Identification of potent phenyl imidazoles as opioid receptor agonists.
Using previously reported opioid receptor (OR) agonist analogs 4a-c as starting points, the structure-activity relationship (SAR) for their related series has been further refined. This SAR study has led to the identification of 2,6-di-Me-Tyr (DMT) analogs 4h and 4j as the most potent OR agonist within the series. In addition, it was discovered that 4-(aminocarbonyl)-2,6-dimethyl-Phe is a reasonable bioisostere surrogate for the DMT moiety, as supported by the OR activities of compounds 4x and 4y.
Johnson & Johnson Pharmaceutical Research & Development, L.L.C., Welsh and McKean Roads, PO Box 776, Spring House, PA 19477-0776, USA. HBreslin@prdus.jnj.com
Henry J
HJ
Breslin
Chaozhong
C
Cai
Tamara A
TA
Miskowski
Santosh V
SV
Coutinho
Sui-Po
SP
Zhang
Pamela
P
Hornby
Wei
W
He
D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D011957:Receptors, Opioid / Q000819:agonists*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D007093:Imidazoles; D011957:Receptors, Opioid