Abstract

The present disclosure provides an improved process for the preparation of glucagon-like peptide-1 agonist peptide. Specifically, it relates to a manufacturing process useful for reducing impurities and increasing the yields and the balance of cost in the preparation of liraglutide or semaglutide.

IPC Classes  ?

• C07K 14/605 - Glucagons
• C07K 14/00 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof

Abstract

The present disclosure provides an improved process for the preparation of glucagon-like peptide-1 agonist peptide. Specifically, it relates to a manufacturing process useful for reducing impurities and increasing the yields and the balance of cost in the preparation of liraglutide or semaglutide.

IPC Classes  ?

• C07K 14/605 - Glucagons

Abstract

The present disclosure provides improved processes for the preparation of Relugolix and intermediates thereof. Relugolix is prepared via intermediates (M7) and (M8): The present disclosure provides improved processes for the preparation of Relugolix and intermediates thereof. Relugolix is prepared via intermediates (M7) and (M8): The present disclosure provides improved processes for the preparation of Relugolix and intermediates thereof. Relugolix is prepared via intermediates (M7) and (M8): wherein X is as described herein. Present disclosure also provides three additional routes to prepare Relugolix and intermediates thereof, where the starting material of ethyl 2-amino-4-methyl-5-(4-nitrophenyl)thiophene-3-carboxylate (SM1) is protected by coupling with an acyl chloride, a hydroxylamine or an oxime.

IPC Classes  ?

• C07D 495/04 - Ortho-condensed systems
• C07D 333/38 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• 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

Abstract

The present disclosure provides improved processes for the preparation of Relugolix and intermediates thereof. Relugolix is prepared via intermediates (M7) and (M8):, wherein X is as described herein. Present disclosure also provides three additional routes to prepare Relugolix and intermediates thereof, where the starting material of ethyl 2- amino-4-methyl-5-(4-nitrophenyl)thiophene-3-carboxylate (SM1) is protected by coupling with an acyl chloride, a hydroxylamine or an oxime.

IPC Classes  ?

• C07D 495/04 - Ortho-condensed systems
• C07D 333/38 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings

Abstract

A one-pot process for preparing cedazuridine of formula (I), A one-pot process for preparing cedazuridine of formula (I), A one-pot process for preparing cedazuridine of formula (I), comprising: subjecting a compound of formula (M3) A one-pot process for preparing cedazuridine of formula (I), comprising: subjecting a compound of formula (M3) A one-pot process for preparing cedazuridine of formula (I), comprising: subjecting a compound of formula (M3) to deprotection and then epimerization in a reactor in the presence of a catalyst to obtain a reaction mixture comprising cedazuridine, wherein R on the compound of formula (M3) is independently selected from the group consisting of Ac (acetyl), Bz (benzoyl), p-nitrobenzoyl and OtBu (tert-butyloxycarbonyl), and the deprotection and epimerization are conducted in the same reactor without isolating after the deprotection and before the epimerization; and isolating cedazuridine from the reaction mixture.

IPC Classes  ?

• C07H 19/06 - Pyrimidine radicals
• C07H 1/06 - SeparationPurification
• B01J 31/02 - Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides

Abstract

The present disclosure relates to a method of preventing or treating brain cancers or brain metastases with mesoporous silica nanoparticles (MSNs) loaded with taxane-based chemotherapeutic drugs, in particular paclitaxel (PTX), cabazitaxel (CTX) or docetaxel (DTX), and the MSNs loaded with PTX, CTX or DTX.

IPC Classes  ?

• A61K 31/337 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
• A61K 9/51 - Nanocapsules
• A61P 35/00 - Antineoplastic agents
• A61P 35/04 - Antineoplastic agents specific for metastasis
• 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

Abstract

A one-pot process for preparing cedazuridine of formula (I), comprising: subjecting a compound of formula (M3) to deprotection and then epimerization in a reactor in the presence of a catalyst to obtain a reaction mixture comprising cedazuridine, wherein R on the compound of formula (M3) is independently selected from the group consisting of Ac (acetyl), Bz (benzoyl), p-nitrobenzoyl and OtBu (tert-butyloxycarbonyl), and the deprotection and epimerization are conducted in the same reactor without isolating after the deprotection and before the epimerization; and isolating cedazuridine from the reaction mixture.

IPC Classes  ?

• C07H 19/06 - Pyrimidine radicals
• C07H 1/06 - SeparationPurification

Abstract

A one-pot process for preparing cedazuridine of formula (I), comprising: subjecting a compound of formula (M3) to deprotection and then epimerization in a reactor in the presence of a catalyst to obtain a reaction mixture comprising cedazuridine, wherein R on the compound of formula (M3) is independently selected from the group consisting of Ac (acetyl), Bz (benzoyl), p-nitrobenzoyl and OtBu (tert-butyloxycarbonyl), and the deprotection and epimerization are conducted in the same reactor without isolating after the deprotection and before the epimerization; and isolating cedazuridine from the reaction mixture.

IPC Classes  ?

• C07H 19/06 - Pyrimidine radicals
• C07H 1/00 - Processes for the preparation of sugar derivatives
• C07H 1/06 - SeparationPurification

Goods & Services

Injection devices for pharmaceuticals; needles for medical use and medical syringes

Abstract

Provided herein are improved processes and methods for preparing osimertinib or a salt thereof, in particular osimertinib mesylate. The improved process removes the necessity of isolating the unstable aniline intermediate of formula (III) and enables the direct coupling to form the amide product of formula (II): The present invention is suitable for a large-scale production, avoiding the isolation of unstable intermediate, thereby providing osimertinib or a mesylate salt thereof in both high yields and high purity.

IPC Classes  ?

• 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
• A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings

Abstract

Provided herein are improved processes and methods for preparing osimertinib or a salt thereof, in particular osimertinib mesylate. The improved process removes the necessity of isolating the unstable aniline intermediate of formula (III) and enables the direct coupling to form the amide product of formula (II): The present invention is suitable for a large-scale production, avoiding the isolation of unstable intermediate, thereby providing osimertinib or a mesylate salt thereof in both high yields and high purity.

IPC Classes  ?

• C07C 303/32 - Preparation of esters or amides of sulfuric acidsPreparation of sulfonic acids or of their esters, halides, anhydrides or amides of salts of sulfonic acids
• C07C 309/04 - Sulfonic acids having sulfo groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton containing only one sulfo group
• 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
• B01J 23/44 - Palladium

Abstract

In certain aspects, the invention provides crystalline forms of ivacaftor N-(2,4-di-tert-butyl-phenyl-5-hydroxy-phenyl)-1,4-dihydro-4-oxoquinoline-3-carboxamide. In related aspects, the invention provides a process for preparing any one of crystalline forms S2, S3, S4 and S5 of ivacaftor. The process includes: forming a solution including crude ivacaftor and a solvent; adding an anti-solvent to the solution to form slurry including a precipitate; isolating the precipitate; and drying the precipitate to provide crystalline form S2, S3, S4, or S5 of ivacaftor.

