Biphenyl versus Phenylpyridazine Derivatives: The Role of the Heterocycle in a Series of Acyl-CoA:Cholesterol Acyl Transferase Inhibitors

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• 作者：Arianna Gelain ; Daniela Barlocco ; Byoung-Mog Kwon ; Tae-Sook Jeong ; Kyung-Ran Im ; Laura Legnani ; Lucio Toma
• 刊名：Journal of Medicinal Chemistry
• 出版年：2008
• 出版时间：March 13, 2008
• 年：2008
• 卷：51
• 期：5
• 页码：1474 - 1477
• 全文大小：284K
• 年卷期：v.51,no.5(March 13, 2008)
• ISSN：1520-4804

文摘

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.