R,2S,5R)-2-isopropyl-N-(4-methoxyphenyl)-5-methylcyclohexane-1-carboxamide (WS-12) for effectively treating dry eye in a subject in need thereof, effectively reducing dry eye in a subject in need thereof, effectively reducing the likelihood of dry eye in a subject in need thereof, or for treating, preventing, or ameliorating signs or symptoms of dry eye in a subject in need thereof.
A61K 31/167 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen atom of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
A61K 47/44 - Oils, fats or waxes according to two or more groups of Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
Provided herein are pyrazole compounds. In particular, provided herein are compounds that affect the function of kinases in a cell and that are useful as therapeutic agents or with therapeutic agents. The compounds provided herein are useful in the treatment of a variety of diseases and conditions including cardiovascular diseases, JAK-associated diseases, such as diseases characterized by abnormal growth, such as cancers, and inflammatory diseases, or eye diseases such as glaucoma. Also provided herein are compositions comprising pyrazole compounds.
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 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 403/14 - 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 405/14 - 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 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
Provided herein are pyrazole compounds. In particular, provided herein are compounds that affect the function of kinases in a cell and that are useful as therapeutic agents or with therapeutic agents. The compounds provided herein are useful in the treatment of a variety of diseases and conditions including cardiovascular diseases, JAK-associated diseases, such as diseases characterized by abnormal growth, such as cancers, and inflammatory diseases, or eye diseases such as glaucoma. Also provided herein are compositions comprising pyrazole compounds.
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 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 403/14 - 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 405/14 - 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 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
Provided herein are azetidine pyrimidine compounds. In particular, provided herein are compounds that affect the function of kinases in a cell, and that are useful as therapeutic agents or with therapeutic agents. The compounds provided herein are useful in the treatment of a variety of diseases and conditions including inflammatory eye diseases such as uveitis, cardiovascular diseases, inflammatory diseases, and diseases characterized by abnormal growth, such as cancers. Also provided herein are compositions comprising azetidine pyrimidine compounds.
A61P 37/00 - Drugs for immunological or allergic disorders
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 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
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
Provided herein are azetidine pyrimidine compounds. In particular, provided herein are compounds that affect the function of kinases in a cell, and that are useful as therapeutic agents or with therapeutic agents. The compounds provided herein are useful in the treatment of a variety of diseases and conditions including inflammatory eye diseases such as uveitis, cardiovascular diseases, inflammatory diseases, and diseases characterized by abnormal growth, such as cancers. Also provided herein are compositions comprising azetidine pyrimidine compounds.
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 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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 31/551 - 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 37/00 - Drugs for immunological or allergic disorders
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 403/04 - 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 403/14 - 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 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
Provided herein are solid forms of alpha-(aminomethyl)-4-(hydroxymethyl)-N-6-isoquinolinyl-(S)- benzeneacetamide mono-tosylate salt ("Compound 1 mono-tosylate"), pharmaceutical compositions containing the solid forms, methods of producing the solid forms, and methods of treating various ocular diseases or disorders by administering the solid forms.
C07D 217/00 - Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
C07C 309/30 - Sulfonic acids having sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton of non-condensed six-membered aromatic rings of six-membered aromatic rings substituted by alkyl groups
Provided herein are compounds and pharmaceutical compositions useful in modulating kinase activity, and related diseases. These compounds are conjugates of glucocorticoids with rho-kinase inhibitors. Also provided herein are methods of treating an eye disease or disorder in a subject. Also provided herein are methods of reducing intraocular pressure in a subject. Also provided herein are methods of modulating kinase activity in a cell. Also provided herein are methods of making the compounds provided herein, and compounds useful for the preparation of the compounds provided herein.
A61K 31/573 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
A61K 31/58 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
A61P 5/44 - GlucocorticosteroidsDrugs increasing or potentiating the activity of glucocorticosteroids
C07J 5/00 - Normal steroids containing carbon, hydrogen, halogen, or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane, and substituted in position 21 by only one singly bound oxygen atom
C07J 41/00 - Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
C07J 43/00 - Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta[a]hydrophenanthrene skeleton
C07J 71/00 - Steroids in which the cyclopenta[a]hydrophenanthrene skeleton is condensed with a heterocyclic ring
13.
