CHEMICAL COMPOUNDS

Abstract: 1,2,3,4-tetrahydronaphthalenes, chromans and thiochromans, of formula (I) wherein r, s and X are as defined in the specification, R<1>, R<2>, R<3> and R<4> are various substituents, also as defined in the specification, pharmaceutical compositions containing them and uses of them for the therapeutic treatment of neurological disorders.

Description: CHEMICAL COMPOUNDS The present invention relates to chemical compounds, in particular 1,2,3,4- tetrahydronaphthalenes, chromans and thiochromans, to processes for their preparation and to chemical intermediates useful in such processes. The present invention further relates to 1,2,3,4-tetrahydronaphthalenes, chromans and thiochromans, to pharmaceutical compositions containing them and to their use in methods of therapeutic treatment of animals including man, in particular in the treatment of neurological disorders. Neurological disorders, for which the present compounds are useful, include stroke, head trauma, transient cerebral ischaemic attack, and chronic neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, diabetic neuropathy, amyotrophic lateral sclerosis, multiple sclerosis and AIDS-related dementia. The compounds useful in the present invention are believed to act by binding with the [ 3 H]-emopamil binding site. Backeround Emopamil has classically been thought of as a neuroprotective agent whose efficacy is most likely derived from actions at either voltage-sensitive calcium channels (VSCC) or 5-HT 2 receptors. An apparent paradox to this logic is that verapamil, although chemically and pharmacologically very similar to emopamil, is not neuroprotective. While the lack of neuroprotective efficacy by verapamil was initially explained by lack of CNS penetration, recent studies suggest other factors may be involved (Keith et al., Br. J. Pharmacol. 113: 379- 384, 1994). [ 3 H]-Emopamil binding defines a unique high affinity site that is not related to VSCC, is found in the brain, but is most prevalent in the liver (Moebius et al., Mol. Pharmacol. 43: 139- 148, 1993). Moebius et al. have termed this the "anti-ischaemic" binding site on the basis of high affinity displacement by several chemically disparate neuroprotective agents. In liver, the [ 3 H]-emopamil binding site is localised to the endoplasmic reticulum. Neuroprotective compounds are known, for example emopamil and ifenprodil, that exhibit high affinity for the [ 3 H]-emopamil binding site. However these are not selective inhibitors and exhibit activity either at neuronal VSCC, the polyamine site of the NMDA receptor (N-Methyl-D-aspartate) and/or the sigma-1 binding site. Summarv of the Invention In one aspect the present invention comprises a class of compounds that show selective action at the [ 3 H]-emopamil binding site and that are neuroprotective without acting directly at either NSCC or ΝMDA receptors, and which exhibit fewer associated side effects such as hypotension seen with emopamil or behavioural manifestations seen with ifenprodil. Accordingly, the present invention provides compounds of formula (I): wherein: R 1 is Ci-βalkyl, C 3 . 6 alkenyl, C 3 _6alkynyl or phenylC 2 _6alkyl; R 2 is hydrogen, optionally substituted Ci.galkyl, optionally substituted C 3 . 8 alkenyl or optionally substituted C 3 . 8 alkynyl; wherein said substituents are chosen from one or more halo, nitro, cyano, hydroxy, trifluoromethyl, trifluoromethoxy, amino, carboxy, carbamoyl, mercapto, sulphamoyl, Cι. 6 alkoxy, Cι. 6 alkanoyl, Cι. 6 alkoxycarbonyl, Cι_6alkanoyloxy, N-(Cι. 6 alkyl)amino, NN-(Cι-6alkyl) 2 amino, Cι. 6 alkanoylamino, N-(Cι_6alkyl)carbamoyl, NN-(Cι. 6 alkyl) 2 carbamoyl, Ci-βalkoxyCi-βalkoxy, Cι-6alkylS(O) a wherein a is 0, 1 or 2, N-(Cι. 6 alkyl)sulphamoyl or NN-(Cι-6alkyl) 2 sulphamoyl, optionally substituted aryl, optionally substituted heterocycle, optionally substituted heteroaryl, optionally substituted C 3 .ι 2 cycloalkyl, or a group of the formula: F-CCHJ X- (IA) wherein F is optionally substituted aryl, optionally substituted carbon linked heteroaryl, optionally substituted carbon-linked heterocycle or optionally substituted C 3 .ι 2 cycloalkyl, p is 0, 1, 2, 3, 4, 5 or 6 and X is a linking group and is selected from -C(O)-, -O-, -OC(O)-, -S-, - S(O)-, -S(O) 2 -, -S(O) 2 ΝR 4 -, -NR 4 S(O) 2 -, -NR 4 -, -C(O)O-, -C(O)NR 4 -, -NR 4 C(O)-, - OC(O)NR 4 -, -C(O)NR 4 SO 2 -, -NR 4 C(O)O-, -C(S)NR 4 - or -NR 4 C(S)- (wherein R 4 is selected from hydrogen, Cι. alkyl); wherein any aryl, heteroaryl, heterocycle or C 3 i 2 cycloalkyl may be optionally substituted on a ring carbon with one or more groups selected from halo, nitro, cyano, hydroxy, trifluoromethyl, trifluoromethoxy, amino, carboxy, carbamoyl, mercapto, sulphamoyl, Ci 6 alkyl, C 2 6 alkenyl, C 2 βalkynyl, Cj 6 alkoxy, Ci δalkanoyl, Ci 6 alkanoyloxy, N-(Cι 6 alkyl)amιno, NN-(Cι 6 alkyl) 2 amιno, Ci 6 alkanoylamιno, N-(Cι 6 alkyl)carbamoyl, NN-(Cι 6 alkyi) 2 carbamoyl, Ci 6 alkylS(O) a wherein a is 0, 1 or 2, Ci 6 alkoxycarbonyl, N-(Cι fi alkyl)sulphamoyl, NN-(Cι 6 alkyl) 2 sulphamoyl or phenylCi 6 alkyl and a heterocycle or heteroaryl containing an -ΝH- group may be optionally substituted on a ring nitrogen with Ci ealkyl, C 2 βalkenyl, C 2 6 alkynyl, Ci 6 alkanoyl, Ci 6 alkylsulphonyl or phenylCi βalkyl, R 3 is halo, hydroxy, Ci ealkyl, Ci 6 alkoxy, haloCi ealkyl, cyano, nitro or C 2 βalkenyl, R 4 is Ci 6 alkyl, r is 0, 1, 2, 3 or 4, wherein the values of R may be the same or different, and s is 0, 1 , 2 or 3 wherein the values of R 4 may be the same or different, or a pharmaceutically-acceptable salt or an in v/vo-hydrolysable ester, amide or carbamate thereof In another aspect, the invention comprises a method for using compounds of Formula (I) for the treatment of neurological disorders such as stroke, head trauma, transient cerebral ischaemic attack, and chronic neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, diabetic neuropathy, amyotrophic lateral sclerosis, multiple sclerosis and AIDS-related dementia In a further aspect, the invention comprises methods for making compounds of formula (I) In yet another aspect, the invention comprises pharmaceutical compositions comprising compounds of formula (I) together excipients, diluents or stabilisers, as further disclosed herein Detailed description of the Invention In this specification the term "alkyl" includes both straight and branched chain alkyl groups but references to individual alkyl groups such as "propyl" are specific for the straight chain version only A similar convention applies to "alkenyl", "alkynyl" and other radicals, for example "phenylCi 6 alkyl" includes 2-phenylethyl, 2-phenylpropyl and 3-phenylpropyl The term "halo" refers to fluoro, chloro, bromo and lodo The term aryl refers to an unsaturated carbon ring. Preferably aryl is phenyl, naphthyl or biphenyl. More preferably aryl is phenyl. The term "heteroaryl" or "heteroaryl ring" refers to, unless otherwise further specified, a monocyclic-, bicyclic- or tricyclic- 5-14 membered ring that is unsaturated or partially unsaturated, with up to five ring heteroatoms selected from nitrogen, oxygen and sulphur wherein a -CH 2 - group can optionally be replaced by a -C(O)-, and a ring nitrogen atom may be optionally oxidised to form the N-oxide. Examples of such heteroaryls include thienyl, furyl, pyranyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, oxazolyl, isoxazolyl, pyridyl, pyridyl-N-oxide, oxopyridyl, oxoquinolyl, pyrimidinyl, pyrazinyl, oxopyrazinyl, pyridazinyl, indolinyl, benzofliranyl, benzimidazolyl, benzothiazolyl, quinolyl, isoquinolinyl, quinazolinyl, xanthenyl, quinoxalinyl, indazolyl, benzofliranyl and cinnolinolyl. The term "heterocyclyl" or "heterocyclic ring" refers to, unless otherwise further specified, a mono- or bicyclic- 5-14 membered ring, that is totally saturated, with up to five ring heteroatoms selected from nitrogen, oxygen and sulphur wherein a -CH 2 - group can optionally be replaced by a -C(O)-. Examples of such heterocyclyls include morpholinyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, piperidinyl, piperazinyl, homopiperidinyl, homopiperazinyl and quinuclidinyl. Where optional substituents are chosen from "one or more" groups it is to be understood that this definition includes all substituents being chosen from one of the specified groups or the substituents being chosen from two or more of the specified groups. In the present invention, examples of Ci_8alkyl include Ci-βalkyl, C]. 