Synthesis and pharmacological evaluation of new 4-2-(7-heterocyclemethoxynaftalen-2-ylmethoxy)ethylbenzoic acids as LTD(4)-antagonists.
A group of new 4-[2-(7-heterocyclemethoxynaftalen-2-ylmethoxy)ethyl]benzoic acids have been synthesized and pharmacologically evaluated as LTD(4)-antagonists. Thiazole derivatives, especially 4-[2-[7-(4-cyclobutylthiazole-2-ylmethoxyl)naphthalen- 2-ylmetho-xy]et hyl]benzoic acid, present considerable activity and improved pharmacokinetic profiles in comparison with our quinoline containing lead molecule confirming the interest of our compounds as potentially oral antiasthmatics and that the 4-alkylthiazole system can be considered as bioisosteric of the quinoline ring at least in our series of compounds.
Ballart
B
B
Departament de Química Organica, Universitat of Barcelona, Martí Franques, 1-11, E-08028, Barcelona, Spain.
Martí
J
J
Velasco
D
D
López-Calahorra
F
F
Pascual
J
J
Luisa García
M
M
Cabré
F
F
Mauleón
D
D
D000818:Animals; D001565:Benzoates / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D004341:Drug Evaluation; D006168:Guinea Pigs; D017998:Leukotriene D4 / Q000037:antagonists & inhibitors*; D008297:Male; D051379:Mice
D001565:Benzoates; D017998:Leukotriene D4