STABLE ISOQUINOLINE-CORTICOSTEROID CONJUGATES AND USES THEREOF
Provided herein are compounds and pharmaceutical compositions useful in modulating kinase activity, and related diseases. These compounds are conjugates of glucocorticoids with rho-kinase inhibitors. Also provided herein are methods of treating an eye disease or disorder in a subject. Also provided herein are methods of reducing intraocular pressure in a subject. Also provided herein are methods of modulating kinase activity in a cell. Also provided herein are methods of making the compounds provided herein, and compounds useful for the preparation of the compounds provided herein.
C07J 5/00 - Normal steroids containing carbon, hydrogen, halogen, or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane, and substituted in position 21 by only one singly bound oxygen atom
C07J 41/00 - Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
C07J 43/00 - Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta[a]hydrophenanthrene skeleton
C07J 71/00 - Steroids in which the cyclopenta[a]hydrophenanthrene skeleton is condensed with a heterocyclic ring
A61P 5/44 - GlucocorticosteroidsDrugs increasing or potentiating the activity of glucocorticosteroids
A61K 31/58 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
A61K 31/573 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
Implant delivery devices, methods of device assembly and methods of using those devices are presented, where the delivery device uses an automatic implant delivery mechanism that eliminates variability in pusher wire speeds by providing a needle assembly having one or more implants positioned within a proximal end of a needle cannula (10), a dampener assembly (13) and a shuttle assembly (14) located within a housing along with the activation member (5), which holds the shuttle assembly (14) in cocked or pre-tensioned state. A lock can be engaged with the activation member (14) to prevent premature firing or triggering of the device.
A61F 9/00 - Methods or devices for treatment of the eyesDevices for putting in contact-lensesDevices to correct squintingApparatus to guide the blindProtective devices for the eyes, carried on the body or in the hand
Implant delivery devices, methods of device assembly and methods of using those devices are presented, where the delivery device uses an automatic implant delivery mechanism that eliminates variability in pusher wire speeds by providing a needle assembly having one or more implants positioned within a proximal end of a needle cannula (10), a dampener assembly (13) and a shuttle assembly (14) located within a housing along with the activation member (5), which holds the shuttle assembly (14) in cocked or pre-tensioned state. A lock can be engaged with the activation member (14) to prevent premature firing or triggering of the device.
A61F 9/00 - Methods or devices for treatment of the eyesDevices for putting in contact-lensesDevices to correct squintingApparatus to guide the blindProtective devices for the eyes, carried on the body or in the hand
A medical implant is disclosed. The medical implant includes a body having a first end having a first cross-sectional dimension, a second end having a second cross-sectional dimension, and a tapered portion extending between the first end and the second end. The first cross-sectional dimension is larger than the second cross-sectional dimension. In some embodiments, the body comprises multiple layers.
A61K 9/00 - Medicinal preparations characterised by special physical form
A61F 9/00 - Methods or devices for treatment of the eyesDevices for putting in contact-lensesDevices to correct squintingApparatus to guide the blindProtective devices for the eyes, carried on the body or in the hand
A medical implant is disclosed. The medical implant includes a body having a first end having a first cross-sectional dimension, a second end having a second cross-sectional dimension, and a tapered portion extending between the first end and the second end. The first cross-sectional dimension is larger than the second cross-sectional dimension. In some embodiments, the body comprises multiple layers.
A61F 9/00 - Methods or devices for treatment of the eyesDevices for putting in contact-lensesDevices to correct squintingApparatus to guide the blindProtective devices for the eyes, carried on the body or in the hand
A61K 9/00 - Medicinal preparations characterised by special physical form
Described herein are compounds, combinations of compounds, compositions, formulations, and methods of treating viruses, viral load, and manifestations of viral infections.
Provided herein are pharmaceutical preparations comprising an aqueous ophthalmic composition that comprises a therapeutically effective amount of WS-12 (1R,2S,5R-2-isopropyl-5-methyl-cyclohexanecarboxy lie acid (4-methoxy phenyl)-amide) for effectively treating or reducing the likelihood of xerophthalmia in a subject, wherein the amount of WS-12 per dose in the aqueous ophthalmic composition is not cytotoxic, and the aqueous ophthalmic composition is housed in a package formed of one or more polyolefin resins, one or more polyester resins, or any combination thereof. The housing of such an aqueous ophthalmic composition in such a package provides a residual rate, i.e. the amount of active WS-12 contained in such an ophthalmic aqueous composition after exposure to an external effects such as light, high temperature of at least about 40° C, increased humidity of up to 25%, or any combination thereof for 1, 2, 3 or more months of at least 80%, at least 90%, at least 95% or at least 98% or more as compared to the amount of active WS-12 in such an aqueous ophthalmic composition before such exposure to any of the external effects.
