Symmetrical approach of spiro-pyrazolidinediones as acetyl-CoA carboxylase inhibitors.
Basic Information
ID: ALA2057206
Journal: Bioorg Med Chem Lett
Title: Symmetrical approach of spiro-pyrazolidinediones as acetyl-CoA carboxylase inhibitors.
Authors: Kamata M, Yamashita T, Kina A, Tawada M, Endo S, Mizukami A, Sasaki M, Tani A, Nakano Y, Watanabe Y, Furuyama N, Funami M, Amano N, Fukatsu K.
Abstract: Spiro-pyrazolidinedione derivatives without quaternary chiral center were discovered by structure-based drug design and characterized as potent acetyl-CoA carboxylase (ACC) inhibitors. The high metabolic stability of the spiro-pyrazolo[1,2-a]pyridazine scaffold and enhancement of the activity by incorporation of a 7-methoxy group on the benzothiophene core successfully led to the identification of compound 4c as an orally bioavailable and highly potent ACC inhibitor. Oral administration of 4c significantly decreased the values of the respiratory quotient in rats, indicating the stimulation of fatty acid oxidation.
CiteXplore: 22677317
DOI: 10.1016/j.bmcl.2012.05.062
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