Design, structure-activity relationship, and highly efficient asymmetric synthesis of 3-phenyl-4-benzylaminopiperidine derivatives as novel neurokinin-1 receptor antagonists
| Autor: | Junya Shirai, Tadatoshi Hashimoto, Yasuharu Yamamoto, Izumi Kamo, Makiko Kawamoto, Takeshi Yoshikawa, Naoki Tarui, Yoshinori Ikeura, Masayuki Yamashita |
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| Rok vydání: | 2011 |
| Předmět: |
Male
Models Molecular Spectrometry Mass Electrospray Ionization Magnetic Resonance Spectroscopy Stereochemistry Clinical Biochemistry Guinea Pigs Pharmaceutical Science Stereoisomerism Motor Activity Crystallography X-Ray Biochemistry Kinetic resolution chemistry.chemical_compound Inhibitory Concentration 50 Structure-Activity Relationship Neurokinin-1 Receptor Antagonists Piperidines Drug Discovery Structure–activity relationship Animals Humans Receptor Molecular Biology Trifluoromethyl Chemistry Organic Chemistry Enantioselective synthesis Nuclear magnetic resonance spectroscopy Combinatorial chemistry Molecular Medicine Acetamide |
| Zdroj: | Bioorganicmedicinal chemistry. 19(21) |
| ISSN: | 1464-3391 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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