4 alkyl such as methyl, ethyl, isopropyl and t-butyl; examples of phenylCi-βalkyl include phenylC 2 - 6 alkyl, benzyl, phenylethyl and phenylpropyl; examples of Ci-βalkoxycarbonyl include methoxycarbonyl, ethoxycarbonyl, n- and i- butoxycarbonyl; examples of Ci-βalkoxy include methoxy, ethoxy and propoxy; examples of Ci-ealkanoylamino include formamido, acetamido and propionylamino; examples of Cι_6 alkyl S(O) a where a is 0, 1 or 2 include Ci-βalkylsulphonyl, methylthio, ethylthio, methylsulphinyl, ethylsulphinyl, mesyl and ethylsulphonyl; examples of Cι. 6 alkanoyl include propionyl and acetyl; examples of N-Cι. 6 alkylamino include N-methylamino and N-ethylamino; examples ofN,N-(Cι-6alkyl) 2 amino include N,N-dimethylamino, NN-diethylamino and N-ethyl- N-methylamino; examples of C 3 .ι 2 cycloalkyl include cyclopropyl and cyclohexyl; examples of C 3 . 8 alkenyl include C 3 . 6 alkenyl, vinyl, allyl and 1-propenyl; examples of Q,_._ alkenyl include allyl and 1-propenyl; examples of C 3 . x alkynyl include C 3 . 6 alkynyl, 1-propynyl and 2-propynyl; examples of C 2 .βalkynyl include ethynyl, 1-propynyl and 2-propynyl; examples of haloC _6alkyl include 2-chloroethyl and 2-bromopropyl; examples ofN-(Cι. 6 alkyl)sulphamoyl include N-methylsulphamoyl and N-ethylsulphamoyl; examples of N,N-(Cι-6alkyl) 2 sulphamoyl include N,N-dimethylsulphamoyl and N-methyl-N- ethylsulphamoyl; examples of N-(Cι. 6 alkyl)carbamoyl include N-methylcarbamoyl and N-ethylcarbamoyl; examples of N,N-(C].6alkyl) 2 carbamoyl include N,N-dimethylcarbamoyl and N-methyl-N- ethylcarbamoyl; examples of Cι. 6 alkanoyloxy include propionyloxy, acetyloxy and formyloxy; examples of Cι_6alkoxyCι.6alkoxy include methoxyethoxy, ethoxymethoxy and propoxypropoxy, and examples of halo Ci-β alkyl include trifluoromethyl, 2-bromoethyl, 3-iodo-2-fluoropropyl and 4- iodobutyl. Preferably R 1 is Cι. 6 alkyl- More preferably R 1 is Cι_ alkyl. Particularly R ! is methyl. Preferably R 2 is hydrogen or optionally substituted Cι. 8 alkyl wherein said optional substituents are as hereinbefore defined. More preferably R 2 is hydrogen or Ci-βalkyl. Particularly R 2 is hydrogen, methyl, n-propyl or isoamyl. Preferably r is 0. Preferably s is 0. In one aspect of the invention preferably X is CH 2 . In another aspect of the invention preferably X is S. In a further aspect of the invention preferably X is O. Therefore in a preferred aspect of the invention there is provided a compound of formula (I) wherein: R 1 is Cι. 6 alkyl; R 2 is hydrogen or optionally substituted Cι_ 8 alkyl wherein said optional substituents are as hereinbefore defined; r is O; s is 0; and X is CH 2 , S or O; or a pharmaceutically-acceptable salt or an in v vo-hydrolysable ester, amide or carbamate thereof. In a more preferred aspect of the invention there is provided a compound of formula (I) wherein: R 1 is Cι- 4 alkyl; R 2 is hydrogen or Cι. 6 alkyl; r is O; s is 0; and X is CH 2 , S or O; or a pharmaceutically-acceptable salt or an in v/ ' vo-hydrolysable ester, amide or carbamate thereof. In a particular aspect of the invention there is provided a compound of formula (I) wherein: R 1 is methyl; R 2 is hydrogen, methyl, n-propyl or isoamyl; r is O; s is 0; and X is CH 2 , S or O; or a pharmaceutically-acceptable salt or an in / ' vo-hydrolysable ester, amide or carbamate thereof. Preferred compounds of the invention are those of Examples. A preferred aspect of the invention relates to any one of the Examples. Preferred aspects of the invention relate to a compound of formula (I) as hereinbefore defined or a pharmaceutically-acceptable salt thereof. Suitable pharmaceutically-acceptable salts include acid addition salts such as methanesulphonate, fumarate, hydrochloride, hydrobromide, citrate, maleate and salts formed with phosphoric and sulphuric acid. In another aspect suitable salts are base salts such as an alkali metal salt for example sodium, an alkaline earth metal salt for example calcium or magnesium, an organic amine salt for example triethylamine, morpholine, N-methylpiperidine, N-ethylpiperidine, procaine, dibenzylamine, N,N-dibenzylethylamine or amino acids for example lysine. There may be more than one cation or anion depending on the number of charged functions and the valency of the cations or anions. A preferred pharmaceutically- acceptable salt is a sodium salt. The compounds of formula (I) possess a chiral centre at the 1-position of the 1,2,3,4- tetrahydronaphthalene ring and the 4-position of the chroman and thiochroman ring. Certain compounds of formula (I) may also have other chiral centres, for example certain of the values of R 2 , R 3 , R 4 , R and certain of the optional substituents may possess chiral centres. It is to be understood that the invention encompasses all such optical isomers and diasteroisomers of compounds of formula (I) that inhibit the [ 3 H]-emopamil binding site. The invention further relates to all tautomeric forms of the compounds of formula (I). It is also to be understood that certain compounds of the formula (I) can exist in solvated as well as unsolvated forms such as, for example, hydrated forms. It is to be understood that the invention encompasses all such solvated and unsolvated forms. In v/ ' vo-hydrolysable esters, amides and carbamates are compounds that hydrolyse in the human body to produce the parent compound. Such esters, amides and carbamates can be identified by administering, for example intravenously to a test animal, the compound under test and subsequently examining the test animal's body fluids. Suitable in v/ ' vo-hydrolysable amides and carbamates include Ν-carbomethoxy and Ν-acetyl. An in v/ ' vo-hydrolysable ester of a compound of the formula (I) containing carboxy or hydroxy group is, for example, a pharmaceutically-acceptable ester which is hydrolysed in the human or animal body to produce the parent acid or alcohol. Suitable pharmaceutically-acceptable esters for carboxy include Ci-βalkoxymethyl esters for example methoxymethyl, Ci.βalkanoyloxymethyl esters for example pivaloyloxymethyl, phthalidyl esters, C 3 .8cycloalkoxy-carbonyloxyCι-6alkyl esters for example 1- cyclohexylcarbonyloxyethyl; l,3-dioxolen-2-onylmethyl esters for example 5-methyl-l,3- dioxolen-2-onylmethyl; and Cι_6alkoxycarbonyloxyethyl esters for example 1- methoxycarbonyloxyethyl and may be formed at any carboxy group in the compounds of this invention An in v/vo-hydrolysable ester of a compound of the formula (1) containing a hydroxy group includes inorganic esters such as phosphate esters and α-acyloxyalkyl ethers and related compounds which as a result of the in vivo hydrolysis of the ester breakdown to give the parent hydroxy group Examples of α-acyloxyalkyl ethers include acetoxymethoxy and 2,2- dimethylpropionyloxymethoxy A selection of in v/vo-hydrolysable ester forming groups for hydroxy include alkanoyl, benzoyl, phenylacetyl and substituted benzoyl and phenylacetyl, alkoxycarbonyl (to give alkyl carbonate esters), dialkylcarbamoyl and N-(dιalkylamιnoethyl)-N- alkylcarbamoyl (to give carbamates), dialkylaminoacetyl and carboxyacetyl Another aspect of the present invention provides a process for preparing a compound of formula (I) or a pharmaceutically-acceptable salt or an /// v/vo-hydrolysable ester, amide or carbamate thereof which process (wherein R 1 , R 2 , R 3 , R 4 , X, r and s are, unless otherwise specified, as defined in formula (I)) comprises of a) reacting a compound of formula (II) (II) wherein L is a leaving group, with a compound of formula (III) (in) wherein R is R , except hydrogen or R 2a a is an amino protecting group, b) for compounds of formula (I) wherein R 2 is hydrogen, reacting a compound of formula (IN) wherein Pg is an amino protecting group, with a compound of formula (N) R'-L (V) wherein L is a leaving group, c) for a compound of formula (I) wherein R 1 is not hydrogen, by reacting a compound of formula (VI) with a compound of formula (Nil) R 2 -L (VII) wherein L is a leaving group, or d) reacting a compound of formula (NIII) with a compound of formula (IX) (IX) wherein R 2a is as defined above, and L is a leaving group, e) reacting a compound of formula (X) (X) with a compound of formula (III), f) for compounds of formula (I) wherein R 1 is Cι. 6 alkyl or phenylC 2 . 6 alkyl, reacting a compound of formula (IN) with a compound of formula (XI) (XI) wherein K is hydrogen, Ci salkyl, or phenylCι. 