Bioisosteric replacement of the pyrazole 5-aryl moiety of N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716A). A novel series of alkynylthiophenes as potent and selective cannabinoid-1 receptor antagonists.

@article{Tseng2008BioisostericRO,
  title={Bioisosteric replacement of the pyrazole 5-aryl moiety of N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716A). A novel series of alkynylthiophenes as potent and selective cannabinoid-1 receptor antagonists.},
  author={Shi-Liang Tseng and Ming-Shiu Hung and Chun-Ping Chang and Jen-Shin Song and Chia-Liang Tai and Hua-Hao Chiu and Wan-Ping Hsieh and Yinchiu Lin and Wan-Ling Chung and Chun-Wei Kuo and Chien-Huang Wu and Cheng-ming Chu and Yen-Shih Tung and Yu-Sheng Chao and Kak-Shan Shia},
  journal={Journal of medicinal chemistry},
  year={2008},
  volume={51 17},
  pages={
          5397-412
        }
}
Replacing the conventional pyrazole 5-aryl substituent of 1 (SR141716A) with the 2-thienyl moiety appended with an appropriate alkynyl unit, a novel class of 5-(5-alkynyl-2-thienyl)pyrazole derivatives, behaving as highly potent CB1 receptor antagonists with good CB1/2 selectivity, was discovered, many of which, as typified by compound 18, showed significant weight reduction in diet-induced obese mouse model, thus pharmacologically validating that the bioisosteric replacement described above is… CONTINUE READING