- THERAPEUTIC COMPOUNDS AND COMPOSITIONS FOR TREATING SOCIAL DISORDERS AND SUBSTANCE USE DISORDERS
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Disclosed herein are compounds, compositions and methods for the treatment of neurological, psychiatric disorders which are characterised by a fundamental disruption of social behaviour, and substance use disorders. In particular, disclosed herein are com
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Paragraph 0170
(2017/01/26)
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- Flexible analogues of WAY-267,464: Synthesis and pharmacology at the human oxytocin and vasopressin 1a receptors
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A previously identified, non-peptidic oxytocin (OT) receptor agonist WAY-267,464 (1) and nine novel derivatives (3, 4a-7a, 4b-7b) were synthesised and evaluated in vitro with the aim of systematically exploring hydrogen bonding interactions and ligand flexibility. All analogues were subjected to competition radioligand binding assays at human oxytocin (OT) and arginine vasopressin 1a (V1a) receptors. Physiological activity was determined using whole cell IP1 accumulation assays. Under these conditions, WAY-267,464 had higher affinity for the V1a receptor compared to the OT receptor (8.5x more selective) with poor functional selectivity (2x selective for OT receptor agonism over V1a receptor antagonism). Methylation of the resorcinol moiety (3) reversed the OT receptor pharmacological profile, removing agonist activity and inducing antagonist activity, without altering V1a receptor pharmacology. All flexible tethered derivatives removed OT receptor affinity and activity resulting in the generation of highly selective V1a receptor ligands.
- Jorgensen, William T.,Gulliver, Damien W.,Werry, Eryn L.,Reekie, Tristan,Connor, Mark,Kassiou, Michael
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p. 730 - 740
(2016/01/09)
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- Pyrazolo[1,4]diazepines as non-peptidic probes of the oxytocin and vasopressin receptors
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An improved synthesis of differently substituted pyrazolo[1,4]diazepine compounds is reported. In addition, we have used this methodology to obtain non-peptidic compounds to probe the oxytocin and vasopressin receptors.
- Reekie, Tristan A.,McGregor, Iain S.,Kassiou, Michael
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supporting information
p. 4568 - 4571
(2015/01/09)
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- Synthesis of biologically active seven-membered-ring heterocycles
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Seven-membered rings that contain one or more heteroatoms are interesting motifs for organic synthesis. In addition to their synthetic interest, they play an important role in industrial and pharmaceutical chemistry with generally increased central nervous system activity when flanked by aromatic rings. Herein we report a brief summary of some key methods of preparation for seven-membered-ring heterocycles and how they have been applied to the synthesis of commercially desirable products. We then detail new methods that we have developed for the synthesis of biologically active compounds containing this motif. Georg Thieme Verlag Stuttgart New York.
- Reekie, Tristan A.,Kavanagh, Madeline E.,Longworth, Mitchell,Kassiou, Michael
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p. 3211 - 3227
(2013/12/04)
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- SUBSTITUTED BICYCLOCARBOXYAMIDE COMPOUNDS
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This invention provides a compound of the formula (I). These compounds are useful for the treatment of disease conditions caused by overactivation of the VR1 receptor such as pain, or the like in mammal. This invention also provides a pharmaceutical composition comprising the above compound.
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Page/Page column 49-50
(2008/12/05)
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- Azide Ring-Opening-Ring-Closure Reactions and Tele-substitutions in Vicinal Azidopyrazole-, Pyrrole- and Indolecarboxaldehydes
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5-Chloro-1-methylpyrazole-4-carboxaldehydes 1 react with excess sodium azide in dimethyl sulfoxide to produce a mixture of 1-azidomethyl-4-cyanopyrazoles 2 and 4-cyano-5-hydroxy-1-methylpyrazoles 3.Application of this reaction to the corresponding 5-chloro-1-phenylpyrazole-4-carboxaldehydes 5 gave 4-cyano-5-hydroxy-1-phenyl-pyrazoles 7 as the sole products in high yields.Likewise, 2-aryl-5-chloro-1-methylpyrrole-3,4-dicarboxaldehydes 9 rearranged to 2-aryl-4-cyano-5-hydroxy-1-methylpyrrole-3-carboxaldehydes 10 in high yields.In the indole series, treatment of 1-aryl-2-chloroindole-3-carboxaldehydes 11 with NaN3 yielded a mixture of 1-aryl-3-cyano-2(3H)-indolones 13 and 1-aryl-5-azido-3-cyanoindoles 12, both products resulting from a ring-opening-ring-closure reaction with concomitant nucleophilic tele-substitution at the 5-position of the indole ring.
- Becher, Jan,Joergensen, Per Lauge,Pluta, Krystian,Krake, Niels J.,Faelt-Hansen, Birgitte
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p. 2127 - 2134
(2007/10/02)
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