5 alkyl, g) reacting a compound of formula (NIII) with a compound of formula (XII). (XII) wherein R .2^a a i •s as defined above, h) for a compound of formula (I) wherein K .2 z i • s optionally substituted Cι. 8 alkyl, by reacting a compound of formula (VI) with a compound of formula (XIII) (XIII) wherein R b is hydrogen or optionally substituted Cι. 7 alkyl, i) reducing a compound of formula (XIV) (XIV) wherein R a is as defined above, j) for a compound of formula (I) wherein R 2 is optionally substituted by reducing a compound of formula (XV) wherein R is as defined above, or k) for compounds of formula (I) wherein R 2 is hydrogen, by deprotection of a compound of formula (XVI) wherein Pg is am amine protecting group, and thereafter if necessary i) converting a compound of the formula (I) into another compound of the formula (I), ii) removing any protecting groups, or iii) forming a pharmaceutically-acceptable salt or in v/vo-hydrolysable ester, amide or carbamate L is a leaving group, suitable values for L are for example, a halogeno or sulphonyloxy group, for example a chloro, bromo, methanesulphonyloxy or toluene-4-sulphonyloxy group. Specific reaction conditions for the reactions a), b), c) and d), above, are as follows. Amines and compounds with suitable leaving groups are reacted together under standard alkylation conditions. For example in the presence of a base, such as an inorganic base for example sodium carbonate or sodium hydroxide or an organic base such as Hunig's base or excess amine, in the presence of an inert solvent for example tetrahydrofuran, dimethyl acetamide or toluene and at a temperature in the range of 50-120 °C, preferably at or near reflux. Compounds of formula (IN) may be prepared according to the following scheme: Reductive amination Compounds of formula (VI) may be prepared according to the following scheme: (V) Alkylation conditions Pg is am amine protecting group. Suitable values for Pg are described herein below. Compounds of formula (VIII) may be prepared according to the following scheme: (V) + alkylation conditions Compounds of formula (II), (III), (IVa), (V), (Via), (VII), (Villa) and (IX) are commercially available compounds, or they are known in the literature, or they are prepared by standard processes known in the art. Specific reaction conditions for the reactions e), f), g) and h), above, are as follows. Ketones or aldehydes may be reacted with amines under standard reductive amination conditions. For example in the presence of a reducing agent such as hydrogen and a hydrogenation catalyst (for example palladium on carbon), or zinc and hydrochloric acid, or sodium cyanoborohydride, or sodium triacetoxyborohydride, or sodium borohydride, iron pentacarbonyl and alcoholic potassium hydroxide, or borane and pyridine or formic acid. The reaction is preferable carried out in the presence of a suitable solvent such as an alcohol, for example methanol or ethanol, and at a temperature in the range of 0-50 °C, preferably at or near room temperature. Compounds of formula (X), (XI), (XII) and (XIII) are commercially available compounds, or they are known in the literature, or they are prepared by standard processes known in the art. Specific reaction conditions for the reactions i) and j), above, are as follows. Compounds of formula (XIV) and (XV) are reduced under standard reduction conditions for reducing an amide to an amine. For example, in the presence of a reducing agent such as borane, sodium borohydride or lithium aluminium hydride, in an inert solvent such as toluene or tetrahydrofuran, and at a temperature in the range of 50-120 °C, preferably at or near reflux. Compounds of formula (XIV) may be prepared according to the following scheme: Compounds of formula (XV) may be prepared according to the following scheme (XVa) k) Compound of formula (XVI) may be deprotected under standard conditions such as those described hereinbelow It will be appreciated that certain of the various ring substituents in the compounds of the present invention may be introduced by standard aromatic substitution reactions or generated by conventional functional group modifications either prior to or immediately following the processes mentioned above, and as such are included in the process aspect of the invention Such reactions and modifications include, for example, introduction of a substituent by means of an aromatic substitution reaction, reduction of substituents, alkylation of substituents and oxidation of substituents The reagents and reaction conditions for such procedures are well known in the chemical art Particular examples of aromatic substitution reactions include the introduction of a nitro group using concentrated nitric acid, the introduction of an acyl group using, for example, an acyl halide and Lewis acid (such as aluminium trichloride) under Friedel Crafts conditions, the introduction of an alkyl group using an alkyl halide and Lewis acid (such as aluminium trichloride) under Friedel Crafts conditions, and the introduction of a halogeno group Particular examples of modifications include the reduction of a nitro group to an amino group by for example, catalytic hydrogenation with a nickel catalyst or treatment with iron in the presence of hydrochloric acid with heating, oxidation of alkylthio to alkylsulphinyl or alkylsulphonyl It will also be appreciated that in some of the reactions mentioned herein it may be necessary/desirable to protect any sensitive groups in the compounds The instances where protection is necessary or desirable and suitable methods for protection are known to those skilled in the art. Conventional protecting groups may be used in accordance with standard practice (for illustration see T.W. Greene, Protective Groups in Organic Synthesis, John Wiley and Sons, 1991). Thus, if reactants include groups such as amino, carboxy or hydroxy it may be desirable to protect the group in some of the reactions mentioned herein. A suitable protecting group for an amino or alkylamino group is, for example, an acyl group, for example an alkanoyl group such as acetyl, an alkoxycarbonyl group, for example a methoxycarbonyl, ethoxycarbonyl or t-butoxycarbonyl group, an arylmethoxycarbonyl group, for example benzyloxycarbonyl, or an aroyl group, for example benzoyl. The deprotection conditions for the above protecting groups necessarily vary with the choice of protecting group. Thus, for example, an acyl group such as an alkanoyl or alkoxycarbonyl group or an aroyl group may be removed for example, by hydrolysis with a suitable base such as an alkali metal hydroxide, for example lithium or sodium hydroxide. Alternatively an acyl group such as a t-butoxycarbonyl group may be removed, for example, by treatment with a suitable acid as hydrochloric, sulphuric or phosphoric acid or trifluoroacetic acid and an arylmethoxycarbonyl group such as a benzyloxycarbonyl group may be removed, for example, by hydrogenation over a catalyst such as palladium-on-carbon, or by treatment with a Lewis acid for example boron tris(trifluoroacetate). A suitable alternative protecting group for a primary amino group is, for example, a phthaloyl group which may be removed by treatment with an alkylamine, for example dimethylaminopropylamine, or with hydrazine. A suitable protecting group for a hydroxy group is, for example, an acyl group, for example an alkanoyl group such as acetyl, an aroyl group, for example benzoyl, or an arylmethyl group, for example benzyl. The deprotection conditions for the above protecting groups will necessarily vary with the choice of protecting group. Thus, for example, an acyl group such as an alkanoyl or an aroyl group may be removed, for example, by hydrolysis with a suitable base such as an alkali metal hydroxide, for example lithium or sodium hydroxide. Alternatively an arylmethyl group such as a benzyl group may be removed, for example, by hydrogenation over a catalyst such as palladium-on-carbon. A suitable protecting group for a carboxy group is, for example, an esterifying group, for example a methyl or an ethyl group which may be removed, for example, by hydrolysis with a base such as sodium hydroxide, or for example a t-butyl group which may be removed, for example, by treatment with an acid, for example an organic acid such as trifluoroacetic acid, or for example a benzyl group which may be removed, for example, by hydrogenation over a catalyst such as palladium-on-carbon The protecting groups may be removed at any convenient stage in the synthesis using conventional techniques well known in the chemical art In order to use a compound of the formula (I) or a pharmaceutically-acceptable salt or /// v/vo-hydrolysable ester, amide or carbamate thereof for the therapeutic