5,6-Diphenylpyridazine derivatives as acyl-CoA:cholesterol acyltransferase inhibitors.
Alkyl-5,6-diphenylpyridazine derivatives combining several main features of ACAT inhibitors, such as a long alkyl side chain linked to a heterocycle and the o-diphenyl system, were synthesized and tested. Moreover, modeling studies on representative terms were performed. Some compounds displayed ACAT inhibition in the micromolar range, both on the enzyme isolated from rat liver microsomes and in cell-free homogenate of murine macrophages.
Giovannoni
M P
MP
Dipartimento di Scienze Farmaceutiche, Università di Firenze, via G. Capponi 9, 50121 Firenze, Italy. mariapaola.giovannoni@unifi.it
Piaz
V D
VD
Kwon
B M
BM
Kim
M K
MK
Kim
Y K
YK
Toma
L
L
Barlocco
D
D
Bernini
F
F
Canavesi
M
M
D000818:Animals; D002474:Cell-Free System; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D066298:In Vitro Techniques; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D008958:Models, Molecular; D011724:Pyridazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D011724:Pyridazines; D002785:Sterol O-Acyltransferase