54212-35-0Relevant academic research and scientific papers
Analogues of (3 R)-7-hydroxy- N -[(1 S)-1-{[(3 R,4 R)-4-(3-hydroxyphenyl)- 3,4-dimethyl-1-piperidinyl]methyl}-2-methylpropyl)-1,2,3,4-tetrahydro-3- isoquinolinecarboxamide (JDTic). Synthesis and in vitro and in vivo opioid receptor antagonist activity
Runyon, Scott P.,Brieaddy, Lawrence E.,Mascarella, S. Wayne,Thomas, James B.,Navarro, Hernán A.,Howard, James L.,Pollard, Gerald T.,Carroll, F. Ivy
experimental part, p. 5290 - 5301 (2010/10/21)
The synthesis of compounds 6, 7a,b, 8a,b, 9a,b, and 10a,b where the amino -NH- group of JDTic (3) was replaced with an aromatic - CH-, CH2, O, S, or SO group was accomplished and used to further characterize the SAR of the compound 3 class of κ opioid receptor antagonists. All of the compounds showed subnanomolar to low nanomolar Ke values at the κ opioid receptor. The most potent compound was 7a, where the amino -NH- group of 3 was replaced by a methylene (-CH2-) group. This compound had a K e = 0.18 nM and was 37- and 248-fold selective for the κ relative to the μ and δ opioid receptors, respectively. Similar to compound 3, compound 7a antagonized selective κ agonist U50,488-induced diuresis after sc administration in rats. In contrast to 3, where κ antagonist activity lasted for three weeks, compound 7a did not show any κ antagonist activity after one week.
