21245-51-2Relevant academic research and scientific papers
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.
Non-metallocene compounds, method for the production thereof and use of the same for the polymerisation of olefins
-
, (2008/06/13)
The invention relates to a method for producing special transition metal compounds, to novel transition metal compounds and to the use of the same for the polymerisation of olefins.
cis-Diazenes. Viscosity Effects, One-Bond Scission, and Cis-Trans Isomerization
Neuman, Robert C.,Grow, Richard H.,Binegar, Glen A.,Gunderson, Howard J.
, p. 2682 - 2688 (2007/10/02)
Effects of solvent viscosity on the rates of overall thermal decomposition, deazatization, and iomerization of several symmetric and unsymmetric cis-diazenes (cis-azoalkanes) have been determined in pure alkanes and mixtures of octane and mineral oil.Increasing viscosity decreases the overall decomposition and deazatization rates for all of these cis-diazenes.While isomerization rates also decrease with increasing viscosity for most of the diazenes, that for cis-N-tert-butyl-N'-1-norbornyldiazene (1) increases.These results are interpreted in terms of deazatization via one-bond scission and an intermediate diazenyl radical, isomerization via nonradical inversion, and the possibility of isomerization via a diazenyl radical for 1.
Decomposition and Isomerization of Bridgehead Cis 1,2-Diazenes (Azoalkanes)
Chae, Woo-Ki,Baughman, Sharon A.,Engel, Paul S.,Bruch, Manfred,Oezmeral, Cenan,et al.
, p. 4824 - 4833 (2007/10/02)
Four acyclic cis 1,2-diazenes, azo-1-adamantane (cis-ada), azo-bicyclooctane (cis-), azo-1-bicycloheptane (cis-), and azo-1-bicyclohexane (cis-) have been generated by UV irradiation of the corresponding trans-isomers.These compounds differ greately in stability, cis- easily surviving at 100 deg C and cis-ada not being isolable.Whereas cis- and cis-only isomerize back to trans on heating, the other two compounds undergo competing loss of nitrogen.The observation that the energy of the transition state for isomerization remains at 42 +/- 1 kcal mol-1 regardless of the cis ground state energy is used to argue that thermal isomerization proceeds via semilinearization rather than rotation.A remarkable correlation of cis ground state energy with cis n,?* excitation energy has emerged from this study.
