Research Center Kyoto, Bayer Yakuhin, Ltd, Kizu, Soraku, Kyoto 619-0216, Japan.
Bioorg Med Chem Lett. 2011 Jun 1;21(11):3354-7. doi: 10.1016/j.bmcl.2011.04.013. Epub 2011 Apr 9.
We have identified naphthol derivatives as inhibitors of the vanilloid receptor TRPV1 by high throughput screening. The initial lead showed high clearance in rats and has been optimized by enhancing the acidity of the phenol group. Compound 6b has reduced clearance, improved potency and is active in rat cystometry models of urinary incontinence after intravenous administration.
我们通过高通量筛选鉴定出萘酚衍生物是香草素受体 TRPV1 的抑制剂。最初的先导化合物在大鼠体内清除率较高，通过增强酚羟基的酸性得到了优化。化合物 6b 降低了清除率，提高了效力，并在大鼠尿失禁膀胱测压模型中具有静脉给药后的活性。
