Novel phthalimide derivatives, designed as leukotriene D(4) receptor antagonists.
A series of phthalimide acid derivatives was synthesized and evaluated as leukotriene D(4) receptor antagonists. The tetrazolephthalimide LASSBio 552 (7) was shown to be able to inhibit the contractile activity induced by 100 nM of LTD(4) in guinea-pig tracheal strips with an IC(50) = 31.2 microM. In addition, LASSBio 552 (7) has been showed to present a better efficacy than zafirlukast (1) used as standard.
Lima
Lídia M
LM
LASSBio, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, PO Box 68006, Rio de Janeiro, 21944-970, Brazil.
de Brito
Fernanda C F
FC
de Souza
Simone D
SD
Miranda
Ana L P
AL
Rodrigues
Carlos R
CR
Fraga
Carlos A M
CA
Barreiro
Eliezer J
EJ
D000818:Animals; D018927:Anti-Asthmatic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007211:Indoles; D020024:Leukotriene Antagonists; D008565:Membrane Proteins; D008958:Models, Molecular; D008968:Molecular Conformation; D009119:Muscle Contraction / Q000187:drug effects; D048448:Phenylcarbamates; D010797:Phthalimides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D018077:Receptors, Leukotriene / Q000737:chemistry; D013449:Sulfonamides; D013777:Tetrazoles / Q000737:chemistry; D014105:Tosyl Compounds / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects / Q000502:physiology
D018927:Anti-Asthmatic Agents; D007211:Indoles; D020024:Leukotriene Antagonists; D008565:Membrane Proteins; D048448:Phenylcarbamates; D010797:Phthalimides; D018077:Receptors, Leukotriene; D013449:Sulfonamides; D013777:Tetrazoles; D014105:Tosyl Compounds; C037431:phthalimide; C412375:cysteinyl leukotriene receptor 2; C083169:leukotriene D4 receptor; C062735:zafirlukast