161712-77-2Relevant articles and documents
PYRIDOPYRAZINE AND PYRIDOTRIAZINE INHIBITORS OF INFLUENZA VIRUS REPLICATION
-
, (2020/05/06)
Provided herein are compounds that can inhibit the replication of influenza viruses, reduce the amount of influenza viruses, and/or treat influenza. (I)
Tetrahydro-2-naphthyl and 2-Indanyl Triazolopyrimidines Targeting Plasmodium falciparum Dihydroorotate Dehydrogenase Display Potent and Selective Antimalarial Activity
Kokkonda, Sreekanth,Deng, Xiaoyi,White, Karen L.,Coteron, Jose M.,Marco, Maria,De Las Heras, Laura,White, John,El Mazouni, Farah,Tomchick, Diana R.,Manjalanagara, Krishne,Rudra, Kakali Rani,Chen, Gong,Morizzi, Julia,Ryan, Eileen,Kaminsky, Werner,Leroy, Didier,Martínez-Martínez, María Santos,Jimenez-Diaz, Maria Belen,Bazaga, Santiago Ferrer,Angulo-Barturen, I?igo,Waterson, David,Burrows, Jeremy N.,Matthews, Dave,Charman, Susan A.,Phillips, Margaret A.,Rathod, Pradipsinh K.
supporting information, p. 5416 - 5431 (2016/07/06)
Malaria persists as one of the most devastating global infectious diseases. The pyrimidine biosynthetic enzyme dihydroorotate dehydrogenase (DHODH) has been identified as a new malaria drug target, and a triazolopyrimidine-based DHODH inhibitor 1 (DSM265) is in clinical development. We sought to identify compounds with higher potency against Plasmodium DHODH while showing greater selectivity toward animal DHODHs. Herein we describe a series of novel triazolopyrimidines wherein the p-SF5-aniline was replaced with substituted 1,2,3,4-tetrahydro-2-naphthyl or 2-indanyl amines. These compounds showed strong species selectivity, and several highly potent tetrahydro-2-naphthyl derivatives were identified. Compounds with halogen substitutions displayed sustained plasma levels after oral dosing in rodents leading to efficacy in the P. falciparum SCID mouse malaria model. These data suggest that tetrahydro-2-naphthyl derivatives have the potential to be efficacious for the treatment of malaria, but due to higher metabolic clearance than 1, they most likely would need to be part of a multidose regimen.
P2X4 RECEPTOR MODULATING COMPOUNDS
-
Paragraph 00254, (2015/06/25)
Provided herein are P2X4 receptor modulating compounds, methods of their synthesis, pharmaceutical compositions comprising the compounds, and methods of their use. The compounds provided herein are useful for the treatment, prevention, and/or management of various disorders, including but not limited to, chronic pain, neuropathy, inflammatory diseases and central nervous system disorders.
