Dibasic benzo[B]thiophene derivatives as a novel class of active site directed thrombin inhibitors: 4. SAR studies on the conformationally restricted C3-side chain of hydroxybenzo[B]thiophenes.
A novel series of benzo[b]thiophene diamine thrombin inhibitors with a conformationally restricted C3-side chain 3 was investigated. The constrained C3-side chain by a cyclohexyl ring contributed to not only an additive but also a synergistic effect on the thrombin inhibitory activity. The SAR studies resulted in the discovery of a potent thrombin inhibitor 27 that was over 750-fold more potent than the initial lead compound 1.
Takeuchi
K
K
Lilly Research Laboratories, A Division of Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Kohn
T J
TJ
Sall
D J
DJ
Denney
M L
ML
McCowan
J R
JR
Smith
G F
GF
Gifford-Moore
D S
DS
D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000737:chemistry* / Q000494:pharmacology; D013917:Thrombin / Q000037:antagonists & inhibitors*
D013876:Thiophenes; C088015:benzothiophene; D013917:Thrombin