2. Academic Validation
  3. Design, synthesis, and structure-activity relationships of spirolactones bearing 2-ureidobenzothiophene as acetyl-CoA carboxylases inhibitors

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. doi: 10.1016/j.bmcl.2011.08.117.
Tohru Yamashita 1,  Makoto Kamata,  Satoshi Endo,  Mitsuo Yamamoto,  Keiko Kakegawa,  Hiroyuki Watanabe,  Katsuhiko Miwa,  Toru Yamano,  Masaaki Funata,  Jyun-Ichi Sakamoto,  Akiyoshi Tani,  Clifford D Mol,  Hua Zou,  Douglas R Dougan,  Biching Sang,  Gyorgy Snell,  Kohji Fukatsu
Affiliations

Affiliation

  • 1 Pharmaceutical Research Division, Takeda Pharmaceutical Company, Ltd, 2-17-85, Jusohonmachi, Yodogawa-ku, Osaka 532-8686, Japan. [email protected]
PMID: 21944854 DOI: 10.1016/j.bmcl.2011.08.117
Abstract

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.

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