treatment (including prophylactic treatment) of mammals including humans, it is normally formulated in accordance with standard pharmaceutical practice as a pharmaceutical composition The pharmaceutical compositions of compounds of this invention may be administered in standard manner for the disease condition that it is desired to treat, for example by oral, topical, parenteral, buccal, nasal, vaginal or rectal administration or by inhalation For these purposes the compounds of this invention may be formulated by means known in the art into the form of, for example, tablets, capsules, aqueous or oily solutions, suspensions, emulsions, creams, ointments, gels, nasal sprays, suppositories, finely divided powders or aerosols for inhalation, and for parenteral use (including intravenous, intramuscular or infusion) sterile aqueous or oily solutions or suspensions or sterile emulsions A preferred route of administration is intravenously in sterile lsotonic solution In addition to the compounds of the present invention the pharmaceutical composition of this invention may also contain, or be co-administered (simultaneously or sequentially) with, one or more pharmacological agents of value in treating one or more disease conditions referred to hereinabove The pharmaceutical compositions of this invention will normally be administered to humans so that, for example, a daily dose of 0 05 to 75 mg/kg body weight (and preferably of 0 1 to 30 mg/kg body weight) is received This daily dose may be given in divided doses as necessary, the precise amount of the compound received and the route of administration depending on the weight, age and sex of the patient being treated and on the particular disease condition being treated according to principles known in the art Typically unit dosage forms will contain about 1 mg to 500 mg of a compound of this invention According to a further aspect of the invention there is provided a pharmaceutical composition which comprises a compound of the formula (I) as defined hereinbefore or a pharmaceutically-acceptable salt or an in v/vo-hydrolysable ester, amide or carbamate thereof, in association with a pharmaceutically-acceptable excipient or carrier According to a further aspect of the present invention there is provided a compound of the formula (I) or a pharmaceutically-acceptable salt or an / / v/vo-hydrolysable ester, amide or carbamate thereof, as defined hereinbefore for use in a method of treatment of the human or animal body by therapy A further feature of the present invention is a compound of formula (I) and pharmaceutically-acceptable salts or an /// v/vo-hydrolysable ester, amide or carbamate thereof, for use as a medicament Conveniently this is a compound of formula (I) or a pharmaceutically-acceptable salt or an /// v/vo-hydrolysable ester, amide or carbamate thereof, for use as a medicament to inhibit the [ 3 H]-emopamιl binding site in a warm-blooded animal such as a human being Thus according to a further aspect of the invention there is provided the use of a compound of the formula (I), or a pharmaceutically-acceptable salt or an /// v/vo-hydrolysable ester, amide or carbamate thereof, in the manufacture of a medicament for use in the inhibition of the [ 3 H]-emopamιl binding site in a warm-blooded animal such as a human being According to a further feature of the invention there is provided a method of inhibiting of the [ H]-emopamιl binding site in a warm-blooded animal, such as a human being, in need of such treatment which comprises administering to said animal an effective amount of a compound of formula (I) or a pharmaceutically-acceptable salt or an in v/vo-hydrolysable ester, amide or carbamate thereof, as defined hereinbefore The following Biological Test Methods, Data and Examples serve to illustrate the present invention Biological Test Methods H-EmopamiI binding to guinea pig liver membranes The method of (-)- 3 H-emopamιl binding was a modification of Zech, C , Staudinger R , Muhlbacher, J and Glossmann, H Novel sites for phenylalkylamines characterisation of a sodium-sensitive drug receptor with (-)-Η-emopamιl Eur J Pharm 208 119-130, 1991 The reaction mixture contained Assay buffer: 10 mM Tπs-HCl, 0 1 mM phenylmethylsulphonyl fluoride (PMSF), 0 2% bovine serum albumin (BSA), pH 7 4 at 4°C Radioligand: 0 96 nM (-)- 3 H-emopamιl (Amersham) Guinea pig liver membranes: 40mg/mL original wet weight Compounds: 1-300 nM Total volume: 500 μl This mixture was incubated for 60 minutes at 37 °C The incubation was terminated by filtering with a Brandel Cell Harvester over Whatman GF/C filters that had been soaked for at least 120 minutes in 0 3% polyethylenimine (PEI) and washed three times with 5 ml of wash buffer containing 10 mM Tris-HCl, 10 mM MgCl 2 , 0 2% BSA, pH 7 4 at 25 °C Specific binding was defined with 10 μM emopamil In general compounds with an IC 50 below 300nM in this test were of interest Guinea-pig liver membrane preparation: Male guinea pigs were sacrificed by CO 2 asphyxiation with dry ice The livers were quickly excised and weighed and rinsed in membrane preparation buffer containing 10 mM Hepes, 1 mM Tris base-EDTA, 250 mM sucrose, pH 7 4 The livers were then minced, homogenised in 10 times volume with a motor driven Teflon-glass homogeniser with three strokes on ice The homogenate was centrifuged at 1000 x g in a SS34 rotor for 5 minutes at 4°C The supernatant was filtered through 4 layers of gauze and then centrifuged at 8000 x g for 10 minutes at 4°C This resulting supernatant was centrifuged at 40,000 x g for 15 minutes at 4°C The resulting pellet was resuspended in assay buffer and centrifuged again at 40,000 x g for 15 minutes at 4°C This pellet was resuspended in assay buffer (2 5 fold with respect to original wet weight) and homogenised with one stroke with the Teflon-glass homogeniser Aliquots of 1 ml were stored at -70°C H-D-888 binding to rat brain cortical membranes The method of H-D-888 binding was a modification of Reynolds, I J , Snowman, A M and Synder, S H (-)-[ 3 H] Desmethoxyverapamil labels multiple calcium channel modular receptors in brain and skeletal muscle membranes differentiation by temperature and dihydropyridines J Pharmacol Exp Ther 237 no 3, 731-738, 1986 The assay tubes contained the following assay buffer: 50 mM Hepes, 0 2% BSA, pH 7 4 radioligand: lηM 3 H-D888 (Amersham) rat cortical membranes: 6 mg/ml original wet weight compounds: 0 3-100 μM Total volume: 1000 μl This mixture was incubated for 60 minutes at 25 °C. The assay was terminated by filtering with a Brandel Cell Harvester over Whatman GF/C filters that had been soaked for at least 120 minutes in 0.3% polyethylenamine (PEI) and washed three times with 5 ml of wash buffer containing 20 mM Hepes, 20 mM MgCl 2 , pH 7.4. Specific binding was measured with 10 μM methoxyverapamil (D-600). This assay was used to determine in vitro selectivity of compounds vs. L-type voltage sensitive calcium channels, i.e. high affinity for the Η-D888 binding site would show a lack of selectivity. Rat brain cortical membrane preparation Male Sprague-Dawley Rats were sacrificed by decapitation and the brains were quickly excised. The cerebellum and brain stem were removed and discarded; and the rest of the brain was rinsed in 320 mM sucrose. The brain was then homogenised in a 10-fold volume of 320mM sucrose with a motor driven Teflon-glass homogeniser using 10 strokes on ice. The homogenate was spun at 1000 x g for 10 minutes at 4 °C in a SS-34 rotor. The supernatant was then spun at 29,000 x g for 20 minutes. The resulting pellet was resuspended in membrane buffer (5 mM Hepes, 0.2% BSA, pH 7.4) to a final concentration of 60 mg original wet weight/ ml. Gerbil Global Model of Cerebral Ischaemia Male Mongolian gerbils (Charles River) weighing 60-70 grams are used in these experiments. They are housed in individual cages with food (Purina Rodent Chow) and water available ad libitum. The animal room is maintained at 23 ± 2 °C, and is on an automatic 12 hour light cycle. The gerbils are brought to the surgical suite and dosed intraperitoneally with the test agent or vehicle, forty five minutes prior to surgery. Drugs are administered at a volume of 5 ml/kg (intraperitoneal). Vehicle is generally saline, with sodium phosphate added to adjust pH, if needed. Forty-five minutes after dosing the gerbils are anaesthetised with halothane (3.3%) which is delivered along with oxygen (1.5 1/M) through a face mask. After the gerbils are anaesthetised, halothane is continued at a maintenance level of 