2399-18-0Relevant articles and documents
2-Amino-1,3-thiazol-4(5H)-ones as potent and selective 11β- hydroxysteroid dehydrogenase type 1 inhibitors: Enzyme-ligand co-crystal structure and demonstration of pharmacodynamic effects in C57Bl/6 mice
Johansson, Lars,Fotsch, Christopher,Bartberger, Michael D.,Castro, Victor M.,Chen, Michelle,Emery, Maurice,Gustafsson, Sonja,Hale, Clarence,Hickman, Dean,Homan, Evert,Jordan, Steven R.,Komorowski, Renee,Li, Aiwen,McRae, Kenneth,Moniz, George,Matsumoto, Guy,Orihuela, Carlos,Palm, Gunnar,Veniant, Murielle,Wang, Minghan,Williams, Meredith,Zhang, Jiandong
experimental part, p. 2933 - 2943 (2009/04/10)
11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) has attracted considerable attention during the past few years as a potential target for the treatment of diseases associated with metabolic syndrome. In our ongoing work on 11β-HSD1 inhibitors, a series of new 2-amino-1,3-thiazol-4(5H)-ones were explored. By inserting various cycloalkylamines at the 2-position and alkyl groups or spirocycloalkyl groups at the 5-position of the thiazolone, several potent 11β-HSD1 inhibitors were identified. An X-ray cocrystal structure of human 11β-HSD1 with compound 6d (Ki = 28 nM) revealed a large lipophilic pocket accessible by substitution off the 2-position of the thiazolone. To increase potency, analogues were prepared with larger lipophilic groups at this position. One of these compounds, the 3-noradamantyl analogue 8b, was a potent inhibitor of human 11β-HSD1 (Ki = 3 nM) and also inhibited 11β-HSD1 activity in lean C57Bl/6 mice when evaluated in an ex vivo adipose and liver cortisone to cortisol conversion assay.
7-Acyl-3-(substituted triazolyl thiomethyl)cephalosporins
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, (2008/06/13)
The compounds of this invention are cephalosporins having various acyl substituents at the 7-position and a substituted triazolyl thiomethyl group at the 3-position of the cephem nucleus and intermediates for the preparation thereof. The 7-acylated compounds have antibacterial activity.
