91820-05-2Relevant articles and documents
Synthesis and evaluation of heteroaryl-substituted dihydronaphthalenes and indenes: Potent and selective inhibitors of aldosterone synthase (CYP11B2) for the treatment of congestive heart failure and myocardial fibrosis
Voets, Marieke,Antes, Iris,Scherer, Christiane,Müller-Vieira, Ursula,Biemel, Klaus,Marchais-Oberwinkler, Sandrine,Hartmann, Rolf W.
, p. 2222 - 2231 (2007/10/03)
In this study, the synthesis and biological evaluation of heteroaryl-substituted dihydronaphthalenes and indenes (1-16) is described. The compounds were tested for activity by use of human CYP11B2 expressed in fission yeast and V79 MZh cells and for selectivity by use of human CYP11B1, CYP17, and CYP19. The most active inhibitor was the 6-methoxydihydronaphthalene 4 (IC 50 = 2 nM), showing a Ki value of 1.3 nM and a competitive type of inhibition. The 5-methoxyindene 3 was found to be the most selective CYP11B2 inhibitor (IC50 = 4 nM; CYP11B1 IC50 = 5684 nM), which also showed only marginal inhibition of human CYP3A4 and CYP2D6. Docking and molecular dynamics studies using our homology-modeled CYP11B2 structure were performed to understand some structure-activity relationships. Caco-2 cell experiments revealed highly cell-permeable compounds, and metabolic studies with 4 using rat liver microsomes showed sufficient stability.
Cascade reactions of β-amino-substituted α,β-unsaturated fischer carbene complexes with 1,5-dien-3-ynes as a convenient access to ring-annelated benzene derivatives
Wu, Yao-Ting,Noltemeyer, Mathias,De Meijere, Armin
, p. 2802 - 2810 (2007/10/03)
Upon heating pentacarbonyl(3-dimethylamino-1-ethoxypropenylidene)chromium complexes 1 with 1,5-dien-3-ynes 2 in pyridine at 80°C, benzene-annelated cyclopentenones 8 and their regioisomers 9, resulting from a sequence of cocyclization, 6π-electrocyclization and hydrolysis, were isolated in 12-75% yield (13 examples). The more flexible the alkenyl substituents were in the dienynes 2, the longer were the reaction times needed to achieve good chemical yields. This new cascade reaction of Fischer carbene complexes provides a direct route to trindanone analogues under milder conditions than traditional methods, and is compatible with more functionalities. Compounds 14 and 15 with steroid-like skeletons were thus prepared in 54-77% yields (4 examples) from complex 1-iPr and the bicyclic alkyne 2. Hexacycles 17 and 18 were accessible with high diastereoselectivity in the triquinane moiety by the same method in 45 % yield,
Mechanism of an Interesting Ring-Contraction Reaction of a Class of Carbocyclic trans-Dibromides and Stereoisomeric Bromohydrins through Solvolysis
Mandal, Asok N.,Bhattacharya, Sudin,Raychaudhuri, Swadesh R.,Chatterjee, Amareshwar
, p. 2856 - 2876 (2007/10/02)
An efficient ring contraction of the trans-dibromides and the bromohydrins (1a-f) through solvolysis under neutral conditions to the aldehydes (3a-d) in good to excellent yields is reported.The role of substituent, influence of stereochemistry, and the effect of ring size on the case of this interesting ring contraction reaction are clearly demonstrated from the results, tabulated in Table 1; a probable mechanism for ring contraction is presented.
AN INTERESTING RING CONTRACTION OF A CLASS OF BROMOHYDRINS AND TRANS-DIBROMIDES
Bhattacharya, S.,Mandal, A. N.,Chaudhuri, S. R. Ray,Chatterjee, A.
, p. 3007 - 3010 (2007/10/02)
An efficient ring contraction of stereoisomeric 1,2-benzo-4-bromo-3-hydroxycyclohept-1-ene and their derivatives (1a-e) to (2a-c) is reported, and a probable mechanism for this ring contraction has been suggested.
