1585988-80-2Relevant academic research and scientific papers
KAPPA-OPIOID RECEPTOR SELECTIVE OPIOID RECEPTOR ANTAGONISTS
-
Paragraph 00290, (2015/08/03)
Potent opioid receptor antagonists and there use as pharmacotherapies for treating depression, anxiety, schizophrenia, eating disorders, and addiction to cocaine, methamphetamine, nicotine, alcohol, and opiates are disclosed.
Design, synthesis, and pharmacological evaluation of JDTic analogs to examine the significance of the 3- and 4-methyl substituents
Carroll, F. Ivy,Gichinga, Moses G.,Kormos, Chad M.,Maitra, Rangan,Runyon, Scott P.,Thomas, James B.,Mascarella, S. Wayne,Decker, Ann M.,Navarro, Hernán A.
, p. 6379 - 6388 (2015/10/05)
The design and discovery of JDTic as a potent and selective kappa opioid receptor antagonist used the N-substituted trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine pharmacophore as the lead structure. In order to determine if the 3-methyl or 4-methyl groups were necessary in JDTic and JDTic analogs for antagonistic activity, compounds 4a-c, and 4d-f which have either the 3-methyl or both the 3- and 4-methyl groups removed, respectively, from JDTic and analogs were synthesized and evaluated for their in vitro opioid receptor antagonist activities using a [35S]GTPγS binding assay. Other ADME properties were also assessed for selected compounds. These studies demonstrated that neither the 3-methyl or 3,4-dimethyl groups present in JDTic and analogs are required to produce potent and selective κ opioid receptor antagonists.
Effect of the 3- and 4-methyl groups on the opioid receptor properties of N-substituted trans -3,4-dimethyl-4-(3-hydroxyphenyl)piperidines
Kormos, Chad M.,Cueva, Juan Pablo,Gichinga, Moses G.,Runyon, Scott P.,Thomas, James B.,Brieaddy, Lawrence E.,Mascarella, S. Wayne,Gilmour, Brian P.,Navarro, Hernán A.,Carroll, F. Ivy
, p. 3140 - 3147 (2014/05/06)
N-substituted trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidines (2a,b) are opioid receptor antagonists where the antagonist properties are not due to the type of N-substituent. In order to gain a better understanding of the contribution that the 3- and 4-methyl groups make to the pure antagonist properties of 2a,b, we synthesized analogues of 2a,b that lacked the 4-methyl (5a,b), 3-methyl (6a,b), and both the 3- and 4-methyl group (7a,b) and compared their opioid receptor properties. We found that (1) all N-methyl and N-phenylpropyl substituted compounds were nonselective opioid antagonists (2) all N-phenylpropyl analogues were more potent than their N-methyl counterparts, and (3) compounds 2a,b which have both a 3- and 4-methyl substituent, were more potent antagonists than analogues 5a,b, 6a,b, and 7a,b. We also found that the removal of 3-methyl substituent of N-methyl and N-phenylpropyl 3-methyl-4-(3-hydroxyphenyl)piperazines (8a,b) gives (4a,b), which are opioid antagonists.
