24779-44-0Relevant articles and documents
3-(αR)-α-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl) -3-hydroxybenzyl)-N-alkyl-N-arylbenzamides: Potent, non-peptidic agonists of both the μ and δ opioid receptors
Bishop, Michael J.,Garrido, Dulce M.,Boswell, G. Evan,Collins, Mark A.,Harris, Philip A.,McNutt, Robert W.,O'Neill, Scott J.,Wei, Ke,Chang, Kwen-Jen
, p. 623 - 633 (2003)
Opioid analgesics with both μ and δ opioid receptor activation represent a new approach to the treatment of severe pain with an improved safety profile. Compounds with this profile may exhibit strong analgesic properties due to μ agonism, with a reduced side effect profile resulting from δ agonism. Replacing the p-diethylamide of the known potent δ opioid receptor selective agonist BW373U86 with a m-diethylamide resulted in a compound with agonist activity at both the μ and δ opioid receptors. Modifying the amide to an N-methyl-N-phenylamide increased agonist potency at both receptors. A series of 3-(αR)-α((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl) -3-hydroxybenzyl)-N-alkyl-N-arylbenzamides have been made to explore the structure-activity relationship (SAR) around the N-methyl-N-phenylamide. Several potent agonists of both the μ and δ opioid receptors have been identified, including (+)-3-((αR)-α ((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3- hydroxybenzyl)-N-(4-flourophenyl)-N-methylbenzamide (23), which has EC50 values of 0.67 and 1.1 nM at the μ (guinea pig ileum assay) and δ (mouse vas deferens assay) opioid receptors, respectively.
