Synthesis and in vitro evaluation of a novel iodinated resiniferatoxin derivative that is an agonist at the human vanilloid VR1 receptor.
Using a 'directed' iodination procedure, novel iodo-resiniferatoxin congeners were synthesized from 4-acetoxy-3-methoxyphenylacetic acid and resiniferinol- 9,13,14-ortho-phenylacetate (ROPA). The 2-iodo-4-hydroxy-5-methoxyphenylacetic acid ester of resiniferinol 5 displayed high affinity binding (K(i)=0.71 nM) for the human vanilloid VR1 receptor and functioned as a partial agonist.
McDonnell
Mark E
ME
Johnson & Johnson Pharmaceutical Research and Development, Welsh and McKean Roads, Spring House, PA 19477, USA.
Zhang
Sui Po
SP
Dubin
Adrienne E
AE
Dax
Scott L
SL
D004224:Diterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D006801:Humans; D066298:In Vitro Techniques; D007455:Iodine / Q000737:chemistry*; D011955:Receptors, Drug / Q000819:agonists*
D004224:Diterpenes; D011955:Receptors, Drug; D007455:Iodine; C024353:resiniferatoxin