Provided herein are heterobicyclic cyclopropanecarboxamide and heterobicyclic carboxamide compounds. In particular, provided herein are compounds that affect the function of kinases in a cell, and that are useful as therapeutic agents or with therapeutic agents. The compounds provided herein are useful in the treatment of a variety of diseases and conditions including eye diseases such as glaucoma, cardiovascular diseases, inflammatory diseases, and diseases characterized by abnormal growth, such as cancers. Also provided herein are compositions comprising heterobicyclic cyclopropanecarboxamide or heterobicyclic carboxamide compounds.
A61K 31/4365 - 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 having sulfur as a ring hetero atom, e.g. ticlopidine
C07D 409/02 - 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
Provided herein are pharmaceutical compositions, intravitreal implants and particle suspensions comprising a polymer matrix and at lest one therapeutic agent that is released in a substantially linear manner for a particular duration.
A61K 31/472 - Non-condensed isoquinolines, e.g. papaverine
A61K 47/34 - Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
Provided herein are pharmaceutical compositions, intravitreal implants and particle suspensions comprising a polymer matrix and at lest one therapeutic agent that is released in a substantially linear manner for a particular duration.
A61K 31/472 - Non-condensed isoquinolines, e.g. papaverine
A61K 47/34 - Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
Provided herein are thienyl cyclopropyl-amino-isoquinoline amide compounds. In particular, provided herein are compounds that affect the function of kinases in a cell and that are useful as therapeutic agents or with therapeutic agents. The compounds provided herein are useful in the treatment of a variety of diseases and conditions including eye diseases such as glaucoma, cardiovascular diseases, diseases characterized by abnormal growth, such as cancers, and inflammatory diseases. Also provided herein are compositions comprising thienyl cyclopropyl-amino-isoquinoline amide compounds.
Provided herein are 8-methyl-8-azabicyclo[3.2.1]octan-3-yl and pyridin-4-ylmethanyl ester and amide compounds and compositions. Also provided herein are methods of preventing or delaying the onset of myopia in a subject in need thereof, comprising administering the compounds or compositions provided herein to the subject. Also provided herein are methods of reducing or preventing the progression of myopia in a subject in need thereof, comprising administering the compounds or compositions provided herein to the subject.
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
A61K 31/4409 - Non-condensed pyridinesHydrogenated derivatives thereof only substituted in position 4, e.g. isoniazid, iproniazid
A61K 31/46 - 8-Azabicyclo [3.2.1] octaneDerivatives thereof, e.g. atropine, cocaine
A61K 47/06 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
A61P 27/10 - Ophthalmic agents for accommodation disorders, e.g. myopia
Provided herein are 8-methyl-8-azabicyclo[3.2.1]octan-3-yl and pyridin-4-ylmethanyl ester and amide compounds and compositions. Also provided herein are methods of preventing or delaying the onset of myopia in a subject in need thereof, comprising administering the compounds or compositions provided herein to the subject. Also provided herein are methods of reducing or preventing the progression of myopia in a subject in need thereof, comprising administering the compounds or compositions provided herein to the subject.
A61K 31/4365 - 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 having sulfur as a ring hetero atom, e.g. ticlopidine
A61K 31/439 - 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 forming part of a bridged ring system, e.g. quinuclidine
A61K 31/4409 - Non-condensed pyridinesHydrogenated derivatives thereof only substituted in position 4, e.g. isoniazid, iproniazid
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 31/4436 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a heterocyclic ring having sulfur as a ring hetero atom
A61K 31/445 - Non-condensed piperidines, e.g. piperocaine
A61K 31/46 - 8-Azabicyclo [3.2.1] octaneDerivatives thereof, e.g. atropine, cocaine
A61K 31/501 - PyridazinesHydrogenated pyridazines not condensed and containing further heterocyclic rings
A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61P 27/10 - Ophthalmic agents for accommodation disorders, e.g. myopia
C07D 213/38 - Radicals substituted by singly-bound nitrogen atoms having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
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 295/088 - 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 attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
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 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 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 451/04 - 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 with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.02,4] nonane ring system
Provided herein are amino isoquinolinyl amide and sulfonamide compounds that affect the function of kinases and other proteins in a cell and that are useful as therapeutic agents. In particular, these compounds are useful in the treatment of eye diseases such as glaucoma and retinal diseases, as anti-inflammatory agents, for the treatment of cardiovascular diseases, and for diseases characterized by abnormal growth, such as cancers.
