5 research outputs found
Antitubercular 2-Pyrazolylpyrimidinones:Structure-Activity Relationship and Mode-of-Action Studies
Lysyl-tRNA synthetase, a target for urgently needed M. tuberculosis drugs
Tuberculosis is a major global cause of both mortality and financial burden mainly in low and middle-income countries. Given the significant and ongoing rise of drug-resistant strains of Mycobacterium tuberculosis within the clinical setting, there is an urgent need for the development of new, safe and effective treatments. Here the development of a drug-like series based on a fused dihydropyrrolidino-pyrimidine scaffold is described. The series has been developed against M. tuberculosis lysyl-tRNA synthetase (LysRS) and cellular studies support this mechanism of action. DDD02049209, the lead compound, is efficacious in mouse models of acute and chronic tuberculosis and has suitable physicochemical, pharmacokinetic properties and an in vitro safety profile that supports further development. Importantly, preliminary analysis using clinical resistant strains shows no pre-existing clinical resistance towards this scaffold
CD4陽性T細胞に発現するA20(tnfaip3) はTh2型アレルギー性気道炎症を抑制する
研究科: 千葉大学大学院医学薬学府(先端医学薬学専攻)学位記番号: 千大院医薬博甲第医1412号博士(医学)千葉大学 = Chiba Universit
Pharmacokinetic optimisation of novel indole-2-carboxamide cannabinoid CB1 antagonists
The pharmacokinetic based optimisation of a novel series of indole-2-carboxamide antagonists of the cannabinoid CB(1) receptor is disclosed. Compound 24 was found to be a highly potent and selective cannabinoid CB(1) antagonist with high predicted human oral bioavailability