Title of Invention	MYCOBACTERIAL INHIBITORS
Abstract	This invention relates to a medicament comprising pyrroline-dione or pyrrolidine-dione compounds of general formula (I) wherein is 0 is used for the treatment of mycobacterial disease such as M.tuberculosis, M.bovis, M.avium and particularly tuberculosis or pharmaceutically acceptable salt or solvate thereof.

Full Text

The present invention relates to a medicament for use in the treatment of mycobacterial diseases, particularly those diseases caused by pathogenic mycobacteria such as Mycobacterium tuberculosis, M. bovis, M. avium and M. marinum. Tuberculosis is still a major public health problem affecting nearly all parts of the world. Based on skin test reactivity it has been estimated that about one-third of the world"s population, i.e., 1.7 billion people, are infected with Mycobacterium tuberculosis. Despite the availability of effective chemotherapies, it is responsible for three million deaths and fiom eight to ten million new cases annually and thus remains the leading cause of death world-wide due to a single infectious agent; 26% of all preventable deaths, J% of all deaths. According to the World Health Organisation, 450,000 deaths per year due to tuberculosis in developing countries occur in children under fifteen years of age, and the disease mostly affects the younger, more productive adults. There are five fiont-line drugs known to be highly effective against M. tuberculosis and five second-line drugs that can be used when resistance to one or more of the front-line drugs is detected. The preferred mode of treatment for tuberculosis is the short course chemother^y in which there are two phases. The fu^t phase consists of a daily regimen for two months with isoniazid (300 mg), rifampicin (600 mg), pyrazinamide (3 g) and ethambutol {1.5 g). The second ptwse or the continuation ph^e consiate of a daily regimen for the next four months with isoniazid and rifampicin. Although infection with drug-sensitive strains of M. tuberculosis can be effectively cured with the short course chemotherapy, the cure rate is very poor in most countries due to poor compliance, which is reflective of the long duration of therapy. The situation is further complicated by the rapid emergence of multi-drug resistant tuberculosis (MDR-TB) strains. For example, in certain populations, the incidence of resistance to isoniazid is as high as 26% and the resistance to rifampicin is about 15%. Prior to 1984, about 10% of tubercle bacilli isolated fiom patients in the United States were resistant to at least one single mycobacterial drug. By 1984, this figure had risen to 52%, of which over half (32%) were resistant to more than one drug (MDR-TB). Ten percent of the recorded MDR-TB cases have occurred in previously healthy people whose mortality rate - 70 to 90% - has been nearly tiie same as that of jmrnunosuppressed individuals with MDR-TB. TTie number of cases of MDR-TB has doubled since 1984 and in many of them the tubercle bacilli are resistant to both isoniazid and rifampicin. The median interval between diagnosis of MDR-TB and death is only four weeks and therefore MDR-TB demands a shorter response time between dia^osis and appropriate commencement of treatment. However, MDR-TB is difficult to treat as such since most patients do not respond very well to the second-line drugs and the cost of alternate treatment procedures, including hospitalisation and possibly surgery, increases the cost to as much as ten times the cost of traditional treatment. Thus, there is an urgent medical need to identify new drugs with significant therapeutic activity against single- or multiple-drug resistant strains of M. tuberculosis and with pluirmacokiuetic properties that permit reduced dosing which will in tum encourage better compliance. Ce alkoxycarbonjd, piperidyl, piperazinyl and morpholinyl, or a group (CH2)yCONH-R^ where y is an integer from 1 lo 6 and R" represents a phenyl group optionally substituted by one or more substituents selected from amino, nitro, hydroxyl, carboxyl, halogen, trifluoromethyl, Cj-Cs alkyl, C|-C6 alkoxy, Ci-Ce alkoxycarbonyl. Piperidyl, piperazinyl and morpholinyl; and either R represents a hydrogen atom or a Ci-Cg alkyl group, or R together with R^ represents a carbon-carbon single bond provided that x is 0, or R^ together with R^ represents a group =CH2, R^ represents a hydrogen atom or is linked to R as defined above, and