Conversion of carbazole carboxamide based reversible inhibitors of Bruton's tyrosine kinase (BTK) into potent, selective irreversible inhibitors in the carbazole, tetrahydrocarbazole, and a new 2,3-dimethylindole series

被引：13

作者：

Liu, Qingjie ^{[1
]}

Batt, Douglas G. ^{[1
]}

Chaudhry, Charu ^{[1
]}

Lippy, Jonathan S. ^{[1
]}

Pattoli, Mark A. ^{[1
]}

Surti, Neha ^{[1
]}

Xu, Songmei ^{[1
]}

Carter, Percy H. ^{[1
]}

Burke, James R. ^{[1
]}

Tino, Joseph A. ^{[1
]}

机构：

[1] Bristol Myers Squibb Co, POB 4000, Princeton, NJ 08543 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2018年 / 28卷 / 18期

关键词：

Bruton's tyrosine kinase; BTK; Indole carboxamide; Carbazole; Irreversible inhibitor; CHRONIC LYMPHOCYTIC-LEUKEMIA; B-CELL MALIGNANCIES; MOLECULAR-PROPERTIES; IBRUTINIB; INDOLES; DESIGN;

D O I：

10.1016/j.bmcl.2018.07.041

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

引用

页码：3080 / 3084

页数：5

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