- Phenyl acetate derivatives, fluorine-substituted on the phenyl group, as rapid recovery hypnotic agents with reflex depression
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We report the synthesis of novel, potentially hypnotic fluorine-substituted phenyl acetate derivatives. We describe the structure-activity relationship that led us to the promising derivative: ethyl 2-(4-(2-(diethylamino)-2-oxoethoxy)-5-ethoxy-2-fluorophenyl) acetate (55). The unique pharmacological features of compound 55 are its relatively high affinity for the GABAA receptor, together with a unique affinity for the NMDA receptor, different to propanidid and AZD3043. In animal models, compound 55 showed stronger hypnotic potency and longer duration of LORR than propanidid and AZD3043, but also maintained a rapid recovery time to walking and behavioral recovery. In particular, compound 55 displayed reflex depression during infusion.
- Zhang, Heng,Xu, Xiangqing,Chen, Yin,Qiu, Yinli,Liu, Xin,Liu, Bi-Feng,Zhang, Guisen
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p. 524 - 539
(2014/12/11)
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- NPY ANTAGONISTS, PREPARATION AND USES
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The present invention concerns novel compounds, their preparation and their uses, therapeutic uses in particular. More specifically it concerns derivative compounds having at least two aromatic cycles, their preparation and their uses, in particular in the area of human or animal health. These compounds have an affinity for the biological receptors of neuropeptide Y, NPY, present in the central and peripheral nervous systems. The compounds of the invention are preferably NPY antagonists, and more particularly antagonists of sub-type NPY Y1, and can therefore be used for the therapeutic or prophylactic treatment of any disorder involving NPY. The present invention also concerns pharmaceutical compositions containing said compounds, their preparation and their uses, as well as treatment methods using said compounds.
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Page/Page column 117-118
(2009/09/28)
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- New series of morpholine and 1,4-oxazepane derivatives as dopamine D 4 receptor ligands: Synthesis and 3D-QSAR model
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Since the identification of the dopamine D43 receptor subtype and speculations about its possible involvement in schizophrenia, much work has been put into development of selective D4 ligands. These selective ligands may be effective antipsychotics without extrapyramidal side effects. This work describes the synthesis of a new series of 2,4-disubstituted morpholines and 2,4-disubstituted 1,4-oxazepanes with selectivity for the dopamine D4 receptor. A 3D-QSAR analysis using the GRID/GOLPE methodology was performed with the purpose to get a better understanding of the relationship between chemical structure and biological activity. Inspection of the coefficient plots allowed us to identify that regions which are important for affinity are situated around the two benzene ring systems, a p-chlorobenzyl group, and the aliphatic amine belonging to the morpholine or 1,4-oxazepane system. In addition, the size of the morpholine or 1,4-oxazepane ring seems to be important for affinity.
- Audouze, Karine,Nielsen, Elsebet ?stergaard.,Peters, Dan
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p. 3089 - 3104
(2007/10/03)
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- SYNTHESIS AND HPLC SEPARATION OF 6-FLUORO-L-DOPA METABOLITES
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The synthesis of 6-fluoro-L-dopa metabolites (3-O-methyl-6-fluorodopa (1b), 6-fluorodopamine (2a), 3-O-methyl-6-fluorodopamine (2b), 3,4-dihydroxy-6-fluorophenylacetic acid (3a) and 6-fluorohomovanillic acid (3b) is described.A HPLC method for their separ
- Luxen, A.,Monclus, M.,Hendrickx, P.-Y.,Masson, C.,Melega, W. P.
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p. 217 - 226
(2007/10/02)
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