Synthesis and antitubercular evaluation of novel dibenzo[b,d]thiophene tethered imidazo[1,2-a]pyridine-3-carboxamides

• Published in: Bioorganic & medicinal chemistry letters Vol. 26; no. 13; pp. 3135 - 3140
• Main Authors: Pulipati, Lokesh, Sridevi, Jonnalagadda Padma, Yogeeswari, Perumal, Sriram, Dharmarajan, Kantevari, Srinivas
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 01.07.2016; Elsevier
• Subjects: Antitubercular agents; Antitubercular Agents - chemical synthesis; Antitubercular Agents - chemistry; Antitubercular Agents - pharmacology; Carboxamide; Cell Proliferation - drug effects; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Dibenzothiophene; Dose-Response Relationship, Drug; HEK293 Cells; Humans; Imidazole; Imidazoles - chemical synthesis; Imidazoles - chemistry; Imidazoles - pharmacology; Life Sciences & Biomedicine; Microbial Sensitivity Tests; Molecular Structure; Mycobacterium tuberculosis; Mycobacterium tuberculosis - drug effects; Pharmacology & Pharmacy; Physical Sciences; Pyridine; Pyridines - chemical synthesis; Pyridines - chemistry; Pyridines - pharmacology; Science & Technology; Structure-Activity Relationship; Thiophenes - chemical synthesis; Thiophenes - chemistry; Thiophenes - pharmacology; Antitubercular agents; Carboxamide; Pyridine; Imidazole; Dibenzothiophene; DRUG; TUBERCULOSIS; POTENT INHIBITORS; EXPLORATION; CLINICAL CANDIDATE; RESISTANT TB; END; OPTIMIZATION; RATIONAL DESIGN; HYBRIDS
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2016.04.088

[Display omitted] A series of novel dibenzo[b,d]thiophene tethered imidazo[1,2-a]pyridine carboxamides 7a–s were designed and synthesized. The required building block, 2-dibenzo[b,d]thiophenyl imidazo[1,2-a]pyridine carboxylic acid (5) was synthesized from commercial dibenzo[b,d]thiophene in good yields following five-step reaction sequence. The desired carboxamides 7a–s was prepared through coupling of acid 5 with various benzyl amines. All the new analogues 7a–s was characterized by their NMR and mass spectral analysis. Among nineteen new compounds 7a–s screened for in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv, three compounds 7k (MIC: 0.78μg/mL); 7e and 7n (MIC: 1.56μg/mL) were identified as potent analogues with low cytotoxicity. The results reported here will help global efforts for identification of potential lead antimycobacterial agents.