University of Greenwich

Dieter Riddall

Michael J Leach

Laurence Harbige

Karl Franzmann

Michael Leach

Paul Barraclough

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. 

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Chatham, United Kingdom

Dieter Riddall