R"* represents a hydrogen atom or a Ci-Cg alkyl group; or a Ci-Cjo alkylamino group optionally substituted by a di(Ci-C6 aU^l)amino substituent group; or an anilino group optionally substituted in the aromatic ring by one or more substituents selected from amino, nitro, hydroxyl, carboxyl, halogen, trifluoromethyl, Ci-Ce alkyl, Ci-Cft alkoxy, Ci-Cs alkoxycarbonyl, piperidyl, piperazinyl and morpholinyl; or a group-SCH2CH20H, -SCH2CH2NH2, -SCH2CH2(NH2X:02H or -SCHjCHaNHCO-R^ where R^ represents a Ci-Cjoalkyl or Cj-Cg cycloalkyl group, or a phenyl group optionally substituted by one or more substituents selected from amino, nitro, hydroxj^, carboxyl, halogen, trifluoromethyl, Ci-Cs alkyl, CpCe alkoxy, Ci-Ce alkoxycarbonyl, piperidyl, piperazinjd and morpholinyl;or R* is linked to R^ as defined above;or R , R"* and R together represent a phenyl group; with the provisos that: (i) R , R , R and R do not each simultaneously represent a hydrogen atom, (ii) when x is 0, R" represents a 4-fluorophenyl group and R* represents a hydrogen atom, then R^ and R^ do not together represent a carbon-carbon single bond, and (iii) when x is 0, R" represents a 4-fluorophenyl group and R~ and R^ both represent hydrogen atom, then R does not represent an aniline, 4-chloroanilino, 2,6-dichloroamlino,3,4-dichloroanilino, 2,5-dichloroanilino, 3-chloro-4-fluoroaniiino or 4-fluoroanilino group; or a pharaiaceutically acceptable salt or solvate thereof, in the manufacture of a medicament for use in the treatment of a mycobacterial disease, in particular mberculosis. In the context of the present specification, unless otherwise stated, an alkyl (substituent) group or an alfcjd moiety in an alkoxy or alkoxycarbon>d substituent group may be linear or branched. Preferably R" in formula (I) represents a hydrogen atom, or a Ci-Cis, more preferably Cj-Cio aikyi or myrtan>i group, or a phenyl or benzjd group optionally substituted in the aromatic ring by one to four, particularly one or two, substituents selected from amino, nitro, hydrox>^, carboxyl, halogen (e.g. fluorine, chlorine or bromine), trifluoromethyl, C|-C4 alkyl {e.g. methyl, ethyl, propjd, isoprop>1 or butyl), Ci-C4 alkoxy (e.g. methoxy, ethoxy, propoxy, or butoxy), C1-C4 alkoxycarbonyl (e.g. methoxycarbonyl, ethoxycartronyl, propoxycarbonyl or butoxycarbonyl), piperidyl, piperazinyl and morpholinjd, or a group (CH2)yCONH-R^ where y is an intega" 1, 2, 3 or 4 and R represents a phenyl group optionally substituted by one to four, particularly one or two, substituents selected from amino, nitro, hydroxyl, carboxjd, halogen (e.g. fluorine, chlorine or bromine), trifluoromethyl, C1-C4 alkyl (e.g. methyl, ethyl, propyl, isopropyl or butyl), C1-C4 alkoxy (e.g. methoxy, ethoxy, propoxy, or butoxy), C1-C4 alkoxycarbonjd (e.g.methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl or butoxycarbonyl), piperidyl, piperazmyl and moipholinyl. The group R" especially represents a hydrogen atom, or a C4-C10 alkyl (e.g. butyl, pentyl, hexyl, hqjtyl, octyl, nonyl or decyl) or myrtanyl group, or a phenyl group substituted by a piperidyl substituent group, or a group (CH2)yCONH-R^ where y is 1 or 2 and R represents a phenyl group substituted by a piperidyl substituent group. Preferably R represents a hydrogen atom or a C1-C4 alkyl, particularly methyl group, or R together with R represents a carbon-carbon single bond provided that x is 0, or R together with R* represents a group =CH2. R* preferably represents a hydrogen atom or a C1-C4 alkyl group (e.g. methyl, ethyl, propjd or butyl); or a C2-C10 alkylamino group optionally substituted by a dJ(Ci-C6 alkyl)amino, especially di(Ci-C4 alkylamino, substituent group; or an aniljno group optionally substituted in the aromatic ring by one to four, particularly one or two. substituents selected from amino, nitro, hydroxyl, caiboxyl, halogen (e.g. fluorine, chlorine or bromine), trifluoromethyl, C1-C4 alky! (e.g. methyl, ethyl, propyl, isopropyl or butyl), C1-C4 alkoxy (e.g. methoxy, ethoxy, propoxy, or butoxy), C1-C4 alkoxycarbonyl (e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl or butoxycarbonyl), piperidyl, piperazinyl and morpholinyl; or a group -SCH2CH2OH, -SCH2CH2NH2, -SCH2CH2(NH2)C02H or -SCH2CH2NHCO-R^ where R^ represents a C5-Cio alkyl or Cj-Ct cycloalkyl groi^, or a phenyl group optioimlly substituted by one or more substituents selected from amino, nitro, hydroxyl, carboxyl, halogen {e.g. fluorine, chlorine or bromine), trifluoromethyl, C1-C4 alkyl (e.g. methyl, ethyl, propyl, isopropyl or butyl), C3-C6 alkoxy (e.g. propoxy, butoxy, pentoxy or hexyloxy), C[-C4 alkoxycarbonyl (e.g. methoxycariwnyl, ethoxycatbonyl, propoxycaibonyl or butoxycarbonyl), piperidyl, piperazinyl and morpholinyl; or R is linked to R as defined above. It is preferred that R^ represents a hydrogen atom, a methyl or ethyl group, a C2-C10 alkylamino group optionally substituted by a di(C2-C4 alkyl)amino substituent group, an aniline group substituted by a piperidyl substituent group,-SCH2CH20H,-SCH2CH2NH2,-SCH2CH2(NH2)C02H, -SCH2CH2NHCO-R^ where R^ represents a C7 alkyl, cyclopropyl, cyclopaityl or cyclohexj^ group or a phenyl group substituted by a nitro, C1-C4 alkyl or C3-C6 alkoxy substituent group, or R is linked to R^ as defined above. Particularly preferred compotmds of formula (I) include: l-Decylpyrrolidine-2,5-dione, l-((6,6-Dimethylbicyclo[3,l,l]hept-3-yl)methyl)-3-methyl-3-pyrroline-2,5-dione, 3-Meth>i-l-nonyl-3-pyrroline-2,5-dione, 5 3-Meth>1ene-l -nonylpyrroUdine-2,5-dione, 3-Methyl-l-octyl-3-pyrroline-2,5-dioiie, 3-Meth>iene-l -octjipyirolidine-2,5-dione, (4-(3-methyl-2,5-dioxo-3-pyrrolinyl)phenyl)piperidine, 1 -Oc^-3-pyrroline-2,5-dione, l-Decyi-3-pyrroline-2,5-dione, 1 -Nonyl-3-pyrroline-2,5-dione, 1 -BotyJ-3-pyiioIiiie-2,5-dione, l-Hexyl-3-pyrroluie-2,5-dione, l-(4-Piperidylphenyl)-3-pyiToline-2,5-dione, HOctyl-3-(octyiainmo)-pyrroUdine"2,5-dione, l-Decyl-3-(decylamino)pyrrolidine"2,5-diDn6, 3-(Octylammo)-3-pyrrolidine-2,5-dione, 3-(Heptylaniino)-l -nonyi pyiTolidme-2,5-dione, 1 -Noii)4-3-(nonylamino) pyrToIidine-2,5-dione, l-Noii)d-3-(octylamino) pynx)lidme-2,5-dione, 2-Amino-3-(3-methyl-l -nonyl-2,5-dioxo-pyiTolidin-3-ylthio)propanoic acid, 2-Aniino-3-{3-methyl-l-octyl-2,5-dioxo-pyiTolidm-3-ylthio)propanoicacid, 2-Amino-3-(l -octyl-2,5-dioxo-pyrrolidm-3-ylthio)propanoic acid, 3-Metiiyl-l -octyipyiroli(Mne-2,5-dione, 3-Meth>4-l -M>nylpyiiolidJne-2,5-dione, 2-(2,5-DioxopyrroUdiuyl)-N-(4-piperidylphenyl)ethanaiiude, 2-(2,5-DioxopyiTolidinyl)-N-(4-piperidylphenyl)propanamide, 3-Ethyl-l -nony lpyiTolidine-2,5-dione, 3-{2-Aminoethjdthio)-! -nonyipyrrolidine-2,5-dione, 2-Ethyl-N-(2-( 1 -nonyi-2,5-dioxopyrrolidin-3->dthio)ediyi)hexanamide, Cyclopropyl-N-{2-(l-nonyI-2,5-dioxopyrrolidin-3-ylthio)ethyl)formamide, {4-But)dphenyl)-N- (2-(l-iion>i-2, 5-dioxopyrroIidin-3-ylthio)ethyl)formamide, {4-Hexyloxyphenyl)-N-(2-(l-non>i-2,5-dioxopyrroUdiii-3-jdthio)ethyl)fonnarmde, (4"Methylpbenyl)-N-(2-(l-nonyI-2,5-dioxt^yrrolidin-3-yltluo)ethyl)fora\amide, 4-(tert-Butyl)pheDjl-N-(2-( 1 -noii>i-2^-dioxopyiTOEdin-3-ylduo)etb>i)foimamide, Cyclopentyl-N-(2-( 1 -nonyl-2,5-dioxopyiTolidin-3-ylthio)ethyl)fonnamide, ethane, Cyclohexyl-N-{2-{l-nonyl-2,5-dioxopyrrolidin-3-ylthio)ethyl)formaimde, {4-Nitrophenyl)-N-(2-(l-noEyI-2,5-dioxopyrrolidin-3-ylthio)ethyI)formamide, 3-({2-{I>ibut>damino)ethyl)anmio)-l -non>ipyrroUdine-2,5-diotte, 3-((2-(Diediy lamino)eth>i)amino)-l -nony lpyrrolidine-2,5-dione, l-Nonjd-3-((4~piperidtnylpbenyl)amino)pyrrolidine-2,5-dione, j-i,nyuroxyemyitnio;-j-meUiyi-l-nonylpyrrolidine-2,5-dione, 3-(2-Aminoethylthio)-3-methyl-l -nonylpyrroUdine-2,5-dione, and 3-Methyl-l -octyl-3-(oct)4amino)pyrrolidine-2,5-dione. The compounds of fonnula (I) are known compounds or may be preparwi using techniques conventional in the art. The compoimds of formula (0 may, if desired, be converted to a phannaceutically-acceptable salt or solvate thereof, preferably an acid addition salt such as a hydrochloride, hydrobromide, phosphate, acetate, fiimarate, maleate, tartrate, citrate, oxalate, methanesulphonate oip-toluenesulphonate, or an alkali metal salt such as a sodium or potassium salt. Certain compounds of formula (I) are capable of existing in stereoisomeric forms. It will be understood that the invention encompasses all geometric and optical isomers of the confounds of fonnula (!) and mixtures thereof including racemates. Tautomers and mixtures thereof also form an aspect of the present invention. The compounds of fonnula (I) are advantageous in that they possess bactericidal activity against mycobacteria, particularly pathogenic mycobacteria such Mycobacterium tuberculosis, M. bovis. M. avium and M. marinum. Accordingly, in another aspect, the invention provides a method of treating a patient suffering frran, or at risk of, a mycobacterial disease, which comprises administering to the patient a therapeutically effective