Discovery of acylurea isosteres of 2-acylaminothiadiazole in the azaxanthene series of glucocorticoid receptor agonists.
作者： Hua Gong , Michael Yang , Zili Xiao , Arthur M. Doweyko , Mark Cunningham
DOI: 10.1016/J.BMCL.2014.06.010
关键词:
摘要: Acylureas and acyclic imides are found to be excellent isosteres for 2-acylamino-1,3,4-thiadiazole in the azaxanthene-based series of glucocorticoid receptor (GR) agonists. The results reported herein show that primary acylureas maintain high affinity selectivity GR while providing improved CYP450 inhibition pharmacokinetic profile over 2-acylamino-1,3,4-thiadiazoles. General methods synthesis a variety from carboxylic acid were utilized described.
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sci-hub.se 参考文章(23)
John Regan, Hossein Razavi, David Thomson, Advances Toward Dissociated Non-Steroidal Glucocorticoid Receptor Agonists Annual Reports in Medicinal Chemistry. ,vol. 43, pp. 141- 154 ,(2008) , 10.1016/S0065-7743(08)00009-2
Zili Xiao, Michael G. Yang, Andrew J. Tebben, Michael A. Galella, David S. Weinstein, Novel two-step, one-pot synthesis of primary acylureas Tetrahedron Letters. ,vol. 51, pp. 5843- 5844 ,(2010) , 10.1016/J.TETLET.2010.09.003
József Haller, Éva Mikics, Gábor B. Makara, The effects of non-genomic glucocorticoid mechanisms on bodily functions and the central neural system. A critical evaluation of findings Frontiers in Neuroendocrinology. ,vol. 29, pp. 273- 291 ,(2008) , 10.1016/J.YFRNE.2007.10.004
John L. Gilmore, James E. Sheppeck, Jim Wang, T.G. Murali Dhar, Cullen Cavallaro, Arthur M. Doweyko, Lorraine Mckay, Mark D. Cunningham, Sium F. Habte, Steven G. Nadler, John H. Dodd, John E. Somerville, Joel C. Barrish, Synthesis and structure–activity relationships of novel indazolyl glucocorticoid receptor partial agonists Bioorganic & Medicinal Chemistry Letters. ,vol. 23, pp. 5448- 5451 ,(2013) , 10.1016/J.BMCL.2013.06.085
Hai-Yun Xiao, Dauh-Rurng Wu, James E. Sheppeck, Sium F. Habte, Mark D. Cunningham, John E. Somerville, Joel C. Barrish, Steven G. Nadler, T.G. Murali Dhar, Heterocyclic glucocorticoid receptor modulators with a 2,2-dimethyl-3-phenyl-N-(thiazol or thiadiazol-2-yl)propanamide core. Bioorganic & Medicinal Chemistry Letters. ,vol. 23, pp. 5571- 5574 ,(2013) , 10.1016/J.BMCL.2013.08.049
Merritt B. Andrus, Wenki Li, Robert F. Keyes, Synthesis of mixed acyclic imides using pentafluorophenyl esters Tetrahedron Letters. ,vol. 39, pp. 5465- 5468 ,(1998) , 10.1016/S0040-4039(98)01112-5
Nicolas C. Nicolaides, Zoi Galata, Tomoshige Kino, George P. Chrousos, Evangelia Charmandari, The Human Glucocorticoid Receptor: Molecular Basis of Biologic Function Steroids. ,vol. 75, pp. 1- 12 ,(2010) , 10.1016/J.STEROIDS.2009.09.002
Robert Newton, Richard Leigh, Mark A. Giembycz, Pharmacological strategies for improving the efficacy and therapeutic ratio of glucocorticoids in inflammatory lung diseases. Pharmacology & Therapeutics. ,vol. 125, pp. 286- 327 ,(2010) , 10.1016/J.PHARMTHERA.2009.11.003
Ilse M. E. Beck, Wim Vanden Berghe, Linda Vermeulen, Keith R. Yamamoto, Guy Haegeman, Karolien De Bosscher, Crosstalk in inflammation :The interplay of glucocorticoid receptor-based mechanisms and kinases and phosphatases Endocrine Reviews. ,vol. 30, pp. 830- 882 ,(2009) , 10.1210/ER.2009-0013
Peter Norman, Boehringer Ingleheim's selective glucocorticoid receptor agonist development candidate: evaluation of WO2010141331, WO2010141332 and WO2010141333. Expert Opinion on Therapeutic Patents. ,vol. 21, pp. 1137- 1142 ,(2011) , 10.1517/13543776.2011.581229