Discovery of Novel Sulfonamides as Potent and Selective Inhibitors Against Human and Mouse 11 β-Hydroxysteroid Dehydrogenase Type 1
会议名称：《2011年全国药物化学学术会议——药物的源头创新》
会议日期：2011年
学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学]
摘 要：正Several classes of non-steroid 11β-HSD1 inhibitors have been developed as promising treatments for Type 2 Diabetes（T2D）.Using a human 11β-HSD1 selective inhibitor as a starting point,we designed and synthesized a new class of derivatives of 1-arylsulfonyl *** was found that the large lipophilic group on the amino part may lead to cross-species potency towards human and mouse,which will benefit the drug development by evaluating the compounds on rodent *** exploring the structure-activity-relationship,（R）-（+）-Bornylamine derivative is identified as the most potent inhibitor against mouse enzyme 11β-HSD1 with IC50 of 18 *** docking studies revealed the possible different interaction modes of S-enantiomer and R-enantiomer bound to h11β-HSD1 and explained the reason that S-enantiomer is more active than its ***,two potent and isoform-selective compounds, （+）-isopinocampheylamine derivative 8m and（R）-（+）-Bornylamine derivative 81,with suitable in vitro properties,are selected for future PK/PD evaluation on rodent *** study not only provides some compounds as novel h11β-HSD1,but also presents the structure-activity-relationship about designing human/mouse potent 11β-HSD1 inhibitors suitable for in vivo evaluation on rodent model.