50793-31-2Relevant academic research and scientific papers
1-substituted 4-arylpiperazine as kappa opioid receptor antagonists
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Page/Page column 17-19, (2016/12/26)
Provided are compounds represented by the formula: where R, Y3, R1, R2, R3, R4, R6, G, R7, E1, E2, A, B, W, X, Y and Z are as defined herein.
Discovery of N-{4-[(3-hydroxyphenyl)-3-methylpiperazin-1-yl]methyl-2- methylpropyl}-4-phenoxybenzamide analogues as selective kappa opioid receptor antagonists
Kormos, Chad M.,Jin, Chunyang,Cueva, Juan Pablo,Runyon, Scott P.,Thomas, James B.,Brieaddy, Lawrence E.,Mascarella, S. Wayne,Navarro, Hernán A.,Gilmour, Brian P.,Carroll, F. Ivy
, p. 4551 - 4567 (2013/07/19)
There is continuing interest in the discovery and development of new κ opioid receptor antagonists. We recently reported that N-substituted 3-methyl-4-(3-hydroxyphenyl)piperazines were a new class of opioid receptor antagonists. In this study, we report the syntheses of two piperazine JDTic-like analogues. Evaluation of the two compounds in an in vitro [35S] GTPγS binding assay showed that neither compound showed the high potency and κ opioid receptor selectivity of JDTic. A library of compounds using the core scaffold 21 was synthesized and tested for their ability to inhibit [35S]GTPγS binding stimulated by the selective κ opioid agonist U69,593. These studies led to N-[(1S)-1-{[(3S)-4-(3-hydroxyphenyl)-3- methylpiperazin-1-yl]methyl}-2-methylpropyl]-4-phenoxybenzamide (11a), a compound that showed good κ opioid receptor antagonist properties. An SAR study based on 11a provided 28 novel analogues. Evaluation of these 28 compounds in the [35S]GTPγS binding assay showed that several of the analogues were potent and selective κ opioid receptor antagonists.
1-SUBSTITUTED 4-ARYLPIPERAZINE AS KAPPA OPIOID RECEPTOR ANTAGONISTS
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Page/Page column 22; 23, (2013/06/27)
Provided are compounds represented by the formula: where R, Y3, R1,R2, R3, R4, R6, G, R7, E1, E2, A, B, W, X, Y and Z are as defined herein.
COMPOSITIONS AND METHODS FOR INHIBITING SPHINGOSINE KINASE
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Page/Page column 44, (2009/12/27)
Amidine analogs that can inhibit the activity of sphingosine kinase 1 and sphingosine kinase 2 (SphK1 and SphK2) are provided. The compounds can prevent angiogenesis in tumor cells.
Design, Synthesis, and Pharmacological Evaluation of Potent Xanthone Dicarboxylic Acid Leukotriene B4 Receptor Antagonists
Jackson, William T.,Boyd, Robert J.,Froelich, Larry L.,Gapinski, D. Mark,Mallett, Barbara E.,Sawyer, J. Scott
, p. 1726 - 1734 (2007/10/02)
In an effort to develop increasingly potent and specific leukotriene B4(LTB4) receptor antagonists, several xanthone dicarboxylic acids were synthesized and evaluated.Two separate synthetic routes were used to construct a xanthone nucleus containing a regiospecific orientation of each carboxylic acid pharmacophore.These compounds represent the major conformationally-restricted analogues of benzophenone dicarboxylic acids previously shown to antagonize the activation of human neutrophils by LTB4.The most potent agent was compound 32, which inhibited the specific binding of LTB4 to receptors on intact human neutrophils (IC50, 6.2 +/- 0.1 nM), LTB4-induced luminol-dependent chemiluminescence (IC50, 55 +/- 11 nM), aggregation (IC50, 133 +/- 42 nM), and chemotaxis (IC50, 899 +/- 176 nM).The compound was a poor antagonist of N-formyl-L-methionyl-L-leucyl-L-phenylalanine-induced chemiluminescence (IC50, 1599 +/- 317 nM) and aggregation (IC50, 2166 +/- 432 nM), indicating specificity in the inhibition of LTB4-stimulated events.Compound 32(LY210073), which was completely devoid of agonist activity, appears to be one of the strongest inhibitors of LTB4 receptor binding reported so far.
