2-Chloro-4-[[(1R,2R)-2-hydroxy-2-methyl-cyclopentyl]amino]-3-methyl-benzonitrile: A Transdermal Selective Androgen Receptor Modulator (SARM) for Muscle Atrophy
作者： Ashraf Saeed , Grant M. Vaught , Kostas Gavardinas , Donald Matthews , Jonathan E. Green
DOI: 10.1021/ACS.JMEDCHEM.5B01168
关键词:
摘要: A transdermal SARM has a potential to have therapeutic benefit through anabolic activity in muscle while sparing undesired effects of benign prostate hyperplasia (BPH) and liver-mediated decrease HDL-C. 2-Chloro-4-[(2-hydroxy-2-methyl-cyclopentyl)amino]-3-methyl-benzonitrile 6 showed the desired preclinical ORX rat model. Compound had minimal effect on HDL-C levels cynomolgus monkeys human cadaver skin permeability, thus making it an effective tool for proof-of-concept studies clinical setting.
rcsb.org
acs.org参考文章(19)
Russell O. Potts, Richard H. Guy, Predicting skin permeability. Pharmaceutical Research. ,vol. 9, pp. 663- 669 ,(1992) , 10.1023/A:1015810312465
Wenqing Gao, Casey E. Bohl, James T. Dalton, Chemistry and structural biology of androgen receptor Chemical Reviews. ,vol. 105, pp. 3352- 3370 ,(2005) , 10.1021/CR020456U
Peter Y. Liu, Alison K. Death, David J. Handelsman, Androgens and cardiovascular disease. Endocrine Reviews. ,vol. 24, pp. 313- 340 ,(2003) , 10.1210/ER.2003-0005
James T. Dalton, Kester G. Barnette, Casey E. Bohl, Michael L. Hancock, Domingo Rodriguez, Shontelle T. Dodson, Ronald A. Morton, Mitchell S. Steiner, The selective androgen receptor modulator GTx-024 (enobosarm) improves lean body mass and physical function in healthy elderly men and postmenopausal women: results of a double-blind, placebo-controlled phase II trial Journal of Cachexia, Sarcopenia and Muscle. ,vol. 2, pp. 153- 161 ,(2011) , 10.1007/S13539-011-0034-6
Kurt W. Weingand, Atherosclerosis research in cynomolgus monkeys (Macaca fascicularis) Experimental and Molecular Pathology. ,vol. 50, pp. 1- 15 ,(1989) , 10.1016/0014-4800(89)90052-X
E. Lichar Dillon, William J. Durham, Randall J. Urban, Melinda Sheffield-Moore, Hormone treatment and muscle anabolism during aging: Androgens Clinical Nutrition. ,vol. 29, pp. 697- 700 ,(2010) , 10.1016/J.CLNU.2010.03.010
Arnold von Eckardstein, Fredrick C.W Wu, Testosterone and atherosclerosis. Growth Hormone & Igf Research. ,vol. 13, ,(2003) , 10.1016/S1096-6374(03)00059-5
William R. Hazzard, Patricia W. Wahl, Claude Gagne, Deborah Applebaum-Bowden, G. Russell Warnick, John J. Albers, Plasma and lipoprotein lipid responses to four hypolipid drugs. Lipids. ,vol. 19, pp. 73- 79 ,(1984) , 10.1007/BF02534494
Nicole K. L. Lee, Helen E. MacLean, Polyamines, androgens, and skeletal muscle hypertrophy. Journal of Cellular Physiology. ,vol. 226, pp. 1453- 1460 ,(2011) , 10.1002/JCP.22569
Michael L. Mohler, Casey E. Bohl, Amanda Jones, Christopher C. Coss, Ramesh Narayanan, Yali He, Dong Jin Hwang, James T. Dalton, Duane D. Miller, Nonsteroidal selective androgen receptor modulators (SARMs): dissociating the anabolic and androgenic activities of the androgen receptor for therapeutic benefit. Journal of Medicinal Chemistry. ,vol. 52, pp. 3597- 3617 ,(2009) , 10.1021/JM900280M