title: Synthesis and structure-activity studies of side chain analogues of the anti-tubercular agent, Q203.
abstract: The anti-tubercular activity of 6-chloro-2-ethyl-N-(4-(4-(4-(trifluoromethoxy)phenyl)piperidin-1-yl)benzyl)imidazo [1,2-a]pyridine-3-carboxamide (Q203) is modified by varying its side chain. In this study, we synthesized Q203 analogues with different side chains and studied their effects on anti-tubercular activity. Many analogues showed good potency against M. tuberculosis replicating in liquid broth culture medium (extracellular activity) regardless of chain length and conformational changes. However, a polar character in the side chain region was unfavorable for anti-tubercular activity. The analogues, 25, 28, 35, and 36, displayed excellent activity against M. tuberculosis replicating inside macrophages (intracellular activity) and promising pharmacokinetic (PK) properties with high drug exposure level and long half-life.
authors.affiliation: Chemistry Platform, Institute Pasteur Korea, 16 Daewangpangyo-ro, 712 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-400, Republic of Korea; College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 151-742, Republic of Korea.
authors.forename: Sunhee
authors.initials: S
authors.lastname: Kang
authors.affiliation: Chemistry Platform, Institute Pasteur Korea, 16 Daewangpangyo-ro, 712 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-400, Republic of Korea.
authors.forename: Young Mi
authors.initials: YM
authors.lastname: Kim
authors.affiliation: Tuberculosis Research Laboratory, Institute Pasteur Korea, 16 Daewangpangyo-ro, 712 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-400, Republic of Korea.
authors.forename: Ryang Yeo
authors.initials: RY
authors.lastname: Kim
authors.affiliation: Chemistry Platform, Institute Pasteur Korea, 16 Daewangpangyo-ro, 712 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-400, Republic of Korea.
authors.forename: Min Jung
authors.initials: MJ
authors.lastname: Seo
authors.affiliation: Chemistry Platform, Institute Pasteur Korea, 16 Daewangpangyo-ro, 712 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-400, Republic of Korea.
authors.forename: Zaesung
authors.initials: Z
authors.lastname: No
authors.affiliation: Qurient Co. Ltd., 242 Pangyo-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-400, Republic of Korea.
authors.forename: Kiyean
authors.initials: K
authors.lastname: Nam
authors.affiliation: College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 151-742, Republic of Korea. Electronic address: pennkim@snu.ac.kr.
authors.forename: Sanghee
authors.initials: S
authors.lastname: Kim
authors.affiliation: Chemistry Platform, Institute Pasteur Korea, 16 Daewangpangyo-ro, 712 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-400, Republic of Korea. Electronic address: silanediol@gmail.com.
authors.forename: Jaeseung
authors.initials: J
authors.lastname: Kim
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D002478:Cells, Cultured; D006207:Half-Life; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D008264:Macrophages / Q000382:microbiology; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000995:Antitubercular Agents; D007093:Imidazoles; D010880:Piperidines; D011725:Pyridines; C584497:telacebec
keywords: Imidazo[1,2-a]pyridine-3-carboxamide (IPA); Pharmacokinetics; Q203; Structure-activity relationship (SAR); Tuberculosis