C07D 217/02 - Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ringAlkylene-bis-isoquinolines
C07D 217/22 - Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
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 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
Provided herein are amino isoquinolinyl amide and sulfonamide compounds that affect the function of kinases and other proteins in a cell and that are useful as therapeutic agents. In particular, these compounds are useful in the treatment of eye diseases such as glaucoma and retinal diseases, as anti-inflammatory agents, for the treatment of cardiovascular diseases, and for diseases characterized by abnormal growth, such as cancers.
A61K 31/4725 - Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
C07D 217/22 - Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
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
Provided herein are compounds and pharmaceutical compositions useful in modulating kinase activity, and related diseases. Also provided herein are methods of treating an eye disease or disorder in a subject. Also provided herein are methods of reducing intraocular pressure in a subject. Also provided herein are methods of modulating kinase activity in a cell. Also provided herein are methods of making the compounds provided herein, and compounds useful for the preparation of the compounds provided herein.
A61K 31/472 - Non-condensed isoquinolines, e.g. papaverine
A61K 31/4725 - Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
A61K 31/56 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids
A61K 47/55 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
Provided herein are mono-(acid) salts of a compound of a Formulae provided herein. Also provided herein are compositions comprising a mono-(acid) salt of a compound of a Formulae provided herein. Also provided herein are pharmaceutical compositions comprising a mono- (acid) salt of a compound of a Formulae provided herein. Also provided herein are methods of treating a disease in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a mono-(acid) salt of a compound of a Formulae provided herein.
C07D 217/02 - Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ringAlkylene-bis-isoquinolines
30.
MONO-(ACID) SALTS OF 6-AMINOISOQUINOLINES AND USES THEREOF
Provided herein are mono-(acid) salts of a compound of a Formulae provided herein. Also provided herein are compositions comprising a mono-(acid) salt of a compound of a Formulae provided herein. Also provided herein are pharmaceutical compositions comprising a mono- (acid) salt of a compound of a Formulae provided herein. Also provided herein are methods of treating a disease in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a mono-(acid) salt of a compound of a Formulae provided herein.
C07D 217/22 - Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
31.
AMINO-BENZOISOTHIAZOLE AND AMINO-BENZOISOTHIADIAZOLE AMIDE COMPOUNDS
Provided herein are amino-benzoisothiazole and benzoisothiadiazole amide compounds. In particular, provided herein are compounds that affect the function of kinases in a cell and that are useful as therapeutic agents or with therapeutic agents. The compounds provided herein are useful in the treatment of a variety of diseases and conditions including eye diseases such as glaucoma, retinal diseases such as acute macular degeneration (AMD) and diabetic macular edema (DME), diseases and conditions characterized by inflammatory processes, cardiovascular diseases, and diseases characterized by abnormal growth, such as cancers. Also provided are compositions (e.g., pharmaceutical compositions) comprising the compounds provided herein.
Provided herein are arylcyclopropyl amino-isoquinoline amide compounds. In particular, the disclosure provides compounds that affect the function of kinases in a cell and that are useful as therapeutic agents or with therapeutic agents. The compounds of the disclosure are useful in the treatment of a variety of diseases and conditions including eye diseases such as glaucoma, cardiovascular diseases, diseases characterized by abnormal growth, such as cancers, and inflammatory diseases. The disclosure further provides compositions containing isoquinoline amide compounds.
C07D 217/22 - Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
C07D 217/02 - Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ringAlkylene-bis-isoquinolines
C07D 217/22 - Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
The present disclosure provides an ophthalmic composition comprising 4-(3-amino-1-(isoquinoiin-6-yiamino)-1-oxopropan-2-yi)benzyi 2,4-dirnethylbenzoate or its pharmaceutically acceptable salts; about 0.01% weight/volume to about 1.0% weight/volume of a buffer; and about 0.01% weight/volume to about 10% weight/volume of a tonicity agent.
An intracameral injector needle having a substantially cylindrical body defining a longitudinal flow path therein, and having a proximal end, a distal end, an outer peripheral face and a bevel region. A first bevel of the bevel region has a first bevel angle with respect to the outer peripheral face. A second bevel of the bevel region extends from the first bevel to the proximal end. The second bevel includes a tip of the intracameral injector needle, and has a second bevel angle with respect to the outer peripheral face, where the second bevel angle is different from the first bevel angle, the first bevel and the second bevel defining a transition therebetween. The transition is at least one of: (1 ) longitudinally positioned between the tip of the intracameral injector needle and a location of a maximum width of the bevel region; and (2) vertically disposed at a position below 50% of a maximum height of the bevel region.
