| 摘要 |
The present disclosure provides compounds and pharmaceutically acceptable salts thereof that are tyrosine kinase inhibitors, in particular BLK, BMX, EGFR, HER2, HER4, ITK, TEC, BTK, and TXK and are therefore useful for the treatment of diseases treatable by inhibition of tyrosine kinases such as cancer and inflammatory diseases such as arthritis, and the like. Also provided are pharmaceutical compositions containing such compounds and pharmaceutically acceptable salts thereof and processes for preparing such compounds and pharmaceutically acceptable salts thereof. |
| 主权项 |
1. A compound of Formula (Id) or a pharmaceutically acceptable salt thereof: wherein: Z2 is —N— or CR2 where R2 is hydrogen or alkyl; R3 and R4 are independently hydrogen, methyl, chloro, fluoro, cyclopropyl, hydroxy, methoxy, cyano, trifluoromethyl or trifluoromethoxy; R6 and R7 are independently hydrogen, methyl, methoxy, fluoro, chloro, trifluoromethyl, trifluoromethoxy, or cyano; —Z-EWG- is -(alkylene)-NR′CO—, -(alkylene)-NR′SO2—, each ring optionally substituted with one or two substituents independently selected from alkyl, hydroxy, or halo and the carbonyl and sulfonyl group in (alkylene)-NR′CO—, -(alkylene)-NR′SO2—, is attached to —C(CN)═CHRc; and each R′ is independently hydrogen or alkyl; and Rc is alkyl, haloalkoxy, substituted alkyl, cycloalkyl, cycloalkyleneNRdRe or cycloalkylene(alkylene)NRdRe (where Rd and Re are independently hydrogen, alkyl, or cycloalkyl), or 3 to 6 membered saturated monocyclic heterocyclyl containing one or two heteroatoms selected from N, O, or S and optionally substituted with one or two substituents selected from hydroxy, alkyl or fluoro; provided that: (a) when then (1) when Rc is cyclopropyl, ten-butyl, —C(CH3)2CH2OH, —C(CH3)2N(CH3)2, cyclopentyl, isopropyl, —C(CH3)2OCH2CH3, or azetidin-3-yl, then Z-EWG- is not and (ii) when Rc is cyclopropyl then Z-EWG- is not where the stereochemistry at *C is (R); (b) when where Rc is cyclopropyl or tert-butyl, then Z-EWG- is not or (c) the compound of Formula (I) is not 2-(3-(4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)piperidine-1-carbonyl)-3-cyclopropylacrylonitrile; or a pharmaceutically acceptable salt thereof. |
