CAS: 1334719-95-7; Q-203

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6-Chloro-2-Ethylimidazo[1,2-A]Pyridine-3-Carboxylic Acid 1216142-18-5

📜Ethyl 6-Chloro-2-Ethylimidazo[1,2-A]Pyridine-3-Carboxylate置于水,1-羟基苯并三唑,盐酸-N-乙基-N'-(3-二甲氨基丙基)碳二亚胺,三乙胺,Lithium Hydroxide体系中,用 乙醇,N,N-二甲基甲酰胺 用作溶剂,化学反应 2.0H,反应生成6-氯-2-乙基-N-[4-[4-[4-(三氟甲氧基)苯基]-1-哌啶]苄基]咪唑并[1,2-A]吡啶-3-甲酰胺
参考文献:Lead Optimization Of A Novel Series Of Imidazo[1,2-A]Pyridine Amides Leading To A Clinical Candidate (Q203) As A Multi-And Extensively-Drug-Resistant Anti-Tuberculosis Agent
标题:Lead Optimization Of A Novel Series Of Imidazo[1,2-A]Pyridine Amides Leading To A Clinical Candidate (Q203) As A Multi-And Extensively-Drug-Resistant Anti-Tuberculosis Agent
摘要:A Critical Unmet Clinical Need To Combat The Global Tuberculosis Epidemic Is The Development Of Potent Agents Capable Of Reducing The Time Of Multi-Drug-Resistant (Mdr) And Extensively-Drug-Resistant (Xdr) Tuberculosis Therapy. In This Paper,We Report On The Optimization Of Imidazo[1,2-A]Pyridine Amide (Ipa) Lead Compound 1,Which Led To The Design And Synthesis Of Q203 (50). We Found That The Amide Linker With Ipa Core Is Very Important For Activity Against Mycobacterium Tuberculosis H37Rv. Linearity And Lipophilicity Of The Amine Part In The Ipa Series Play A Critical Role In Improving In Vitro And In Vivo Efficacy And Pharmacokinetic Profile. The Optimized Ipas 49 And 50 Showed Not Only Excellent Oral Bioavailability (80.2% And 90.7%,Respectively) With High Exposure Of The Area Under Curve (Auc) But Also Displayed Significant Colony-Forming Unit (Cfu) Reduction (1.52 And 3.13 Log10 Reduction At 10 Mg/kg Dosing Level,Respectively) In Mouse Lung.
Doi:10.1021/jm5003606