A61F 9/00 - Methods or devices for treatment of the eyesDevices for putting in contact-lensesDevices to correct squintingApparatus to guide the blindProtective devices for the eyes, carried on the body or in the hand
The present disclosure provides an ophthalmic composition comprising 4-(3-amino-1-(isoquinoiin-6-yiamino)-1-oxopropan-2-yi)benzyi 2,4-dirnethylbenzoate or its pharmaceutically acceptable salts; about 0.01% weight/volume to about 1.0% weight/volume of a buffer; and about 0.01% weight/volume to about 10% weight/volume of a tonicity agent.
Disclosed are alpha-axyl-beta-axmno isoquinoline amide compounds and substituted benzamide compounds. In particular, the invention provides compounds that affect the function of kinases in a cell and that are useful as therapeutic agents or with therapeutic agents. The compounds of the invention are useful in the treatment of a variety of diseases and conditions including eye diseases such as glaucoma, cardiovascular diseases, and diseases characterized by abnormal growth, such as cancers. The invention further provides compositions containing isoquinoline amide compounds.
A61K 31/472 - Non-condensed isoquinolines, e.g. papaverine
C07D 217/02 - Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ringAlkylene-bis-isoquinolines
Disclosed are alpha-axyl-beta-axmno isoquinoline amide compounds and substituted benzamide compounds. In particular, the invention provides compounds that affect the function of kinases in a cell and that are useful as therapeutic agents or with therapeutic agents. The compounds of the invention are useful in the treatment of a variety of diseases and conditions including eye diseases such as glaucoma, cardiovascular diseases, and diseases characterized by abnormal growth, such as cancers. The invention further provides compositions containing isoquinoline amide compounds.
C07D 333/22 - Radicals substituted by doubly bound hetero atoms, or by two hetero atoms other than halogen singly bound to the same carbon atom
C07C 237/48 - 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 six-membered aromatic ring being part of a condensed ring system of the same carbon skeleton
39.
PROCESS FOR THE PREPARATION OF KINASE INHIBITORS AND INTERMEDIATES THEREOF
Described are processes for the synthesis of certain compounds, useful for treating diseases, e.g. eye disease, such as glaucoma and ocular hypertension, in a subject.
Described are processes for the synthesis of compounds of Formula (I):(I);and pharmaceutically acceptable salts thereof, which may be useful for treating diseases, e.g. eye disease, such as glaucoma and ocular hypertension, in a subject.
A61K 31/235 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group
A61K 31/421 - 1,3-Oxazoles, e.g. pemoline, trimethadione
A61K 31/472 - Non-condensed isoquinolines, e.g. papaverine
C07C 69/767 - Esters of carboxylic acids having an esterified carboxyl group bound to a carbon atom of a six-membered aromatic ring esterified with unsaturated alcohols having the esterified hydroxy group bound to an acyclic carbon atom
C07D 217/02 - Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ringAlkylene-bis-isoquinolines
The disclosure teaches precisely engineered biodegradable drug delivery systems and methods of making and utilizing such systems. In aspects, the biodegradable drug delivery systems taught herein comprise intravitreal ocular implants suitable for delivery of corticosteroids to the posterior segment of a human eye. The intravitreal ocular implants described herein have a desired extended drug release profile suitable for treating inflammation of the human eye.
A61K 31/711 - Natural deoxyribonucleic acids, i.e. containing only 2'-deoxyriboses attached to adenine, guanine, cytosine or thymine and having 3'-5' phosphodiester links
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
42.
INTRAVITREAL DRUG DELIVERY SYSTEMS FOR THE TREATMENT OF OCULAR CONDITIONS
The disclosure teaches precisely engineered biodegradable drug delivery systems and methods of making and utilizing such systems. In aspects, the biodegradable drug delivery systems taught herein comprise intravitreal ocular implants suitable for delivery of corticosteroids to the posterior segment of a human eye. The intravitreal ocular implants described herein have a desired extended drug release profile suitable for treating inflammation of the human eye.
