943606-84-6Relevant academic research and scientific papers
An Efficient Second-Generation Manufacturing Process for the pan-RAF Inhibitor Belvarafenib
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)
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.
ISOQUINOLINE-5-CARBOXAMIDE DERIVATIVE HAVING INHIBITORY ACTIVITY FOR PROTEIN KINASE
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Paragraph 0075, (2015/06/03)
A compound selected from the group consisting of an isoquinoline-5-carboxamide derivative of formula (I), a pharmaceutically acceptable salt, an isomer, a hydrate and a solvate thereof is effective for the prevention or treatment of diseases associated with abnormal cell growth, which are caused by abnormal activation of a protein kinases.
ISOQUINOLINE-5-CARBOXAMIDE DERIVATIVE HAVING INHIBITORY ACTIVITY FOR PROTEIN KINASE
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, (2015/07/15)
A compound selected from the group consisting of an isoquinoline-5-carboxamide derivative of formula (I), a pharmaceutically acceptable salt, an isomer, a hydrate and a solvate thereof is effective for the prevention or treatment of diseases associated with abnormal cell growth, which are caused by abnormal activation of a protein kinases.
THIENO[3,2-D]PYRIMIDINE DERIVATIVES HAVING INHIBITORY ACTIVITY FOR PROTEIN KINASES
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Paragraph 0222; 0223, (2015/01/06)
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.
THIENO[3,2-d]PYRIMIDINE DERIVATIVES HAVING INHIBITORY ACTIVITY FOR PROTEIN KINASES
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, (2013/07/19)
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
Selective inhibitors of the mutant B-Raf pathway: Discovery of a potent and orally bioavailable aminoisoquinoline
Smith, Adrian L.,DeMorin, Frenel F.,Paras, Nick A.,Huang, Qi,Petkus, Jeffrey K.,Doherty, Elizabeth M.,Nixey, Thomas,Kim, Joseph L.,Whittington, Douglas A.,Epstein, Linda F.,Lee, Matthew R.,Rose, Mark J.,Babij, Carol,Fernando, Manory,Hess, Kristen,Le, Quynh,Beltran, Pedro,Carnahan, Josette
supporting information; experimental part, p. 6189 - 6192 (2010/03/24)
The discovery and optimization of a novel series of aminoisoquinolines as potent, selective, and efficacious inhibitors of the mutant B-Raf pathway is presented. The N-linked pyridylpyrimidine benzamide 2 was identified as a potent, modestly selective inhibitor of the B-Raf enzyme. Replacement of the benzamide with an aminoisoquinoline core significantly improved kinase selectivity and imparted favorable pharmacokinetic properties, leading to the identification of 1 as a potent antitumor agent in xenograft models. 2009 American Chemical Society.
RAF KINASE MODULATORS AND METHODS OF USE
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, (2009/01/24)
The present invention comprises a new class of compounds capable of modulating the activity of Raf kinase and, accordingly, useful for treatment of Raf kinase mediated diseases, including melanomas, tumors and other cancer-related conditions. The compounds have a general Formula (I) wherein each of A1, A2, A3, A4, A5, A6, A7, A8, A9, bond B, X, rings Z1 and Z2, R1 and R3 are defined herein. The invention further comprises pharmaceutical compositions, methods for treatment of Raf kinase mediated diseases, and intermediates and processes useful for the preparation of compounds of the invention.
NITROGEN-CONTAINING BICYCLIC HETEROARYL COMPOUNDS AND METHODS OF USE
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Page/Page column 66, (2008/06/13)
The present invention comprises a new class of compounds capable of modulating Raf kinase and, accordingly, useful for treatment of Raf kinase mediated diseases, including melanomas, tumors and other cancer-related conditions. The compounds have Formula (I) wherein R1 is Formula (II), (III) or (IV) and A1, A2, A3, A4, X, Z, Z', R1, R2, R3, R4, R5 and R6 are defined herein. The invention further comprises pharmaceutical compositions, methods for treatment of Raf kinase mediated diseases, and intermediates and processes useful for the preparation of compounds of the invention.
Pyrroloquinolines for treatment of obesity
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, (2008/06/13)
A chemical compound of formula (I), wherein R1to R3are independently selected from hydrogen and alkyl; R4is selected from hydrogen, alkyl, alkoxy, formyl and cyano; X1is selected from N and C—R7; X2is selected from N and C—R8; X3is selected from N and C—R9; X4is selected from N and C—R10; wherein at least one of X1, X2, X3and X4is N; and R5to R10are independently selected from hydrogen, halogen, hydroxy, alkyl, aryl, alkoxy, aryloxy, alkylthio, arylthio, alkylsulfoxyl, alkylsulfonyl, arylsulfoxyl, arylsulfonyl, amino, monoalkylamino, dialkylamino, nitro, cyano, carboxaldehyde, alkylcarbonyl, arylcarbonyl, aminocarbonyl, monoalkylaminocarbonyl, dialkylaminocarbonyl, alkoxycarbonylamino, aminocarbonyloxy, monoalkylaminocarbonyloxy, dialkylaminocarbonyloxy, monoalkylaminocarbonylamino and dialkylaminocarbonylamino, and the use thereof in therapy, particularly for the treatment of disorders of the central nervous system; damage to the central nervous system; cardiovascular disorders; gastrointestinal disorders; diabetes insipidus; and sleep apnea, and particularly for the treatment of obesity.
