title: 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.
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.
authors.affiliation: Medicinal Chemistry Research Laboratories II, Mitsubishi Tanabe Pharma Corporation, 2-2-50 Kawagishi, Toda, Saitama 335-8505, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Sakamoto
authors.affiliation: Medicinal Chemistry Research Laboratories II, Mitsubishi Tanabe Pharma Corporation, 2-2-50 Kawagishi, Toda, Saitama 335-8505, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Koga
authors.affiliation: Medicinal Chemistry Research Laboratories II, Mitsubishi Tanabe Pharma Corporation, 2-2-50 Kawagishi, Toda, Saitama 335-8505, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Hikota
authors.affiliation: Medicinal Chemistry Research Laboratories II, Mitsubishi Tanabe Pharma Corporation, 2-2-50 Kawagishi, Toda, Saitama 335-8505, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsuki
authors.affiliation: Pharmacology Research Laboratories II, Mitsubishi Tanabe Pharma Corporation, 2-2-50 Kawagishi, Toda, Saitama 335-8505, Japan.
authors.forename: Michino
authors.initials: M
authors.lastname: Murakami
authors.affiliation: Pharmacology Research Laboratories II, Mitsubishi Tanabe Pharma Corporation, 2-2-50 Kawagishi, Toda, Saitama 335-8505, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Kikkawa
authors.affiliation: Advanced Medical Research Laboratories, Mitsubishi Tanabe Pharma Corporation, 2-2-50 Kawagishi, Toda, Saitama 335-8505, Japan.
authors.forename: Kotomi
authors.initials: K
authors.lastname: Fujishige
authors.affiliation: Advanced Medical Research Laboratories, Mitsubishi Tanabe Pharma Corporation, 2-2-50 Kawagishi, Toda, Saitama 335-8505, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Kotera
authors.affiliation: 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.
authors.forename: Kenji
authors.initials: K
authors.lastname: Omori
authors.affiliation: Medicinal Chemistry Research Laboratories II, Mitsubishi Tanabe Pharma Corporation, 2-2-50 Kawagishi, Toda, Saitama 335-8505, Japan. Electronic address: morimoto.hiroshi@md.mt-pharma.co.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Morimoto
authors.affiliation: Medicinal Chemistry Research Laboratories II, Mitsubishi Tanabe Pharma Corporation, 2-2-50 Kawagishi, Toda, Saitama 335-8505, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Yamada
mesh_terms: D000818:Animals; D007172:Erectile Dysfunction / Q000188:drug therapy*; D006801:Humans; D008297:Male; D058986:Phosphodiesterase 5 Inhibitors; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011817:Rabbits
chemical_list: D058986:Phosphodiesterase 5 Inhibitors; D011743:Pyrimidines; C553414:avanafil
keywords: Avanafil; Erectile dysfunction; PDE5; PDE6