IPC Classes  ?

• C07D 215/56 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3 with oxygen atoms in position 4
• A61K 31/47 - QuinolinesIsoquinolines

Abstract

In certain aspects, the invention provides crystalline forms of ivacaftor N-(2,4-di-tert-butyl-phenyl-5-hydroxy-phenyl)-1,4-dihydro-4-oxoquinoline-3-carboxamide. In related aspects, the invention provides a process for preparing any one of crystalline forms S2, S3, S4 and S5 of ivacaftor. The process includes: forming a solution including crude ivacaftor and a solvent; adding an anti-solvent to the solution to form slurry including a precipitate; isolating the precipitate; and drying the precipitate to provide crystalline form S2, S3, S4, or S5 of ivacaftor.

IPC Classes  ?

• C07D 215/56 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3 with oxygen atoms in position 4

Abstract

The present invention provides improved processes for purifying semaglutide or liraglutide. Semaglutide or liraglutide is purified via two sequential RP-HPLC purifications followed by a salt-exchange step, where a pH is kept constant in the first and second purification steps. In particular, the processes utilize a halogenated solvent in a sample preparation step, which provides better solubility and an environment suitable for decarboxylation for crude semaglutide or liraglutide prior to a RP-HPLC purification.

IPC Classes  ?

• C07K 1/16 - ExtractionSeparationPurification by chromatography
• C07K 14/605 - Glucagons

Abstract

NN-benzylidene protected compound of formula IV: The present invention is suitable for a large-scale production, avoiding the use of potential genotoxic substances and can be performed under mild conditions.

IPC Classes  ?

• C07D 239/54 - Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
• A61K 31/513 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine

Abstract

The present invention provides improved processes for the preparation of elagolix and intermediates thereof. The intermediate of formula VII is achieved by a coupling reaction of a compound of formula V and a N-benzylidene protected compound of formula IV: The present invention is suitable for a large-scale production, avoiding the use of potential genotoxic substances and can be performed under mild conditions.

IPC Classes  ?

• C07D 239/54 - Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals

Abstract

HH)phthalazin-1-one). In related aspects, the invention provides a processe for preparing the novel crystalline form of olaparib. The process includes forming a solution comprising crude olaparib and an organic solvent; adding the solution to an anti-solvent to form a slurry comprising a precipitate; isolating the precipitate; and drying the precipitate to obtain a crystalline form III of olaparib.

IPC Classes  ?

• C07D 237/32 - Phthalazines with oxygen atoms directly attached to carbon atoms of the nitrogen-containing ring
• A61K 31/502 - PyridazinesHydrogenated pyridazines ortho- or peri-condensed with carbocyclic ring systems, e.g. cinnoline, phthalazine
• A61P 35/00 - Antineoplastic agents

Abstract

Crystalline form S1 of irinotecan free base characterized by a powder X-ray diffraction pattern with peaks at about 8.7±0.2, 13.1±0.2, 14.5±0.2, 17.4±0.2, 18.4±0.2, 20.9±0.2, 24.0±0.2 and 27.5±0.2 degrees two-theta degrees two-theta, and crystalline form S2 of irinotecan free base characterized by a powder X-ray diffraction pattern with peaks at about 7.1±0.2, 10.6±0.2, 12.4±0.2, 20.6±0.2, 21.6±0.2 and 24.2±0.2 degrees two-theta.

IPC Classes  ?

• C07D 491/22 - Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups , , or in which the condensed system contains four or more hetero rings

Abstract

Crystalline form S1 of irinotecan free base characterized by a powder X-ray diffraction pattern with peaks at about 8.7±0.2, 13.1±0.2, 14.5±0.2, 17.4±0.2, 18.4±0.2, 20.9±0.2, 24.0±0.2 and 27.5±0.2 degrees two-theta degrees two-theta, and crystalline form S2 of irinotecan free base characterized by a powder X-ray diffraction pattern with peaks at about 7.1±0.2, 10.6±0.2, 12.4±0.2, 20.6±0.2, 21.6±0.2 and 24.2±0.2 degrees two-theta.

IPC Classes  ?

• C07D 491/22 - Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups , , or in which the condensed system contains four or more hetero rings

Abstract

The present invention provides improved processes for purifying liraglutide. Liraglutide is purified via two sequential RP-HPLC purifications followed by a salt-exchange step, where a pH is kept constant in the first and second purification steps. In particular, the processes utilize a halogenated solvent in a sample preparation step, which provides better solubility and an environment suitable for decarboxylation for crude liraglutide prior to a RP-HPLC purification.

IPC Classes  ?

• C07K 1/20 - Partition-, reverse-phase or hydrophobic interaction chromatography
• C07K 14/605 - Glucagons

Abstract

The present invention provides improved processes for purifying liraglutide.Liraglutide is purified via two sequential RP-HPLC purifications followed by a salt-exchangestep, where a pH is kept constant in the first and second purification steps. In particular, theprocesses utilize a halogenated solvent in a sample preparation step, which provides bettersolubility and an environment suitable for decarboxylation for crude liraglutide prior to aRP-HPLC purification.

IPC Classes  ?

• C07K 1/20 - Partition-, reverse-phase or hydrophobic interaction chromatography
• C07K 1/12 - General processes for the preparation of peptides by hydrolysis

Abstract

In certain aspects, the invention provides a novel crystalline form of olaparib (4-[(3-[(4-cyclopropylcarbonyl)piperazin-4-yl]carbonyl)-4-fluorophenyl]methyl(2H)phthalazin-1-one). In related aspects, the invention provides a processe for preparing the novel crystalline form of olaparib. The process includes forming a solution comprising crude olaparib and an organic solvent; adding the solution to an anti-solvent to form a slurry comprising a precipitate; isolating the precipitate; and drying the precipitate to obtain a crystalline form III of olaparib.

IPC Classes  ?

• C07D 237/32 - Phthalazines with oxygen atoms directly attached to carbon atoms of the nitrogen-containing ring

Abstract

The present invention developed a hypothesis testing approach to analyze the high-dimensional LC-MS data to assess the extent of similarity between a reference drug and generics.

IPC Classes  ?

