Substituted pyrimidines as cannabinoid CB1 receptor ligands.
Cannabinoid CB1 receptors have been the avenue 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 substituted pyrimidines based on chemical structure of Merck's taranabant, a cannabinoid CB1 receptor inverse agonist. Noticeably, N4-((2S,3S)-3-(3-bromophenyl)-4-(4-chlorophenyl)butan-2-yl)-N6-butylpyrimidine-4,6-diamine (13b) demonstrated good binding affinity and decent selectivity for CB1 receptor (IC(50)=16.3nM, CB2/CB1=181.6).
Kim
Min Ju
MJ
Central Research Laboratories, Green Cross Corporation, Yongin, Gyeonggi-Do 446-770, Republic of Korea.
Kim
Jong Yup
JY
Seo
Hee Jeong
HJ
Lee
Junwon
J
Lee
Sung-Han
SH
Kim
Mi-Soon
MS
Kang
Jahyo
J
Kim
Jeongmin
J
Lee
Jinhwa
J
D000818:Animals; D019440:Anti-Obesity Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008024:Ligands; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors* / Q000378:metabolism
D019440:Anti-Obesity Agents; D008024:Ligands; D011743:Pyrimidines; D043884:Receptor, Cannabinoid, CB1