- Novel Radiolabeled Vanilloid with Enhanced Specificity for Human Transient Receptor Potential Vanilloid 1 (TRPV1)
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Transient receptor potential vanilloid 1 (TRPV1) has emerged as a promising therapeutic target. While radiolabeled resiniferatoxin (RTX) has provided a powerful tool for characterization of vanilloid binding to TRPV1, TRPV1 shows 20-fold weaker binding to
- Pearce, Larry V.,Ann, Jihyae,Jung, Aeran,Thorat, Shivaji A.,Herold, Brienna K. A.,Habtemichael, Amelework D.,Blumberg, Peter M.,Lee, Jeewoo
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- Efficient synthesis of benzene-fused 6/7-membered amides: Via Xphos Pd G2 catalyzed intramolecular C-N bond formation
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An efficient approach for benzene-fused 6/7-membered amides via intramolecular amidation of aryl chlorides catalyzed by a Buchwald-Hartwig second generation Pd catalyst (Xphos Pd G2) has been successfully developed. This catalyst system allows the primary amides which have only modest nucleophilicity to be coupled successfully even with electron rich aryl chlorides in short reaction time. The intramolecular amidation reaction also has good chemoselectivity and excellent functional group compatibility.
- Xu, Zhou,Li, Ke,Zhai, Rongliang,Liang, Ting,Gui, Xiaodie,Zhang, Rongli
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p. 51972 - 51977
(2017/11/22)
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- FUNCTIONALLY SELECTIVE LIGANDS OF DOPAMINE D2 RECEPTORS
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The present invention relates to novel functionally selective ligands of dopamine D2 receptors, including agonists, antagonists, and inverse agonists. The invention further relates to the use of these compounds for treating central nervous system disorders related to D2 receptors.
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- "TRPV1 VANILLOID RECEPTOR ANTAGONISTS WITH A BICYCLIC PORTION"
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The invention discloses compounds of formula I wherein Y is a group of formula A, B, C, D, or E: and W, Q, n, R1, R2, R3, U1-U5, J and K have the meanings given in the description. The compounds of formula I are TRPV1 antagonists and are useful as active
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- TRPV1 vanilloid receptor antagonists with a bicyclic portion
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The invention discloses compounds of formula I wherein Y s selected from a group of formula and W, Q, n, R1, R2, R3, U1-U5 have the meanings given in the description. The compounds of formula I are TRPV1 antagonists and are useful as active ingredients of pharmaceutical compositions for the treatment of pain and other conditions ameliorated by the inhibition of the vanilloid receptor TRPV1. 1.
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- ALKYL-SUBSTITUTED 3' COMPOUNDS HAVING 5-HT6 RECEPTOR AFFINITY
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The present disclosure provides compounds having affinity for the 5-HT6 receptor which are of the formula (I): wherein R1, R2, Ar, m and n are as defined herein. The disclosure also relates to methods of preparing such compounds, compositions containing such compounds, and methods of use thereof.
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Page/Page column 32
(2010/02/17)
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- CONDENSED HETEROCYCLIC COMPOUNDS HAVING 5-HT6 RECEPTOR AFFINITY
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The present disclosure provides compounds having affinity for the 5-HT6 receptor which are of the formula (I) wherein R1, A, B, D, E, G, Q, Ar, n, m, and p are as defined herein. The disclosure also relates to methods of preparing such compounds, compositions containing such compounds, and methods of use thereof.
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Page/Page column 80
(2010/04/03)
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- ACYCLIC COMPOUNDS HAVING 5-HT6 RECEPTOR AFFINITY
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The present disclosure provides compounds having affinity for the 5-HT6 receptor which are of the formula (I): wherein R1, R2, R5, Q, G, Ar, m, and n are as defined herein. The disclosure also relates to methods of preparing such compounds, compositions containing such compounds, and methods of use thereof.
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Page/Page column 56
(2010/03/02)
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- 4'-AMINO CYCLIC COMPOUNDS HAVING 5-HT6 RECEPTOR AFFINITY
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The present disclosure provides compounds having affinity for the 5-HT6 receptor which are of the formula (I): formula (I) wherein Cy is selected from formula (Il) and wherein R1, R2, R3, Q, G, Ar, m, n and p are as defined herein. The disclosure also relates to methods of preparing such compounds, compositions containing such compounds, and methods of use thereof.
