Discovery Research, Dr. Reddy's Laboratories Ltd, Bollaram Road, Miyapur, Hyderabad 500049, India.
Bioorg Med Chem Lett. 2011 Aug 15;21(16):4913-8. doi: 10.1016/j.bmcl.2011.06.017. Epub 2011 Jul 7.
The synthesis and biological evaluation of novel pyrazole and imidazole carboxamides as CB1 antagonists are described. As a part of eastern amide SAR, various chemically diverse motifs were introduced on rimonabant template. The central pyrazole core was also replaced with its conformationally constrained motif and imidazole moieties. In general, a range of modifications were well tolerated. Several molecules with low- and sub-nanomolar potencies were identified as potent CB1 receptor antagonists. The in vivo proof of principle for weight loss is demonstrated with a lead compound in DIO mice model.
本文描述了新型吡唑和咪唑甲酰胺类化合物作为 CB1 拮抗剂的合成和生物评价。作为东部酰胺 SAR 的一部分，在利莫那班模板上引入了各种化学结构不同的基序。中央吡唑核心也被其构象受限的基序和咪唑部分取代。总的来说，一系列的修饰都能很好地耐受。一些具有低纳摩尔和亚纳摩尔效力的分子被鉴定为有效的 CB1 受体拮抗剂。在 DIO 小鼠模型中，用一个先导化合物证明了减肥的体内原理。