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
A61K 31/711 - Natural deoxyribonucleic acids, i.e. containing only 2'-deoxyriboses attached to adenine, guanine, cytosine or thymine and having 3'-5' phosphodiester links
Described herein are compounds and compositions for treating glaucoma and/or reducing intraocular pressure. Compositions may comprise an isoquinoline compound and a prostaglandin or a prostaglandin analog. Compounds described herein include those in which an isoquinoline compound is covalently linked to a prostaglandin or a prostaglandin analog, and those in which an isoquinoline compound and a prostaglandin free acid together form a salt.
Described herein are compounds and compositions for treating glaucoma and/or reducing intraocular pressure. Compositions may comprise an isoquinoline compound and a prostaglandin or a prostaglandin analog. Compounds described herein include those in which an isoquinoline compound is covalently linked to a prostaglandin or a prostaglandin analog, and those in which an isoquinoline compound and a prostaglandin free acid together form a salt.
Drug delivery devices comprising a non-bioabsorbable polymer structure configured to support a composition comprising an active agent. The devices include a plurality of portions fused together and a recess configured to support the composition. At least one of the portions includes an impermeable polymer and at least one other portion includes a rate-limiting water- permeable polymer. The rate-limiting water-permeable polymer allows for transportation of the active agent to an exterior of the device.
Provided are compounds that are inhibitors of both rho kinase and of a monoamine transporter (MAT) act to im-prove the disease state or condition. Further provided are compositions comprising the compounds. Further provided are methods for treating diseases or conditions, the methods comprising administering compounds according to the invention. One such dis-ease may be glaucoma for which, among other beneficial effects, a marked reduction in intraocular pressure (lOP) may be achieved.
C07C 237/00 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
C07D 217/00 - Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
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 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 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
48.
DUAL MECHANISM INHIBITORS FOR THE TREATMENT OF DISEASE
Provided are compounds that are inhibitors of both rho kinase and of a monoamine transporter (MAT) act to improve the disease state or condition. Further provided are compositions comprising the compounds. Further provided are methods for treating diseases or conditions, the methods comprising administering compounds according to the invention. One such disease may be glaucoma for which, among other beneficial effects, a marked reduction in intraocular pressure (lOP) may be achieved.
C07D 217/00 - Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
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 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 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
C07C 237/00 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
Provided are compounds, compositions, and methods for treating diseases and conditions wherein an inhibitor of a kinase, such as rho kinase (ROCK), and an inhibitor of one or more of the monoamine transporters, such as NET or SERT, act in concert to improve the condition.
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
A61P 9/00 - Drugs for disorders of the cardiovascular system
Provided are compounds that are inhibitors of both rho kinase and of a monoamine transporter (MAT) act to improve the disease state or condition. Further provided are compositions comprising the compounds. Further provided are methods for treating diseases or conditions, the methods comprising administering compounds according to the invention. One such disease may be glaucoma for which, among other beneficial effects, a marked reduction in intraocular pressure (10P) may beachieved. Compounds according to the invention include those according to Formula l:(see formula I)wherein B, O, Z, X1, R1, R2, A, R3, X2, and X3, are as defined in the specification.
C07D 217/02 - Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ringAlkylene-bis-isoquinolines
Provided are compounds, compositions, and methods for treating diseases and conditions wherein an inhibitor of a kinase, such as rho kinase (ROCK), and an inhibitor of one or more of the monoamine transporters, such as NET or SERT, act in concert to improve the condition.
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
A61P 9/00 - Drugs for disorders of the cardiovascular system
A61K 31/5575 - Eicosanoids, e.g. leukotrienes having a cyclopentane ring, e.g. prostaglandin E2, prostaglandin F2-alpha
C07C 279/14 - Derivatives of guanidine, i.e. compounds containing the group the singly-bound nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of guanidine groups bound to acyclic carbon atoms of a carbon skeleton being further substituted by carboxyl groups
C07C 291/02 - Compounds containing carbon and nitrogen and having functional groups not covered by groups containing nitrogen-oxide bonds
C07C 405/00 - Compounds containing a five-membered ring having two side-chains in ortho position to each other, and having oxygen atoms directly attached to the ring in ortho position to one of the side-chains, one side-chain containing, not directly attached to the ring, a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, and the other side-chain having oxygen atoms attached in gamma-position to the ring, e.g. prostaglandins
53.
