title: Biarylmethoxy Nicotinamides As Novel and Specific Inhibitors of Mycobacterium tuberculosis.
abstract: A whole cell based screening effort on a focused library from corporate collection resulted in the identification of biarylmethoxy nicotinamides as novel inhibitors of M. tuberculosis (Mtu) H37Rv. The series exhibited tangible structure-activity relationships, and during hit to lead exploration, a cellular potency of 100 nM was achieved, which is an improvement of >200-fold from the starting point. The series is very specific to Mtu and noncytotoxic up to 250 μM as measured in the mammalian cell line THP-1 based cytotoxicity assay. This compound class retains its potency on several drug sensitive and single drug resistant clinical isolates, which indicate that the compounds could be acting through a novel mode of action.
authors.affiliation: Alkem Laboratories, Ltd. , Peenya Industrial Estate, Bangalore 560058, India.
authors.forename: Chaitanya Kumar
authors.initials: CK
authors.lastname: Kedari
authors.affiliation: AstraZeneca India Pvt., Ltd. , Avishkar, Bellary Road, Bangalore 560024, India.
authors.forename: Nilanjana
authors.initials: N
authors.lastname: Roy Choudhury
authors.affiliation: AstraZeneca India Pvt., Ltd. , Avishkar, Bellary Road, Bangalore 560024, India.
authors.forename: Sreevalli
authors.initials: S
authors.lastname: Sharma
authors.affiliation: AstraZeneca India Pvt., Ltd. , Avishkar, Bellary Road, Bangalore 560024, India.
authors.forename: Parvinder
authors.initials: P
authors.lastname: Kaur
authors.affiliation: AstraZeneca India Pvt., Ltd. , Avishkar, Bellary Road, Bangalore 560024, India.
authors.forename: Supreeth
authors.initials: S
authors.lastname: Guptha
authors.affiliation: AstraZeneca India Pvt., Ltd. , Avishkar, Bellary Road, Bangalore 560024, India.
authors.forename: Manoranjan
authors.initials: M
authors.lastname: Panda
authors.affiliation: Alkem Laboratories, Ltd. , Peenya Industrial Estate, Bangalore 560058, India.
authors.forename: Kakoli
authors.initials: K
authors.lastname: Mukerjee
authors.affiliation: AstraZeneca India Pvt., Ltd. , Avishkar, Bellary Road, Bangalore 560024, India.
authors.forename: Vasanthi
authors.initials: V
authors.lastname: Ramachandran
authors.affiliation: Alkem Laboratories, Ltd. , Peenya Industrial Estate, Bangalore 560058, India.
authors.forename: Balachandra
authors.initials: B
authors.lastname: Bandodkar
authors.affiliation: AstraZeneca India Pvt., Ltd. , Avishkar, Bellary Road, Bangalore 560024, India.
authors.forename: Sreekanth
authors.initials: S
authors.lastname: Ramachandran
authors.affiliation: AstraZeneca India Pvt., Ltd. , Avishkar, Bellary Road, Bangalore 560024, India.
authors.forename: Subramanyam J
authors.initials: SJ
authors.lastname: Tantry
keywords: MMIC; anti-TB; biarylmethoxy nicotinamides; clinical isolates