title: Discovery of Highly Potent Dual CysLT1 and CysLT2 Antagonist.
abstract: The benzoxazine derivative, (2S)-4-(3-carboxypropyl)-8-{[4-(4-phenylbutoxy)benzoyl]amino}-3,4-dihydro-2H-1,4-benzoxazine-2-carboxylic acid (19, ONO-2050297), was identified as the first potent dual CysLT1 and CysLT2 antagonist with IC50 values of 0.017 μM (CysLT1) and 0.00087 μM (CysLT2), respectively.
authors.affiliation: Medicinal Chemistry Research Laboratories and Department of Biology & Pharmacology, Ono Pharmaceutical Co., Ltd. , 3-1-1 Sakurai, Shimamoto-cho, Mishima-gun, Osaka 618-8585, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Itadani
authors.affiliation: Medicinal Chemistry Research Laboratories and Department of Biology & Pharmacology, Ono Pharmaceutical Co., Ltd. , 3-1-1 Sakurai, Shimamoto-cho, Mishima-gun, Osaka 618-8585, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Takahashi
authors.affiliation: Medicinal Chemistry Research Laboratories and Department of Biology & Pharmacology, Ono Pharmaceutical Co., Ltd. , 3-1-1 Sakurai, Shimamoto-cho, Mishima-gun, Osaka 618-8585, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Ima
authors.affiliation: Medicinal Chemistry Research Laboratories and Department of Biology & Pharmacology, Ono Pharmaceutical Co., Ltd. , 3-1-1 Sakurai, Shimamoto-cho, Mishima-gun, Osaka 618-8585, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Sekiguchi
authors.affiliation: Medicinal Chemistry Research Laboratories and Department of Biology & Pharmacology, Ono Pharmaceutical Co., Ltd. , 3-1-1 Sakurai, Shimamoto-cho, Mishima-gun, Osaka 618-8585, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Fujita
authors.affiliation: Medicinal Chemistry Research Laboratories and Department of Biology & Pharmacology, Ono Pharmaceutical Co., Ltd. , 3-1-1 Sakurai, Shimamoto-cho, Mishima-gun, Osaka 618-8585, Japan.
authors.forename: Yoshisuke
authors.initials: Y
authors.lastname: Nakayama
authors.affiliation: Medicinal Chemistry Research Laboratories and Department of Biology & Pharmacology, Ono Pharmaceutical Co., Ltd. , 3-1-1 Sakurai, Shimamoto-cho, Mishima-gun, Osaka 618-8585, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Takeuchi
keywords: CysLT1; CysLT2; Cysteinyl leukotrienes; asthma; dual antagonist