Discovery and metabolic stabilization of potent and selective 2-amino-N-(adamant-2-yl) acetamide 11β-hydroxysteroid dehydrogenase type 1 inhibitors

…, BK Sorensen, D Wodka, Q Shuai, J Wang…

Index: Rohde, Jeffrey J.; Pliushchev, Marina A.; Sorensen, Bryan K.; Wodka, Dariusz; Shuai, Qi; Wang, Jiahong; Fung, Steven; Monzon, Katina M.; Chiou, William J.; Pan, Liping; Deng, Xiaoqing; Chovan, Linda E.; Ramaiya, Atul; Mullally, Mark; Henry, Rodger F.; Stolarik, DeAnne F.; Imade, Hovis M.; Marsh, Kennan C.; Beno, David W. A.; Fey, Thomas A.; Droz, Brian A.; Brune, Michael E.; Camp, Heidi S.; Sham, Hing L.; Frevert, Ernst Uli; Jacobson, Peer B.; Link Journal of Medicinal Chemistry, 2007 , vol. 50, # 1 p. 149 - 164

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Citation Number: 69

Abstract

Starting from a rapidly metabolized adamantane 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitor 22a, a series of E-5-hydroxy-2-adamantamine inhibitors, exemplified by 22d and (±)-22f, was discovered. Many of these compounds are potent inhibitors of 11β- HSD1 and are selective over 11β-HSD2 for multiple species (human, mouse, and rat), unlike other reported species-selective series. These compounds have good cellular potency ...