title: Mono- or diphenylpyridazines connected to N-(2,4-difluorophenyl)-N'-heptylurea as acyl-CoA:cholesterol acyltransferase inhibitors.
abstract: Mono- and diphenylpyridazine ureido derivatives, structurally related to DuP 128, were synthesized and tested for their inhibitory activity against ACAT isolated from rat liver microsomes. Several compounds displayed ACAT inhibition in the micromolar range. The amino derivatives 4a-c were also tested against hACAT-1 and hACAT-2 isoforms. They retained the same trend shown in the previous assay. Modeling studies on representative terms were performed. Significant similarities between the geometrical features of the model DuP 128 and the most active pyridazine derivatives were observed.
authors.affiliation: Istituto di Chimica Farmaceutica e Tossicologica, Università di Milano, Viale Abruzzi 42, 20131 Milano, Italy. daniela.barlocco@unimi.it
authors.forename: Arianna
authors.initials: A
authors.lastname: Gelain
authors.forename: Ilaria
authors.initials: I
authors.lastname: Bettinelli
authors.forename: Daniela
authors.initials: D
authors.lastname: Barlocco
authors.forename: Byoung-Mog
authors.initials: BM
authors.lastname: Kwon
authors.forename: Tae-Sook
authors.initials: TS
authors.lastname: Jeong
authors.forename: Kyung-Hyun
authors.initials: KH
authors.lastname: Cho
authors.forename: Lucio
authors.initials: L
authors.lastname: Toma
mesh_terms: D000101:Acetyl-CoA C-Acetyltransferase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D000818:Animals; D002460:Cell Line; D006801:Humans; D066298:In Vitro Techniques; D008862:Microsomes, Liver / Q000201:enzymology; D008958:Models, Molecular; D010671:Phenylurea Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D020033:Protein Isoforms / Q000037:antagonists & inhibitors; D011724:Pyridazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D013329:Structure-Activity Relationship; D000097587:Sterol O-Acyltransferase 2
chemical_list: D000101:Acetyl-CoA C-Acetyltransferase; D010671:Phenylurea Compounds; D020033:Protein Isoforms; D011724:Pyridazines; D002785:Sterol O-Acyltransferase; D000097587:Sterol O-Acyltransferase 2; C506639:ACAT1 protein, human