Synthesis and evaluation of a new series of tri-, di-, and mono-N-alkylcarbamylphloroglucinols as conformationally constrained inhibitors of cholesterol esterase.

ABSTRACT: 1,3,5-Tri-N-alkylcarbamylphloroglucinols (1-4) are synthesized as conformationally constrained analogs of triacylglycerols (TGs) to probe Jenck's proximity effect in the cholesterol esterase inhibition. For the cholesterol esterase inhibition, inhibitors 1-4 are 220-760-fold more potent than 1,2,3-tri-N-alkylcarbamylglycerols (13-15) that are substrate analogs of TG. Comparison of tridentate inhibitors 1-4, bidentate inhibitors 3,5-di-N-n-alkylcarbamyloxyphenols (5-8) and monodentate inhibitors 5-N-n-alkylcarbamyloxyresorcinols (9-12) indicates that inhibitory potencies are as followed: tridentate inhibitor > bidentate inhibitor > monodentate inhibitor. The log k(i) and pK(i) values of tridentate inhibitors, bidentate inhibitors, and monodentate inhibitors are linearly correlated with th

SUBMITTER: Lin MC 

PROVIDER: S-EPMC3631363 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature