868604-86-8Relevant articles and documents
ALKANOYLAMINO BENZAMIDE ANILINE HDAC INHIBITOR COMPOUNDS
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, (2010/12/29)
The present invention provides a compound of general Formula (I) having histone deacetylase (HDAC) inhibitory activity, a pharmaceutical composition comprising the compound, and a method useful to treat diseases using the compound.
A convergent process for the preparation of adamantane 11-β-HSD-1 inhibitors
Becker, Calvin L.,Engstrom, Kenneth M.,Kerdesky, Francis A.,Tolle, John C.,Wagaw, Seble H.,Wang, Weifeng
, p. 1114 - 1118 (2013/01/03)
A convergent, scalable process was developed for the synthesis of adamantane 11-β-hydroxysteroid dehydrogenase-1 inhibitors E-4-(2-methyl-2-(4-(5-(trifluoromethyl)pyridin-2-yl)piperazin-1-yl) propionylamino)adamantane-1-carboxylic acid (1) and E-4-(2-methyl-2-(4-(5- (trifluoromethyl)pyridin-2-yl)piperazin-1-yl)propionylamino)-adamantane-1- carboxamide (2) to rapidly deliver material for development. The process was high yielding and provided 1 in 52% overall yield over six total steps with a five-step longest linear sequence and 2 in 45% overall yield over seven total steps with a six-step longest linear sequence. A process to prepare active pharmaceutical ingredient (API) of >99% purity at the kilogram scale has been developed under tight delivery timelines.
Discovery and metabolic stabilization of potent and selective 2-amino-N-(adamant-2-yl) acetamide 11β-hydroxysteroid dehydrogenase type 1 inhibitors
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
, p. 149 - 164 (2008/02/01)
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 and improved microsomal stability. Pharmacokinetic profiling in rodents indicated moderate to large volumes of distribution, short half-lives, and a pharmacokinetic species difference with the greatest exposure measured in rat with 22d. One hour postdose liver, adipose, and brain tissue 11β-HSD1 inhibition was confirmed with (±)-22f in a murine ex vivo assay. Although 5,7-disubstitued-2-adamantamines provided greater stability, a single, E-5-position, polar functional group afforded inhibitors with the best combination of stability, potency, and selectivity. These results indicate that adamantane metabolic stabilization sufficient to obtain short-acting, potent, and selective 11β-HSD1 inhibitors has been discovered.
Inhibitors of the 11-beta-hydroxysteroid dehydrogenase Type 1 enzyme and their therapeutic application
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Page/Page column 12, (2008/06/13)
The present invention relates to the use of inhibitors of the 11-beta-hydroxysteroid dehydrogenase Type 1 enzyme. The present invention further relates to the use of inhibitors of 11-beta-hydroxysteroid dehydrogenase Type 1 enzyme for the treatment or pro
Inhibitors of the 11-beta-hydroxysteroid dehydrogenase Type 1 enzyme and their therapeutic application
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Page/Page column 21, (2010/02/14)
The present invention relates to the use of inhibitors of the 11-beta-hydroxysteroid dehydrogenase Type 1 enzyme. The present invention further relates to the use of inhibitors of 11-beta-hydroxysteroid dehydrogenase Type 1 enzyme for the treatment or pro
Inhibitors of the 11-beta-hydroxysteroid dehydrogenase Type 1 enzyme
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Page/Page column 40, (2010/02/14)
The present invention relates to compounds which are inhibitors of the 11-beta-hydroxysteroid dehydrogenase Type 1 enzyme. The present invention further relates to the use of inhibitors of 11-beta-hydroxysteroid dehydrogenase Type 1 enzyme for the treatme
Inhibitors of the 11-beta-hydroxysteroid dehydrogenase Type 1 enzyme
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Page/Page column 28, (2008/06/13)
The present invention relates to compounds which are inhibitors of the 11-beta-hydroxysteroid dehydrogenase Type 1 enzyme. The present invention further relates to the use of inhibitors of 11-beta-hydroxysteroid dehydrogenase Type 1 enzyme for the treatment of non-insulin dependent type 2 diabetes, insulin resistance, obesity, lipid disorders, metabolic syndrome, and other diseases and conditions that are mediated by excessive glucocorticoid action.
Inhibitors of the 11-beta-hydroxysteroid dehydrogenaseType 1 enzyme and their therapeutic application
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, (2008/06/13)
The present invention relates to the use of inhibitors of the 11-beta-hydroxysteroid dehydrogenase Type 1 enzyme. The present invention further relates to the use of inhibitors of 11-beta-hydroxysteroid dehydrogenase Type 1 enzyme for the treatment or prophylactically treatment of non-insulin dependent type 2 diabetes, insulin resistance, obesity, lipid disorders, metabolic syndrome, and other diseases and conditions mediated by excessive glucocorticoid action.
