| Literature DB >> 26522089 |
Candice Soares de Melo, Soares de Melo Candice1, Tzu-Shean Feng1, Renier van der Westhuyzen1, Richard K Gessner1, Leslie J Street1, Garreth L Morgans2, Digby F Warner3, Atica Moosa4, Krupa Naran4, Nina Lawrence5, Helena I M Boshoff6, Clifton E Barry6, C John Harris7, Richard Gordon8, Kelly Chibale9.
Abstract
Whole-cell high-throughput screening of a diverse SoftFocus library against Mycobacterium tuberculosis (Mtb) generated a novel aminopyrazolo[1,5-a]pyrimidine hit series. The synthesis and structure activity relationship studies identified compounds with potent antimycobacterial activity. The SAR of over 140 compounds shows that the 2-pyridylmethylamine moiety at the C-7 position of the pyrazolopyrimidine scaffold was important for Mtb activity, whereas the C-3 position offered a higher degree of flexibility. The series was also profiled for in vitro cytotoxicity and microsomal metabolic stability as well as physicochemical properties. Consequently liabilities to be addressed in a future lead optimization campaign have been identified.Entities:
Keywords: Aminopyrazolopyrimidine; Antibacterial agent; Infectious diseases; Mycobacterium tuberculosis
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Year: 2015 PMID： 26522089 DOI： 10.1016/j.bmc.2015.10.021
Source DB: PubMed Journal: Bioorg Med Chem ISSN： 0968-0896 Impact factor: 3.641