1031849-79-2Relevant 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
, 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.
TRICYCLIC COMPOUND AND MEDICAL USE THEREOF
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Page/Page column 77, (2009/09/28)
The present invention provides a compound represented by the formula wherein R1 is a hydrocarbon group optionally having substituent(s), amino optionally having substituent(s), hydroxy optionally having a substituent or a heterocyclic group optionally having substituent(s), R2 is a hydrogen atom or a hydrocarbon group optionally having substituent(s), R3 is a hydrogen atom, a halogen atom, a hydrocarbon group optionally having substituent(s), amino optionally having substituent(s), hydroxy optionally having a substituent or mercapto optionally having a substituent, Xa to Xe are each a carbon atom or a nitrogen atom, m is 0 to 2, and ring A to ring C are each a ring optionally having substituent(s), or a salt thereof, which is useful as an agent for the prophylaxis or treatment of a disease relating to an action of melatonin, and the like.
