476458-89-6Relevant articles and documents
Discovery of azetidinone acids as conformationally-constrained dual PPARα/γ agonists
Wang, Wei,Devasthale, Pratik,Farrelly, Dennis,Gu, Liqun,Harrity, Thomas,Cap, Michael,Chu, Cuixia,Kunselman, Lori,Morgan, Nathan,Ponticiello, Randy,Zebo, Rachel,Zhang, Litao,Locke, Kenneth,Lippy, Jonathan,O'Malley, Kevin,Hosagrahara, Vinayak,Zhang, Lisa,Kadiyala, Pathanjali,Chang, Chiehying,Muckelbauer, Jodi,Doweyko, Arthur M.,Zahler, Robert,Ryono, Denis,Hariharan, Narayanan,Cheng, Peter T.W.
, p. 1939 - 1944 (2008/09/20)
A novel class of azetidinone acid-derived dual PPARα/γ agonists has been synthesized for the treatment of diabetes and dyslipidemia. The preferred stereochemistry in this series for binding and functional agonist activity against both PPARα and PPARγ receptors was shown to be 3S,4S. Synthesis, in vitro and in vivo activities of compounds in this series are described. A high-yielding method for N-arylation of azetidinone esters is also described.
Synthesis and biological activity of new 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase inhibitors: 2-oxetanones with a side chain mimicking the folded structure of 1233A.
Hashizume,Ito,Yamada,Nagashima,Kanao,Tomoda,Sunazuka,Kumagai,Omura
, p. 512 - 520 (2007/10/02)
To mimic the folded side chain conformation of 1233A (1), which is a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase inhibitor, 1233A analogs with aromatic rings in the side chain were synthesized. The 2-oxetanone moiety was kept intact. Among 1233A and its synthetic analogs, trans-3-hydroxymethyl-4-[2-(7-methoxycarbonyl-1-naphthyl)ethyl]-2-oxe tanone (23) showed the highest HMG-CoA synthase inhibitory activity in vitro. The structure-activity relationship at the side chain is discussed.
