國家衛生研究院 NHRI:Item 3990099045/8180

NHRI > Institute of Biotechnology and Pharmaceutical Research > Shau-Hua Ueng > Periodical Articles > Item 3990099045/8180

Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/8180

Title:	Discovery, structure-activity relationship studies, and anti-nociceptive effects of 1-phenyl-3,6,6-trimethyl-1,5,6,7-tetrahydro-4H-indazol-4-one as novel opioid receptor agonists
Authors:	Cheng, MF;Ou, LC;Chen, SC;Chang, WT;Law, PY;Loh, HH;Chao, YS;Shih, C;Yeh, SH;Ueng, SH
Contributors:	Institute of Biotechnology and Pharmaceutical Research
Abstract:	The μ-Opioid receptor (MOR) is the major opioid receptor targeted by most analgesics in clinical use. However, the use of all known MOR agonists is associated with severe adverse effects. We reported that the 1-phenyl-3,6,6-trimethyl-1,5,6,7-tetrahydro-4H-indazol-4-ones are novel opioid receptor agonists. Subsequent structural modification resulted in the potent MOR/KOR (κ-opioid receptor) agonists 19, 20, and 21. Testing the analgesic effect of these in WT B6 mice (tail-flick test) gave ED50 values of 8.4, 10.9, and 26.6 mg/kg, respectively. The 1-phenyl-3,6,6-trimethyl-1,5,6,7-tetrahydro-4H-indazol-4-one core could be addressed in 1 or 2 synthetic steps with moderate to high percent of yield. In the adenylyl cyclase assay, compound 19 displayed a MOR/KOR agonist profile, with IC50 values of 0.73 and 0.41 μM, respectively. Current results suggest that compound 19 is a promising lead to go further development and in vitro / in vivo adverse effects studies.
Date:	2014-09
Relation:	Bioorganic and Medicinal Chemistry. 2014 Sep;22(17): 4694-4703.
Link to:	http://dx.doi.org/10.1016/j.bmc.2014.07.012
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0968-0896&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000341293300019
Cited Times(Scopus):	http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84906936838
Appears in Collections:	[Shau-Hua Ueng] Periodical Articles [Shiu-Hwa Yeh] Periodical Articles [Chuan Shih(2014-2017)] Periodical Articles [Yu-Sheng Chao(2002-2013)] Periodical Articles

Files in This Item:

File	Description	Size	Format
SDO0968089614005161.pdf		838Kb	Adobe PDF	720	View/Open

Loading...