Discovery of novel S1P2 antagonists. Part 1: discovery of 1,3-bis(aryloxy)benzene derivatives.
The structure-activity relationships of a novel series of sphingosine-1-phosphate receptor antagonists have been examined in detail. The initial hit compound 1 was modified through synthesis to improve its S1P2 activity. The synthesis of a series of analogs revealed that 1,3-bis(aryloxy)benzene derivatives, as represented by 22, are potent and selective S1P2 antagonists.
Minase Research Institute, Ono Pharmaceutical Co., Ltd, 3-1-1 Sakurai, Shimamoto, Mishima, Osaka 618-8585, Japan. Electronic address: kusumi@ono.co.jp.
Kensuke
K
Kusumi
Ono Pharma UK Ltd, MidCity Place, 71 High Holborn, London WC1V 6EA, United Kingdom.
Koji
K
Shinozaki
Minase Research Institute, Ono Pharmaceutical Co., Ltd, 3-1-1 Sakurai, Shimamoto, Mishima, Osaka 618-8585, Japan.
Toshiya
T
Kanaji
Minase Research Institute, Ono Pharmaceutical Co., Ltd, 3-1-1 Sakurai, Shimamoto, Mishima, Osaka 618-8585, Japan.
Haruto
H
Kurata
Minase Research Institute, Ono Pharmaceutical Co., Ltd, 3-1-1 Sakurai, Shimamoto, Mishima, Osaka 618-8585, Japan.
Atsushi
A
Naganawa
Minase Research Institute, Ono Pharmaceutical Co., Ltd, 3-1-1 Sakurai, Shimamoto, Mishima, Osaka 618-8585, Japan.
Kazuhiro
K
Otsuki
Minase Research Institute, Ono Pharmaceutical Co., Ltd, 3-1-1 Sakurai, Shimamoto, Mishima, Osaka 618-8585, Japan.
Takeshi
T
Matsushita
Minase Research Institute, Ono Pharmaceutical Co., Ltd, 3-1-1 Sakurai, Shimamoto, Mishima, Osaka 618-8585, Japan.
Tetsuya
T
Sekiguchi
Minase Research Institute, Ono Pharmaceutical Co., Ltd, 3-1-1 Sakurai, Shimamoto, Mishima, Osaka 618-8585, Japan.
Akito
A
Kakuuchi
Head Office, Ono Pharmaceutical Co., Ltd, 8-2, Kyutaromachi 1-chome, Chuo-ku, Osaka 541-8564, Japan.
Takuya
T
Seko
D001555:Benzene Derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D006801:Humans; D015394:Molecular Structure; D049349:Receptors, Lysosphingolipid / Q000037:antagonists & inhibitors*; D000081025:Sphingosine-1-Phosphate Receptors; D013329:Structure-Activity Relationship
D001555:Benzene Derivatives; D049349:Receptors, Lysosphingolipid; C477522:S1PR2 protein, human; D000081025:Sphingosine-1-Phosphate Receptors
Antagonist; G protein-coupled receptors; Sphingosine-1-phosphate receptor 2