The design and synthesis of potent, selective benzodiazepine sulfonamide bombesin receptor subtype 3 (BRS-3) agonists with an increased barrier of atropisomerization.
The design and synthesis of potent, selective benzodiazepine sulfonamide bombesin receptor subtype 3 (BRS-3) agonists with an increased barrier of atropisomerization.
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DOI：
10.1016/j.bmc.2012.03.029
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发表时间：
2012-05
影响因子：
3.5
通讯作者：
H. Chobanian;Yan Guo;Ping Liu;T. Lanza;M. Chioda;Linda L. Chang;T. Kelly;Y. Kan;O. Palyha;X. Guan;D. Marsh;J. Metzger;Kate A Raustad;Sheng-Ping Wang;A. Strack;Judith N. Gorski;Randy R Miller;Jianmei Pang;K. Lyons;J. Dragovic;J. G. Ning;W. Schafer;C. Welch;Xiaoyi Gong;Yinghong Gao;V. Hornak;M. Reitman;R. Nargund;L. Lin
中科院分区：
文献类型：
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作者：
H. Chobanian;Yan Guo;Ping Liu;T. Lanza;M. Chioda;Linda L. Chang;T. Kelly;Y. Kan;O. Palyha;X. Guan;D. Marsh;J. Metzger;Kate A Raustad;Sheng-Ping Wang;A. Strack;Judith N. Gorski;Randy R Miller;Jianmei Pang;K. Lyons;J. Dragovic;J. G. Ning;W. Schafer;C. Welch;Xiaoyi Gong;Yinghong Gao;V. Hornak;M. Reitman;R. Nargund;L. Lin
蛙皮素受体亚型3（BRS-3）是主要在下丘脑中表达的孤儿G蛋白偶联受体，其在糖尿病和肥胖症的发病中起作用。我们在此报告了我们在鉴定与先前描述的MK-77251 Chobanian et al.（2012）相关的强效选择性蛙皮素受体亚型-3（BRS-3）激动剂方面取得的进展，该激动剂将通过增加C-2位的空间体积来防止阻转异构化。因此，这将通过抑制在室温/高温下长时间内可能发生的外消旋化而使这类化合物的临床开发更具成本效益。
Bombesin receptor subtype 3 (BRS-3) is an orphan G-protein coupled receptor expressed primarily in the hypothalamus which plays a role in the onset of both diabetes and obesity. We report herein our progress made towards identifying a potent, selective bombesin receptor subtype-3 (BRS-3) agonist related to the previously described MK-77251Chobanian et al. (2012) that would prevent atropisomerization through the increase of steric bulk at the C-2 position. This would thereby make clinical development of this class of compounds more cost effective by inhibiting racemization which can occur over long periods of time at room/elevated temperature.