Discovery of Highly Potent Dual CysLT1 and CysLT2 Antagonist

Satoshi Itadani; Shinya Takahashi; Masaki Ima; Tetsuya Sekiguchi; Manabu Fujita; Yoshisuke Nakayama; Jun Takeuchi

doi:10.1021/ml500298y

Discovery of Highly Potent Dual CysLT1 and CysLT2 Antagonist

ACS Med Chem Lett. 2014 Oct 6;5(11):1230-4. doi: 10.1021/ml500298y. eCollection 2014 Nov 13.

Authors

Satoshi Itadani¹, Shinya Takahashi¹, Masaki Ima¹, Tetsuya Sekiguchi¹, Manabu Fujita¹, Yoshisuke Nakayama¹, Jun Takeuchi¹

Affiliation

¹ 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.

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.

Keywords: CysLT1; CysLT2; Cysteinyl leukotrienes; asthma; dual antagonist.