Combinatorial synthesis and biological evaluation of isoxazole-based libraries as antithrombotic agents.
The 3-substituted phenyl-5-isoxazolecarboxaldehydes have been identified as activated aldehydes for the generation of isoxazole-based combinatorial libraries on solid phase through automation. Three highly functionalized isoxazole-based libraries comprising of 32, 96 and 45 compounds each have been synthesized in parallel format using Baylis Hillman reaction, Michael addition, reductive amination and alkylation reactions. With an objective of lead generation all the three libraries were evaluated for their antithrombin activity in vivo.
Medicinal Chemistry Division, Central Drug Research Institute, Lucknow 226001, India. batra_san@yahoo.co.uk
S
S
Batra
T
T
Srinivasan
S K
SK
Rastogi
B
B
Kundu
A
A
Patra
A P
AP
Bhaduri
M
M
Dixit
D000447:Aldehydes / Q000737:chemistry; D000818:Animals; D001760:Bleeding Time; D020650:Combinatorial Chemistry Techniques; D016208:Databases, Factual; D004353:Drug Evaluation, Preclinical; D005343:Fibrinolytic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D007555:Isoxazoles / Q000737:chemistry* / Q000494:pharmacology*; D051379:Mice; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013329:Structure-Activity Relationship; D020246:Venous Thrombosis / Q000139:chemically induced
D000447:Aldehydes; D005343:Fibrinolytic Agents; D007555:Isoxazoles