1.5-2 % along with oxygen. The ventral surface of the neck is shaved and cleaned with alcohol. Surgical procedures are carried out on a thermostat-controlled heating pad set to 37 °C. An incision is made in the neck, the carotid arteries are dissected away from the surrounding tissue, and isolated with a 5 cm length of Silastic tubing. When both arteries have been isolated they are clamped with microaneurysm chps (Roboz Instruments) The arteries are visually inspected to determine that the blood flow has been stopped After 5 minutes the clips are gently removed from the arteries and blood flow begins again A sham control group is treated identically but is not subjected to carotid artery occlusion The incisions are closed with suture and the gerbils removed from the anaesthesia masks and placed on another heating pad to recover from the anaesthesia When they have regained the righting reflex and are beginning to walk around, they are again dosed with the test compound and returned to their home cages This occurs approximately five minutes after the end of surgery Twenty-four hours post ischaemia gerbils are tested for spontaneous locomotor activity, using a Photobeam Activity System from San Diego Instruments They are individually placed in Plexiglas chambers measuring 27 5 cm x 27 5 cm x 15 cm deep The chambers are surrounded by photocells, and every time a beam is broken one count is recorded Each gerbil is tested for two hours, and cumulative counts are recorded at 30, 60, 90, and 120 minutes Mean counts are recorded for each group and drug groups are compared to control with an ANOVA and Bonferroni post test After each gerbil is tested it is returned to its home cage At this time gerbils are also observed for any changes from normal behaviour For the next two days no specific testing is performed, but the gerbils are observed two to three times per day for any unusual behaviours or obvious neurological symptoms (1 e ataxia, convulsions, stereotypic behaviour) Four days post ischaemia the gerbils are sacrificed by decapitation and their brains removed and preserved in 10% buffered formalin Brains were removed, fixed and stained with hematoxy n and eosin Under a light microscope, hippocampal fields were observed and graded for damage to the CA1 subfield 0 to 4 scale, with 0 representing no damage and 4 representing extensive damage Transient focal ischaemia in rats The method was as described by Lin, T-N , He, Y Y , Wu, G , Khan, M And Hsu, C Y Effect of brain edema on infarct volume in a focal model cerebral ischaemia model in rats Stroke 24 1 17-121, 1993, which model is considered to be relevant to the clinical situation Male Long-Evans rats 250-350 g were used Surgery leading to focal ischaemia was conducted under anaesthesia with 100 mg/kg ketamine and 5 mg/kg I m xylazine Rectal temperature was monitored and maintained at 37 0 + 0 5 °C The right middle cerebral artery (MCA) was exposed using microsurgical techniques The MCA trunk was hgated immediately above the rhinal fissure with 10-0 suture Complete interruption of blood flow was confirmed under an operating microscope Both common carotid arteries were then occluded using nontraumatic aneurysm clips After a predetermined duration of ischaemia (45 min), blood flow was restored in all three arteries Twenty-four hours post occlusion, rats were killed under ketamine anaesthesia by intracardiac perfusion with 200 ml of 0 9% NaCl The brain was removed and processed with 2% tπphenyltetrazolium chloride to identify and quantitate the infarcted brain region Compounds were administered by intravenous infusion for 4 hours Data The following results were obtained in the 3 H-Emopamιl binding to guinea pig liver membranes test Examples The invention is now illustrated but not limited by the following Examples in which unless otherwise stated - (l) concentrations were carried out by rotary evaporation /// vacuo, (n) operations were carried out at ambient temperature, that is in the range 18-26 °C and under a nitrogen atmosphere otherwise stated, (in) column chromatography (by the flash procedure) was performed on Merck Kieselgel silica (Art 9385) unless otherwise stated, (iv) yields are given for illustration only and are not necessarily the maximum attainable, (v) the structure of the end-products of the formula 1 were generally confirmed by NMR and mass spectral techniques - proton magnetic resonance spectra were determined in DMSO- δ 6 unless otherwise stated using a Vaπan Gemini 2000 spectrometer operating at a field strength of 300 MHz, chemical shifts are reported in parts per million downfield from tetramethylsilane as an internal standard (δ scale) and peak multiplicities are shown thus s, singlet, bs, broad singlet, d, doublet, AB or dd, doublet of doublets, t, triplet, dt, double of triplets, m, multiplet, bm, broad multiplet and unless otherwise stated 1H NMR is quoted, (vi) TLC's were monitored on silica gel plates Silica Gel GHLF (Analtech), 250 microns, plates (2 5 x 10 cm) The detection methods used were UV light, iodine, and chloroplatinate (vii) Kugelrohr distillation was using apparatus supplied by Aldrich Chemical Co, it is bulb- to-bulb short path distillation, the air bath temperature at which the material distils is denoted as the boiling point, (viii) intermediates were not generally fully characterised and purity was in general assessed mass spectral (MS) or NMR analysis, (ix) Solvents were dried over magnesium sulphate unless otherwise stated, and (x) the following abbreviations (also used hereinabove) may be used - DMSO is dimethylsulphoxide, CDC1 3 is deuterated chloroform, THF is tetrahydrofuran, DCM is dichloromethane, TLC is thin layer chromatography, EA is Elemental Analysis, and DMAC is dimethyl acetamide Example 1 1 -Methyl-4-[N-methyl-N-( 1,2,3 ,4-tetrahydro- 1 -naphthalenyl amino]pιperidine A flask under a nitrogen atmosphere was charged with l-methyl-4-(methylamino) piperidine (3 6 ml, 24 1 mmol) and DMAC (15 ml) Potassium iodide (300 mg) was added followed by the addition of a solution of 1 -chloro- 1, 2,3, 4-tetrahydronaphthalene (Method F) (2 0 g, 12 mmol) in DMAC (6 ml) This solution was then heated in an oil bath at 60 °C for 20 hours The reaction mixture was partitioned between water and ethyl acetate, washed with brine and dried Filtration and evaporation of solvent gave a yellow liquid (2 25 g) This was purified by Kugelrohr distillation to give the title compound as a viscous yellow oil, (1 77 g) bp (air bath temperature) 100-105 °C at 100 mtorr ΝMR (CDC1 3 ) 2 13 (s, 3H), 2 26 (s, 3H), 4 01-4 04 (m, IH,), 7 02-7.16 (m, 3H), 7 67-7 69 (d, IH), EA Calcd for Cι 7 H 2 6Ν 2 C, 79 02, H, 10 14, N, 10 84, found C, 78 86, H, 10 09, N, 10 57 Examples 2-3 Following the procedure Example 1 and using the appropriate starting materials (Methods G or H) the following compounds were prepared All Kugelrohr boiling points for distillations are quoted at air bath temperature 1 DMF was the solvent for the reaction and triethylamine was added with the potassium iodide Example 4 (S>4-[N-methyl-N-π,2,3,4-tetrahydro-l-napthalenyl)amino]pιperidιne A solution of (S)-l-ter/-butoxycarbonyl-4-[N-methyl-N-(l,2,3,4-tetrahydro-l- napthalenyl)amino]piperidine (Method A) (3 95 g,l 1 5 mmol) in DCM (25 ml) under a nitrogen atmosphere was cooled in an ice bath Trifluoroacetic acid (10 ml), was added and the reaction mixture was allowed to warm to ambient temperature The solvent was removed in vacuo and the residue was treated with aqueous potassium carbonate and extracted with ethyl acetate and dried Removal of solvent in vacuo gave 1 53 g of a yellow oil ΝMR (CDC1 3 ) 2 13 (s, 3H), 4 02-4 05 (m, IH), 6 97-7 16 (m, 3H), 7 66-7 68 (d, IH), m/z 245 (M+H) + Example 5 (SVl-λ/-Propyl-4-[N-methyl-N-(l,2,3.4-tetrahydro-l-napthalenyl)aminolpiperidine A flask under a nitrogen atmosphere was charged with lithium aluminium hydride (0 19 g, 5 1 mmol) of and THF (4 ml) A solution of (S)-l-propionyl-4-[N-methyl-N-(l,2,3,4- tetrahydro-l-napthalenyl)amino]piperidιne (Method D) (0 65 g, 2 2 mmol) in THF (5 ml) was added dropwise and the reaction mixture was stirred overnight Water (0 20 ml) was added portionwise followed by aqueous sodium hydroxide solution (15%, 0 20 ml) and water (0 60 ml) The suspension was filtered, washed with THF and the filtrate was dried Removal of solvent gave an oil which was Kugelrohr distilled to give an oil, 0 53 g, bp (air bath temperature) 138-144 °C at 400 mtorr TLC (ethyl acetate) R f 0 11, ΝMR (CDC1 3 ) 0 87-0 92 (t, 3H), 2 13 (s, 3H), m/z 287 (M+H) + Examples 6-7 Following the procedure Example 5 and using the appropriate starting materials (Methods A or E) the following compounds were prepared All Kugelrohr boiling points for distillations are quoted at air bath temperature 1 Solution refluxed for on hour after stirring overnight Example 8 l-Methyl-4-[N-methyl-N-(l,2,3,4-tetrahydro-l-naphthalenyl)amino]piperidine bismaleate salt Treatment of 1 -methyl-4-[N-methyl-N-( 1 ,2,3 ,4-tetrahydro- 1 -naphthalenyl)amino] piperidine (Example 1) (0 60 g) in ethanol (5 ml) with maleic acid (1 32, 1 1 3 mmol) dispersed in diethyl ether (20 ml) followed by dilution with two 20 ml portions of diethyl ether gave a white solid which was dried at 55 °C at 200 mtorr, 0 37 g Mp 184-185 °C, EA Calcd for CπH 26 Ν r 2C 4 H 4 O 4 -0 2H 2 O C, 60 77, H, 7 01 , N, 5 67 , found C, 60 42, H, 6 83, N, 5 49 Examples 9-13 Using the procedure of Example 8, salts of the Examples were prepared The following bismaleate salts are provided by way of illustration Example 14 (S -l-Methyl-4- N-methyl-N-f3,4-dihvdro-2H-benzothιopyran-4-yl aminolpiperidιne A flask under nitrogen was charged with lithium aluminum hydride (0 625 g, 16 47 mmol) and 15 ml dry TΗF (S)-l-/er/-Butoxycarbonyl-4-[N-methyl-N-(3,4-dihydro-2H- benzothιopyran-4-yl)amino]pιperidine (1 7 g, 4 70 mmol) in 30 ml dry TΗF was added dropwise and the reaction was stirred overnight at ambient temperature Saturated sodium sulphate was added dropwise and the solid were removed by filtration The filtrate was concentrated in vacuo and the residue was partitioned between ether and water and the organic extract was dried Filtration and evaporation afforded a residual oil Kugelrohr distillation gave 1 40 g of a viscous oil, bp 120-130 °C (air bath temperature) at 70 mtorr, 'ΗΝMR (300 MHz, CDC13) δ 2 20 (s, 3H, ΝCHJ), 2 26 (s, 3Η, ΝCH5) EA Calcd for Cι 6 Η 24 N 2 S C, 69 52, H, 8 75, N, 10 13, Found C, 69 42, H, 8 74, N, 9 95 This material in 5 ml of ethanol was treated with a dispersion of 1 3 g of maleic acid in 15 ml ether to form a white precipitate After dilution with ether and stirring, the solid was collected by filtration and dried (50 °C at 100 mtorr) to give 1 98 g, mp 130-131 °C EA Calcd for Cι 6 H 24 N 2 S-2C 4 H 4 O 4 -0 25H 2 O C, 56 18, H, 6 38, N, 5 46, Found C, 56 18, H, 6 34, N, 5 31 Example 15 (S -4-[ " N-methyl-N-(3,4-dihvdro-2H-benzothιopyran-4-yl)amino]pιperidine As in Example 4, (S)-l-/ert-Butoxycarbonyl-4-[N-methyl-N-(3,4-dιhydro-2H- benzothιopyran-4-yl)amino]piperidine (2 90 g, 8 0 mmol) was reacted with trifluroacetic acid to give 1 5 g of a viscous oil Kugelrohr distillation gave 0 80g, bp (air bath temperature) 130- 150 °C at 100 mtorr, m/z 263 (M + Η) + Example 16 (S)-l-n-Propyl-4- N-methyl-N-f3,4-dihydro-2H-benzothiopyran-4-yl)amino]piperidιne As in Example X, 0 71 g of (S)-l-Propιonyl-4-[N-methyl-N-(3,4-dihydro-2H- benzothiopyran-4-yl)amino]pιperidine was reduced with lithium aluminum hydride to give 0 50 g of an oil Kugelrohr distillation gave 0 34 g, bp (air bath temperature) 150 °C at 50 mtorr, m/z 305 (M + Η) + , [α] D 23 -6 0° (c = 0 33, methanol), homogeneous by TLC (silica gel, CH 2 C1 2 CH 3 OH ΝH 4 OH 89 10 1) R 0 61 , 1 HNMR (300 MHz, CDC13) δ 0 86-0 91 (t, 3H, CH2CH3), 2 91(s, 3Η, NCH5) This base was dissolved in 5 ml ethanol and 10 ml ether and was treated with 0 35 g of maleic acid in 15 ml of ether The resulting solid was collected by filtration and dried to yield 0 26 g, mp 144-145 °C EA Calcd for Cι 8 Η 28 N 2 S 2C 4 H4O 4 -0 lH 2 O C, 57 99, H, 6 77, N, 5.20, Found C, 57 59, H, 6 73, N, 5 21 Exa ple 17 (S)-l-Benzyl-4- N-methyl-N-(3,4-dihydro-2H-benzothιopyran-4-yl amιnolpiperidine A flask under nitrogen was charged sequentially with (S)-l-methylamιno-3,4-dihydro- 2H-benzothiopyran (1 0 g, 5 4 mmol), 15 ml of methanol, 0 60 ml of ethanolic ΗC1, Ν-benzyl- 4-pipeπdone (0 90g, 4 85 mmol) and sodium cyanoborohydride (0 47 g, 7 48 mmol) and stirred overnight at ambient temperature An additional 300 mg of sodium cyanoborohydride was added and stirring continued for two days TLC (silica gel, 1 10 CΗ3OΗ CH 2 C1 2 ) now indicated only a trace of the piperidone After concentration in vacuo, the residue was partitioned between sodium bicarbonate solution and ethyl acetate and dried (MgSO 4 ) Removal of solvent left 1 05 g of a yellow oil This was heated in a Kugelrohr at 80 °C and 90 mtorr to remove volatile, leaving 1 Og, TLC (ibid) R 0 55, 'HΝMR (300 MHz, CDC13) δ 3 49 (s, 2H, ArCH2Ν) This material was dissolved in ether and was treated with an ether solution containing 1 0 g of maleic acid The resulting solid was collected and dried in vacuo to yield 1 15 g, mp 156 5-157 5 °C EA Calcd for C 2 2Η 28 N 2 S-2C 4 Η4θ 4 C, 61 63, H, 6 21, N, 4 79, Found C, 61.08, H, 6 15, N, 4 75 Example 18 (S -l-Benzyl-4-[N-methyl-N-(3,4-dihydro-2H-benzopyran-4-yl amino " |piperidine As described in Example W, (S)-l-methylamino-3,4-dihydro-2H-benzopyran (1 0 g, 6 0 mmol) was reacted with Ν-benzyl-4-pιperidone (1 12 g, 5 97 mmol) When TLC (silica gel, 1.10 CΗ3OΗ CH 2 C1 ) indicated only a trace of the piperidone, the reaction was worked up as described Removal of solvent left 2 1 g of a yellow oil This was heated in a Kugelrohr at 100 °C and 90 mtorr to remove volatile, leaving 1 4 g, TLC (ibid) R 0 58 This base, 1 35 g, was dissolved in 12 ml of ether - ethanol (1 1) and was treated with an ether solution containing 0 95 g of maleic acid The resulting solid was collected and dried in vacuo to yield 1 82 g, mp 183-183 5 °C EA Calcd for C 2 2H 28 N 2 O 2C 4 H 4 O 4 -0 2H2O C, 62 97, H, 6 41, N, 4 90, Found C, 62 74, H, 6 27, N, 4 77 Example 19 (S -l-Benzyl-4-[ " N-methyl-N-π,2,3,4-tetrahvdro-l-naphthalenyl)amino]pιperidιne As described in Method A, (S)-l-methylamino-l,2,3,4-tetrahydronapthalene (0 40 g, 2 50 mmol) was reacted with Ν-benzy-4-piperidone (0 47 g, 0 46 mmol) to give 0 78 g This material was purified by column chromatography on silica gel, eluting with ether hexane (1 2) to yield 0 56 g of a yellow oil, homogeneous by TLC (silica gel, same solvent) R 0 22, [α] D 24 + 49° (c = 0 76, methanol), 'NMR (300 MHz, CDC1,) δ 2 12 (s, 3H, N-CH 5 ), 3 50 (s, 2Η, ArCH,) EA Calcd for C23Η30N2 C, 82 58, H, 9 04, N, 8 37, Found C, 82 25, H, 8 80, N, 8 21 This base, 0 51 g, was dissolved in 5 ml of ethanol and was treated with 20 ml of an ether solution saturated with maleic acid The resulting solid was collected and dried in vacuo to yield 0 85 g, mp 186-187 °C EA Calcd for C^ttmNa 2C 4 H 4 O 4 C, 65 71, H, 6 76, N, 4 94, Found C, 65 66, H, 6 75, N, 5 01 Preparation of Starting Materials The starting materials for the Examples above are either commercially available or are readily prepared by standard methods from known materials For example the following reactions are illustrations but not limitations of the preparation of the starting materials used in the above reactions Method A (S)-l-tert-Butoxycarbonyl-4-[N-methyl-N-(1.2,3.4-tetrahydro-l-napthalenyl)amino]piperidine A flask equipped under a nitrogen atmosphere was charged sequentially with (S)-l- methylamino-l,2,3,4-tetrahydronapthalene (Method B) (3 39 g , 21 0 mol) in 90 ml THF, methanol (45 ml), tert-butyl 4-oxo-l -piperidine carboxyate (4 61 g, 23 1 mmol), ΝaBH 3 CΝ (2 01 g, 32 mmol) and acetic acid (0 47 ml, 8 2 mmol) After stirring overnight at ambient temperature, the reaction mixture was concentrated in vacuo The residue was treated with aqueous sodium bicarbonate and extracted with ethyl acetate and dried Removal of solvent in vacuo gave 8 37 g of a yellow oil This material was purified by column chromatography on silica gel with diethyl ether elution to give 5 01 g of a viscous yellow oil TLC R f 0 50 (1 3 ether hexane), NMR (CDC1 3 ) 1 49 (s, 9H), 2.12 (s, 3H), m/z 345 (M+H) + Method B (SVl-Methylamιno-l,2.3.4-tetrahydronapthalene A flask under a nitrogen atmosphere was charged with lithium aluminium hydride (2 55 g, 67 2 mmol), and 38 ml of THF (S)-N-Formyl-l-(l,2,3,4-tetrahydro)naphthylamιne (Method C) (4 07 g, 23 2 mmol), in THF (35 ml) was added dropwise The reaction mixture was warmed to reflux for four hours and stirred overnight at ambient temperature The reaction mixture was cooled to 0 °C and was treated sequentially dropwise with water (2 6 ml), aqueous sodium hydroxide solution (15%, 2 6 ml) and water (7 8 ml) to form a suspension This mixture was filtered, washed with THF and the filtrate was dried Removal of solvent left an oil, 3 87 g Kugelrohr distillation gave the title compound, 3 50 g, bp (air bath temperature) 65-72 °C at 25 mtorr TLC R f 0 22 (9 1 chloroform