• G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
• G01N 30/72 - Mass spectrometers
• G01N 1/40 - Concentrating samples
• G01N 30/06 - Preparation
• G01N 30/88 - Integrated analysis systems specially adapted therefor, not covered by a single one of groups

Abstract

A process for preparing sugammadex sodium comprising: reacting a γ-cyclodextrin of formula (I) with triphosgene in the presence of N-methyl-2-pyrrolidone to provide a compound of formula (II); and reacting the compound of formula (II) with 3-mercapto propionic acid in the presence of a sodium base and an organic solvent to provide sugammadex sodium formula (III): wherein X in formula (II) is chloro.

IPC Classes  ?

• C08B 37/16 - CyclodextrinDerivatives thereof
• A61K 31/724 - Cyclodextrins
• A61P 21/00 - Drugs for disorders of the muscular or neuromuscular system

Abstract

Crystalline form S1 of lifitegrast characterized by a powder X-ray diffraction pattern with peaks at about 10.7±0.2, 16.2±0.2, 19.9±0.2, 22.1±0.2, 24.7±0.2, and 25.9±0.2 degrees two-theta, crystalline form S2 of lifitegrast characterized by a powder X-ray diffraction pattern with peaks at about 16.4±0.2, 24.9±0.2, and 26.2±0.2 degrees two-theta, and processes of making thereof are provided.

IPC Classes  ?

• 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

Abstract

A process for preparing cangrelor tetrasodium comprising: a) reacting a compound of formula M1 with morpholine to form a compound of formula M2; and b) reacting the compound of formula M2 with ciodronic acid to provide cangrelor tetrasodium

IPC Classes  ?

• C07F 9/6561 - Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
• A61K 31/675 - Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
• A61P 7/02 - Antithrombotic agentsAnticoagulantsPlatelet aggregation inhibitors

Abstract

The present disclosure provides efficient, economical, and improved processes for synthesizing lifitegrast and intermediates thereof. The currently discloses processes provide a direct synthetic route, avoiding protection or deprotection steps. The currently disclosed process also provides processes for synthesizing lifitegrast using a reduced number of synthetic steps.

IPC Classes  ?

• 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
• A61K 9/00 - Medicinal preparations characterised by special physical form
• A61K 31/4725 - Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
• A61P 27/02 - Ophthalmic agents

Abstract

The present disclosure provides efficient, economical, and improved processes for synthesizing lifitegrast and intermediates thereof. The currently discloses processes provide a direct synthetic route, avoiding protection or deprotection steps. The currently disclosed process also provides processes for synthesizing lifitegrast using a reduced number of synthetic steps.

IPC Classes  ?

• 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

Abstract

The present disclosure provides efficient, economical, and improved processes for synthesizing lifitegrast and intermediates thereof. The currently discloses processes provide a direct synthetic route, avoiding protection or deprotection steps. The currently disclosed process also provides processes for synthesizing lifitegrast using a reduced number of synthetic steps.

IPC Classes  ?

• 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
• A61K 31/4725 - Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
• A61K 9/00 - Medicinal preparations characterised by special physical form
• A61P 27/02 - Ophthalmic agents

Abstract

A process for preparing a compound of formula I': or a pharmaceutically acceptable salt thereof, in which R represents optionally substituted or unsubstituted alkyl group, comprising reacting a compound of formula III: with a carboxylic acid in the presence of a coupling reagent and an organic solvent to obtain the compound of formula I'

IPC Classes  ?

• 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 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
• A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• A61K 31/4725 - Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings

Abstract

The present invention provides efficient, economical, and environmentally friendly processes for synthesizing apalutamide and intermediates thereof. Also provided herein are novel compounds and intermediates thereof.

IPC Classes  ?

• 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
• 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
• A61P 35/00 - Antineoplastic agents

Abstract

A process for preparing sugammadex sodium comprising: reacting a γ-cyclodextrin of formula I with a halogenating agent in the presence of N-methyl-2-pyrrolidone to provide a compound of formula II; and reacting the compound of formula II with 3-mercapto propionic acid in the presence of a sodium base and an organic solvent to provide sugammadex sodium formula III:

IPC Classes  ?

• C08B 37/16 - CyclodextrinDerivatives thereof
• A61K 31/724 - Cyclodextrins

Abstract

Provided herein are novel processes and methods for making 4-[(3-[(4-cyclopropylcarbonyl)piperazin-1-yl]carbonyl)-4-fluorophenyl]methyl(2H)phthalazin-1-one (Olaparib) and intermediates thereof. Olaparib is a poly ADP ribose polymerase (PARP) inhibitor useful in the treatment of cancers. Benefits of the present disclosure include the use of less toxic compounds and improved yields.

IPC Classes  ?

• C07D 237/32 - Phthalazines with oxygen atoms directly attached to carbon atoms of the nitrogen-containing ring

Abstract

Provided herein are novel processes and methods for making 4-[(3-[(4-cyclopropylcarbonyl)piperazin-1-yl]carbonyl)-4-fluorophenyl]methyl(2H)phthalazin-1-one (Olaparib) and intermediates thereof. Olaparib is a poly ADP ribose polymerase (PARP) inhibitor useful in the treatment of of cancers. Benefits of the present disclosure include the use of less toxic compounds and improved yields.

IPC Classes  ?

• C07D 403/10 - 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 aromatic rings
• A61K 31/502 - PyridazinesHydrogenated pyridazines ortho- or peri-condensed with carbocyclic ring systems, e.g. cinnoline, phthalazine

Abstract

The present invention provides processes for the preparation of ataluren. Intermediates for preparing ataluren are also provided.

IPC Classes  ?

• C07D 271/07 - 1,2,4-OxadiazolesHydrogenated 1,2,4-oxadiazoles with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
• A61K 31/4245 - Oxadiazoles

Abstract

Crystalline forms of pemetrexed diacid are provided (Forms 1 and 2) which are readily produced for either laboratory-scale or industrial scale. Processes for the preparation of Forms 1 and 2 are also provided.

IPC Classes  ?

• C07D 487/00 - Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups
• C07D 487/04 - Ortho-condensed systems

Abstract

In certain aspects, the invention provides crystalline forms of olaparib (4-[(3-[(4- cyclopropylcarbonyl)piperazin-4-yl]carbonyl)-4-fluorophenyl]methyl(2H)phthalazin- 1 -one). In related aspects, the invention provides processes for preparing the crystalline forms of olaparib. The processes include: forming a solution comprising crude olaparib and an organic solvent; adding an anti-solvent to the solution to form a slurry comprising a precipitate; isolating the precipitate; and drying the precipitate to obtain a crystalline form I of olaparib or a crystalline form II of olaparib.

IPC Classes  ?

