Liu Qingjie, Batt Douglas G, Chaudhry Charu, Lippy Jonathan S, Pattoli Mark A, Surti Neha, Xu Songmei, Carter Percy H, Burke James R, Tino Joseph A
Bristol-Myers Squibb Company, PO Box 4000, Princeton, NJ 08543-4000, USA.
Bristol-Myers Squibb Company, PO Box 4000, Princeton, NJ 08543-4000, USA.
Bioorg Med Chem Lett. 2018 Oct 1;28(18):3080-3084. doi: 10.1016/j.bmcl.2018.07.041. Epub 2018 Jul 30.
Incorporation of a suitably-placed electrophilic group transformed a series of reversible BTK inhibitors based on carbazole-1-carboxamide and tetrahydrocarbazole-1-carboxamide into potent, irreversible inhibitors. Removal of one ring from the core of these compounds provided a potent irreversible series of 2,3-dimethylindole-7-carboxamides having excellent potency and improved selectivity, with the additional advantages of reduced lipophilicity and molecular weight.
引入一个位置合适的亲电基团，可将一系列基于咔唑-1-甲酰胺和四氢咔唑-1-甲酰胺的可逆性布鲁顿酪氨酸激酶（BTK）抑制剂转化为强效的不可逆抑制剂。从这些化合物的核心结构中去除一个环，得到了一系列强效的不可逆2,3-二甲基吲哚-7-甲酰胺，它们具有优异的活性和提高的选择性，还具有降低亲脂性和分子量的额外优势。
