361547-56-0Relevant articles and documents
Carreira alkynylations with paraformaldehyde. A mild and convenient protocol for the hydroxymethylation of complex base-sensitive terminal acetylenes via alkynylzinc triflates
Hale, Karl J.,Xiong, Ziyue,Wang, Liping,Manaviazar, Soraya,Mackle, Ryan
supporting information, p. 198 - 201 (2015/01/30)
A new synthetic protocol for the hydroxymethylation of terminal acetylenes is described that involves stoichiometric Carreira alkynylation with solid paraformaldehyde (HO[CH2O]nH) in PhMe at 60 °C. Significantly, the method can be su
N-(MONOCYCLIC ARYL),N'-PYRAZOLYL-UREA, THIOUREA, GUANIDINE AND CYANOGUANIDINE COMPOUNDS AS TRKA KINASE INHIBITORS
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Paragraph 00571, (2014/06/11)
Compounds of Formula (I) or stereoisomers, tautomers, or pharmaceutically acceptable salts, solvates or prodrugs thereof, wherein Ring A, Ring C and X are as defined herein, are inhibitors of TrkA kinase and are useful in the treatment of diseases which can be treated with a TrkA kinase inhibitor such as pain, cancer, inflammation/inflammatory diseases, neurodegenerative diseases, certain infectious diseases, Sjogren's syndrome, endometriosis, diabetic peripheral neuropathy, prostatitis or pelvic pain syndrome.
BICYCLIC HETEROARYL UREA, THIOUREA, GUANIDINE AND CYANOGUANIDINE COMPOUNDS AS TRKA KINASE INHIBITORS
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Paragraph 00502, (2014/06/11)
Compounds of Formula I or stereoisomers, tautomers, or pharmaceutically acceptable salts, solvates or prodrugs thereof, wherein Ring A, Ring C and X are as defined herein, are inhibitors of TrkA kinase and are useful in the treatment of diseases which can be treated with a TrkA kinase inhibitor such as pain, cancer, inflammation/inflammatory diseases, neurodegenerative diseases, certain infectious diseases, Sjogren's syndrome, endometriosis, diabetic peripheral neuropathy, prostatitis and pelvic pain syndrome.
N-(ARYLALKYL)-N'-PYRAZOLYL-UREA, THIOUREA, GUANIDINE AND CYANOGUANIDINE COMPOUNDS AS TRKA KINASE INHIBITORS
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Paragraph 00700, (2014/06/11)
Compounds of Formula I or stereoisomers, tautomers, or pharmaceutically acceptable salts, solvates or prodrugs thereof, wherein Ring A, Ring C, X, Ra, Rb, Rc, Rd and n are as defined herein, are inhibitors of TrkA kinase and are useful in the treatment of diseases which can be treated with a TrkA kinase inhibitor such as pain, cancer, inflammation/inflammatory diseases, neurodegenerative diseases, certain infectious diseases, Sjogren's syndrome, endometriosis, diabetic peripheral neuropathy, prostatitis or pelvic pain syndrome.
THIAZOLYL AND OXAZOLYL UREA, THIOUREA, GUANIDINE AND CYANOGUANIDINE COMPOUNDS AS TRKA KINASE INHIBITORS
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Paragraph 00387, (2014/06/11)
Compounds of Formula (I) or stereoisomers, tautomers, or pharmaceutically acceptable salts, solvates or prodrugs thereof, wherein Ring A, Ring C and X are as defined herein, are inhibitors of TrkA kinase and are useful in the treatment of diseases which can be treated with a TrkA kinase inhibitor such as pain, cancer, inflammation, neurodegenerative diseases, certain infectious diseases, Sjogren's syndrome, endometriosis, diabetic peripheral neuropathy, prostatitis or pelvic pain syndrome.
N-BICYCLIC ARYL,N'-PYRAZOLYL UREA, THIOUREA, GUANIDINE AND CYANOGUANIDINE COMPOUNDS AS TRKA KINASE INHIBITORS
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Paragraph 00499, (2014/06/11)
Compounds of Formula (I): or stereoisomers, tautomers, or pharmaceutically acceptable salts, solvates or prodrugs thereof, wherein Ring A, Ring C and X are as defined herein, are inhibitors of TrkA kinase and are useful in the treatment of diseases which can be treated with a TrkA kinase inhibitor such as pain, cancer, inflammation/inflammatory diseases, neurodegenerative diseases, certain infectious diseases, Sjogren's syndrome, endometriosis, diabetic peripheral neuropathy, prostatitis or pelvic pain syndrome.
