Abstract: A substituted triazolopyridazine derivative, its use in cognition enhancement therapy, compositions containing it and processes for its manufacture.

Abstract: The invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof: wherein X is CH2, O or S. The compounds inhibit gamma secretase without affecting Notch signalling, and hence find use in the treatment or prevention of Alzheimer's disease.

Abstract: A compound of formula I, or a salt or prodrug thereof: wherein: Z represents C1-6 alkyl, C3-7 cycloalkyl, C4-7 cycloalkenyl, aryl, C3-7 heterocycloalkyl, heteroaryl or di(C1-6)alkylamino, any of which groups may be optionally substituted; R1 represents an optionally substituted five-membered heteroaromatic ring selected from oxazole, thiazole, isoxazole, isothiazole, imidazole, pyrazole, oxadiazole, thiadiazole, triazole and tetrazole; or R1 represents an optionally substituted six-membered heteroaromatic ring selected from pyrazine, pyrimidine and pyridazine; and R2 represents cyano(C1-6)alkyl, hydroxy(C1-6)alkyl, C3-7 cycloalkyl(C1-6)alkyl, propargyl, C3-7 heterocycloalkylcarbonyl(C1-6)alkyl, aryl(C1-6)alkyl or heteroaryl(C1-6)alkyl, any of which groups may be optionally substituted; its use in treating anxiety and pharmaceutical compositions comprising it; a subclass of compounds which are useful in enhancing cognition, such as Alzheimer's Disease, is also disclosed.

Abstract: The present invention relates to a method of enhancing cognition without producing convulsions which method comprises administering to a subject in need thereof a cognition enhancing amount of a compound which is a GABAa selective alpha5 receptor inverse agonist.

Abstract: The present invention relates to a process for the preparation of morpholine derivatives of formula (I) which are useful as a therapeutic agents.

Abstract: A pharmaceutical product comprising an SSRI and a non-sedating anxiolytic compound, which is a modulator of the benzodiazepine binding site of the human GABAA receptor, having a binding affinity for the &agr;3 subunit of the human GABAA receptor of 10 nM or less, which elicits at least a 40% potentiation of the GABA EC20 response in stably transfected recombinant cell lines expressing the &agr;3 subunit of &agr;3 and which elicits at most a 30% potentiation of the GABA EC20 response in stably transfected cell lines expressing the &agr;1 subunit of the human GABAA receptor is disclosed for simultaneous, separate or sequential administration.

Abstract: 4-oxo-tetrahydroindozole-3-carboxamide compounds according to Formula (I), or a pharmaceutically acceptable salt thereof, are GABA-A Alpha 5 ligands useful for enhancing cognition:

Abstract: The present invention relates compounds of the formula (I): wherein R1, R2, R3, R4 and R5 represent a variety of substituents; R6 represents hydrogen, CORa, CO2Ra, COCONRaRb, COCO2Ra, C1-6alkyl optionally substituted by a group selected from (CO2Ra, CONRaRb, hydroxy, CN, CORa, NRaRb, C(NOH)NRaRb, CONHphenyl(C1-4alkyl), COCO2Ra, CONHNRaRb, C(S)NRaRb, CONRaC1-6alkylR12, CONR13C2-6alkenyl, CONR13C2-6alkynyl, COCONRaRb, CONRaC(NRb)NRaRb, CONRaheteroaryl, and phenyl optionally substituted by one, two or three substituents selected from C1-6alky, C1-6alkoxy, halogen and trifluoromethyl); or R6 represents a group of formula —CH2C≡CCH2NR7R8 where R7 and R8 are as defined below; or R6 represents C1-6alkyl, optionally substituted by oxo, substituted by a 5-membered or 6-membered heterocyclic ring containing 1, 2 or 3 nitrogen atoms optionally substituted by ═O or ═S and optionally substituted by a group of the formula ZNR7R8; or a pharmaceutical acceptable salt thereof.

Abstract: The present invention relates to the treatment or prevention of depression and/or anxiety by the administration of a combination of a specific class of NK-1 receptor antagonists and an antidepressant or anti-anxiety agent. The present invention also provides preclinical screens for anxiolytic and antidepressant activity of NK-1 receptor antagonists.

