2-aminothiazole-derived opioids. Bioisosteric replacement of phenols.
A series of aminothiazole-derived morphinans, benzomorphans, and morphine were synthesized. Although their affinities were somewhat lower than their phenol prototypes, one compound (9a, ATPM) has been identified possessing high affinity and selectivity at the kappa receptor. Functional assays showed that 9a was a full kappa but partial mu agonist; the efficacy at kappa was significantly greater than at mu receptors. This novel compound may be valuable for the development of long-acting analgesics and drug abuse medication.
Zhang
Ao
A
Alcohol and Drug Abuse Research Center, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, MA 02478, USA.
Xiong
Wennan
W
Hilbert
James E
JE
DeVita
Emily K
EK
Bidlack
Jean M
JM
Neumeyer
John L
JL
D000818:Animals; D001575:Benzomorphans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D016466:CHO Cells; D006224:Cricetinae; D009019:Morphinans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009022:Morphine Derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D009294:Narcotics / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010636:Phenols / Q000737:chemistry*; D011869:Radioligand Assay; D017465:Receptors, Opioid, delta / Q000819:agonists; D017473:Receptors, Opioid, kappa / Q000819:agonists; D017450:Receptors, Opioid, mu / Q000819:agonists; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D001575:Benzomorphans; D009019:Morphinans; D009022:Morphine Derivatives; D009294:Narcotics; D010636:Phenols; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D013844:Thiazoles