Shishido Yuji, Jinno Madoka, Ikeda Takafumi, Ito Fumitaka, Sudo Masaki, Makita Naoya, Ohta Atsuko, Iki-Taki Ayako, Ohmi Takashi, Kanai Yoshihito, Tamura Tetsuya, Shimojo Masato
Pfizer Global Research & Development, Nagoya Laboratories, 5-2 Taketoyo, Aichi 470-2394, Japan.
Bioorg Med Chem Lett. 2008 Feb 1;18(3):1072-8. doi: 10.1016/j.bmcl.2007.12.007. Epub 2007 Dec 10.
From hit compounds identified by high throughput screening (HTS), we have found compound 1 as a lead TRPV1 antagonist and confirmed its potential as a treatment for pain. Compound 1 has led to potent TRPV1 antagonistic benzamide derivatives ((+/-)-2: human IC(50)=23 nM, (+/-)-3: human IC(50)=14 nM in the capsaicin-induced calcium influx assay) containing indole and naphthyl moieties, obtained by elaboration of the tryptamine scaffold or via bioisosteric replacements.
从通过高通量筛选（HTS）鉴定出的活性化合物中，我们发现化合物1是一种先导TRPV1拮抗剂，并证实了其作为疼痛治疗药物的潜力。化合物1已衍生出含有吲哚和萘基部分的强效TRPV1拮抗苯甲酰胺衍生物（（±）-2：人IC50 = 23 nM，（±）-3：在辣椒素诱导的钙内流试验中，人IC50 = 14 nM），这些衍生物是通过对色胺骨架进行修饰或通过生物电子等排体替换获得的。