• C07D 237/32 - Phthalazines with oxygen atoms directly attached to carbon atoms of the nitrogen-containing ring
• C07D 403/10 - 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 aromatic rings
• A61K 31/502 - PyridazinesHydrogenated pyridazines ortho- or peri-condensed with carbocyclic ring systems, e.g. cinnoline, phthalazine

Abstract

The present invention provides efficient, economical, and improved methods for synthesizing ibrutinib and intermediates thereof. The invention involves a unique biphasic acylation reaction system which advantageously allows for easy separation of ibrutinib from the reaction mixture without additional extraction and wash steps. The isolated ibrutinib formed using the methods described herein can be useful in the preparation of an amorphous form of ibrutinib. In some embodiments, the isolated ibrutinib produced by the processes described herein is a homogenous solution of ibrutinib and DMSO which may be directly used in the formation of the amorphous polymorph. In some embodiments, the isolated ibrutinib is solid ibrutinib. The solid ibrutinib may also be used in the formation of amorphous ibrutinib.

IPC Classes  ?

• A01N 43/90 - Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
• A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
• C07D 487/00 - Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups
• C07D 487/04 - Ortho-condensed systems
• C07F 9/6561 - Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed 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

Abstract

The present disclosure provides processes for preparing brexpiprazole. The present disclosure also provides processes for the purification of brexpiprazole. The processes for preparing and purifying brexpiprazole of the present invention provide substantial improvements over currently known methods. In certain embodiments, the conversion of Formula XI and XII to form XIII provides increased selectivity over previously reported methods. This offers increased yield and purity. The improved process for purifying brexpiprazole disclosed herein provides brexpiprazole with superior purity and is also more suitable for industrial production.

IPC Classes  ?

• 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 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 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• A61K 31/381 - Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
• A61K 31/4704 - 2-Quinolinones, e.g. carbostyril

Abstract

The present invention provides efficient, economical, and improved methods for synthesizing ibrutinib and intermediates thereof. The invention involves a unique biphasic acylation reaction system which advantageously allows for easy separation of ibrutinib from the reaction mixture without additional extraction and wash steps. The isolated ibrutinib formed using the methods described herein can be useful in the preparation of an amorphous form of ibrutinib. In some embodiments, the isolated ibrutinib produced by the processes described herein is a homogenous solution of ibrutinib and DMSO which may be directly used in the formation of the amorphous polymorph. In some embodiments, the isolated ibrutinib is solid ibrutinib. The solid ibrutinib may also be used in the formation of amorphous ibrutinib.

IPC Classes  ?

• C07D 487/04 - Ortho-condensed systems
• 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
• A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings

Abstract

The present invention provides novel crystalline forms of apremilast hemitoluene solvate, apremilast hydrate, and apremilast anhydrate and an amorphous form of apremilast, and processes for the preparation of these forms.

IPC Classes  ?

• C07D 209/48 - Iso-indolesHydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
• A61K 31/4035 - Isoindoles, e.g. phthalimide

Abstract

The present invention provides novel crystalline forms of apremilast hemitoluene solvate, apremilast hydrate, and apremilast anhydrate and an amorphous form of apremilast, and processes for the preparation of these forms.

IPC Classes  ?

• C07D 209/50 - Iso-indolesHydrogenated iso-indoles with oxygen and nitrogen atoms in positions 1 and 3
• C07D 209/48 - Iso-indolesHydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide

Abstract

The present invention provides a process for the efficient preparation of enzalutamide of the following formula I:

IPC Classes  ?

• C07D 233/86 - Oxygen and sulfur atoms, e.g. thiohydantoin

Abstract

The present invention provides a process for the efficient preparation of enzalutamide of the following formula I:

IPC Classes  ?

• C07D 233/86 - Oxygen and sulfur atoms, e.g. thiohydantoin
• A61K 31/4164 - 1,3-Diazoles

Abstract

The present invention provides a process for the efficient preparation of enzalutamide.

IPC Classes  ?

• C07D 233/86 - Oxygen and sulfur atoms, e.g. thiohydantoin

Abstract

The present invention provides novel processes for the preparation of regadenoson having the formula (I). In some embodiments, the intermediates for the synthesis of regadenoson are also provided.

IPC Classes  ?

• C07H 19/16 - Purine radicals
• C07H 19/167 - Purine radicals with ribosyl as the saccharide radical

Abstract

Crystalline forms of pemetrexed diacid are provided (Forms 1 and 2) which are readily produced for either laboratory-scale or industrial scale. Processes for the preparation of Forms 1 and 2 are also provided.

IPC Classes  ?

• C07D 487/04 - Ortho-condensed systems

Abstract

Crystalline forms of pemetrexed diacid are provided (Forms 1 and 2) which are readily produced for either laboratory-scale or industrial scale. Processes for the preparation of Forms 1 and 2 are also provided.

IPC Classes  ?

• C07D 487/04 - Ortho-condensed systems
• A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
• A61P 35/00 - Antineoplastic agents

Abstract

Crystalline forms of pemetrexed diacid are provided (Forms 1 and 2) which are readily produced for either laboratory-scale or industrial scale. Processes for the preparation of Forms 1 and 2 are also provided.

IPC Classes  ?

• A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
• C07D 487/04 - Ortho-condensed systems

Abstract

Crystalline forms of pemetrexed diacid are provided (Forms 1 and 2) which are readily produced for either laboratory-scale or industrial scale. Processes for the preparation of Forms 1 and 2 are also provided.

IPC Classes  ?

• C07D 487/00 - Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups
• C07D 487/04 - Ortho-condensed systems

Abstract

This invention provides a novel method for the preparation of 2,3- disubstituted-4-oxy-cyclopentan-l-one compounds that are useful for the synthesis of prostaglandins and prostaglandin analogs of industrial relevance. The method comprises the metal -catalyzed asymmetric 1,4-conjugate addition of vinylboron compounds to 2- substituted-4-oxy-cyclopent-2-en-l-ones. This method relies on the use of less toxic, easily- handled reagents, and can be performed under milder conditions than offered by some conventional methods, affording 2,3-disubstituted-4-oxy-cyclopentan-l-one compounds enantio- and diastereoselectively, which are precursors to the said prostaglandin and prostaglandin analogs, in high yield.

IPC Classes  ?