methanol), [α] D 23 +1 1 (c, 1 05 in methanol), ΝMR (CDC1 3 ) 2 44 (s, 3H), 3 60-3 73 (m, IH), m z 176 (M-H) Method C (S)-N-Formyl-l-fl,2,3,4-tetrahydro)naphthylamιne A flask under a nitrogen atmosphere was charged with formic acid (98%, 1 43 ml, 38 mmol) and anhydrous THF (75 ml) Carbonyldnmidazole (6 16 g, 38 mmol), was added portionwise (gas evolution) and the reaction mixture was stirred for 20 minutes S-(+)-l- (l,2,3,4-Tetrahydro)naphthylamιne (3 71 g, 25 2 mmol) in 100 ml of THF was added dropwise over 20 minutes The mixture was stirred overnight, poured into water (250 ml) and extracted with three portions of ethyl acetate This organic extract was washed with five portions of water and was then dried Removal of solvent gave 4 06 g of a white solid TLC R f 0 67 (9 1, chloroform methanol), ΝMR (CDCU) 5 26-5 33 (m, IH), 8 28 (s, IH), m/z 174 (M-H) Method D (S)-l-Propιonyl-4-[N-methyl-N-(l,2,3,4-tetrahydro-l-napthalenyl)amιno]pιpeπdιne A flask under a nitrogen atmosphere was charged with (S)-4-[N-methyl-N-(l, 2,3,4- tetrahydro-l-napthalenyl)amιno]pιpeπdιne (Example 4) (0 67 g, 2 74 mmol) in DCM (10 ml) Triethylamine, (0 28 ml, 3 2 mmol) was added Propionyl chloride (0 28 ml, 3 2 mmol), in DCM (3 ml) was then added dropwise This mixture was concentrated in vacuo and the residue was treated with aqueous potassium carbonate and extracted with ethyl acetate which was dried (MgSO 4 ) Removal of solvent gave 0 66 g TLC (ethyl acetate) R f 0 60, ΝMR (CDC1 3 ) 1 13-1 21 (t, 3H), 2 27-2 40 (q, 2H), m/z 301 (M+H) + Method E (SVl-Isovaleroyl-4-[N-methyl-N-(l,2,3,4-tetrahydro-l-napthalenyl amino]piperidine Following the procedure of Method D (S)-4-[N-methyl-N-(l,2,3,4-tetrahydro-l- napthalenyl)amino]piperidιne (Example 4) (0 82 g (3 36 mmol) was reacted with isovaleroyl chloride (0 49 ml, 4 0 mmol) to give 0 92 g of a yellow oil TLC, R f 0 77 (ethyl acetate), ΝMR (CDC1 3 ) 0 97-1 04 (m, 6H), 2 16 (s, 3H), m z 329 (M + H) + Method F 1 -Chloro- 1,2.3.4-tetrahydronaphthalene A flask under a nitrogen atmosphere was charged with 1,2,3,4-tetrahydro-l-naphthol (34 3 g, 0 23 mol) in dry diethyl ether (420 ml) Pyridine (4 7 ml) was added and the flask was cooled to 16 °C in a bath of water and ice A solution of thionyl chloride (50 7 ml, 0 70 mol) in ether (140 ml) was then added dropwise in 25 minutes and stirring continued overnight while allowing the bath to warm to ambient temperature The reaction mixture was then poured into cold brine (400 g ice and 800 ml brine) and the organic phase was separated The aqueous phase was extracted with diethyl ether (2x150 ml) and the combined organic extract was dried with sodium sulphate Filtration and removal of solvent in vacuo gave the title compound (36 9 g) as an oil This material was used without further purification Method G 4-Chloro-3,4-dihydro-2H-benzothιopyran A flask equipped with a condenser bearing a nitrogen inlet was charged with 4- hydroxy-3,4-dihydro-2H-benzothiopyran (2 1 g, 12 63 mmol) in dry diethyl ether (40 ml) Pyridine (1 0 ml) was added A solution of thionyl chloride (6 5 ml, 89 0 mmol) in ether (20 ml) was then added dropwise in 30 minutes and stirring continued overnight The reaction mixture was then poured into ice/water (100 gm) and the organic phase was separated The aqueous layer was again extracted with ether and the combined extract was washed with brine and dried with magnesium sulphate Filtration and removal of solvent gave a yellow oil (2 35 g) ΝMR (CDCI 3 ) 2.32-2 42 (m, 1Η), 2 57-2 65 (m, 1Η), 2 85-2 92 (m, 1Η), 3 57-3 68 (t, 1Η), 5 31-5 33 (m, 1Η), 7 01-7 29 (m, 4Η) This material was used without further purification Method H 4-Chloro-3.4-dihydro-2H-benzopyran A flask equipped with a condenser protected with anhydrous calcium sulphate (8 mesh), was charged with 4-hydroxy-3,4-dιhydro-2H-benzopyran (2 1 g, 13 78 mmol) in dry diethyl ether (40 ml) Pyridine (0 3 ml) was added A solution of thionyl chloride (5 5 ml, 74 4 mmol) in ether (15 ml) was then added dropwise in 10 minutes and stirring continued overnight The reaction mixture was then poured into ice/water (50 g) and diluted with ether (100 ml) The organic phase was separated, washed with brine and dried with sodium sulphate Filtration and removal of solvent in vacuo using a rotary evaporator and water bath at 35 °C gave a yellow oil (2 98 g) TLC (9 1 hexane ethyl acetate), R 0 56, NMR (CDC1 3 ) 2 23-2 31 (m, 1Η), 2 41-2 51 (m, 1Η), 4 28-4 34 (m, 1Η), 4 41-4 49 (m, 1Η), 5 21-5 23 (1Η), 6 80-6 83 (d, 1Η), 6 87-6 92 (t, 1Η), 7 16-7 21 (t, 1Η), 7 25-7 29 (d, 1Η) This material was used without further purification Method I (S -/V-Formyl-4-amino-3,4-dihydro-2H-benzothiopyran S-(-)-4-Amino-3,4-dihydro-2H-benzothιopyran (6 0 g, 35 9 mmol) was formylated following the procedure for the above naphthylamine The TΗF was removed in vacuo and the residue was partitioned between ethyl acetate and IN ΗC1 and the ethyl acetate extract was washed with water and dried Removal of solvent afforded 5 40 g, mp 140-141 °C, [α]o 23 - 192° (c = 0 406, methanol), homogeneous by TLC R 0 65 (1 20, methanol methylene chloride), 'ΗNMR (300 MHz, CDC13) δ 8 21 (s, IH, CHO) Method J (S -N-Formyl-4-amino-3,4-dihydro-2H-benzopyran S-(-)-4-Amιno-3,4-dihydro-2H-benzopyran (5 0 g, 33 5 mmol) was formylated following the procedure for the above naphthylamine The TΗF was removed in vacuo and the residue was partitioned between ethyl acetate and IN ΗC1 and the ethyl acetate extract was washed with water and dried Removal of solvent afforded 4 13 g of a white solid, homogeneous by TLC R f 0 66 (1 20, methanol methylene chloride) [α] D 23 -165° (c = 0 76, methanol), J Η MR (300 MHz, CDC13) δ 8 23 (s, IH, CHO) Method K (S)-l-Methylamino-3,4-dihydro-2H-benzothiopyran A flask under nitrogen was charged with lithium aluminum hydride (4.0 g, 105 mmol) and 40 ml dry TΗF. (S)-N-Formyl-4-amino-3,4-dihydro-2H-benzothiopyran (5.3 g, 27.6 mmol) in 50 ml dry TΗF was added dropwise and the reaction was stirred overnight and then heated to reflux for 4 hr. The cooled reaction mixture was treated dropwise with saturated sodium sulphate and the solid was removed by filtration. The filtrate was concentrated in vacuo and the residue was partitioned between ether and water and the organic extract was dried. Filtration and evaporation afforded a residual oil, 4.40 g. Kugelrohr distillation gave 4.30 g of a yellow oil, bp 80 °C (air bath temperature) at 55 mtorr; 'ΗΝMR (300 MHz, CDC13) δ 2.52 (s, 3H, ΝCH3). Method L (S>l-Methylamino-3.4-dihydro-2H-benzopyran (S)-N-Formyl-4-amino-3,4-dihydro-2H-benzopyran (4.13 g, 23.0 mmol) was reduced with lithium aluminum hydride following the procedure for the above benzothiopyran. This afforded an oil, 4.40 g. Kugelrohr distillation gave 4.30 g of a yellow oil, bp 80 °C (air bath temperature) at 55 mtorr; [α] D 23 -115° (c = 0.51, methanol); 'ΗΝMR (300 MHz, CDC13) δ 2.52 (s, 3H, ΝCH3). Method M (SVl-tert-Butoxycarbonyl-4-[N-methyl-N-f3,4-dihydro-2H-benzothiopyran-4- yDaminolpiperidine (S)-l-Methylamino-3,4-dihydro-2H-benzothiopyran (2.90 g, 16.0 mmol) was reacted with tert-butyl 4-oxo-l -piperidine carboxylate (3.00 g, 15.0 mmol) as described for the aminonaphthalene above to give a viscous oil. This material was heated in a Kugelrohr (90- 100 °C at 100 mtorr) to remove unreacted amine, leaving a residual oil of 2.9 g, homogeneous by TLC: Rf 0.15 (ethyl acetate). Method Ν (S -l-Propionyl-4-[N-methyl-N-(3.4-dihydro-2H-benzothiopyran-4-yl amino]piperidine (S)-4-[N-methyl-N-(3,4-dihydro-2H-benzothiopyran-4-yl)amino]piperidine was reacted with propionyl chloride as described for the aminonaphthalene to give 0.88 g of an oil. TLC (silica gel, diethyl ether) indicated a major (Rf 0.25) and a minor (Rf 0.80) component. Purification by column chromatography on silica gel, eluting with diethyl ether, yielded 0.72 g of the lower R f component; m/z 319 (M + H) + ; 'HNMR (300 MHz, CDC13) δ 1.25 (t, 3H, CH2CH3), 2.26 (q, 2Η, CH2CH3). Example 20 Following conventional procedures well known in the pharmaceutical art the following representative pharmaceutical dosage forms containing a compound of formula (I) can be prepared: (a) Tablet mg/tablet Compound of formula (I) 50.0 Mannitol, USP 223.75 Croscarmellose sodium 60 Maize starch 15.0 Hydroxypropylmethylcellulose (HPMC), USP 2.25 Magnesium stearate 3.0 (b) Capsule mg/capsule Compound of formula (I) 10.0 Mannitol, USP 488.5 Croscarmellose sodium 15.0 Magnesium stearate 1.5 (c) Injection For intravenous administration, a compound of formula (I) is dissolved in an isotonic sterile solution (5 mg/ml).

