Diamino benzo[b]thiophene derivatives as a novel class of active site directed thrombin inhibitors: 3. Enhancing activity by imposing conformational restriction in the C-4" side chain.
The preparation and biological evaluation of a series of benzo[b]thiophene diamine thrombin inhibitors possessing conformationally restricted C-4" linkers are reported. Compared to the parent compounds 1a/b, the unsaturated derivatives 3a/b exhibited a modest twofold increase in thrombin inhibitory activity, while the more lipophilic carbocyclic ring containing analogs 4a/b affected an eightfold enhancement in potency.
Bastian
J A
JA
Lilly Research Laboratories, Eli Lilly & Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA.
Chirgadze
N
N
Denney
M L
ML
Gifford-Moore
D S
DS
Sall
D J
DJ
Smith
G F
GF
Wikel
J H
JH
D000991:Antithrombins / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D013876:Thiophenes / Q000737:chemistry / Q000494:pharmacology*
D000991:Antithrombins; D013876:Thiophenes; C088015:benzothiophene