| Structural highlights
Publication Abstract from PubMed
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 Gly(2162) and Glu(2230), we used ligand- and structure-based drug design to discover spirolactones bearing a 2-ureidobenzothiophene moiety.
Design, synthesis, and structure-activity relationships of spirolactones bearing 2-ureidobenzothiophene as acetyl-CoA carboxylases inhibitors.,Yamashita T, Kamata M, Endo S, Yamamoto M, Kakegawa K, Watanabe H, Miwa K, Yamano T, Funata M, Sakamoto J, Tani A, Mol CD, Zou H, Dougan DR, Sang B, Snell G, Fukatsu K Bioorg Med Chem Lett. 2011 Nov 1;21(21):6314-8. Epub 2011 Sep 6. PMID:21944854[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Yamashita T, Kamata M, Endo S, Yamamoto M, Kakegawa K, Watanabe H, Miwa K, Yamano T, Funata M, Sakamoto J, Tani A, Mol CD, Zou H, Dougan DR, Sang B, Snell G, Fukatsu K. Design, synthesis, and structure-activity relationships of spirolactones bearing 2-ureidobenzothiophene as acetyl-CoA carboxylases inhibitors. Bioorg Med Chem Lett. 2011 Nov 1;21(21):6314-8. Epub 2011 Sep 6. PMID:21944854 doi:10.1016/j.bmcl.2011.08.117
|
