- An Efficient Second-Generation Manufacturing Process for the pan-RAF Inhibitor Belvarafenib
-
Herein, the development of a streamlined manufacturing process for the pan-RAF inhibitor belvarafenib (GDC-5573) is reported. The process to belvarafenib features a number of efficient key reactions, including a robust and scalable Pd-catalyzed carbonylation reaction to generate thienopyrimidine 2 and a highly chemoselective Pt/V/C-catalyzed nitro group reduction to access the penultimate intermediate 3. The final amide coupling was accomplished by a mild and safe protocol employing N,N,N′,N′-tetramethylchloroformamidinium hexafluorophosphate as the coupling reagent, which afforded belvarafenib on a multikilogram production scale after recrystallization.
- Zell, Daniel,Dalziel, Michael E.,Carrera, Diane E.,Stumpf, Andreas,Bachmann, Stephan,Mercado-Marin, Eduardo,Koenig, Stefan G.,Zhang, Haiming,Gosselin, Francis
-
p. 2338 - 2350
(2021/09/28)
-
- SHP2 PHOSPHATASE INHIBITORS AND METHODS OF USE THEREOF
-
The present disclosure relates to novel compounds including formula (X) and pharmaceutical compositions thereof, and methods for inhibiting the activity of SHP2 phosphatase with the compounds and compositions of the disclosure. The present disclosure further relates to, but is not limited to, methods for treating disorders associated with SHP2 deregulation with the compounds and compositions of the disclosure.
- -
-
Paragraph 0267
(2019/10/15)
-
- Synthetic process of 7-bromo-4-chlorothieno [3,2-D] pyrimidine
-
The invention relates to a synthetic method of 7-bromo-4-chlorothieno [3,2-D] pyrimidine. The synthetic method comprises the following steps: adding 3-amino-2-methyl formate thiophene and formamide into ethylene glycol monomethyl ether, heating to 120-140 DEG C to reflux, then adding saturated salt water when a solvent is not reduced anymore, and filtering to obtain solid 4-hydroxyl thieno-pyrimidine; adding 4-hydroxyl thieno-pyrimidine, N-bromo-succinimide and sodium hexametahposphate into acetone, reacting at 5-30 DEG C, filtering, adding water into a filtrate, stirring, filtering, and collecting solids to obtain 4-hydroxyl-7-bromo-thieno-pyrimidine; and adding the 4-hydroxyl-7-bromo-thieno-pyrimidine into phosphorus oxychloride, heating to reflux, then pouring into ice water, stirring until solids are generated, filtering, and drying in the air to obtain 7-bromo-4-chlorothieno [3,2-D] pyrimidine. By use of the synthetic process, the total yield of the 7-bromo-4-chlorothieno [3,2-D] pyrimidine is improved, the cost is effectively reduced. The synthetic method of 7-bromo-4-chlorothieno [3,2-D] pyrimidine is suitable for industrial large-scale synthesis application.
- -
-
Paragraph 0022
(2016/10/08)
-
- FUSED PYRIMIDINE DERIVATIVES HAVING INHIBITORY ACTIVITY ON FMS KINASES
-
Disclosed are a fused pyrimidine derivative of formula (I), and a pharmaceutically acceptable salt, stereoisomer, hydrate and solvate thereof, which have an excellent inhibitory activity on FMS kinases, and a pharmaceutical composition comprising the same is effective in preventing or treating diseases caused by abnormal activation of FMS kinases such as immunologic diseases, metabolic diseases, inflammatory diseases, cancers and tumors.
- -
-
-
- THIENO[3,2-D]PYRIMIDINE DERIVATIVES HAVING INHIBITORY ACTIVITY FOR PROTEIN KINASES
-
Provided are a thieno[3,2-d]pyrimidine derivative of formula (I) or a pharmaceutically acceptable salt thereof having inhibitory activity for protein kinase, and a pharmaceutical composition comprising same for prevention and treatment of abnormal cell growth diseases.
- -
-
-
- NOVEL PYRIMIDINE DERIVATIVE AND PHARMACEUTICAL COMPOSITION INCLUDING SAME AS AN ACTIVE INGREDIENT
-
The present invention relates to a compound represented by formula (I) for inhibiting the activity of diacylglycerol O-acyltransferase type 1 (DGAT1), and pharmaceutically acceptable salts thereof, and a pharmaceutical composition comprising same as an active ingredient. The compound of the present invention may be used effectively in the treatment or prevention of a disease or condition mediated by the activity of DGAT1 such as obesity, type II diabetes, dyslipidemia, metabolic syndrome, and the like, without any adverse effects: wherein A, B, X, and R5 to R7 are the same as defined in the specification.
- -
-
Paragraph 0036; 0041; 0042
(2014/06/24)
-
- NOVEL PYRIMIDINE DERIVATIVE AND PHARMACEUTICAL COMPOSITION INCLUDING SAME AS AN ACTIVE INGREDIENT
-
The present invention relates to a compound represented by formula (I) for inhibiting the activity of diacylglycerol O-acyltransferase type 1 (DGAT1), and pharmaceutically acceptable salts thereof, and a pharmaceutical composition comprising same as an active ingredient. The compound of the present invention may be used effectively in the treatment or prevention of a disease or condition mediated by the activity of DGAT1 such as obesity, type II diabetes, dyslipidemia, metabolic syndrome, and the like, without any adverse effects: wherein A, B, X, and R5 to R7 are the same as defined in the specification.