amoimt of a compound of formula (I), or a phannaceutically-acceptable salt or solvate thereof, as defined above. The compounds of formula (I) and phannaceutically-acceptable salts and solvates thereof may be used on their own but will generally be administered in the form of a pharmaceutical composition in which the formula (I) compoimd/salt/solvaie (active ingredient) is in association with a phannaceutically-acceptable adjuvant, diluent or cairier. Depending on the mode of administration, the pharmaceutical composition will preferably comprise from 0.05 to 99 %w (per cent by wei^t), more preferably from 0.10 to 70 %w. of active ingredient, and, fix>m 1 to 99.95 %w, more preferably from 30 to 99.90 %w, of a pharmaceuticaliy-acceptable adjuvant, diluent or carrier, all percentages by weight being based on total composition. The pharmaceutical composition may additionalVy contain another anti-tubercular agent and/or various other ingredients known in the art, for example, a lubricant, stabilising agent, buffering agent, emulsifying agent, viscosity-regulating agent, surfactant, preservative, flavoring or colorant. The daily dosage of formula (I) compound administered will, of course, vary with the compound employed, the mode of administration, the treatment desired and ttie mycobacteria] disease indicated. However, in general, satisfactory results will be obtained when the compound of formula (!) is administCTed at a daily dosage not exceeding 1 g, e.g. in the range from 10 to 50 mg^g body weight. The compounds of formula (I) may be administered systemically, e.g. by oral administration in the form of tablets, c^sules, syrups, powders or granules, or by parenteral administration in the form of solutions or suspensions. The present invention will now be fiirther explained with reference to the following illustmtive examples. Example:! l-DecyipyrTolidme-2.5-dione (CH£)gCH3 Succinimide (O.l M) dissolved in dry dimethylformamide was treated with sodium hydride (0.1 M) at a temperature of 0° C. Nonyl bromide (0.1 M) was then added and the reaction mixture was stirred at room temperature for three hours. The reaction mixture was concentrated in vacuo and the residue extracted into ethyl acetate. The ethyl acetate layer was washed with water, dried over sodhira sulphate and concentrated in vacuo. The residue obtained was chromatographed over silica gel to afford the desired product. "HNMR: 5 0.75 {3H, t), 1.10-1.20 (12H, m), 1.35-1.45 (2H, m), 2.55 (4H, s), 3.35 (2H, dd) A solution of phthaUc anhydride (0,1 M) in pyridine (20 ml) was treated with (-)-cis-myrtanylamine (0.1 M). The reaction mixture was heated to 90°C for six hours. The reaction mixture was then concentrated in vacuo and the residue was extracted into ethyl acetate. The ethj^ acetate layer was washed with water and with cold aqueous hydrochloric acid, then dried over sodium sulphate and finally concentrated in vacuo. The residue obtained was cbromatographed over silica gel to afford the desired product. "HNMR: 5 0.85 {IH, d), 1.2 (6H,d), 1.5- 1.65 (2H, m), 1.80-2.05 (4H, m), 2.27-2.35 (IH, m), 2.45-2.60 (IH, m), 3.60-3.75 (2H, m), 7.65-7.70 (2H, m), 7.78-7.85 (2H,m) acetate layer was washed with water and with cold aqueous hydrochloric acid, then dried over sodium sulphate and finally concentrated in vacuo. The residue obtained was chromatographed over silica gel to afford the desired product. "HNMR: 5 0.8 (3H, t), 1.15-1.30 (12H, m), 1.4-1.55 (2H, m), 2.05 (3H, s), 3.4 (2H, dd A solution of citraconic anhydride (0.1 M) in pyridine {20 ml) was treated with octjdamine (0.1 M). The reaction mixture was heated to 90""C for six hours. The reaction mixture was then concentrated in vacuo and the residue was extracted into ethyl acetate. The ethyl acetate layer was washed with water and with cold aqueous hydrochloric acid, then dried over sodium sulphate and finally concentrated in vacuo. The residue obtained was chiomatogr^hed over sihca gel to afTord the desired product. "HNMR: 6 0.85 (3H, t), 1.15-1.30 (12H, m), 1.45-1.60 (2H, m), 2.05 (2H, s), 3.45 (2H,dd),6.27(lH,s) A solution of citraconic anhydride (0.1 M) in pyridine (20 ml) was treated with 4-{l-piperidyl)aniline (0.1 M). The reaction mixture was heated to 90°C for six hours. The reaction mixture was thrai concentrated in vacuo and the residue was extracted into ethyl acetate. The ethyl acetate layer was washed with water and with cold aqueous hydrochloric acid, then