• C07C 45/61 - Preparation of compounds having C=O groups bound only to carbon or hydrogen atomsPreparation of chelates of such compounds by reactions not involving the formation of C=O groups
• C07C 45/65 - Preparation of compounds having C=O groups bound only to carbon or hydrogen atomsPreparation of chelates of such compounds by reactions not involving the formation of C=O groups by splitting-off hydrogen atoms or functional groupsPreparation of compounds having C=O groups bound only to carbon or hydrogen atomsPreparation of chelates of such compounds by reactions not involving the formation of C=O groups by hydrogenolysis of functional groups
• C07C 49/647 - Unsaturated compounds containing a keto group being part of a ring having unsaturation outside the ring
• C07C 69/003 - Esters of saturated alcohols having the esterified hydroxy group bound to an acyclic carbon atom

Abstract

This invention provides a novel method for the preparation of 2,3-disubstituted -4-oxy-cyclopentan1-one compounds that are useful for the synthesis of prostaglandins and prostaglandin analogs of industrial relevance. The method comprises the metal-catalyzed asymmetric 1,4-conjugate addition of vinylboron compounds to 2-substituted -4-oxy-cyclopent-2-en-1-ones. This method relies on the use of less toxic, easily-handled reagents, and can be performed under milder conditions than offered by some conventional methods, affording 2,3-disubstituted-4-oxy-cyclopentan-1-one compounds enantio- and diastereoselectively, which are precursors to the said prostaglandin and prostaglandin analogs, in high yield.

IPC Classes  ?

• C07F 7/04 - Esters of silicic acids
• C07F 7/18 - Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
• C07F 5/02 - Boron compounds

Abstract

The present application discloses a stereoselective process for the preparation of β-C-arylglucosides that does not require the use of conventional carbohydrate protecting groups.

IPC Classes  ?

• C07H 1/00 - Processes for the preparation of sugar derivatives
• C07H 7/04 - Carbocyclic radicals
• C07H 7/06 - Heterocyclic radicals
• C07H 19/01 - Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radicalNucleosidesMononucleotidesAnhydro derivatives thereof sharing oxygen
• A61K 31/70 - CarbohydratesSugarsDerivatives thereof

Abstract

The invention provides a process for the preparation of leuprolide or its pharmaceutical acceptable salts by a combination of solid phase synthesis and post assembly solution phase amidation. The invention also relates to applying a non-protected leuprolide precursor to prepare leuprolide or its pharmaceutically acceptable salts.

IPC Classes  ?

• C07K 7/06 - Linear peptides containing only normal peptide links having 5 to 11 amino acids

Abstract

The present invention provides novel processes for the preparation of regadenoson having the formula (I). In some embodiments, the intermediates for the synthesis of regadenoson are also provided.

IPC Classes  ?

• C07H 19/167 - Purine radicals with ribosyl as the saccharide radical

Abstract

The present disclosure relates to a method for selecting a pool of molecules comprising detecting if the pool of molecules has binding specificity to an agent. A method for selecting a pool of biological markers in or on a cell, a composition comprising a pool of molecules, a method for delivering a therapeutic agent, and a method for diagnosing a condition in a subject are also provided.

IPC Classes  ?

• G01N 33/10 - Starch-containing substances, e.g. dough
• G01N 33/543 - ImmunoassayBiospecific binding assayMaterials therefor with an insoluble carrier for immobilising immunochemicals
• G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer

Abstract

The present invention provides novel processes for the preparation of Fondaparinux sodium by using the compound of formula ABC5. In some embodiments, the intermediates for the synthesis of Fondaparinux sodium, are also provided.

IPC Classes  ?

• C07H 15/18 - Acyclic radicals, substituted by carbocyclic rings
• C07H 1/06 - SeparationPurification
• A61K 31/7024 - Esters of saccharides

Abstract

The present invention provides improved processes of preparing Fondaparinux sodium comprising converting a compound of formula ABCDE4 to Fondaparinux sodium at a reaction pH of no more than about 9.0. In some embodiments, the intermediates for the synthesis of Fondaparinux sodium, are also provided.

IPC Classes  ?

• C07H 1/00 - Processes for the preparation of sugar derivatives
• A61K 31/7024 - Esters of saccharides

Abstract

The present invention describes an analytical method for detecting and quantitating poly-sulfated oligosaccharides, including Fondaparinux sodium, using hydrophilic interaction ultra-performance liquid chromatography (HILIC-UPLC) coupled with a charged aerosol detector (CAD) or a mass spectrometer (MS). This analytical method provides in-process control in a total synthesis of highly sulfated oligosaccharides by separation, quantification and mass identification. Systems and conditions utilizing such methods are also provided.

IPC Classes  ?

• G01N 30/88 - Integrated analysis systems specially adapted therefor, not covered by a single one of groups
• G01N 30/72 - Mass spectrometers

Abstract

The present invention provides intermediates for preparing abiraterone, and processes for preparing abiraterone and intermediates thereof. The intermediates include a compound of formula (IV), wherein R represents a hydroxy-protecting group.

IPC Classes  ?

• C07J 43/00 - Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta[a]hydrophenanthrene skeleton
• C07J 31/00 - Normal steroids containing one or more sulfur atoms not belonging to a hetero ring

Abstract

The present invention relates to a novel process of making ixabepilone, ixabepilone derivatives and analogues, and intermediates thereof.

IPC Classes  ?

• 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
• C07D 491/044 - Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
• C07D 285/14 - ThiadiazolesHydrogenated thiadiazoles condensed with carbocyclic rings or ring systems

Abstract

The present disclosure relates to a method for selecting a pool of molecules comprising detecting if the pool of molecules has binding specificity to an agent. A method for selecting a pool of biological markers in or on a cell, a composition comprising a pool of molecules, a method for delivering a therapeutic agent, and a method for diagnosing a condition in a subject are also provided.

IPC Classes  ?

• G01N 33/53 - ImmunoassayBiospecific binding assayMaterials therefor
• G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer
• C40B 30/04 - Methods of screening libraries by measuring the ability to specifically bind a target molecule, e.g. antibody-antigen binding, receptor-ligand binding

Abstract

A compound of formula (X): which can be used as an intermediate to make lapatinib or its pharmaceutically acceptable salt.

IPC Classes  ?

• C07D 239/72 - QuinazolinesHydrogenated quinazolines
• 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

Goods & Services

Active pharmaceutical ingredients sold as an integral component of pharmaceutical preparations; medicines for use in human.

