Yokokawa, Fumiaki, Wang, Gang, Wong, Josephine, Rao, Srinivasa P.S., Manjunatha, Ujjini Havaldar, Lakshminarayana, Suresh Bangalore, Herve, Maxime Marcel, Kounde, Cyrille Stephane, Tan, Bee Huat, Thayalan, Pamela, Ng, Seow Hwee, Nanjundappa, Mahesh Bangalore, Zhang, Chengzhi, Wagner, Beatrix, Dix, Ina, Kuhen, Kelli, Glynne, Richard, Smith, Paul William, Bifani, Juan Pablo, Jiricek, Jan, Seah, Peck Gee, Liu, Wei, Chen, Pei-Yu, Lee, Kok Sin, Chan, Wai Ling, Ma, Ida, Chatterjee, Arnab, Pethe, Kevin, Tan, Maria, Goh, Anne, Ang, Shi-Hua and Seah, Peck Gee (2013) Discovery of Tetrahydropyrazolopyrimidine Carboxamide De-rivatives as Potent and Orally Active Novel Anti-Tubercular Agents. ACS Medicinal Chemistry Letters, 4 (5). pp. 451-455. ISSN 1948-5875

Abstract

ABSTRACT: Tetrahydropyrazolopyrimidine scaffold was identified as a hit series from a Mycobacterium tuberculosis (Mtb) whole cell high through-put screening (HTS) campaign. A series of derivatives of this class were synthesized to evaluate their structure-activity relationship (SAR) and structure-property relationship (SPR). Compound 9 showed potent bactericidal effect and activity against multi-drug resistant tuberculosis (MDR TB) strains. Furthermore compound 9 had a promising in vivo DMPK profile in mouse and exhibited potent in vivo activity in a mouse efficacy model, achieving a reduction of 3.5 log CFU of Mtb after oral administration to infected mice once a day at 100 mg/kg for 28 days. Thus the compound 9 is a potential candidate for inclusion in combination therapies for both drug-sensitive and drug-resistant TB.

Item Type:	Article
Date Deposited:	13 Oct 2015 13:13
Last Modified:	13 Oct 2015 13:13
URI:	https://oak.novartis.com/id/eprint/9563