dried over sodium sulphate and finally concentrated in vacuo. The residue obtained was chromatographed over silica gel to afford the desired product. "HNMR: 5 1.5-1.75 (6H, m), 2.12 (3H, s), 3.18 (4H, t), 6.4 (IH, br s), 6.95 (2H, d), 7.1(2H,d) To a solution of maleic anhydride (0.1 M) in acetone (150 ml), maintained at 0° C, was added octylamine (0.1 M) dropwise over a 15 minute period. The reaction mixture was stirred for an additional period of one hour, and the white crystalline N-octyl maleimic acid that separated was filtered and dried. A mixture of N-octyl maleimic acid (0.1 M) and sodiimi acetate (0.1 M) in acetic anhydride (150 ml) was heated on a steam bath for two hours. The acetic anhydride was removed under vacuum and the residual Uquid product was taken up in ethyl acetate, 10 washed with water, dried with sodium sulfate and concentrated to give a viscous liquid. Purification by flash chromatography (10% ethyl acetate in petroleum ether) yielded the desired product. "HNMR: 5 0.82 (3H, t), 1.15-1.4 (lOH, m), 1.48-1.6 (2H, m), 3.45 (2H, dd), 6.65 (2H, s) The procedure of Example 10 was repeated using butylamine in place of octjdamine. "HNMR: 5 0.9 (3H, t), 1.25 (2H, m), 1.6 (2H, m), 3.5 (2H, dd), 6.65 (2H, s) The procedure of Example 10 was repeated using 4-(piperidyl)aniline in place of octylamine. "HNMR: 5 1.5-1.65 (6H, m), 3.0-3.12 (4H, m), 6.80 {2H, s), 6.95 (2H, d), 7.1 (2H, d) A mixture of N-decyl maleimide {0.01 M) prepared as described in Example ll above, decylamine (0.01 M), triethylamine [catalytic, 0.1 equivalent] in acetonitrile (25 ml) was stirred for 24 hours at room temperature. Acetonitrile was removed under vacuum to leave a residual liquid product which was flash chromatographed (25% ethyl acetate in petroleiun ether) to yield a white solid as the desired product. "HNMR: 5 0.8 (6H, t), 1.15-1.35 (24H. ra), 1.45-1.65 {4H, m), 1.7 (IH, s), 2.45-2.65 (3H, ra), 2.88 (IH, dd), 3.25 (2H, dd), 3.71 (IH, dd) A mixture of N-nonyl maleimide {0.01 M) prepared as described in Example 12 above, heptylamine (O.OI M), triethylamine [catalytic, 0.1 equivalent] in acetonitrile (25 ml) was stirred for 24 hours at room temperature. Acetonitrile was removed under vacuum to leave a residual liquid product which was flash chromatographed {25% ethyl acetate in petroleum ether) to yield a white solid as the desired product. A mixture of N-nonyl maleimide (0.01 M) prepared as described in Example 12 above, oct>iamine (0.01 M), triethylamine [catalytic, O.l eqiiivalent] in acetonitrile (25 ml) wasstirred for 24 hours at room temperature. Acetonitrile was removed under vacuum to leavea residual liquid product, which was flash chiomatographed (25% ethyl acetate in petroleumether) to yield a white solid as the desired product. "HNMR: 5 0.8-0.9 (6H, m), 1.18-1.30 (20H, m), 1.35-1.60 (4H, m), 2.5-2.6 (3H, m), is 2.7-3.0 (5H, m), 3.45 (2H, dd) The procedure according to Example 22 was repeated using the imide of Example 8 above. "HNMR: 5 0.85 (3H, t), 1.15-1.32 (lOH, m), 1.3 (3H, d), 1.4-1.52 (2H, m), 2.65-2.85 (2H, m), 3.00-3.30 (2H, m), 3.42 (2H. t), 3.85 (IH, dd) 10% Palladium on carbon catalyst (5 wt%) was added to a stirred solution of N-nonyl citraconimide {0.02 M) prepared as described in Example 5 above in methanol {100 ml). Hydrogen gas was bubbled through this solution for three hours. The solution was then filtered over celite and concentrated in vacuo. Chromatography over silica gel gave the desired product. "HNMR: 5 0.85 {3H, t), 1.15-1.3 (lOH, m), 1.3 (3H, d), 1.47-1.60 (2H, m), 2.28 (IH, dd), 2.77-2.95 (2H, m), 3.45 (2H, dd) A solution of glycine benzyl ester hydrochloride {0.1 mM) in diethj^ ether was treated with triethylamine (0.11 mM) and then with succinic anhydride (0.11 mM). The reaction mixture was stirred at room temperature for two hours and then partitioned between 10% aqueous hydrochloric acid and ethyl acetate. The ethyl acetate layer was separated, dried over sodium sulphate and concentrated in vacuo to afford a yellow oil. This oil was dissolved in acetic anhydride{20 ml) containing sodium acetate {0.1 mM) and heated to 90°C for three hours. The reaction mixture was cooled, poured into water and extracted thrice with ethyl acetate. The ethyl acetate layer was separated, dried over sodium sulphate and concentrated in vacuo to afford a yellow oil. Chromatography over silica gel gave the succinoyl glycine benzyl ester. 