College of Pharmacy, Sookmyung Women's University, Seoul 141-742, Korea.
Arch Pharm Res. 2012 Feb;35(2):321-6. doi: 10.1007/s12272-012-0212-x. Epub 2012 Feb 28.
A series of chain branched 1,3-dibenzylthiourea derivatives were designed, synthesized, and evaluated for their antagonist activity against TRPV1. The synthesized chain branched 1,3-dibenzylthioureas 9a-g were tested for their antagonist activities against TRPV1 by (45)Ca(2+)-influx assay using neonatal rat cultured spinal sensory neurons. Fluorinated ethyl-branched analog 9g showed the most potent antagonist activity with an IC(50) value of 0.41 μM, but all of the chain branched analogs were less potent than the parent compounds MK-056 and SC-0030, indicating that chain branching on the benzylic position of B-ring is detrimental to potency. Optimized receptor binding seems to be interfered by chain branching, and resulted in decrease in potency.
设计、合成了一系列支链 1,3-二苄基硫脲衍生物，并评估了它们对 TRPV1 的拮抗剂活性。合成的支链 1,3-二苄基硫脲 9a-g 采用原代培养的新生大鼠脊髓感觉神经元 (45)Ca(2+)-内流法检测对 TRPV1 的拮抗活性。氟乙基支链类似物 9g 表现出最强的拮抗活性，IC(50)值为 0.41 μM，但所有支链类似物的活性均低于母体化合物 MK-056 和 SC-0030，表明 B 环苄基位置的支链化不利于活性。优化的受体结合似乎受到支链的干扰，导致活性降低。
