Shibuya, Kimiyuki published the artcileDesign, synthesis and pharmacology of aortic-selective acyl-CoA: Cholesterol O-acyltransferase (ACAT/SOAT) inhibitors, Application of 15-Bromopentadecanoic acid, the main research area is ACAT SOAT inhibitor aorta selectivity antiatherosclerotic lipid accumulation atherosclerosis; ACAT-1 (aortic ACAT); ACAT-2 (intestinal ACAT); Acyl-CoA:cholesterol O-acyltransferase (ACAT/SOAT); Atherosclerosis; Cholesterol esters (CEs); Double-induced fit; Isoform-selectivity; Lipid-accumulation areas.
We describe our mol. design of aortic-selective acyl-CoA:cholesterol O-acyltransferase (ACAT, also abbreviated as SOAT) inhibitors, their structure-activity relationships (SARs) and their pharmacokinetic (PK) and pharmacol. profiles. The connection of two weak ligands-N-(2,6-diisopropylphenyl)acetamide (50% inhibitory concentration [IC50] = 8.6 μM) and 2-(methylthio)benzo[d]oxazole (IC50 = 31 μM)-via a linker comprising a 6 methylene group chains yielded a highly potent mol., 9-(benzo[d]oxazol-2-ylthio)-N-(2,6-diisopropylphenyl)nonanamide (3h) that exhibited high potency (IC50 = 0.004 μM) toward aortic ACAT. This head-to-tail design made it possible to markedly enhance the activity to 2150- to 7750-fold and to discriminate the isoform-selectivity based on the double-induced fit mechanism. At doses of 1 and 3 mg/kg, 3h significantly decreased the lipid-accumulation areas in the aortic arch to 74 and 69%, resp. without reducing the plasma total cholesterol level in high fat- and cholesterol-fed F1B hamsters. Here, we demonstrate the antiatherosclerotic effect of 3h in vivo via its direct action on aortic ACAT and its powerful modulator of cholesterol level. This mol. is a potential therapeutic agent for the treatment of diseases involving ACAT-1 overexpression.
Bioorganic & Medicinal Chemistry published new progress about Antiatherosclerotics. 56523-59-2 belongs to class bromides-buliding-blocks, name is 15-Bromopentadecanoic acid, and the molecular formula is C15H29BrO2, Application of 15-Bromopentadecanoic acid.
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary