Crystal structures, binding interactions, and ADME evaluation of brain penetrant N-substituted indazole-5-carboxamides as subnanomolar, selective monoamine oxidase B and dual MAO-A/B inhibitors

详细信息    查看全文

• 作者：Nikolay T. Tzvetkov^a ; ^{ntzvetkov@ntzlab.com} ; Hans-Georg Stammler^b ; Beate Neumann^b ; Silvia Hristova^c ; Liudmil Antonov^c ; Marcus Gastreich^d
• 关键词：ADME ; MAO inhibitors ; Molecular modeling ; Indazole-5-carboxamides ; Parkinson's disease ; X-ray
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2017
• 出版时间：15 February 2017
• 年：2017
• 卷：127
• 期：Complete
• 页码：470-492
• 全文大小：3206 K
• 卷排序：127

文摘

Selective MAO-B and dual MAO-A/B inhibitors have been developed. N-methylated indazole-5-carboxamides show high GI and BBB in vitro permeability, 13a and 13b can be highlighted. Visual SAR guidance with new modeling techniques successfully applied. Comprehensive binding mode and pharmacophore feature analyses conducted.