Design and synthesis of novel and potent GPR119 agonists with a spirocyclic structure

Autor:	Isamu Matsuda, Suwa Katsunori, Kenta Aoki, Kazuhito Harada, Jun Mizukami, Sumiaki Fukuda, Sho Kadowaki, Takashi Inaba, Takashi Watanabe, Yoshitoshi Kodama, Shinji Yata, Yasuhiro Oe
Rok vydání:	2018
Předmět:	0301 basic medicine Stereochemistry Clinical Biochemistry Compound 17 Pharmaceutical Science Inhibitory postsynaptic potential Biochemistry Receptors G-Protein-Coupled Rats Sprague-Dawley Structure-Activity Relationship 03 medical and health sciences chemistry.chemical_compound Cyclohexanes Drug Discovery medicine Animals Humans Hypoglycemic Agents Insulin Spiro Compounds Insulin secretion Molecular Biology IC50 Glucose tolerance test Dose-Response Relationship Drug Molecular Structure medicine.diagnostic_test Organic Chemistry Glucose Tolerance Test Rats Piperazine Glucose 030104 developmental biology GPR119 chemistry Drug Design Molecular Medicine Piperidine Injections Intraperitoneal
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 28:1228-1233
ISSN:	0960-894X
DOI:	10.1016/j.bmcl.2018.02.044
Popis:	Exploration of alternative structures of the substituted piperidine or piperazine ring which are characteristic in most of the reported GPR119 agonists provided novel spirocyclic cyclohexane derivatives. The representative 17 with a high three-dimensionality exhibited potent agonistic activity (EC50 = 4 nM) with no CYP inhibitory activity (IC50 >10 μM). Compound 17 also displayed hypoglycemic activity with insulin secretion dependent on glucose concentration in an intraperitoneal glucose tolerance test in rats.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cf9b6294d0af2043cb0f11fc589e6c54 https://doi.org/10.1016/j.bmcl.2018.02.044 Zobrazit plný text záznamu Full Text from ScienceDirect