University of Greenwich

Btg International Limited

Other

Michael J Leach

Laurence Harbige

Dieter Riddall

Karl Franzmann

Paul Barraclough

Alistair Allen Miller

Richard M Hyde

Malcolm S Nobbs

Mohammed Sharief

Anthony P Dolan

Laurence S Harbige

Anthony Patrick Btg International Limited Dolan

Laurence S The University Of Greenwich Harbige

The present invention relates to interferon-gamma (IFN-&#x3b3;) inhibitors, and their utility in treating or controlling diseases that can be treated or controlled through inhibition of IFN-&#x3b3; production, such as Alzheimer's disease, prion diseases, multiple sclerosis, epilepsy, rheumatoid arthritis, inflammatory bowel disease, uveitis, autoimmune skin diseases, psoriasis, Sj&#xf6;gren's syndrome, Crohn's disease, and type 1 diabetes mellitus. The compounds are of Formula 1, 2 3, or are solvates, tautomers, or pharmaceutically acceptable salts thereof. 

Triazine derivatives as interferon-gamma inhibitors

A method of treating a disorder. The method includes administering to a subject in need thereof a compound of general formula (I): Each of A, N*, X, Y, R1, and R2 is defined herein. Also disclosed are compounds of the formula and a pharmaceutical composition containing such a compound.

Cyclic triazo and diazo sodium channel blockers

A method of treating a disorder such as epilepsy, multiple sclerosis, glaucoma and uveitis, cerebral traumas and cerebral ischaemias, stroke, head injury, spinal cord injury, surgical trauma, neurodegenerative disorders, motorneurone disease, Alzheimer's disease, Parkinson's disease, chronic inflammatory pain, neuropathic pain, migraine, bipolar disorder, mood, anxiety and cognitive disorders, schizophrenia, or trigeminal autonomic cephalalgias. The method includes administering to a subject in need thereof substituted 1,2,4-triazine compounds of formula (I): Each of A, N*, X, Y, Z, R1, and R2 is defined herein. Also disclosed are compounds of the formula and a pharmaceutical composition containing such a compound.

The present invention relates to triazine compounds having sodium channel blocking properties, and to use of the compounds for preparation of medicaments for treatment of associated disorders. The compounds are of formula I: 

Cyclic triazo sodium channel blockers

The present invention relates to triazine compounds having sodium channel blocking properties, and to use of the compounds for preparation of medicaments for treatment of associated disorders. The compounds are of formula (I): in which z is a single bond or an optionally substituted linking group, R1 is a halo-alkyl group; and A is an optionally substituted aromatic heterocyclic or carbocyclic ring system; or a salt thereof. 

The present invention relates to triazine compounds having sodium channel blocking properties, and to use of the compounds for preparation of medicaments for treatment of associated disorders. The triazine compounds are of formula (I) wherein: R1 is hydrogen or a substituent group; R2 is amino or a substituent group; N* is amino when R1 is hydrogen or &#x2550;NH when R1 is a substituent group; R3 and R4 are both carbocyclic, heterocyclic or alkyl groups and may be same or different; and R5 is hydrogen, alkyl or a cyclic aryl group, with the proviso that: when R3 and R4 are both alkyl they are linked to form a cycloalkyl group, and R5 is a cyclic aromatic group; and when R3 and R4 are both carbocyclic or heterocyclic groups, R5 is hydrogen or an alkyl group; or a salt thereof. 

Compounds of general structure in which X and Y are each N or C with at least one of X and Y being N; Z is a single bond or an optionally substituted linking group R1 is hydrogen or a substituent group; R2 is amino or a substituent group; N* is amino when RI is hydrogen or &#x2550;NH when R1 is a substituent group; or N* is a group NRaRb where Ra and Rb are independently H or an alkyl group; or N* is an optionally substituted piperazinyl ring; and A is an optionally substituted heterocyclic or carbocyclic ring system which may be linked to the triazo/diazo ring through R2 to form a fused multicyclic ring; are indicated as suitable for treatment of disorders in mammals that are susceptible to sodium channel blockers and antifolates, and particularly disorders such epilepsy, multiple sclerosis, glaucoma and uevitis, cerebral traumas and cerebral ischaemias, stroke, head injury, spinal cord injury, surgical trauma, neurodegenerative disorders, motorneurone disease, Alzheimer's disease, Parkinson's disease, chronic inflammatory pain, neuropathic pain, migraine, bipolar disorder, mood, anxiety and cognitive disorders, schizophrenia and trigeminal autonomic cephalalgias; for treatment of mammalian cancers; and for treatment of malaria. 

Compounds of formula (I) especially where Ris an optionally substituted alkyl, aralkyl or heterocyclyl-alkyl group, are shown to have activity as sodium channel blockers or as antifolates. Some novel compounds where Ris an aralkyl or heterocyclyl-alkyl are disclosed. 

Medical use of triazine derivatives

A method of treating a patient in need of therapy for a cytokine dysregulation comprising administering to that patient a therapeutically effective dose of a compound of general formula: (I) wherein Rand Rtogether form a group &#x2014;(CH)&#x2014;CRR&#x2014;(CH)&#x2014; wherein n and m are independently selected integers 0, 1 or 2 and Rand Rare independently selected from H, Calkyl, Calkoxy, Cn hydroxyalkyl, Calkenyl and Caryl or aralykyl and Ris the a fatty acyl group of an essential polyunsaturated fatty acid. 

Cytokine modulators using cyclic glycerides of essential polyunsaturated fatty acids

A method is provided for treating a patient in need of therapy for a neurodegenerative disease comprising administering to that patient a therapeutically effective dose of a lipid glyceride comprising a glycerol moiety and a fatty acid moiety, the fatty acid moiety being selected from the group consisting of &#x3b3;-linolenic acid, dihomo-&#x3b3;-linolenic acid and arachidonic acid characterized in that the selected fatty acid moiety is attached to the glycerol moiety at its sn-2 position. Preferably the method is that wherein the lipid is administered for a duration and at a dose sufficient to maintain or elevate TGF-&#x3b2;1 levels in the patient to therapeutic levels.

Treatment of neurodegenerative conditions

Method for treating a patient in need of therapy for a neurodegenerative disease by administering to that patient a therapeutically effective dose of a triglyceride oil containing both &#x3b3;-linolenic acid and linolenic acid residues as triglyceride ester. The ratio of &#x3b3;-linolenic acid to linolenic acid residues at the sn-2 position of the triglyceride is at least 0.8. The amount of &#x3b3;-linolenic acid residues at the sn-2 position is at least 18%. The oil is administered at a dose sufficient to maintain or elevate TGF-&#x3b2;1 levels in the patient at a therapeutic level.

Use of triglyceride oils containing &#x3b3;-linolenic acid residues and linoleic acid residues for the treatment of neurodegenerative disease

A class of substituted phenylpyrimidine compounds are disclosed which are potent inhibitors of the excitatory amino acid, glutamate. Such compounds are useful in the treatment or prevention of a range of CNS disorders including cerebral ischaemic damage and epilepsy.

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London, United Kingdom

Michael J Leach