Goods & Services

(1) Active pharmaceutical ingredients sold as integral components of pharmaceutical reparations for human purposes, namely, pharmaceutical preparations for the treatment of cancer, autoimmune diseases, Infectious diseases, namely, respiratory infections, eye infections, dysentery, bacterial enteritis, pneumonia, Inflammatory bowel diseases, inflammatory connective tissue diseases, inflammatory muscle diseases, genetic diseases, respiratory diseases, diseases of the circulatory system, metabolic diseases, namely, diabetes, hypoglycemia, gout, osteoarthritis, muscular dystrophy, anaemia, hypothyroidism, eye diseases, psychiatric and other brain diseases and disorders, namely, anxiety, mood disorders, schizophrenia, cognitive and bipolar disorders, epilepsy, Alzheimer's, cerebral palsy, Parkinson's disease, multiple sclerosis, seizures, blood and hemopoietic diseases, diseases of the urinary system, digestive diseases, endocrine diseases, bone and muscle diseases; medicines for human purposes, namely, pharmaceutical preparations for the treatment of cancer, autoimmune diseases, infectious diseases, namely, respiratory infections, eye infections, dysentery, bacterial enteritis, pneumonia, inflammatory bowel diseases, inflammatory connective tissue diseases, inflammatory muscle diseases, genetic diseases, respiratory diseases, diseases of the circulatory system, metabolic diseases, namely, diabetes, hypoglycemia, gout, osteoarthritis, muscular dystrophy, anaemia, hypothyroidism, eye diseases, digestive disease, psychiatric and other brain diseases and disorders, namely, anxiety, mood disorders, schizophrenia, cognitive and bipolar disorders, epilepsy, Alzheimer's, cerebral palsy, Parkinson's disease, multiple sclerosis, seizures, blood and hemopoietic diseases, diseases of the urinary system, digestive diseases, endocrine diseases, bone and muscle diseases; nutritional additives for medical purposes for use in foods and dietary supplements for human consumption.

Goods & Services

Active pharmaceutical ingredients sold as integral components of pharmaceutical preparations for treating cancer, autoimmune diseases, infectious diseases, inflammatory diseases, genetic diseases, respiratory diseases, mental diseases, ophthalmic diseases, digestive diseases, endocrine diseases, diseases of muscle-skeletal system, metabolic disorder diseases, diseases of central nervous system, cardiovascular diseases; medicines for use in humans for treating cancer, autoimmune diseases, infectious diseases, inflammatory diseases, genetic diseases, respiratory diseases, mental diseases, ophthalmic diseases, digestive diseases, endocrine diseases, diseases of muscle-skeletal system, metabolic disorder diseases, diseases of central nervous system, cardiovascular diseases

Abstract

The present invention provides efficient and economical methods for synthesis of (-)-2-exo-morpholinoisoborne-10-thiol, its enantiomer, and related chiral catalysts. Novel compounds and methods of asymmetric synthesis are also disclosed.

IPC Classes  ?

• C07C 315/06 - SeparationPurificationStabilisationUse of additives
• C07C 321/16 - Sulfides, hydropolysulfides, or polysulfides having thio groups bound to acyclic carbon atoms of a saturated carbon skeleton containing rings
• C07D 295/00 - 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

Abstract

The present invention relates to processes for making cabazitaxel, cabazitaxel analogues and intermediates thereof. The invention provides novel compounds useful in the synthesis of cabazitaxel.

IPC Classes  ?

• 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 305/14 - Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms condensed with carbocyclic rings or ring systems
• A61K 31/337 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
• A61P 35/00 - Antineoplastic agents

Abstract

The present invention provides processes for stereoselectively preparing C-arylglucosides that can be useful as synthetic building block or drugs, including SGLT2 inhibitors.

IPC Classes  ?

• C07H 1/00 - Processes for the preparation of sugar derivatives
• C07H 7/04 - Carbocyclic radicals
• C07H 7/06 - Heterocyclic radicals
• C07H 19/01 - Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radicalNucleosidesMononucleotidesAnhydro derivatives thereof sharing oxygen
• A61K 31/70 - CarbohydratesSugarsDerivatives thereof

Abstract

The present invention provides amorphous forms and the crystalline complexes of SGLT2 inhibitors as a novel material, in particular in pharmaceutically acceptable form. The crystalline forms of SGLT2 inhibitor canagliflozin are designated as Forms CS1, CS2, CS3, CS4 and CS5.

IPC Classes  ?

• A61K 31/7004 - Monosaccharides having only carbon, hydrogen and oxygen atoms
• A61K 31/7034 - Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
• C07H 7/04 - Carbocyclic radicals

Abstract

A novel process of making 7,10-dialkyl-10-DAB of formula (I) which is useful as a key intermediate for the preparation of cabazitaxel, comprises selective elaboration of positions 7 and 10 of 10-deacetylbaccatin III.

IPC Classes  ?

• C07D 305/14 - Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms condensed with carbocyclic rings or ring systems
• A61K 31/337 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
• A61P 35/00 - Antineoplastic agents

Abstract

, The present invention provides crystalline forms, including an anhydrate form, of cabazitaxel and processes for the preparation of these forms, designated as Forms C1, C2, C3, C4, C5, C6, C7, C8, C8b, C9 and C9p.

IPC Classes  ?

• C07D 305/14 - Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms condensed with carbocyclic rings or ring systems
• A61K 31/337 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
• A61P 35/00 - Antineoplastic agents

Abstract

The present invention provides a process for making lapatinib and its pharmaceutically acceptable salt by use of new intermediates. A new process for obtaining a pharmaceutical form of lapatinib ditosylate monohydrate is also provided.

IPC Classes  ?

• C07D 239/72 - QuinazolinesHydrogenated quinazolines

Abstract

A method of purifying a compound from a mixture through a chromatographic column loaded with a column adsorbent. The method comprises: applying the mixture to the chromatographic column; eluting the mixture with an elution solvent composition; and collecting the compound; wherein at least one of the column adsorbent and elution solvent is selected based on one of solubility parameters of the compound, column adsorbent, elution solvent, and conformation energy of the compound.

IPC Classes  ?

• B01D 15/32 - Bonded phase chromatography, e.g. with normal bonded phase, reversed phase or hydrophobic interaction
• C07K 1/20 - Partition-, reverse-phase or hydrophobic interaction chromatography
• G01N 30/02 - Column chromatography
• C07K 1/16 - ExtractionSeparationPurification by chromatography

Abstract

A process of making a pemetrexed salt comprising: a) reacting a compound of formula II or an acid salt thereof, wherein each of R1 and R2 is independently a C1-C6 alkyl group, with an aqueous basic solution at a temperature of no more than 10°C to obtain a first mixture comprising the pemetrexed salt; b) isolating the pemextrexed salt from the first mixture.

IPC Classes  ?

• C07D 487/04 - Ortho-condensed systems
• A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
• A61P 35/00 - Antineoplastic agents

Abstract

The present invention provides an efficient and scalable process to prepare the compound of formula 4 by reduction of the corresponding α-acyloxy sulfides.

IPC Classes  ?

