- Design, synthesis, and structure-activity relationships of spirolactones bearing 2-ureidobenzothiophene as acetyl-CoA carboxylases inhibitors
-
The co-crystal structure of the human acetyl-coenzyme A 2 (ACC2) carboxyl transferase domain and the reported compound CP-640186 (1b) suggested that two carbonyl groups are essential for potent ACC2 inhibition. By focusing on enhancing the interactions between the two carbonyl groups and the amino acid residues Gly2162 and Glu2230, we used ligand- and structure-based drug design to discover spirolactones bearing a 2-ureidobenzothiophene moiety
- Yamashita, Tohru,Kamata, Makoto,Endo, Satoshi,Yamamoto, Mitsuo,Kakegawa, Keiko,Watanabe, Hiroyuki,Miwa, Katsuhiko,Yamano, Toru,Funata, Masaaki,Sakamoto, Jyun-Ichi,Tani, Akiyoshi,Mol, Clifford D.,Zou, Hua,Dougan, Douglas R.,Sang, BiChing,Snell, Gyorgy,Fukatsu, Kohji
-
p. 6314 - 6318
(2011/11/29)
-
- SPIRO-RING COMPOUND
-
The present invention aims to provide a compound having an acetyl-CoA carboxylase (ACC) inhibitory action, which is useful for the prophylaxis or treatment of obesity, diabetes, hypertension, hyperlipidemia, cardiac failure, diabetic complications, metabolic syndrome, sarcopenia, cancer and the like, and has superior efficacy. The present invention provides a compound represented by the formula (I): wherein R1 is a hydrogen atom or a substituent; ring P is an optionally substituted 6-membered nitrogen-containing aromatic heterocycle; ring Q is an optionally further substituted 5- to 7-membered nitrogen-containing non-aromatic heterocycle; and ring R is an optionally fused 5- to 7-membered non-aromatic ring, which is further optionally substituted, or a salt thereof.
- -
-
Page/Page column 50
(2009/12/23)
-