DRUG DELIVERY DEVICES FOR DELIVERY OF THERAPEUTIC AGENTS
Drug delivery devices comprising a non-bioabsorbable polymer structure and a composition comprising an active agent have been discovered. The drug delivery devices may be used to treat ocular conditions, among other diseases and conditions. In addition, a method of treating an ocular condition has been discovered comprising implanting a drug delivery device which releases the active agent at a rate of Q = 0.001 x N x C wherein C is the topical effective concentration (in milligram/mL) of the active agent and N=0.01 to 0.5 for prostaglandins in their ester, amide, free acid or salt form, and N=0.5 to 5 for any active agent other than prostaglandins in their ester, amide, free acid or salt form.
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 47/32 - Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers
A61K 47/34 - Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
A61K 47/36 - PolysaccharidesDerivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
54.
BETA-AND GAMMA-AMINO-ISOQUINOLINE AMIDE COMPOUNDS AND SUBSTITUTED BENZAMIDE COMPOUNDS
Disclosed are beta and gamma-amino isoquinoline amide compounds and substituted benzamide compounds. In particular, the invention provides compounds that affect the function of kinases in a cell and that are useful as therapeutic agents or with therapeutic agents. The compounds of the invention are useful in the treatment of a variety of diseases and conditions including eye diseases such as glaucoma, cardiovascular diseases, and diseases characterized by abnormal growth, such as cancers. The invention further provides compositions containing the beta or gαmmα-amino isoquinoline amide compounds or substituted benzamide compounds.
C07D 217/02 - Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ringAlkylene-bis-isoquinolines
C07D 333/24 - 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 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 405/12 - 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 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 413/12 - 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 chain containing hetero atoms as chain links
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
A61K 31/472 - Non-condensed isoquinolines, e.g. papaverine
Disclosed are beta and gamma-amino isoquinoline amide compounds and substitutedbenzamide compounds. In particular, the invention provides compounds that affect the functionof kinases in a cell and that are useful as therapeuticagents or with therapeutic agents. The compounds of the invention are useful in the treatment of a variety of diseases and conditions including eye diseases such as glaucoma, cardiovasculardiseases, and diseases characterized by abnormal growth, such as cancers. The invention further provides compositions containing the beta or gamma-amino isoquinoline amide compounds or substituted benzamide compounds.
C07D 217/02 - Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ringAlkylene-bis-isoquinolines
C07D 333/24 - 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 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 405/12 - 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 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 413/12 - 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 chain containing hetero atoms as chain links
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
56.
6- AND 7-AMINO ISOQUINOLINE COMPOUNDS AND METHODS FOR MAKING AND USING THE SAME
6- and 7-amino isoquinoline compounds are provided that influence, inhibit or reduce the action of a kinase. Phar-maceutical compositions including therapeutically effective amounts of the 6- and 7-aminoisoquinoline compounds and pharma-ceutically acceptable carriers are also provided. Various methods using the compounds and/or compositions to affect disease states or conditions such as cancer, obesity and glaucoma are also provided.
A61K 31/4725 - Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
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
C07D 217/02 - Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ringAlkylene-bis-isoquinolines
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
57.
6-AND 7-AMINO ISOQUINOLINE COMPOUNDS AND METHODS FOR MAKING AND USING THE SAME
6- and 7-amino isoquinoline compounds are provided that influence, inhibit or reduce the action of a kinase. Pharmaceutical compositions including therapeutically effective amounts of the 6- and 7-aminoisoquinoline compounds and pharmaceutically acceptable carriers are also provided. Various methods using the compounds and/or compositions to affect disease states or conditions such as cancer, obesity and glaucoma are also provided.
C07D 217/02 - Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ringAlkylene-bis-isoquinolines
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
A61K 31/4709 - Non-condensed quinolines containing further heterocyclic rings
6-Amino isoquinoline compounds are provided that influence, inhibit or reduce the action of a kinase. Pharmaceutical compositions including therapeutically effective amounts of the 6-aminoisoquinoline compounds and pharmaceutically acceptable carriers are also provided. Various methods using the compounds and/or compositions to affect disease states or conditions such as cancer, obesity and glaucoma are also provided.
C07D 217/14 - Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring other than aralkyl radicals
This invention relates to novel homotopic prodrugs and medicaments and methods for their preparation, testing and use. In one embodiment, the homotopic prodrug has the general formula (I) wherein (II) is a biologically-active moiety comprising a carboxylic acid functional group, and Rb is a homotopically-symmetrical alcohol bonded to the biologically-active moiety through the carboxylic acid functional group to form an ester linkage, as well as optical isomers, enantiomers, pharmaceutically acceptable salts, biohydrolyzable amides, esters, and imides thereof and combinations thereof.
