Probing BRD Inhibition Substituent Effects in Bulky Analogues of (+)‐JQ1
نویسندگان
چکیده
A series of bulky organometallic and organic analogues the bromodomain (BRD) inhibitor (+)-JQ1 have been prepared. The most potent, N-[(adamantan-1-yl)methyl]-2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetraazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]acetamide, 2e, showed excellent potency with an KD=ca. 130 nm vs. BRD4(1) a ca. 2-fold selectivity over BRD4(2) (KD=ca. 260 nm). Its binding to first BRD4 was determined by protein cocrystal structure.
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ژورنال
عنوان ژورنال: Helvetica Chimica Acta
سال: 2021
ISSN: ['1522-2675', '0018-019X']
DOI: https://doi.org/10.1002/hlca.202000214