- -
-
Paragraph 0121-0123
(2014/06/24)
-
- THIENO[3,2-d]PYRIMIDINE DERIVATIVES HAVING INHIBITORY ACTIVITY ON PROTEIN KINASES
-
The present invention relates to a thieno[3,2-d]pyrimidine derivative of formula (I), or a pharmaceutically acceptable salt, hydrate or solvate thereof, which has an excellent inhibitory activity on protein kinases, and a pharmaceutical composition comprising the same is effective in preventing or treating abnormal cell growth diseases.
- -
-
-
- THIENO[3,2-d]PYRIMIDINE DERIVATIVES HAVING INHIBITORY ACTIVITY FOR PROTEIN KINASES
-
Provided are a thieno[3,2-d]pyrimidine derivative of formula (I) or a pharmaceutically acceptable salt thereof having inhibitory activity for protein kinase, and a pharmaceutical composition comprising same for prevention and treatment of abnormal cell growth diseases
- -
-
-
- NEW BICYCLIC COMPOUND FOR MODULATING G PROTEIN-COUPLED RECEPTORS
-
The present invention relates to a bicyclic compound for modulating G protein-coupled receptors. The inventive compound provides preventing or treating a disease associated with the modulation of G protein-coupled receptors, particularly GPR119 G protein-coupled receptors.
- -
-
-
- NEW BICYCLIC COMPOUND FOR MODULATING G PROTEIN-COUPLED RECEPTORS
-
The present invention relates to a bicyclic compound for modulating G protein-coupled receptors. The inventive compound provides preventing or treating a disease associated with the modulation of G protein-coupled receptors, particularly GPR119 G protein-coupled receptors.
- -
-
-
- BICYCLIC HETEROARYL DERIVATIVES HAVING INHIBITORY ACTIVITY FOR PROTEIN KINASE
-
The present invention relates to a novel bicyclic heteroaryl derivative, a pharmaceutically acceptable salt thereof, a hydrate thereof, and a solvate thereof having an improved inhibitory activity for protein kinases, and a pharmaceutical composition for preventing or treating an abnormal cell growth disorder comprising same as an active ingredient.
- -
-
-
- BICYCLIC HETEROCYCLE DERIVATIVES AND METHODS OF USE THEREOF
-
Compounds of structural formula I: are GPR119 agonists and are useful for the treatment, control or prevention of disorders responsive to agonism of GPR119, such as metabolic-related disorders such as type I diabetes, type II diabetes, inadequate glucose tolerance, insulin resistance, hyperglycemia, hyperlipidemia, hypertriglyceridemia, hypercholesterolemia, dyslipidemia or syndrome X. The compounds are also reported as being useful for controlling weight gain, controlling food intake, and inducing satiety in mammals.
- -
-
Page/Page column 54
(2012/01/06)
-
- THIENO[3,2-d]PYRIMIDINE DERIVATIVES HAVING INHIBITORY ACTIVITY ON PROTEIN KINASES
-
The present invention relates to a thieno[3,2-d]pyrimidine derivative of formula (I), or a pharmaceutically acceptable salt, hydrate or solvate thereof, which has an excellent inhibitory activity on protein kinases, and a pharmaceutical composition comprising the same is effective in preventing or treating abnormal cell growth diseases.
- -
-
-
- BICYCLIC HETEROARYL DERIVATIVES HAVING INHIBITORY ACTIVITY FOR PROTEIN KINASE
-
The present invention relates to a novel bicyclic heteroaryl derivative, a pharmaceutically acceptable salt thereof, a hydrate thereof, and a solvate thereof having an improved inhibitory activity for protein kinases, and a pharmaceutical composition for preventing or treating an abnormal cell growth disorder comprising same as an active ingredient.
- -
-
-
- HETEROCYCLIC COMPOUNDS AND METHODS OF USE
-
In one aspect, the present invention provides for a compound of Formula I; in which the variable X1a, X1b, X1c, X1d, Q, A, R1, B, L, E, and the subscripts m and n have the meanings as described herein. In another aspect, the present invention provides for pharmaceutical compositions comprising compounds of Formula I as well as methods for using compounds of Formula I for the treatment of diseases and conditions (e.g., cancer, thrombocythemia, etc) characterized by the expression or over-expression of Bcl-2 anti-apoptotic proteins, e.g., of anti-apoptotic Bcl-xL proteins.
- -
-
Page/Page column 167-168
(2010/08/04)
-
- The efficient one-step chlorination of methylsulfanyl group on pyrimidine ring system with sulfuryl chloride
-
A facile one-step transformation of methylsulfanyl and arylsulfanyl groups on pyrimidine ring system into the corresponding chloride group was achieved using sulfuryl chloride in acetonitrile/dichloromethane.
- Ham, Young Jin,Lee, Duck-Hyung,Choi, Hwan Geun,Hah, Jung-Mi,Sim, Taebo
-
experimental part
p. 4609 - 4611
(2010/09/18)
-
- Small molecule thienopyrimidine-based protein tyrosine kinase inhibitors
-
Various thienopyrimidine-based analog compounds are able to selectively inhibit the Src family of tyrosine kinases. These compounds are useful in the treatment of various diseases including hyperproliferative diseases, hematologic diseases, osteoporosis, neurological diseases, autoimmune diseases, allergic/immunological diseases, or viral infections.
- -
-
Page/Page column 39
(2010/02/15)
-
- Thienopyrimidine-based inhibitors of the Src family
-
Various thienopyrimidine-based analog compounds that selectively inhibit the Src family of tyrosine kinases. These compounds are thienopyrimidines and contain a hydrozone bridge created by heating a thienopyrimidine hydrazine with an aldehyde in ethanol at reflux. Such compounds are useful in the treatment of various diseases including hyperproliferative diseases, hematologic diseases, osteoporosis, neurological diseases, autoimmune diseases, allergic/immunological diseases, or viral infections.
- -
-
-