Synthesis and evaluation of pyridine-derived bedaquiline analogues containing modifications at the A-ring subunit

Basic Information

ID: CHEMBL4732038

Journal: RSC Med Chem

Title: Synthesis and evaluation of pyridine-derived bedaquiline analogues containing modifications at the A-ring subunit

Authors: Barbaro, Lisa, Nagalingam, Gayathri, Triccas, James A., Tan, Lendl, West, Nicholas P., Baell, Jonathan B., Priebbenow, Daniel L.

Abstract: Despite promising efficacy, the clinical use of the anti-tubercular therapeutic bedaquiline has been restricted due to safety concerns. To date, limited SAR studies have focused on the quinoline ring (A-ring), and as such, we set out to explore modifications within this region in an attempt to discover new bedaquiline variants with an improved safety profile. We herein report the development of unique synthetic strategies that facilitated access to novel bedaquiline analogues leading to the discovery that anti-tubercular activity could be retained following replacement of the quinoline motif with pyridine heterocycles. This discovery is anticipated to open up multiple new avenues for exploration in the design of improved anti-tubercular therapeutics.

CiteXplore: 34223160

DOI: 10.1039/d1md00063b

Patent ID: ---

ChEMBL ID	Target Similarity	Compound Similarity	Reference	Title	PubMed ID	DOI
CHEMBL4130520	1	0.01	ACS Med Chem Lett (2017) 8:1019-1024	6-Cyano Analogues of Bedaquiline as Less Lipophilic and Potentially Safer Diarylquinolines for Tuberculosis.	29057044	10.1021/acsmedchemlett.7b00196
CHEMBL4351009	1	0.01	Eur J Med Chem (2019) 179:208-217	hERG optimizations of IMB1603, discovery of alternative benzothiazinones as new antitubercular agents.	31254922	10.1016/j.ejmech.2019.06.053