10% Palladium on carbon catalyst (5 wt%) was added to a stirred solution of the succino>i benzyl ester (0.009 M) in methanol (50 ml). Hydrogen gas was bubbled through this solution for three hours. The solution was then filtered over celite and concentrated in vacuo to give the corresponding acid as a white solid. A solution of the acid (O.I mM) in dry dichloromethane was cooled to 0° Cand treated with dimethylfonnamide (0.1 mM) followed by oxalyl chloride (0.1 mM). The cooling bath was removed and the reaction mixture was refluxed for one hour. 4-(piperidyl)amline (0.1 mM) was then added to the reaction mixture and this solution was stirred for two hours at room temperature. The reaction was then diluted with dichloromethane, washed with saturated aqueous sodium bicarbonate and water. The organic layer was dried over sodium sulphate and concentrated in vacuo. The residue obtained was chromatographed to afford the desired product. "HNMR: 5 1.5-1.7 (6H, m), 2.8 (4H, s), 3.10 (4H, t), 4.3 (2H, s), 6.85 (2H, d),7.30 (2H, d), 7.42(1H, br s) A solution of succinimide (15.15 mM) in tetrahydrofUran (15 ml) containing hexamethji phosphorus triamide at -78 °C was treated with a solution of lithium diisopropjdamide (30.30 mM) in tetrahydrofiiran (25 ml). This solution was stirred at -78 °C for one hour and then treated with ethyl iodide (15.90 mM). The reaction mixture was stirred at -78 °C for 30 minutes, warmed up to room temperature and quenched with saturated aqueous ammonium chloride. The organic layer was separated and the aqueous layer extracted with ethyl acetate(3 x 25 ml). The combined organic layers were washed with 10% aqueous sodium thiosulfate, brine, dried over sodium sulfate and concentrated in vacuo. Chromatography over silica gel afforded pure 3-ethyl succinimide. A solution of 3-ethyl succinimide (4.72 mM) in dimethylformamide (10 ml) was treated with sodiiun hydride (5.20 mM) and nonyl bromide (5.20 mM). The reaction mixture was stirred at room temperature for two hours and then quenched with saturated aqueous ammonium chloride. The organic layer was separated and the aqueous layer extracted with ethyl acetate(3 x 25 ml). The combined organic layers were washed with 10% aqueous sodium thiosulfate, brine, dried over sodium sulfate and concentrated in vacuo. Chromatography over silica gel afforded the desired product, pure 3-ethyW- nonyl succinimide. "HNMR: 5 0.8 (3H, t), 0.9 (3H, t), 1.15-1.35 (12H, m), 1.45-1.65 (3H, m), 1.80-1.95 (IH, m), 2.35 (IH, dd), 2.6-2.95 {2H, m), 3.45 (2H, dd) N-nonyl,3-niercapto ethylamino maleimide (0.5 mM) prepared as described in Example 30 above in 2ml of dichloromethane was treated with one equivalent of triethylamine and one equivalent of 2-etliylhexanoyl chloride. The reaction mixture was stirred for five hours. The dichloromethane was then evi^orated to leave a residue to which a saturated sodium bicarbonate solution (2 ml) was added with stirring for 30 minutes, followed by -ethyl acetate (2 ml) with stirring for a fiirther 30 minutes. The ethyl acetate layer was then separated and concentrated to yield the desired product. The procedure of Example 31 was repeated using instead 4-terT-butylbenzo>i chloride. ExaDiDle:37 Cvdoi>entvl-N-(2-fl-nonvl-23-dio?[OPvrrolidin-3-vlthio)ethvnformamide. ethane The procedure of Example 31 was repeated using instead 4-mtroben20>l chloride. The procedure of Example 40 was rej)eated using instead 3-diethylaniino-methylpropylamine. A solution of N-nonjd citraconimide (0.5 mM) prepared as described in Example 5 above in dimethylfonnamide (10 ml) was treated with triethylamine (0.5 mM) and then 2-mercaptoethanoi (0.5 mM) was added dropwise. The progress of the reaction was monitored by thin layer chromatography and when the starting material could no longer be detected the reaction mixture was concentrated in vacuo. The residue obtained was dissolved in ethyl acetate, washed with water and dried over sodium sulfate. Purification by chromatography yielded the desired product. A solution of N-oct>i citraconimide (0.223 g, 1 mM) prepared as described in Example 7 above in acetonitrile (2 ml) was treated with triethylamlne (0.14 ml, I mM) and then octylamine (0.165 ml, 1 mM) was added dropwise. The progress of the reaction was monitored by thin layer chromatography and when the starting material could no longer be detected the reaction mixture was concentrated in vacuo. The residue obtained was dissolved in ethyl acetate, washed with water and dried over sodium sulfate. Purification by chromatography yielded the desired product. "HNMR: 8 0.8 (6H, t). 