4-(2-(pyrrolidine/piperidine-1-yl)benzyl)-piperazine urea TRPV1 antagonist and preparation method and application thereof

• Main Authors: GAO MENGKANG, QIAO ZHENRUI, HU JING, YAN LIN, WANG YUSUI, QIAO YUE
• Format: Patent
• Language: Chinese; English
• Published: 28.07.2020
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

The invention discloses a novel 4-(2-(pyrrolidine/piperidine-1-yl)benzyl)-piperazine urea type TRPV1 antagonist and a preparation method and application thereof. The invention relates to a compound ina general formula (I) and a pharmaceutically acceptable salt thereof, in the formula, n is equal to 1 or 2, R is H, F, Cl, Br, I, CF3, CH3 or OH, and Ar is phenyl or aromatic heterocyclic group. Thecompounds have a strong analgesic effect, the activity of part of the compounds is far higher than that of a TRPV1 receptor antagonist BCTC, almost no body temperature rise side effect exists, and theinvention further relates to the preparation method of the compounds and pharmaceutical preparations containing the compounds. 本发明公开了一种4-(2-(吡咯烷/哌啶-1-基)苄基)-哌嗪脲类新型TRPV1拮抗剂及其制备方法和应用。尤其涉及通式（Ⅰ）中化合物及其药学上可接受的盐，式中，n=1或2，R为H、F、Cl、Br、I、CF、CH或OH；Ar为苯基或芳香杂环基。这类化合物具有较强的镇痛作用，部分化合物活性远高于TRPV1受体拮抗剂BCTC，并且几乎无体温升高副作用，本发明还涉及该类化合物的制备方法及含有它们的药物制剂。