Pentacycle derivatives as cannabinoid CB1 receptor ligands.
Cannabinoid CB-1 receptors have been the focus of extensive studies since the first clinical results of rimonabant (SR141716) for the treatment of obesity and obesity-related metabolic disorders were reported in 2001. To further evaluate the properties of CB receptors, we have designed and efficiently prepared a series of pentacycle derivatives. Five of the new compounds which displayed high in vitro rCB1 binding affinities were assayed for binding to hCB2 receptor. Noticeably, 2-(5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-(5-methyl-1,3,4-thiadiazol-2-yl)-1H-pyrazol-3-yl)-5-(1-(trifluoromethyl)cyclopropyl)-1,3,4-oxadiazole (16l) demonstrated good binding affinity and decent selectivity for rCB1 receptor (IC(50)=1.72 nM, hCB2/rCB1=142).
Central Research Laboratories, Green Cross Corporation, Yongin, Gyeonggi-Do 446-770, Republic of Korea.
Suk Ho
SH
Lee
Hee Jeong
HJ
Seo
Min Ju
MJ
Kim
Suk Youn
SY
Kang
Sung-Han
SH
Lee
Kwangwoo
K
Ahn
Minwoo
M
Lee
Ho-Kyun
HK
Han
Jeongmin
J
Kim
Jinhwa
J
Lee
D000818:Animals; D015195:Drug Design; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D008024:Ligands; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1