Smithkline Beecham Corporation

Glaxo Group Limited

Kevin Thewlis

Christopher Norbert Johnson

Geoffrey Stemp

Simon Edward Ward

Clive Leslie Branch

Roderick Alan Porter

Amanda Johns

Steven Coulton

Stephen Harrison

Daniel Marcus Bradley

Mervyn Thompson

Daniele Andreotti

Harshad Kantilal Rami

Luca Arista

Simone Spada

Francesca Cardullo

Antonio Keuok Keong Vong

Alexander B Smith

Disclosed are N-aroyl cyclic amine derivatives having the formula: wherein the substituent variables are as defined herein, and their use as pharmaceuticals.

N-aroyl cyclic amines

This invention relates to potentiation of the glutamate receptor by novel compounds of formula (I):  The invention also relates to the use of the derivatives in treating diseases and conditions mediated by potentiation of the glutamate receptor, compositions containing the derivatives and processes for their preparation.

Compounds which potentiate glutamate receptor and uses thereof in medicine

This case discloses compounds of formula (I) wherein Ris Calkyl, haloCalkyl, Calkenyl, amino, monoCalkylamino or diCalkylamino; Rand R, which may be the same or different, are hydrogen, halogen, Calkyl, haloCalkyl, Calkoxy, haloCalkoxy, cyano or amino; each R, which may be the same or different, is Calkyl, halogen, haloCalkyl, Calkoxy, haloCalkoxy, cyano, nitro or amino; p is 0, 1 or 2; each R, which may be the same or different, is Calkyl, halogen, haloCalkyl, Calkoxy, haloCalkoxy, cyano, nitro or amino; q is 0, 1 or 2; Ris &#x2014;NRSOR, &#x2014;NRC(&#x2550;O)R, &#x2014;NR(C&#x2550;O)N(R), &#x2014;(C&#x2550;O)R, &#x2014;CHNRSOR, &#x2014;CHNRC(&#x2550;O)R, CHNR(C&#x2550;O)N(R)or &#x2014;CH(C&#x2550;O)R; where Rand each R, which may be the same or different, is hydrogen or Calkyl; Rand Rare Calkyl or haloCalkyl; or Rand R, or Rand R, together with the interconnecting atoms, may form a 5- or 6-membered ring; n is 1 or 2; and Rand R, which may be the same or different, are hydrogen, halogen, Calkyl, haloCalkyl, Calkoxy, haloCalkoxy, cyano or amino. It also discloses methods for preparing the compounds and their use in therapy such as treating schizophrenia. 

Compounds of formula (I) and salts are provided: along with pharmaceutical compositions, uses in treating a disease or condition mediated by a reduction or imbalance in glutamate receptor function such as schizophrenia or cognition impairment.

Compounds which potentiate AMPA receptor and uses thereof in medicine

Compounds of formula (I) or a pharmaceutically acceptable salt, solvate or prodrug thereof, are disclosed: wherein Ris Calkyl, haloCalkyl, Calkenyl, amino, monoCalkylamino or diCalkylamino; Rand R, which may be the same or different, are hydrogen, halogen, Calkyl, haloCalkyl, Calkoxy, haloCalkoxy, cyano, amino, monoCalkylamino or diCalkylamino; each R, which may be the same or different, is Calkyl, halogen, Calkyl, haloCalkyl, Calkoxy, haloCalkoxy, cyano, nitro, amino, monoCalkylamino or diCalkylamino; p is 0, 1 or 2; n is 1 or 2; Rand R, which may be the same or different, are hydrogen, halogen, Calkyl, haloCalkyl, Calkoxy, haloCalkoxy, cyano, amino, monoCalkylamino or diCalkylamino; and Het is thienyl, pyridyl, pyrimidinyl, pyridazinyl, pyrimidinyl, pyrazinyl, imidazolyl, pyrazolyl, pyrrolyl, quinolyl, thiazolyl or furyl, each of which may be substituted by one or more groups independently selected from the list consisting of Calkyl, Calkoxy, acetyl, halogen, haloCalkyl, cyano, nitro, amino, monoCalkylamino and diCalkylamino. Methods of preparation of the compounds, and uses thereof in medicine, for example treatment of schizophrenia, are also disclosed.

Compounds of formula (I) and salts are provided: along with pharmaceutical compositions, uses in medicine, e.g., treating disease or condition mediated by a reduction or imbalance in glutamate receptor function, such as schizophrenia or cognition impairment.

This invention relates to N-aroyl cyclic amine derivatives and their use as orexin antagonists wherein:

This invention relates to morpholine derivatives of formula (I) and their use as antagonists of orexin receptors.

Morpholine derivatives as antagonists of orexin receptors

The present invention relates to novel compounds of formula (I) or a pharmaceutically acceptable salt thereof, wherein Ar is phenyl, naphthyl, a monocyclic heteroaromatic group or a bicyclic heteroaromatic group, said Ar group being optionally substituted by 1-4 substituents, which may be the same or different, and which are selected from the group consisting of: halogen, hydroxy, cyano, nitro, trifluoromethyl, trifluoromethoxy, C1-6alkyl, trifluoromethanesulfonyloxy, pentafluoroethyl, C1-6alkoxy, arylC1-6alkoxy, C1-6alkylthio, C1-6alkoxyC1-6-alkyl, C3-7cycloalkylC1-6alkoxy, C1-6alkanoyl, C1-6alkoxycarbonyl, C1-6alkylsulfonyl, C1-6alkylsulfinyl, C1-6alkylsulfonyloxy, C1-6alkylsulfonylC1-6alkyl, arylsulfonyl, arylsulfonyloxy, arylsulfonylC1-6alkyl, C1-6alkylsulfonamido, C1-6alkylamido, C1-6alkylsulfonamidoC1-6alkyl, C1-6alkylamidoC1-6alkyl, arylsulfonamido, arylcarboxamido, alkylsulfonamidoC1-6alkyl, arylcarboxamidoC1-6alkyl, aroyl, arolC1-6alkyl, arylC1-6alkanoyl, a group R&#x3c;3&#x3e;OCO(CH2)s, R&#x3c;3&#x3e;CON(R&#x3c;4&#x3e;)(CH2)s, R&#x3c;3&#x3e;R&#x3c;4&#x3e;NCO(CH2)s or R&#x3c;3&#x3e;R&#x3c;4&#x3e;NSO2(CH2) where each of R&#x3c;3&#x3e; and R&#x3c;4&#x3e; independently represents a hydrogen atom or C1-4alkyl or R&#x3c;3&#x3e; and R&#x3c;4&#x3e; form part of a C3-6azacyloalkane or C3-6(2-oxo)azacycloalkane ring and s represents zero or an integer from 1 to 4, and a group Ar&#x3c;1&#x3e;Z, wherein Z represents a single bond, O, S or CH2 and Ar&#x3c;1&#x3e; represents a phenyl or a monocyclic heteroaromatic group, said Ar&#x3c;1&#x3e; group being optionally substituted by 1-3 substituents, which may be the same or different, and which are selected from the group consisting of a halogen, hydroxy, cyano, trifluoromethyl, C1-6alkyl, C1-6alkoxy or C1-6alkanoyl; when Ar is a phenyl or a monocyclic heteroaromatic group, substitutents positioned ortho to one another may be linked to form a 5- or 6-membered ring; R&#x3c;1&#x3e; is hydrogen, C1-6alkyl, C3-6alkenyl, C3-6alkynyl or arylC1-6alkyl; R&#x3c;2&#x3e; is halogen, C1-6alkyl, cyano, CF3, C1-6alkanoyl, C1-6alkoxy or hydroxy; X is CH or N; Y is a single bond, O, or C&#x2550;O; p is 0, 1 or 2; r is 0, 1, 2 or 3; m is 2, 3 or 4; n and q are independently 1 or 2. Processes for preparing the compounds, pharmaceutical compositions containing them and their use as medicaments for various CNS disorders, including deression and/or anxiety, are also disclosed.

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Harlow, United Kingdom

Kevin Thewlis