ABSTRACT
This paper describes the synthesis, pharmacological evaluation and docking studies of a series of new sulindac analogues. Overall, the designed compounds revealed good, in vivo, antinociceptive activity and satisfactory anti-inflammatory profile. Flexible molecular docking with COX-1/COX-2 has shown putative binding modes of the designed compounds while the theoretical evaluation of cell permeability based on Lipinski's rule of five has helped rationalize the biological results.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/chemistry , Drug Design , Sulindac/analogs & derivatives , Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Cell Membrane Permeability , Computer Simulation , Cyclooxygenase 1/metabolism , Cyclooxygenase 2/metabolism , Humans , Prodrugs , Protein Binding , Structure-Activity Relationship , Sulindac/pharmacologyABSTRACT
A series of pyrazolo[3,4-b]thieno[2,3-d]pyridine alkanoic acid derivatives has been synthesized and evaluated as thromboxane synthetase inhibitors and leukotriene D(4) receptor antagonists. The glutaric acid derivative LASSBio341 (6) was shown to be active in arachidonic acid-induced platelet aggregation (IC(50)=0.14 microM) and inhibition of the contraction of guinea pig tracheal strip induced with LTD(4) (IC(50) = 43.7 microM), displaying still in vivo anti-inflammatory profile.
