Article

Design, structure-activity relationship, and highly efficient asymmetric synthesis of 3-phenyl-4-benzylaminopiperidine derivatives as novel neurokinin-1 receptor antagonists.

Pharmaceutical Research Division, Takeda Pharmaceutical Co. Ltd, 2-17-85, Jusohonmachi, Yodogawa-ku, Osaka 532-8686, Japan.
Bioorganic & medicinal chemistry (Impact Factor: 2.82). 09/2011; 19(21):6430-46. DOI: 10.1016/j.bmc.2011.08.070
Source: PubMed

ABSTRACT We synthesized a series of novel 3-phenyl-4-benzylaminopiperidine derivatives that were identified as potent tachykinin NK(1) receptor antagonists by structural modification of the 3-benzhydrylpiperidone derivative through high-throughput screening. N-{2-[(3R,4S)-4-({2-Methoxy-5-[5-(trifluoromethyl)-1H-tetrazol-1-yl]benzyl}amino)-3-phenyl-1-piperidinyl]-2-oxoethyl}acetamide ((+)-39) was found to be one of the most potent tachykinin NK(1) receptor antagonists with high metabolic stability. Highly efficient asymmetric synthesis of (+)-39 was achieved via dynamic kinetic resolution.

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