2. Academic Validation
  3. Biarylpyrazolyl oxadiazole as potent, selective, orally bioavailable cannabinoid-1 receptor antagonists for the treatment of obesity

Biarylpyrazolyl oxadiazole as potent, selective, orally bioavailable cannabinoid-1 receptor antagonists for the treatment of obesity

  • J Med Chem. 2008 Nov 27;51(22):7216-33. doi: 10.1021/jm800843r.
Suk Ho Lee 1,  Hee Jeong Seo,  Sung-Han Lee,  Myung Eun Jung,  Ji-Hyun Park,  Hyun-Ju Park,  Jakyung Yoo,  Hoseop Yun,  Jooran Na,  Suk Youn Kang,  Kwang-Seop Song,  Min-ah Kim,  Chong-Hwan Chang,  Jeongmin Kim,  Jinhwa Lee
Affiliations

Affiliation

  • 1 Central Research Laboratories, Green Cross Corporation, 303 Bojeong-dong, Giheung-gu, Yongin 446-770, Korea.
PMID: 18954042 DOI: 10.1021/jm800843r
Abstract

Since the CB1 Cannabinoid Receptor antagonist 1 (SR141716, rimonabant) was previously reported to modulate food intake, CB1 antagonism has been considered as a new therapeutic target for the treatment of obesity. In the present study, biarylpyrazole analogues based on a pyrazole core coupled with 1,3,4-oxadiazole were synthesized and tested for CB1 receptor binding affinity. Thorough SAR studies to optimize pyrazole substituents as well as 1,3,4-oxadiazole ring led to several novel CB1 antagonists with IC(50) approximately 1 nM for the CB1 receptor binding. Among these analogues, we identified 2-(4-((1H-1,2,4-triazol-1-yl)methyl)-5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-1H-pyrazol-3-yl)-5-(1-(trifluoromethyl)cyclopropyl)-1,3,4-oxadiazole 43c as a promising precandidate for the development as an antiobesity agent.

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