The role of the side chain in determining relative delta- and kappa-affinity in C5'-substituted analogues of naltrindole.
The role of the side chain in 5'-substituted analogues of naltrindole has been further explored with the synthesis of series of amides, amidines, and ureas. Amidines (8, 13) had greatest selectivity for the kappa receptor, as predicted from consideration of the message-address concept. It was also found that an appropriately located carbonyl group, in ureas (10) and amides (7), led to retention of affinity and antagonist potency at the delta receptor.
Black
Shannon L
SL
Department of Pharmacy and Pharmacology, University of Bath, Bath, BA2 7AY, UK.
Jales
Andrew R
AR
Brandt
Wolfgang
W
Lewis
John W
JW
Husbands
Stephen M
SM
D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000578:Amidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D006801:Humans; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014508:Urea / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D000577:Amides; D000578:Amidines; D009292:Narcotic Antagonists; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D009271:Naltrexone; D014508:Urea; C055382:naltrindole