• C07C 213/10 - SeparationPurificationStabilisationUse of additives
• C07C 215/08 - Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being saturated and acyclic with only one hydroxy group and one amino group bound to the carbon skeleton
• C07C 317/24 - SulfonesSulfoxides having sulfone or sulfoxide groups and doubly-bound oxygen atoms bound to the same carbon skeleton

Abstract

Provided are systems, apparatus, materials and methods for directly monitoring products and intermediates of solid phase chemical synthesis such as solid phase peptide synthesis.

IPC Classes  ?

• G01N 33/483 - Physical analysis of biological material
• H01J 49/26 - Mass spectrometers or separator tubes
• G01N 27/62 - Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating the ionisation of gases, e.g. aerosolsInvestigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electric discharges, e.g. emission of cathode

Abstract

A method for screening cells with high level expression of a target protein is disclosed. The method includes introducing into a plurality of host cells a DNA construct that encodes both a target protein and an inhibitor to an endogenous selectable marker in the host cells, screening host cells harboring the DNA construct for the expression of the endogenous selectable marker, and isolating cells with reduced expression of the selectable marker. Also disclosed is a DNA construct configured to express both the target protein and the inhibitor inside the host cell.

IPC Classes  ?

• C12N 15/00 - Mutation or genetic engineeringDNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purificationUse of hosts therefor

Goods & Services

Active pharmaceutical ingredients for medicine; medicines for use in human; nutritional additives for medical purposes; pharmaceutical and veterinary preparations. Scientific and technological services and research and design relating thereto; industrial analysis and research services; chemical research services; chemistry services; chemical analysis services; biological research; biological research and analysis services; research service relating to manufacturing process of medicines and pharmaceuticals; pharmaceutical research service.

Abstract

Provided are a process for preparing lapatinib and its pharmaceutically acceptable salt by use of new intermediates, and a process for obtaining a pharmaceutical form of lapatinib ditosylate monohydrate.

IPC Classes  ?

• 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 239/94 - Nitrogen atoms

Abstract

The present invention provides a process for making lapatinib and its pharmaceutically acceptable salt by use of new intermediates. A new process for obtaining a pharmaceutical form of lapatinib ditosylate monohydrate is also provided.

IPC Classes  ?

• 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 239/94 - Nitrogen atoms

Abstract

A process of making entecavir comprising converting a compound of formula (M5) to entecavir, wherein the two PGs on the formula (M5) are taken together to form an optionally substituted six- or seven-member cyclic ring.

IPC Classes  ?

• C07D 473/18 - Heterocyclic compounds containing purine ring systems with oxygen, sulfur, or nitrogen atoms directly attached in positions 2 and 6 one oxygen and one nitrogen atom, e.g. guanine
• C07D 307/33 - Oxygen atoms in position 2, the oxygen atom being in its keto or unsubstituted enol form
• C07C 35/06 - Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a ring other than a six-membered aromatic ring monocyclic containing five-membered rings
• C07D 307/20 - Oxygen atoms
• C07C 69/03 - Esters of acyclic saturated monocarboxylic acids having the carboxyl group bound to an acyclic carbon atom or to hydrogen esterified with alcohols having the esterified hydroxy group bound to a carbon atom of a ring other than a six-membered aromatic ring

Abstract

A process of making entecavir comprising converting a compound of formula (M5) wherein the two PGs on the formula (M5) are taken together to form an optionally substituted six- or seven-member cyclic ring.

IPC Classes  ?

• C07D 473/00 - Heterocyclic compounds containing purine ring systems
• C07D 307/93 - Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems condensed with a ring other than six-membered
• C07C 47/00 - Compounds having —CHO groups

Abstract

A process for the preparation of topiramate in an one pot reaction comprises the following steps: A) reacting 2,3:4, 5 -bis -O- { 1-methylethylidene) -β-D-f ructopyranose with sulfurylchloride in xylene in the presence of an organic or inorganic base to form 2,3:4, 5-bis-O- (1-methylethylidene) -β-D-f ructopyranose sulfuryl chloride, B) adding a second organic solvent to the mixture obtained in step A) C) reacting the mixture obtained in step B) with ammonia to form topiramate.

IPC Classes  ?

• C07H 9/04 - Cyclic acetals

Abstract

The present invention provides for a method of characterizing and classifying a sample containing a complex molecule, such as a peptide or polypeptide mixture, protein, protein mixture, biologic and biosimilar by using physical analysis, such as mass spectrometry, and statistic methods.

IPC Classes  ?

• H01J 17/26 - Means for producing, introducing, or replenishing gas or vapour during operation of the tube

Abstract

Crystalline form of cladribine characterized by a powder X-ray diffraction pattern having a peak at about 26.1° ± 0.2° two-theta (2θ) is disclosed. An amorphous form of cladribine is also disclosed herein. Either of these forms of cladrbine can be incorporated with a pharmaceutically acceptable carrier to form a pharmaceutical composition for treating cancer.

IPC Classes  ?

• C07H 19/16 - Purine radicals
• C07H 19/167 - Purine radicals with ribosyl as the saccharide radical
• A61K 31/7076 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
• A61P 35/00 - Antineoplastic agents

Abstract

A method for producing a β-enriched protected decitabine comprising: a) coupling a protected 2-deoxy-ribofuranose with a protected 5-azacytosine in the presence of a catalyst to form a reaction mixture comprising the protected decitabine of formula (I); and b) quenching the reaction mixture of step a) with a base. The β-enriched protected decitabine so made may be deprotected to produce a decitabine product in a high yield and purity.

IPC Classes  ?

• C07D 251/02 - Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
• C07H 19/12 - Triazine radicals

Abstract

A method for producing a .beta.-enriched protected decitabine comprising: a) coupling a protected 2-deoxy-ribofuranose with a protected 5-azacytosine in the presence of a catalyst to form a reaction mixture comprising the protected decitabine of formula (I); and b) quenching the reaction mixture of step a) with a base. The .beta.-enriched protected decitabine so made may be deprotected to produce a decitabine product in a high yield and purity.

IPC Classes  ?

• C07D 251/02 - Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
• C07H 19/12 - Triazine radicals

Abstract

The present invention provides for new crystalline and amorphous forms of 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione, and methods of making the same.

IPC Classes  ?

• 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 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID]
• A61P 37/00 - Drugs for immunological or allergic disorders
• 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
• A61P 35/00 - Antineoplastic agents

Abstract

A process for the preparation of cladribine of API grade is provided by direct coupling of O-protected 2-deoxy-ribofuranose with silylated 2-chloroadenine followed by deprotection of the resultant protected nucleoside in a separate step and then a purification step. Following the coupling, the desired N-9-glycosylated β-anomer of the nucleoside is directly isolated as a solid from the coupling reaction mixture by filtration in relatively high purity and yield, and it does not require purification.

