Amino acid conjugates as kappa opioid receptor agonists.
A novel series of kappa (kappa) opioid receptor agonists were synthesized by incorporating the key structural features of known kappa opioid agonists while replacing the aryl acetamide portion with substituted amino acid conjugates. Compounds 3j (Ki = 6.7 nM), 3k (Ki = 3.6 nM), 3l (Ki = 4.6 nM), 3m (Ki = 0.83 nM) and 3o (Ki = 2 nM) possessed potent affinities for the kappa opioid receptor in vitro with reasonable selectivity over other opioid receptors.
Kumar
Virendra
V
Adolor Corporation, 700 Pennsylvania Drive, Exton, PA 19341, USA. vkumar@adolor.com
Guo
Deqi
D
Daubert
Jeffrey D
JD
Cassel
Joel A
JA
DeHaven
Robert N
RN
Mansson
Erik
E
DeHaven-Hudkins
Diane L
DL
Maycock
Alan L
AL
D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry*; D006801:Humans; D015394:Molecular Structure; D017473:Receptors, Opioid, kappa / Q000819:agonists*
D000596:Amino Acids; D017473:Receptors, Opioid, kappa