Biphenyl versus phenylpyridazine derivatives: the role of the heterocycle in a series of acyl-CoA:cholesterol acyl transferase inhibitors.
A series of alkylamido- ( 1) and alkylaminobiphenyl ( 2) derivatives were synthesized as possible bioisosters of the reported ACAT inhibitors phenylpyridazine analogues ( I). Both 1 and 2 were tested on the human ACAT-1 and ACAT-2 isoforms. The amino derivatives 2 were found to be inactive, contrary to the related pyridazine derivatives. By contrast, the ortho -substituted amides 1a and 1d showed an interesting activity. These results support the essential role of the pyridazine nucleus. Modeling studies were also performed.
Gelain
Arianna
A
Istituto di Chimica Farmaceutica e Tossicologica, Universita di Milano, Milano, Italy.
Barlocco
Daniela
D
Kwon
Byoung-Mog
BM
Jeong
Tae-Sook
TS
Im
Kyung-Ran
KR
Legnani
Laura
L
Toma
Lucio
L
D001713:Biphenyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D006801:Humans; D008958:Models, Molecular; D011724:Pyridazines / Q000138:chemical synthesis* / Q000737:chemistry; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D013329:Structure-Activity Relationship
D001713:Biphenyl Compounds; D011724:Pyridazines; D002785:Sterol O-Acyltransferase