Claims: CLAIMS: Any compound of formula (I): (I) wherein: R 1 is Ci-βalkyl, C 3 -6alkenyl, C 3 -f,alkynyl or phenylC 2 . 6 alkyl; R 2 is hydrogen, Cι.«alkyl, C 3 .8alkenyl or C3- 8 alkynyl; wherein said C]. 8 alkyl, C 3 . 8 alkenyl or C 3 _ x alkynyl are optionally substituted with one or more groups selected from halo, nitro, cyano, hydroxy, trifluoromethyl, trifluoromethoxy, amino, carboxy, carbamoyl, mercapto, sulphamoyl, Ci-βalkoxy, Cι. 6 alkanoyl, Ci-βalkoxycarbonyl, Cι. 6 alkanoyloxy, N-(Cι- 6 alkyl)amino, NN-(Cι-6alkyι) 2 amino, Cι. 6 alkanoylamino, N-(Cι-f,alkyl)carbamoyl, NN-(Cι-6alkyl) 2 carbamoyl, Cι. 6 alkoxyCι-6alkoxy, Cι_6alkylS(O) a wherein a is 0, 1 or 2, N-(Cι. 6 alkyl)sulphamoyl or NN- (Cι. 6 alkyl) 2 sulphamoyl, optionally substituted aryl, optionally substituted heterocycle, optionally substituted heteroaryl, optionally substituted C 3 -ι 2 cycloalkyl, or a group of the formula: F-(CH 2 ) X- (IA) wherein F is optionally substituted aryl, optionally substituted carbon linked heteroaryl, optionally substituted carbon-linked heterocycle or optionally substituted C 3 .ι 2 cycloalkyl, p is 0, 1, 2, 3, 4, 5 or 6 and X is a linking group and is selected from -C(O)-, -O-, -OC(O)-, -S-, - S(O)-, -S(O) 2 -, -S(O) 2 ΝR 4 -, -NR 4 S(O) 2 -, -NR 4 -, -C(O)O-, -C(O)NR 4 -, -NR 4 C(O)-, - OC(O)NR 4 -, -C(O)NR 4 SO 2 -, -NR 4 C(O)O-, -C(S)NR 4 - or -NR 4 C(S)-, wherein R 4 is selected from hydrogen or Cι_ alkyl; wherein any aryl, heteroaryl, heterocycle or C 3 -ι 2 cycloalkyl is optionally substituted on a ring carbon with one or more groups selected from halo, nitro, cyano, hydroxy, trifluoromethyl, trifluoromethoxy, amino, carboxy, carbamoyl, mercapto, sulphamoyl, Cι_ 6 alkyl, C 2 -6alkenyl, C . 6 alkynyl, Cι. 6 alkoxy, C]. 6 alkanoyl, Ci 6 alkanoyloxy, N-(Cι 6 alkyl)amino, NN-(Cι-6alkyl) 2 amino, Cι. 6 alkanoylamino, N-(C]. 6 alkyl)carbamoyl, NN-(Cι.6alkyl) 2 carbamoyl, Cι- 6 alkylS(O) a wherein a is 0, 1 or 2, Ci-ealkoxycarbonyl, N-(Cι. 6 alkyl)sulphamoyl, N,N-(Cι. 6 alkyl) 2 sulphamoyl or phenylCi ealkyl and a heterocycle or heteroaryl containing an -ΝH- group may be optionally substituted on a ring nitrogen with Ci ealkyl, C 2 _6alkenyl, C 2 6 alkynyl, Cι. 6 alkanoyl, Cι-6alkylsulphonyl or phenylCi ealkyl, R 3 is selected from halo, hydroxy, Ci-βalkyl, 6 alkoxy, haloCι_6alkyl, cyano, nitro or C 2 . 6 alkenyl, R 4 is Cι. 6 alkyl, X is selected from -CH 2 -, -O- or -S-, r is 0, 1 , 2, 3 or 4, wherein each R 3 moiety may be the same or different, and s is 0, 1, 2, or 3 wherein each R 4 moiety may be the same or different, or a pharmaceutically-acceptable salt or an in v/vo-hydrolysable ester, amide or carbamate of any foregoing compound 2 A compound according to Claim 1 , wherein R 1 is Ci-βalkyl, R 2 is hydrogen or Cj.salkyl wherein said Cι. 8 alkyl is optionally substituted, r is O, s is 0, and X is selected from CH 2 , S or O, or a pharmaceutically-acceptable salt or an in v/vo-hydrolysable ester, amide or carbamate thereof 3 A compound according to Claim 2, wherein R 1 is C alkyl, R 2 is hydrogen or C]. 6 alkyl, or a pharmaceutically-acceptable salt or an /// v/vo-hydrolysable ester, amide or carbamate thereof A compound according to Claim 3, wherein R 1 is methyl, R 2 is selected from hydrogen, methyl, n-propyl or isoamyl, or a pharmaceutically-acceptable salt or an in v/vo-hydrolysable ester, amide or carbamate thereof 5 A compound according to Claim 1, selected from l-Methyl-4-[N-methyl-N-(l,2,3,4-tetrahydro-l-naphthalenyl)amιno]pιpeπdιne, l-Methyl-4-[N-methyl-N-(3,4-dιhydro-2H-benzothιopyran-4-yl)amιno]pιpeπdιne, l-Methyl-4-[N-methyl-N-(3,4-dιhydro-2H-benzopyran-4-yl)amιno]pιpeπdιne, (S)-4-[N-methyl-N-(l,2,3,4-tetrahydro-l-napthalenyl)amιno]pιpeπdιne, (S)- 1 -//-Propyl-4-[N-methyl-N-( 1 ,2,3 ,4-tetrahydro- 1 -napthalenyl)amιno]pιpeπdιne, (S)-l-Isoamyl-4-[N-methyl-N-(l, 2,3, 4-tetrahydro-l -napthalenyl) aminojpiperidine, (S)- 1 -Methyl-4-[N-methyl-N-( 1 ,2,3 ,4-tetrahydro- 1 -napthalenyl) aminojpiperidine, l-Methyl-4-[N-methyl-N-(l,2,3,4-tetrahydro-l-naphthalenyl)amιno]pιpeπdιne bismaleate salt, l-Methyl-4-[N-methyl-N-(3,4-dιhydro-2H-benzothιopyran-4-yl)amιnojpιpeπdιne bismaleate salt, 1 -Methyl-4-[N-methyl-N-(3,4-dιhydro-2H-benzopyran-4-yl)amιnojpιpeπdme bismaleate salt, (S)- 1 -«-Propyl-4-[N-methyl-N-( 1 ,2,3 ,4-tetrahydro- 1 -napthalenyl) aminojpiperidine bismaleate salt, (S)-l-Isoamyl-4-[N-methyl-N-(l, 2,3, 4-tetrahydro-l -napthalenyl) aminojpiperidine bismaleate salt, (S)-l-Methyl-4-[N-methyl-N-(l,2,3,4-tetrahydro-l-napthalenyl)amιnojpιpeπdιne bismaleate salt, (S)-l-Methyl-4-[N-methyl-N-(3,4-dιhydro-2H-benzothιopyran-4-yl)amιno]pιpeπdme, (S)-4-[N-methyl-N-(3,4-dιhydro-2H-benzothιopyran-4-yl)amιno]pιpeπdιne, (S)-l-n-Propyl-4-[N-methyl-N-(3,4-dιhydro-2H-benzothιopyran-4-yl)amιnojpιpeπdιne, (S)-l-Benzyl-4-[N-methyl-N-(3,4-dιhydro-2H-benzothιopyran-4-yl)amιno]pιpeπdιne, (S)- 1 -Benzyl-4-[N-methyl-N-(3 ,4-dιhydro-2H-benzopyran-4-yl)amιno]pιpeπdιne, and (S)-l-Benzyl-4-[N-methyl-N-(l,2,3,4-tetrahydro-l-naphthalenyl)amιnojpιpeπdιne 6 A process for preparing a compound of formula (I) according to Claim 1, or a pharmaceutically-acceptable salt or an m v/vo-hydrolysable ester, amide or carbamate thereof which process comprises a) reacting a compound of formula (II) (II) wherein L is a leaving group, with a compound of formula (III) (HI) wherein R , 2a a is R , except hydrogen or R a is an amino protecting group, or b) for compounds of formula (I) wherein R 2 is hydrogen, reacting a compound of formula (IV) wherein Pg is an amino protecting group, with a compound of formula (V) R'-L (V) wherein L is a leaving group, or c) for a compound of formula (I) wherein R 1 is not hydrogen, by reacting a compound of formula (VI) with a compound of formula (VII): R 2 -L (VII) wherein L is a leaving group; or d) reacting a compound of formula (VIII): with a compound of formula (IX): wherein R > 2a a i ■ s as defined above; and L is a leaving group; or e) reacting a compound of formula (X): (X) with a compound of formula (III); or f) for compounds of formula (I) wherein R 1 is Cι_ 6 alkyl or phenylC^ealkyl; reacting a compound of formula (IV) with a compound of formula (XI): O K^H (XI) wherein K is hydrogen, C1.5a.kyl, or phenylCi-salkyl; or g) reacting a compound of formula (VIII) with a compound of formula (XII): (XII) wherein R 2a is as defined above; or h) for a compound of formula (I) wherein R 2 is optionally substituted C]. 8 alkyl; by reacting a compound of formula (VI) with a compound of formula (XIII): O R H (XIII) wherein R b is hydrogen or optionally substituted Cι_ alkyl; or i) reducing a compound of formula (XIV): wherein R a is as defined above; or j) for a compound of formula (I) wherein R 2 is optionally substituted Cι. 8 alkyl; by reducing a compound of formula (XV): wherein R is as defined above; or k) for compounds of formula (I) wherein R is hydrogen; by deprotection of a compound of formula (XVI): wherein Pg is am amine protecting group; and thereafter if necessary: converting a compound of the formula (I) into another compound of the formula (I); removing any protecting groups; or forming a pharmaceutically-acceptable salt or in v/ ' vo-hydrolysable ester, amide or carbamate. 7. A pharmaceutical composition comprising a compound of the formula (I) according to Claim 1, a pharmaceutically-acceptable salt or an in v/ ' vo-hydrolysable ester, amide or carbamate thereof, in association with a pharmaceutically-acceptable excipient or carrier. 8 A compound of formula (I) according to Claim 1, a pharmaceutically-acceptable salt or an in v/vo-hydrolysable ester, amide or carbamate thereof, for use as a medicament to inhibit the [ 3 H]-emopamιl binding site in a warm-blooded animal 9 The use of a compound of formula (I) according to Claim 1, or a pharmaceutically- acceptable salt or an in v/vo-hydrolysable ester, amide or carbamate thereof, in the manufacture of a medicament for use in the inhibition of the [ 3 H]-emopamιl binding site in a warm-blooded animal 10 A method of treating neurological disorders comprising administering to a subject suffering therefrom a therapeutically-effective amount of a compound of the formula (I) according to Claim 1, a pharmaceutically-acceptable salt or an /// v/vo-hydrolysable ester, amide or carbamate thereof 11 The method according to Claim 10, for treating stroke, head trauma, transient cerebral ischaemic attack, and chronic neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, diabetic neuropathy, amyotrophic lateral sclerosis, multiple sclerosis and AIDS-related dementia 12 The method according to Claim 10, for treating neurological disorders treatable by inhibiting the [ 3 Hj-emopamιl binding site

Inventors: MCLAREN CHARLES DAVID, SIMON-BIERENBAUM RICHARD ELLIO, WARAWA EDWARD JOHN, MCLAREN, CHARLES, DAVID, SIMON-BIERENBAUM, RICHARD, ELLIOT, WARAWA, EDWARD, JOHN
Applicants: ASTRAZENECA UK LTD, MCLAREN CHARLES DAVID, SIMON BIERENBAUM RICHARD ELLIO, WARAWA EDWARD JOHN, ASTRAZENECA UK LIMITED, MCLAREN, CHARLES, DAVID, SIMON-BIERENBAUM, RICHARD, ELLIOT, WARAWA, EDWARD, JOHN
Application year: 2000
Main classification: C07D405
IPC codes: A61K31, A61P3, A61P9, A61P25, A61P31, C07D211, C07D405, C07D409