Synthesis and evaluation of 4-(2-hydroxypropyl)piperazin-1-yl) derivatives as Hsp90 inhibitors
We previously reported 4-(3-((6-bromonaphthalen-2-yl)oxy)-2-hydroxypropyl)-N,N-dimethylpiperazine-1-sulfonamide (1) as a novel heat shock protein 90 inhibitor with moderate activity. In our ongoing efforts for the discovery of Hsp90 modulators we undertake structural investigations on 1. Series of the titled compound were designed, synthesized and evaluated. We have found that compounds with a hydroxyl group at C-4 of the aryl ring on the piperazine moiety possess Hsp90 inhibition properties. Compound 6f with improved activity could be further developed and optimized as Hsp90 inhibitor.
Regioselective ring-opening of epoxides by carbazole: A direct preparation of novel N-(β-hydroxyalkyl)carbazoles
The influence of various parameters including solvent, base and temperature on the reaction between carbazole and epoxides was studied This led to the development of a regioselective ring-opening of epoxides by the potassium salt of carbazole in DMSO at 100 °C which is a straightforward way to prepare new N-(β-hydroxyalkyl)carbazoles in good to excellent yields. Fifteen new compounds are described.
Soltani Rad, Mohammad Navid,Behrouz, Somayeh,Ahrari, Samira
p. 137 - 140
(2016/04/20)
Thienopyrimidines as β3-adrenoceptor agonists: Hit-to-lead optimization
Resulting from a vHTS based on a pharmacophore alignment on known β3-adrenoceptor ligands, an aryloxypropanolamine scaffold comprising a thienopyrimidine moiety was further optimized as a human β3-AR agonist, yielding a lead compound with an excellent cellular activity of EC50 = 20 pM, selectivity over hβ1- and hβ2-adrenoceptors and a promising safety profile.