The discovery of avanafil for the treatment of erectile dysfunction: a novel pyrimidine-5-carboxamide derivative as a potent and highly selective phosphodiesterase 5 inhibitor

  • Bioorg Med Chem Lett. 2014 Dec 1;24(23):5460-5. doi: 10.1016/j.bmcl.2014.10.008.
Toshiaki Sakamoto  1 ,  Yuichi Koga  1 ,  Masataka Hikota  1 ,  Kenji Matsuki  1 ,  Michino Murakami  2 ,  Kohei Kikkawa  2 ,  Kotomi Fujishige  3 ,  Jun Kotera  3 ,  Kenji Omori  4 ,  Hiroshi Morimoto  5 ,  Koichiro Yamada  1
Affiliations
  • 1. Medicinal Chemistry Research Laboratories II, Mitsubishi Tanabe Pharma Corporation, 2-2-50 Kawagishi, Toda, Saitama 335-8505, Japan.
  • 2. Pharmacology Research Laboratories II, Mitsubishi Tanabe Pharma Corporation, 2-2-50 Kawagishi, Toda, Saitama 335-8505, Japan.
  • 3. Advanced Medical Research Laboratories, Mitsubishi Tanabe Pharma Corporation, 2-2-50 Kawagishi, Toda, Saitama 335-8505, Japan.
  • 4. Advanced Medical Research Laboratories, Mitsubishi Tanabe Pharma Corporation, 2-2-50 Kawagishi, Toda, Saitama 335-8505, Japan; Industry and Academia Cooperation Research Project, Laboratory of Target and Drug Discovery, Graduate School of Pharmaceutical Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
  • 5. Medicinal Chemistry Research Laboratories II, Mitsubishi Tanabe Pharma Corporation, 2-2-50 Kawagishi, Toda, Saitama 335-8505, Japan. Electronic address: [email protected].
PMID: 25455484 DOI: 10.1016/j.bmcl.2014.10.008
Abstract

Novel pyrimidine-5-carboxamide derivatives bearing a 3-chloro-4-methoxybenzylamino group at the 4-position were identified as potent and highly selective phosphodiesterase 5 inhibitors. Among them, we successfully found 10j (avanafil) which exhibited a potent relaxant effect on isolated rabbit cavernosum (EC30=2.1 nM) and a high isozyme selectivity.

Keywords
Avanafil; Erectile dysfunction; PDE5; PDE6.
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