以四氢喹啉类似物作为EPAC抑制剂的构效关系研究
Structure-Activity Relationship Studies with Tetrahydroquinoline Analogs as EPAC Inhibitors.
作者信息
Sonawane Yogesh A, Zhu Yingmin, Garrison Jered C, Ezell Edward L, Zahid Muhammad, Cheng Xiaodong, Natarajan Amarnath
机构信息
Eppley Institute for Research in Cancer and Allied Diseases, Fred and Pamela Buffett Cancer Center, Departments of Pharmaceutical Sciences, Environmental, Agricultural and Occupational Health, and Genetics Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, Nebraska 68022, United States.
Department of Integrative Biology and Pharmacology and Texas Therapeutics Institute, University of Texas Health Science Center, Houston, Texas 77030, United States.
出版信息
ACS Med Chem Lett. 2017 Oct 2;8(11):1183-1187. doi: 10.1021/acsmedchemlett.7b00358. eCollection 2017 Nov 9.
EPAC proteins are therapeutic targets for the potential treatment of cardiac hypertrophy and cancer metastasis. Several laboratories use a tetrahydroquinoline analog, CE3F4, to dissect the role of EPAC1 in various disease states. Here, we report SAR studies with tetrahydroquinoline analogs that explore various functional groups. The most potent EPAC inhibitor exists as a mixture of inseparable (major) and (minor) rotamers. The rotation about the -formyl group indeed impacts the activity against EPAC.
EPAC蛋白是心脏肥大和癌症转移潜在治疗的靶点。几个实验室使用四氢喹啉类似物CE3F4来剖析EPAC1在各种疾病状态中的作用。在此，我们报告了对探索各种官能团的四氢喹啉类似物的构效关系研究。最有效的EPAC抑制剂以不可分离的（主要）和（次要）旋转异构体混合物形式存在。围绕甲酰基的旋转确实会影响对EPAC的活性。
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