Naphtho and benzo analogues of the kappa opioid agonist trans-(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl] benzeneacetamide.
Further elaboration on the structure-activity relationships in our U-50,488 series has revealed that benzologation of this cyclohexane-1,2-diamine derivative provides compounds which either maintain the interaction with the kappa receptor (e.g. compounds 3a and 5a in the phenylacetamido series) or eliminate the mu receptor mediated analgesia (e.g. compounds 3-6 in the benzamido series). Naphthologation also caused the elimination of mu receptor mediated analgesia (e.g. compounds 17a and 17b).
Freeman
J P
JP
Department of Chemistry and Biochemistry, University of Notre Dame, Indiana 46556.
Michalson
E T
ET
D'Andrea
S V
SV
Baczynskyj
L
L
Von Voigtlander
P F
PF
Lahti
R A
RA
Smith
M W
MW
Lawson
C F
CF
Scahill
T A
TA
Mizsak
S A
SA
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics; D000818:Animals; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D009292:Narcotic Antagonists; D011759:Pyrrolidines / Q000737:chemistry / Q000494:pharmacology*; D017473:Receptors, Opioid, kappa; D013329:Structure-Activity Relationship
D000700:Analgesics; D009292:Narcotic Antagonists; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer