KMID : 0043320120350020321
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Archives of Pharmacal Research 2012 Volume.35 No. 2 p.321 ~ p.326
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Chain branching approach in structure modification of TRPV1 receptor antagonist MK056 and its analogs
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Jang Mi-Jung
Ryu Chong-Hyun Park Young-Ho Kim Hee-Doo
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Abstract
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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 45Ca2+-influx assay using neonatal rat cultured spinal sensory neurons. Fluorinated ethyl-branched analog 9g showed the most potent antagonist activity with an IC50 value of 0.41 ¥ìM, 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.
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KEYWORD
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Chain branching, TRPV1, 1, 3-Dibenzylthioureas, Antagonist, 45Ca2+-influx assay
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