IPC Classes  ?

• C07H 19/00 - Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radicalNucleosidesMononucleotidesAnhydro derivatives thereof
• C07H 19/22 - Pteridine radicals
• A01N 43/04 - Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atom with one hetero atom
• A61K 31/70 - CarbohydratesSugarsDerivatives thereof

Abstract

A process for making a capecitabine or its derivative comprising (a) reacting a compound of the formula (II): wherein each of R1 and R2 independently represents a hydroxyl protecting group, with an acylating agent of formula (III): X-C(=O)-R3, wherein X is an acyl activating group in an organic solvent to produce an acylated compound; (b) deprotecting the acylated compound to obtain the compound of formula (I); and (c) purifying the compound of formula (I) with a solvent.

IPC Classes  ?

• C07H 19/067 - Pyrimidine radicals with ribosyl as the saccharide radical
• C07D 239/47 - One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
• C07D 239/553 - Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms with halogen atoms or nitro radicals directly attached to ring carbon atoms, e.g. fluorouracil

Abstract

A method for screening cells with high level expression of a target protein is disclosed. The method includes introducing into a plurality of host cells a DNA construct that encodes both a target protein and an inhibitor to an endogenous selectable marker in the host cells, screening host cells harboring the DNA construct for the expression of the endogenous selectable marker, and isolating cells with reduced expression of the selectable marker. Also disclosed is a DNA construct configured to express both the target protein and the inhibitor inside the host cell.

IPC Classes  ?

• C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving nucleic acids
• C12N 15/63 - Introduction of foreign genetic material using vectorsVectorsUse of hosts thereforRegulation of expression
• C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides

Abstract

The present invention provides for a method of characterizing and classifying a sample of peptide or polypeptide mixtures or a biomolecule comprising a polypeptide component by using mass spectrometry and statistic methods for analyzing the mass spectrometry results The present invention also discloses a method of synthesizing glatiramer acetate utilizing tetrabutylammonium hydroxide.

IPC Classes  ?

• C12Q 1/37 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving hydrolase involving peptidase or proteinase
• G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
• C40B 20/08 - Direct analysis of the library members per se by physical methods, e.g. spectroscopy
• C40B 30/10 - Methods of screening libraries by measuring physical properties, e.g. mass
• G01N 27/00 - Investigating or analysing materials by the use of electric, electrochemical, or magnetic means

Abstract

The present invention provides for a method of characterizing and classifying a sample of peptide or polypeptide mixtures or a biomolecule comprising a polypeptide component by using mass spectrometry and statistic methods for analyzing the mass spectrometry results.

IPC Classes  ?

• H01J 17/26 - Means for producing, introducing, or replenishing gas or vapour during operation of the tube

Abstract

The present invention provides for a method of characterizing and classifying a sample of peptide or polypeptide mixtures or a biomolecule comprising a polypeptide component by using mass spectrometry and statistic methods for analyzing the mass spectrometry results The present invention also discloses a method of synthesizing glatiramer acetate utilizing tetrabutylammonium hydroxide

IPC Classes  ?

• A61K 31/785 - Polymers containing nitrogen
• G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing

Goods & Services

(1) Active pharmaceutical ingredients sold as an integral component of pharmaceutical preparations, namely: active pharmaceutical ingredients used for the manufacture of pharmaceutical products having activity in the cardiovascular area, in the gastrointestinal area, in the central nervous system, as anti-osteoporosis agents, as anti-glaucoma agents, as anti-virals, as anti-diabetics, as anti-histaminic, as anti-asthmatics, as anti-inflammatories and for oncological therapy. (2) Medicines for human purposes, namely, pharmaceutical preparations for the treatment of cancer, autoimmune diseases, infectious diseases, namely : herpes, hepatitis, acquired immune deficiency syndrome (AIDS), respiratory infections, eye infections, topical infections, swine dysentery, bacterial enteritis, Bluecomb, pneumonia, swine bacterial infectious diseases, Measles and Malaria, inflammatory diseases, namely : chronic inflammatory diseases, inflammatory bowel diseases, inflammatory connective tissue diseases, inflammatory pelvic diseases, genetic diseases, respiratory diseases, diseases of the circulatory system, metabolic diseases, namely : diabetes, hypoglycaemia, gout, osteoarthritis, muscular dystrophy, anemia, eye diseases, digestive disease, nervous and mental diseases, namely : Alzheimer's disease, Parkinson's disease, Hungtington's disease, Pick's disease, dementia, amyotrophic lateral sclerosis, multiple sclerosis, stroke, ischaemia, epilepsy, brain injury, brain diseases, encephalitis, spinal cord injury, spinal cord diseases, cerebral paralysis, seizure disorders, central nervous system movement disorders, central nervous system infections, nociceptive and neuropathic pain, central nervous system inflammation, chronic inflammatory diseases, Down's syndrome, Lewy body disease and mood disorders, namely depression, schizophrenia and bipolar disorders, blood and hemopoietic diseases, diseases of the urinary system, digestive diseases, endocrine diseases, bone and muscle diseases. (3) Nutritional additives for medical purposes for use in foods and dietary supplements for human consumption.

Abstract

The present invention provides a method for producing a protected precursor of Decitabine as well as the Decibatine final product in high yield and purity.

IPC Classes  ?

• A01N 43/04 - Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atom with one hetero atom
• A61K 31/70 - CarbohydratesSugarsDerivatives thereof

Abstract

a) coupling a protected 2-deoxy-ribofuranose with a protected 5-azacytosine in the presence of a catalyst to form a reaction mixture comprising the protected decitabine of formula I; and b) quenching the reaction mixture of step a) with a base. The β-enriched protected decitabine so made may be deprotected to produce a decitabine product in a high yield and purity.

IPC Classes  ?

• C08B 37/00 - Preparation of polysaccharides not provided for in groups Derivatives thereof
• C07H 5/04 - Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium to nitrogen
• C07H 5/06 - Aminosugars

Abstract

The present invention relates to the efficient commercial synthesis of Bivalirudin.

IPC Classes  ?

• A61K 38/00 - Medicinal preparations containing peptides
• C07K 1/00 - General processes for the preparation of peptides

Abstract

The present invention provides for an efficient process for making Pramlinitide, as well as novel intermediates for the making of the same.

IPC Classes  ?

• A61K 38/00 - Medicinal preparations containing peptides
• C07K 1/00 - General processes for the preparation of peptides