Abstract: 1,2,4-triazolo[4,3-b]pyridazine derivatives, possessing an optionally substituted cycloalkyl, phenyl or heteroaryl substituent as the 3-position and an amino moiety at the 6-position, are selective ligands for GABAA receptors, in particular having high affinity for the &agr;2 and/or &agr;3 subunit thereof, are useful in the treatment of anxiety and convulsions.

Abstract: Compounds according to Formula (I) or a salt thereof are GABA-A Alpha 5 ligands useful for enhancing cognition:

Abstract: Substituted or 6,7-ring fused 1,2,3-triazolo[1,5-&agr;]-pyrimidine derivatives are selective ligands for GABAA receptors useful in the treatment of disorders of the central nervous system, including anxiety and convulsions.

Abstract: Pyrazolo[4,3-c]pyridin-3-one derivatives substituted at the 2-position by an optionally substituted aryl or heteroaryl moiety, and having pendant substituents at the 7-position and optionally also at the 6-position, are selective ligands for GABAA receptors, particularly having high affinity for the &agr;2 and/or &agr;3 subunit, and are useful in the treatment and/or prevention of disorders of the central nervous system, including anxiety and convulsions.

Abstract: The present invention relates to the treatment or prevention of depression and/or anxiety by the administration of a combination of a specific class of NK-1 receptor antagonists and fluoxetine.

Abstract: 1,2,4-triazolo[4,3-b]pyridazine derivatives, represented by wherein Z represents an optionally substituted tetrahydropyridinyl substituent, are selective ligands for GABAA receptors, in particular having high affinity for the &agr;2 and/or &agr;3 subunit thereof, are useful in the treatment of anxiety and convulsions.

Abstract: 3-(Piperidin-4-yl)-1H-indole derivatives bearing an optionally substituted phenyl moiety at the 2-position of the indole ring system and an alkyl or aryl-alkyl substituent on the nitrogen atom of the piperndine ring are selective antagonists of the human 5-HT2A receptor. They are therefore useful as pharmaceutical agents, especially in the treatment and/or prevention of adverse conditions of the central nervous system, including psychotic disorders such as schizophrenia.

Abstract: 1,2,4-triazolo[4,3-b]pyridazine derivatives are ligands for GABAA receptors useful in the treatment of disorders of dementing illnesses.

Abstract: 1,2,4-triazolo[4,3-b]pyridazine derivatives, represented by wherein Z represents cyclobutyl or pyrrolidin-1-yl, are selective ligands for GABAA receptors, in particular having high affinity for the &agr;2 and/or &agr;3 subunit thereof, are useful in the treatment of anxiety and convulsions.

Abstract: The present invention relates to a process for the preparation of mopholine derivatives of formula (I) which are useful as a therapeutic agents.

Abstract: A compound of formula I, or a salt or prodrug thereof: wherein: Z represents C1-6 alkyl, C3-7 cycloalkyl, C4-7 cycloalkenyl, aryl, C3-7 heterocycloalkyl, heteroaryl or di(C1-6)alkylamino, any of which groups may be optionally substituted; R1 represents an optionally substituted five-membered heteroaromatic ring selected from oxazole, thiazole, isoxazole, isothiazole, imidazole, pyrazole, oxadiazole, thiadiazole, triazole and tetrazole; or R1 represents an optionally substituted six-membered heteroaromatic ring selected from pyrazine, pyrimidine and pyridazine; and R2 represents cyano(C1-6)alkyl, hydroxy(C1-6)alkyl, C3-7 cycloalkyl(C1-6)alky, propargyl, C3-7 heterocycloalkylcarbonyl(C1-6)alkyl, aryl(C1-6)alkyl or heteroaryl(C1-6)alkyl, any of which groups may be optionally substituted; its use in treating anxiety and pharmaceutical compositions comprising it; a subclass of compounds which are useful in enhancing cognition, such as Alzheimer's Disease, is also disclosed.