1.10-1.28 (20H, m), 1.3 (3H, s), 1.32-1.58 (4H, m), 2.25-2.48 (2H, m), 2.50 & 2.80 (2H, ABq), 3.42 (2H, dd) Example 46 Each of the compounds of Examples 1 to 45 was assessed for bactericidal activity against M. tuberculosis by measuring its minimum inhibitory concentration (MIC) in the "BACTEC" (trade mark) system developed by Becton-Dickinson Diagnostic Instrument Systems, Sparks, U.S.A., which is based on a radiometric principle whereby carbon dioxide released by the catabolism of C-palmitate is spectrophotometrically detected and quantitated in arbitrary units of measurement referred to as growth index (GI) units. Thus, "BACTEC" vials were inoculated with 0.1 ml of M. tuberculosis (final bacterial concentration, 1 x 10^ colony forming units per ml) and 0.1 ml oftest compound in a range of concentrations. GI values were monitored until a value of ^ 30 was achieved for the 1:100 dilution control. For the purpose of this test, MIC is defined as the minimum concentration of test compound that effects a >95% inhibition of the culture in comparison to the undiluted control, when the control reaches a GI value of 999. Endpoint determination (>99% inhibition) is based on a conventional t % resistance cutHDfF, wherein the organism is considered resistant to a particular concentration of test compound if growth of greater than 1 % of the bacterial population is observed. Thus, a comparison is made between growth of the organism in the presence of a pre¬determined concentration oftest compound and growth of the same organism diluted 1:100 in the absence of any test con^round. The change in the GI values (AGI)isused to determine the endpoint susceptibility of the organism to the test compound. If the AGI of the 1:100 control isgreata-thanthe AGI in the presence of the test compound, then the concentration of test con^und used is considered to be bactericidal (>99% inhibition) for the organism. The MIC of the compounds of Examples 1 to 46 were determined for the following strains of M. tuberculosis: H37RV, H37Ra, 1 clinical isolate susceptible to isoniazid, rifampicin, ethambutol and streptomycin [E: 22/95; Estonia], 1 clinical isolate resistant to isomazid [H: 997/94; Honduras], 1 clinical isolate resistant to isoniazid and ethambutol [E:5/94; Estonia], 1 clinical isolate resistant to isomazid and rifampicin [H: 44/95; Honduras], 1 clinical isolate resistant to isomazid and streptomycin [S: 150/96; Sweden], 1 clinical isolate resistant to isoniazid, rifampicin and streptomycin [AA:063; Ethiopia], 3 clinical isolates resistant to isoniazid, rifampicin, streptomycin and ethambutol [P:24/95; Estonia, S: 39/95; Nepal, S:42/95; China, H: 1005/94; Honduras], and were found in all cases to be less than or equal to 20 fig/ml. Therefore, the compounds of Examples 1 to 46 demonstrate effective bactericidal activity against the above strains of M. tuberculosis which include single- and multiple-drug resistant strains. The present invention relates to a medicament for use in the treatment of mycobacterial diseases, particularly those diseases caused by pathogenic mycobacteria such as Mycobacterium tuberculosis, M. bovis, M. avium and M. murium. Tuberculosis is still a major public health problem affecting nearly all parts of the world. Based on skin test reactivity it has been estimated that about one-third of the world"s population, i.e., 1.7 billion people, are infected with Mycobacterium tuberculosis. Despite the availability of effective chemotherapies, it is responsible for three million deaths and from eight to ten million new cases annually and thus remains the leading cause of death world-wide due to a single infectious agent; 26% of all preventable deaths, J% of all deaths. According to the World Health Organisation, 450,000 deaths per year due to tuberculosis in developing countries occur in children under fifteen years of age, and the disease mostly affects the younger, more productive adults. There are five front-line drugs known to be highly effective against M. tuberculosis and five second-line drugs that can be used when resistance to one or more of the front-line drugs is detected. The preferred mode of treatment for tuberculosis is the short course chemotherapy in which there are two phases. The first phase consists of a daily regimen for two months with isoniazid (300 