Lawrence K B, Venepalli B R, Appell K C, Goswami R, Logan M E, Tomczuk B E, Yanni J M
Life Sciences Research Laboratories, Eastman Kodak Company, Rochester, New York 14650-2158.
J Med Chem. 1992 Apr 3;35(7):1273-9. doi: 10.1021/jm00085a015.
The synthesis of unsymmetrical naphth[2,3-d]imidazolium and bridged naphth[2,3-d]imidazolium derivatives and their substance P (SP) antagonist activity are described. All compounds were evaluated for their ability to displace SP from neurokinin-1 (NK-1) receptor sites using standard receptor binding methodology (rat forebrain membrane). 1,3-Diethyl-2-[3-(1,3-dihydro-1,3,3-timethyl-2H-indol-2-ylidene) -1-propenyl]-1H-naphth[2,3-d]imidazolium chloride (7a), a representative compound in this series, was further evaluated for SP antagonist activity in a guinea pig ileum contractility assay. In vivo SP antagonist activity of 7a was demonstrated using SP-induced salivation and paw edema models performed in rats.
描述了不对称萘并[2,3 - d]咪唑鎓和桥连萘并[2,3 - d]咪唑鎓衍生物的合成及其P物质（SP）拮抗活性。使用标准受体结合方法（大鼠前脑膜）评估所有化合物从神经激肽 - 1（NK - 1）受体位点置换SP的能力。该系列中的代表性化合物1,3 - 二乙基 - 2 - [3 - （1,3 - 二氢 - 1,3,3 - 三甲基 - 2H - 吲哚 - 2 - 亚基）-1 - 丙烯基]-1H - 萘并[2,3 - d]咪唑鎓氯化物（7a），在豚鼠回肠收缩试验中进一步评估其SP拮抗活性。使用在大鼠中进行的SP诱导的唾液分泌和爪肿胀模型证明了7a的体内SP拮抗活性。
