1208987-81-8Relevant articles and documents
Synthesis and SAR of pyridothiazole substituted pyrimidine derived HCV replication inhibitors
Girijavallabhan, Vinay M.,Alvarez, Carmen,Bennett, Frank,Chen, Lei,Gavalas, Stephen,Huang, Yuhua,Kim, Seong-Heon,Kosinski, Aneta,Pinto, Patrick,Rizvi, Razia,Rossman, Randall,Shankar, Bandarpalle,Tong, Ling,Velazquez, Francisco,Venkatraman, Srikanth,Verma, Vishal A.,Kozlowski, Joseph,Shih, Neng-Yang,Piwinski, John J.,MacCoss, Malcolm,Kwong, Cecil D.,Bansal, Namita,Clark, Jeremy L.,Fowler, Anita T.,Kezar III, Hollis S.,Valiyaveettil, Jacob,Reynolds, Robert C.,Maddry, Joseph A.,Ananthan, Subramaniam,Secrist III, John A.,Li, Cheng,Chase, Robert,Curry, Stephanie,Huang, Hsueh-Cheng,Tong, Xiao,Njoroge, F. George,Arasappan, Ashok
, p. 5652 - 5657 (2012)
Introduction of a nitrogen atom into the benzene ring of a previously identified HCV replication (replicase) benzothiazole inhibitor 1, resulted in the discovery of the more potent pyridothiazole analogues 3. The potency and PK properties of the compounds were attenuated by the introductions of various functionalities at the R1, R2 or R3 positions of the molecule (compound 3). Inhibitors 38 and 44 displayed excellent potency, selectivity (GAPDH/MTS CC50), PK parameters in all species studied, and cross genotype activity.
Pyridofuran substituted pyrimidine derivatives as HCV replication (replicase) inhibitors
Bennett, Frank,Kezar III, Hollis S.,Girijavallabhan, Vinay,Huang, Yuhua,Huelgas, Regina,Rossman, Randall,Shih, Neng-Yang,Piwinski, John J.,MacCoss, Malcolm,Kwong, Cecil D.,Clark, Jeremy L.,Fowler, Anita T.,Geng, Feng,Roychowdhury, Abhijit,Reynolds, Robert C.,Maddry, Joseph A.,Ananthan, Subramaniam,Secrist III, John A.,Li, Cheng,Chase, Robert,Curry, Stephanie,Huang, Hsueh-Cheng,Tong, Xiao,George Njoroge,Arasappan, Ashok
scheme or table, p. 5144 - 5149 (2012/09/07)
Introduction of nitrogen atom into the benzene ring of a previously identified HCV replication (replicase) benzofuran inhibitor 2, resulted in the discovery of the more potent pyridofuran analogue 5. Subsequent introduction of small alkyl and alkoxy ligands into the pyridine ring resulted in further improvements in replicon potency. Replacement of the 4-chloro moiety on the pyrimidine core with a methyl group, and concomitant monoalkylation of the C-2 amino moiety resulted in the identification of several inhibitors with desirable characteristics. Inhibitor 41, from the monosubstituted pyridofuran and inhibitor 50 from the disubstituted series displayed excellent potency, selectivity (GAPDH/MTS CC50) and PK parameters in all species studied, while the selectivity in the thymidine incorporation assay (DNA·CC50) was low.
SUBSTITUTED PYRIDINE AND PYRIMIDINE DERIVATIVES AND THEIR USE IN TREATING VIRAL INFECTIONS
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Page/Page column 156, (2010/04/03)
The present invention provides compounds of Formula (I): and tautomers, isomers, and esters of said compounds, and pharmaceutically acceptable salts, solvates, and prodrugs of said compounds, wherein wherein each of R, R1, X, Y, Z, R2, R3, R4, R5, R6, R7, R8, R9, R18, R19 and n is selected independently and as defined herein. Compositions comprising such compounds are also provided. The compounds of the invention are effective as inhibitors of HCV, and are useful, alone and together with other therapeutic agents, in treating or preventing diseases or disorders such as viral infections and virus-related disorders.
