Synthesis and SAR studies of indole-based MK2 inhibitors
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- 作者：Zhaoming Xiong ; Donghong Amy Gao ; Derek A. Cogan ; Daniel R. Goldberg ; Ming-Hong Hao ; Neil Moss ; Edward Pack ; Chris Pargellis ; Donna Skow ; Thomas Trieselmann ; Brian Werneburg ; Andre White
- 关键词：MAPKAP-k2 ; MK2 ; β ; -Carbolinone ; Pyrazino[1 ; 2-a]indolone ; Diazepino[1 ; 2-a]indolone
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2008
- 出版时间：15 March 2008
- 年：2008
- 卷：18
- 期：6
- 页码：1994-1999
- 全文大小：236 K
文摘
Chemistry has been developed to specifically functionalize two structurally similar classes of indole-based MK2 inhibitors at positions prompted by a combination of X-ray crystallographic and computer assisted drug design. A gain in molecular potency was obtained by introducing aminomethyl groups to the lactam rings of 6-arylcarbamoyl-tetrahydro-β-carbolinone and 6-arylcarbamoyl-dihydropyrazino[1,2-a]indolone MK2 inhibitors. In addition, improvements in molecular potency were achieved by expansion of the lactam from a 6- to 7-membered ring leading to 7-arylcarbamoyl-tetrahydro-[1,4]diazepino[1,2-a]indolones.