2-({6-[(3R)-3-amino-3-methylpiperidine-1-yl]-1, 3-dimethyl-2, 4-dioxo-1, 2, 3, 4-tetrahydro-5H-pyrrolo [3, 2-d] pyrimidine-5-yl} methyl)-4-fluorobenzonitrile (DSR-12727) …

…, T Hashizuka, Y Honda, J Deguchi, T Nakagawa…

Index: Nishio, Yukihiro; Kimura, Hidenori; Sawada, Naoyuki; Sugaru, Eiji; Horiguchi, Masakuni; Ono, Michiko; Furuta, Yudai; Sakai, Mutsuko; Masui, Yumi; Otani, Misato; Hashizuka, Takahiko; Honda, Yayoi; Deguchi, Jiro; Nakagawa, Tsutomu; Nakahira, Hiroyuki Bioorganic and Medicinal Chemistry, 2011 , vol. 19, # 18 p. 5490 - 5499

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Citation Number: 16

Abstract

We report on the identification of 2-({6-[(3R)-3-amino-3-methylpiperidine-1-yl]-1, 3-dimethyl- 2, 4-dioxo-1, 2, 3, 4-tetrahydro-5H-pyrrolo [3, 2-d] pyrimidine-5-yl} methyl)-4- fluorobenzonitrile (DSR-12727)(7a) as a potent and orally active DPP-4 inhibitor without mechanism-based inactivation of CYP3A. Compound 7a showed good DPP-4 inhibitory activity (IC50= 1.1 nM), excellent selectivity against related peptidases and other off- ...