2. Academic Validation
  3. Discovery of AAT-008, a novel, potent, and selective prostaglandin EP4 receptor antagonist

Discovery of AAT-008, a novel, potent, and selective prostaglandin EP4 receptor antagonist

  • Bioorg Med Chem Lett. 2017 Mar 1;27(5):1186-1192. doi: 10.1016/j.bmcl.2017.01.067.
Yoshiyuki Okumura 1,  Tatsuya Yamagishi 2,  Seiji Nukui 3,  Kazunari Nakao 4
Affiliations

Affiliations

  • 1 AskAt Inc., 4F Ito Bldg., 4-11-28 Meieki Nakamura-ku, Nagoya 450-0002, Japan. Electronic address: yoshiyuki.okumura@askat.co.jp.
  • 2 Discovery Research, RaQualia Pharma Inc, 8F Daiwa Meieki Bldg., 1-21-19 Meieki Minami, Nakamura-ku, Nagoya 450-0003, Japan.
  • 3 INC Research, 16F Shinagawa East One Tower, 2-16-1 Konan, Minato-ku, Tokyo 108-0075, Japan.
  • 4 Discovery Research, Mochida Pharmaceutical Co., Ltd., 722 Uenohara, Jimba, Gotemba, Shizuoka 412-8524, Japan.
PMID: 28169162 DOI: 10.1016/j.bmcl.2017.01.067
Abstract

Starting from acylsufonamide HTS hit 2, a novel series of para-N-acylaminomethylbenzoic acids was identified and developed as selective prostaglandin EP4 receptor antagonists. Structural modifications on lead compound 4a were explored with the aim of improving potency, physicochemical properties, and animal PK predictive of QD (once a day) dosing regimen in human. These efforts led to the discovery of the clinical candidate AAT-008 (4j), which exhibited significantly improved pharmacological profiles over grapiprant (1).

Keywords

Autoimmune diseases; Cancer; Clinical candidate; EP4 receptor antagonist; Inflammation; Pain; Prostaglandin E2; Structure–activity relationship (SAR).

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