C07C 219/10 - Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton having esterified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having at least one of the hydroxy groups esterified by a carboxylic acid having the esterifying carboxyl group bound to an acyclic carbon atom of a carbon skeleton containing rings
C07C 233/65 - Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
C07C 251/48 - Oximes with oxygen atoms of oxyimino groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with the carbon atom of at least one of the oxyimino groups bound to a carbon atom of a six-membered aromatic ring
C07C 317/44 - SulfonesSulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton
C07C 405/00 - Compounds containing a five-membered ring having two side-chains in ortho position to each other, and having oxygen atoms directly attached to the ring in ortho position to one of the side-chains, one side-chain containing, not directly attached to the ring, a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, and the other side-chain having oxygen atoms attached in gamma-position to the ring, e.g. prostaglandins
C07C 409/38 - Peroxy compounds the —O—O— group being bound between a C=O group and a carbon atom, not further substituted by oxygen atoms, i.e. esters of peroxy acids
C07C 69/736 - Ethers the hydroxy group of the ester being etherified with a hydroxy compound having the hydroxy group bound to a carbon atom of a six-membered aromatic ring
C07C 69/612 - Esters of carboxylic acids having a carboxyl group bound to an acyclic carbon atom and having a six-membered aromatic ring in the acid moiety
C07C 69/618 - Esters of carboxylic acids having a carboxyl group bound to an acyclic carbon atom and having a six-membered aromatic ring in the acid moiety having unsaturation outside the six-membered aromatic ring
C07D 295/145 - 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 carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
C07D 295/15 - 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 carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
C07D 333/00 - Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
C07D 207/273 - 2-Pyrrolidones with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to other ring carbon atoms
Isoquinoline compounds are provided that influence, inhibit or reduce the action of a G-protein receptor kinase . Pharmaceutical compositions including therapeutically effective amounts of the isoquinoline compounds and pharmaceutically acceptable carriers are also provided. Various methods using the compounds and/or compositions to affect disease states or conditions such as cancer, osteoporosis and glaucoma are also provided.
C07D 217/02 - Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ringAlkylene-bis-isoquinolines
A61K 31/472 - Non-condensed isoquinolines, e.g. papaverine
PHENYLAMINO-ACETIC ACID ⏧1-(PYRIDIN-4-YL)-METHYLIDENE]-HYDRAZIDE DERIVATIVES AND RELATED COMPOUNDS AS MODULATORS OF G PROTEIN-COUPLED RECEPTOR KINASES FOR THE TREATMENT OF EYE DISEASES
Hydrazide compounds with GPCR desensitization inhibitory activity are provided that may be used to influence, inhibit or reduce the action of a G-protein receptor kinase. Pharmaceutical compositions including therapeutically effective amounts of the hydrazide compounds and pharmaceutically acceptable carriers are also provided. Various methods using the compounds and/or compositions to affect disease states or conditions controlled or influenced by GPCRs are also provided. Various methods using the compounds and/or compositions to affect disease states or conditions such as cancer osteoporosis and glaucoma are also provided. (Formula (I)). A is selected from a heteroaryl group (i): wherein X1, X2, X3 and X4 are, independently, CH, O, S or N-R6, with the proviso that at least one of X2 or X3 is O, S or N-R6; and a heteroaryl group (ii): wherein X5 and X9 are CH or C-halogen, X6 and X8 are CH, and X7 is N, and wherein the six-membered heteroaryl group may be further fused with an unsubstituted six-member aryl group; R1, R2, R3, R4, and R5 are, independently, hydrogen; halogen; C1-C4 alkyl; amino; nitro; cyano; heteroaryl; carboxy, carbonylamino; aminosulfonyl; sulfonylamino; aminoacyl; thioalkyl; sulfonyl; acyl; heterocycle; -OR; -O-C1-C4alkyl-heterocycle; -C(O)NH-C1-C4alkyl-heterocycle; -C(O)NH-heteroaryl; -C(O)NH-aryl; or carboxylamino; wherein R is C1-C4 alkyl; aryl, heteroaryl, C1-C4 alkyl aryl or C1-C4 alkyl heteroaryl; R6 is H or C1-C4 alkyl; R7 is hydrogen, C1-C4 alkyl or C1-C4 alkoxy; and X is N-R6.
A61K 31/381 - Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
A61K 31/341 - 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 not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
A61K 31/513 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
patents
