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  3. 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

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

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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