Design, synthesis and pharmacological evaluation of novel pyrazolo[3,4-b]thieno[2,3-d]pyridine acid derivatives: a new class of anti-inflammatory and anti-platelet agents.
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.
Cardoso
Carla R
CR
Instituto de Química, Universidade Federal do Rio de Janeiro, 21949-900, RJ, Rio de Janeiro, Brazil.
de Brito
Fernanda C F
FC
da Silva
Kelli C M
KC
de Miranda
Ana L P
AL
Fraga
Carlos A M
CA
Barreiro
Eliezer J
EJ
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D004195:Disease Models, Animal; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004487:Edema / Q000188:drug therapy; D020024:Leukotriene Antagonists; D008565:Membrane Proteins; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D010998:Pleurisy / Q000188:drug therapy; D011720:Pyrazoles / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011725:Pyridines / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D018077:Receptors, Leukotriene; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D000893:Anti-Inflammatory Agents; C465966:LASSBio 341; D020024:Leukotriene Antagonists; D008565:Membrane Proteins; D010975:Platelet Aggregation Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D018077:Receptors, Leukotriene; D013876:Thiophenes; C412375:cysteinyl leukotriene receptor 2; D013930:Thromboxane-A Synthase; C083169:leukotriene D4 receptor