BICYCLIC UREA, THIOUREA, GUANIDINE AND CYANOGUANIDINE COMPOUNDS USEFUL FOR THE TREATMENT OF PAIN
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Paragraph 00640, (2014/06/11)
Compounds of Formula I: or stereoisomers, tautomers, or pharmaceutically acceptable salts, solvates or prodrugs thereof, wherein Ring A, Ring C and X are as defined herein, are inhibitors of TrkA kinase and are useful in the treatment of diseases which can be treated with a TrkA kinase inhibitor such as pain, cancer, inflammation/inflammatory diseases, neurodegenerative diseases, certain infectious diseases, Sjogren's syndrome, endometriosis, diabetic peripheral neuropathy, prostatitis and pelvic pain syndrome.
Identification of 1-(3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)-3-(5-(1,1, 1-trifluoro-2-methylpropan-2-yl)isoxazol-3-yl)urea hydrochloride (CEP-32496), a highly potent and orally efficacious inhibitor of V-RAF murine sarcoma viral oncogene homologue B1 (BRAF) V600E
Rowbottom, Martin W.,Faraoni, Raffaella,Chao, Qi,Campbell, Brian T.,Lai, Andiliy G.,Setti, Eduardo,Ezawa, Maiko,Sprankle, Kelly G.,Abraham, Sunny,Tran, Lan,Struss, Brian,Gibney, Michael,Armstrong, Robert C.,Gunawardane, Ruwanthi N.,Nepomuceno, Ronald R.,Valenta, Ianina,Hua, Helen,Gardner, Michael F.,Cramer, Merryl D.,Gitnick, Dana,Insko, Darren E.,Apuy, Julius L.,Jones-Bolin, Susan,Ghose, Arup K.,Herbertz, Torsten,Ator, Mark A.,Dorsey, Bruce D.,Ruggeri, Bruce,Williams, Michael,Bhagwat, Shripad,James, Joyce,Holladay, Mark W.
scheme or table, p. 1082 - 1105 (2012/04/04)
The Ras/RAF/MEK/ERK mitogen-activated protein kinase (MAPK) signaling pathway plays a central role in the regulation of cell growth, differentiation, and survival. Expression of mutant BRAFV600E results in constitutive activation of the MAPK pathway, which can lead to uncontrolled cellular growth. Herein, we describe an SAR optimization campaign around a series of quinazoline derived BRAFV600E inhibitors. In particular, the bioisosteric replacement of a metabolically sensitive tert-butyl group with fluorinated alkyl moieties is described. This effort led directly to the identification of a clinical candidate, compound 40 (CEP-32496). Compound 40 exhibits high potency against several BRAFV600E-dependent cell lines and selective cytotoxicity for tumor cell lines expressing mutant BRAFV600E versus those containing wild-type BRAF. Compound 40 also exhibits an excellent PK profile across multiple preclinical species. In addition, significant oral efficacy was observed in a 14-day BRAFV600E-dependent human Colo-205 tumor xenograft mouse model, upon dosing at 30 and 100 mg/kg BID.
PYRROLIDINYL UREA AND PYRROLIDINYL THIOUREA COMPOUNDS AS TRKA KINASE INHIBITORS
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Page/Page column 102, (2012/12/13)
Compounds of Formula I: or stereoisomers, tautomers, or pharmaceutically acceptable salts, or solvates or prodrugs thereof, where R1, R2, Ra, Rb, Rc, Rd, X, Y, B, and Ring C are as defined herein, and wherein the Y-B moiety and the NH-C(=X)-NH moiety are in the trans configuration, are inhibitors of TrkA kinase and are useful in the treatment of diseases which can be treated with a TrkA kinase inhibitor such as pain, cancer, inflammation, neurodegenerative diseases and certain infectious diseases.
BIARYL COMPOUNDS AND METHODS OF USE THEREOF
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Page/Page column 179, (2011/04/13)
Provided herein are compounds for treatment of KIT, CSF-1R and/or FLT3 kinase mediated diseases. Also provided are pharmaceutical compositions comprising the compounds and methods of using the compounds and compositions.
