4-（3-三氟甲基吡啶-2-基）哌嗪-1-羧酸（5-三氟甲基吡啶-2-基）酰胺的鉴定与生物学评价，一种高亲和力的TRPV1（VR1）香草酸受体拮抗剂
Identification and biological evaluation of 4-(3-trifluoromethylpyridin-2-yl)piperazine-1-carboxylic acid (5-trifluoromethylpyridin-2-yl)amide, a high affinity TRPV1 (VR1) vanilloid receptor antagonist.
作者信息
Swanson Devin M, Dubin Adrienne E, Shah Chandra, Nasser Nadia, Chang Leon, Dax Scott L, Jetter Michele, Breitenbucher J Guy, Liu Changlu, Mazur Curt, Lord Brian, Gonzales Lisa, Hoey Kenway, Rizzolio Michele, Bogenstaetter Michael, Codd Ellen E, Lee Doo H, Zhang Sui-Po, Chaplan Sandra R, Carruthers Nicholas I
机构信息
Johnson & Johnson Pharmaceutical Research and Development L.L.C., 3210 Merryfield Row, San Diego, California 92121, USA.
出版信息
J Med Chem. 2005 Mar 24;48(6):1857-72. doi: 10.1021/jm0495071.
High throughput screening using the recombinant human TRPV1 receptor was used to identify a series of pyridinylpiperazine ureas (3) as TRPV1 vanilloid receptor ligands. Exploration of the structure-activity relationships by parallel synthesis identified the essential pharmacophoric elements for antagonism that permitted further optimization via targeted synthesis to provide a potent orally bioavailable and selective TRPV1 modulator 41 active in several in vivo models.
利用重组人TRPV1受体进行高通量筛选，以鉴定一系列吡啶基哌嗪脲（3）作为TRPV1香草酸受体配体。通过平行合成探索构效关系，确定了拮抗作用的基本药效基团，从而能够通过靶向合成进一步优化，以提供一种在多种体内模型中具有活性的强效口服生物可利用且选择性的TRPV1调节剂41。
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