Discovery of N-[(2S)-5-(6-Fluoro-3-pyridinyl)-2,3-dihydro-1H-inden-2-yl]-2-propanesulfonamide, a Novel Clinical AMPA Receptor Positive Modulator
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- 作者：Simon E. Ward ; Mark Harries ; Laura Aldegheri ; Daniele Andreotti ; Stuart Ballantine ; Benjamin D. Bax ; Andrew J. Harris ; Andy J. Harker ; Jesper Lund ; Rosemary Melarange ; Anna Mingardi ; Claudette Mookher
- 刊名：Journal of Medicinal Chemistry
- 出版年：2010
- 出版时间：August 12, 2010
- 年：2010
- 卷：53
- 期：15
- 页码：5801-5812
- 全文大小：1024K
- 年卷期：v.53,no.15(August 12, 2010)
- ISSN：1520-4804
文摘
A series of AMPA receptor positive allosteric modulators has been optimized from poorly penetrant leads to identify molecules with excellent preclinical pharmacokinetics and CNS penetration. These discoveries led to 17i, a potent, efficacious CNS penetrant molecule with an excellent pharmacokinetic profile across preclinical species, which is well tolerated and is also orally bioavailable in humans.