1031926-80-3Relevant academic research and scientific papers
Synthesis of a novel series of tricyclic dihydrofuran derivatives: Discovery of 8,9-dihydrofuro[3,2-c ]pyrazolo[1,5-a ]pyridines as melatonin receptor (MT1/MT2) ligands
Koike, Tatsuki,Takai, Takafumi,Hoashi, Yasutaka,Nakayama, Masaharu,Kosugi, Yohei,Nakashima, Masato,Yoshikubo, Shin-Ichi,Hirai, Keisuke,Uchikawa, Osamu
experimental part, p. 4207 - 4218 (2011/08/05)
Novel tricyclic dihydrofuran derivatives were designed, synthesized, and evaluated as melatonin receptor (MT1/MT2) ligands based on the previously reported 1,6-dihydro-2H-indeno[5,4-b]furan 1a. By screening the central tricyclic cores, we identified 8,9-dihydrofuro[3,2-c]pyrazolo[1,5-a] pyridine as a potent scaffold with a high ligand-lipophilicity efficiency (LLE) value. Subsequent optimization of the side chains led to identification of the potent MT1/MT2 agonist 4d (MT1, Ki = 0.062 nM; MT2, Ki = 0.420 nM) with good oral absorption and blood-brain barrier (BBB) penetration in rats. The oral administration of compound 4d exhibited a sleep-promoting action in freely moving cats at 0.1 mg/kg.