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Page/Page column 98; 99
(2010/04/06)
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- PYRROLIDINE-SUBSTITUTED AZAINDOLE COMPOUNDS HAVING 5-HT6 RECEPTOR AFFINITY
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The present disclosure provides compounds having affinity for the 5-HT6 receptor which are of the formula (I): wherein R1, R2, A, B, D, E, G, Ar, and n are as defined herein. The disclosure also relates to methods of preparing such compounds, compositions containing such compounds, and methods of use thereof.
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Page/Page column 42; 43
(2010/02/17)
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- HETEROCYCLIDENE-N-(ARYL)ACETAMIDE DERIVATIVE
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The blow-described formula (I): [Ch. 1] a compound represented by formula (I) : (wherein k, m, n, and p each represent 0 to 2; j and q represents 0 or 1; R1 represents a halogen atom, a hydrocarbon group, a heterocyclic group, an alkoxy group,
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Page/Page column 106
(2009/12/23)
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- 3' SUBSTITUTED COMPOUNDS HAVING 5-HT6 RECEPTOR AFFINITY
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The present disclosure provides compounds having affinity for the 5-HT6 receptor which are of the formula (I): wherein Q, R1, R4, m and Ar are as defined herein. The disclosure also relates to methods of preparing such compounds, compositions containing such compounds, and methods of use thereof.
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Page/Page column 115-116
(2009/04/25)
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- 4' SUBSTITUTED COMPOUNDS HAVING 5-HT6 RECEPTOR AFFINITY
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The present disclosure provides compounds having affinity for the 5-HT6 receptor which are of the formula (I): wherein R1, R2, R5, R6, B, D, E, G, Q, x and n are as defined herein. The disclosure also relates to methods of preparing such compounds, compositions containing such compounds, and methods of use thereof.
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Page/Page column 43
(2009/01/24)
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- 6' SUBSTITUTED COMPOUNDS HAVING 5-HT6 RECEPTOR AFFINITY
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The present disclosure provides compounds having affinity for the 5-HT6 receptor which are of the formula (I): wherein R1—R4 A, B, D, E, and G are as defined herein. The disclosure also relates to methods of preparing such compounds, compositions containing such compounds, and methods of use thereof.
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Page/Page column 64; 65
(2008/12/08)
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- 4-Piperidinecarboxamide modulators of vanilloid VR1 receptor
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This invention is directed to vanilloid receptor VR1 ligands. More particularly, this invention relates to hetero isonipecotic amides that are potent modulators of VR1 which are useful for the treatment and prevention of disease conditions in mammals.
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Page/Page column 68
(2010/11/08)
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- Synthesis, structure-activity relationships, and biological properties of 1-heteroaryl-4-[ω-(1H-indol-3-yl)alkyl]piperazines, novel potential antipsychotics combining potent dopamine D2 receptor antagonism with potent serotonin reuptake inhibition
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A series of novel bicyclic 1-heteroaryl-4-[ω-(1H-indol-3-yl)alkyl] piperazines was synthesized and evaluated on binding to dopamine D2 receptors and serotonin reuptake sites. This class of compounds proved to be potent in vitro dopamine D2 receptor antagonists and in addition were highly active as serotonin reuptake inhibitors. Some key representatives showed potent pharmacological in vivo activities after oral dosing in both the antagonism of apomorphine-induced climbing and the potentiation of 5-HTP-induced behavior in mice. On the basis of the preclinical data, 8-{4-[3-(5-fluoro-1H- indol-3-yl)propyl]piperazin-1-yl}-4H-benzo[1,4]oxazin-(R)-2-methyl-3-one (45c, SLV314) was selected for clinical development. In vitro and in vivo studies revealed that 45c has favorable pharmacokinetic properties and a high CNS plasma ratio. Molecular modeling studies showed that the bifunctional activity of 45c can be explained by its ability to adopt two different conformations fitting either the dopamine D2 receptor pharmacophore or the serotonin transporter pharmacophore.
- Smid, Pieter,Coolen, Hein K. A. C.,Keizer, Hiskias G.,Van Hes, Rolf,De Moes, Jan-Peter,Den Hartog, Arnold P.,Stork, Bob,Plekkenpol, Rob H.,Niemann, Leonarda C.,Stroomer, Cees N. J.,Tulp, Martin Th. M.,Van Stuivenberg, Herman H.,McCreary, Andrew C.,Hesselink, Mayke B.,Herremans, Arnoud H. J.,Kruse, Chris G.
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p. 6855 - 6869
(2007/10/03)
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