mg), rifampin (600 mg), pyrazinamide (3 g) and ethambutol {1.5 g). The second phase or the continuation phase consists of a daily regimen for the next four months with isoniazid and rifampin. Although infection with drug-sensitive strains of M. tuberculosis can be effectively cured with the short course chemotherapy, the cure rate is very poor in most countries due to poor compliance, which is reflective of the long duration of therapy. The situation is further complicated by the rapid emergence of multi-drug resistant tuberculosis (MDR-TB) strains. For example, in certain populations, the incidence of resistance to isoniazid is as high as 26% and the resistance to rifampin is about 15%. Prior to 1984, about 10% of tubercle bacilli isolated from patients in the United States were resistant to at least one single mycobacterial drug. By 1984, this figure had risen to 52%, of which over half (32%) were resistant to more than one drug (MDR-TB). Ten percent of the recorded MDR-TB cases have occurred in previously healthy people whose mortality rate - 70 to 90% - has been nearly the same as that of imrnunosuppressed individuals with MDR-TB. The number of cases of MDR-TB has doubled since 1984 and in many of them the tubercle bacilli are resistant to both isoniazid and rifampin. The median interval between diagnosis of MDR-TB and death is only four weeks and therefore MDR-TB demands a shorter response time between diagnosis and appropriate commencement of treatment. However, MDR-TB is difficult to treat as such since most patients do not respond very well to the second-line drugs and the cost of alternate treatment procedures, including hospitalisation and possibly surgery, increases the cost to as much as ten times the cost of traditional treatment. Thus, there is an urgent medical need to identify new drugs with significant therapeutic activity against single- or multiple-drug resistant strains of M. tuberculosis and with pharmacokinetic properties that permit reduced dosing which will in turn encourage better compliance. In accordance with the present invention, there is therefore provided the use of a compound of general formula wherein X is 0 or 1; R1 represents a hydrogen atom, or a C1-C20 alkyl or myrtanyl group, or a phenyl or benzyl group optionally substituted in the aromatic ring by one or more substituents selected from amino, nitro, hydroxyl, carboxyl, halogen, trifluoromethyl C1-C6 alkyl, C1-C6 alkoxy, C1- Ce alkoxycarbonjd, piperidyl, piperazinyl and morpholinyl, or a group (CH2)yCONH-R^ where y is an integer from 1 lo 6 and R" represents a phenyl group optionally substituted by one or more substituents selected from amino, nitro, hydroxyl, carboxyl, halogen, trifluoromethyl, Cj-Cs alkyl, C|-C6 alkoxy, Ci-Ce alkoxycarbonyl. Piperidyl, piperazinyl and morpholinyl; and either R represents a hydrogen atom or a Ci-Cg alkyl group, or R together with R^ represents a carbon-carbon single bond provided that x is 0, or R^ together with R^ represents a group =CH2, R^ represents a hydrogen atom or is linked to R as defined above, and R"* represents a hydrogen atom or a Ci-Cg alkyl group; or a Ci-Cjo alkylamino group optionally substituted by a di(Ci-C6 aU^l)amino substituent group; or an anilino group optionally substituted in the aromatic ring by one or more substituents selected from amino, nitro, hydroxyl, carboxyl, halogen, trifluoromethyl, Ci-Ce alkyl, Ci-Cft alkoxy, Ci-Cs alkoxycarbonyl, piperidyl, piperazinyl and morpholinyl; or a group-SCH2CH20H, -SCH2CH2NH2, -SCH2CH2(NH2X:02H or -SCHjCHaNHCO-R^ where R^ represents a Ci-Cjoalkyl or Cj-Cg cycloalkyl group, or a phenyl group optionally substituted by one or more substituents selected from amino, nitro, hydroxj^, carboxyl, halogen, trifluoromethyl, Ci-Cs alkyl, CpCe alkoxy, Ci-Ce alkoxycarbonyl, piperidyl, piperazinjd and morpholinyl;or R* is linked to R^ as defined above;or R , R"* and R together represent a phenyl group; with the provisos that: (i) R , R , R and R do not each simultaneously represent a hydrogen atom, (ii) when x is 0, R" represents a 4-fluorophenyl group and R* represents a hydrogen atom, then R^ and R^ do not together represent a carbon-carbon single bond, and (iii) when x is 0, R" represents a 4-fluorophenyl group and R~ and R^ both represent hydrogen atom, then R does not represent an aniline, 4-chloroanilino, 2,6-dichloroamlino,3,4-dichloroanilino, 2,5-dichloroanilino, 3-chloro-4-fluoroaniiino or 4-fluoroanilino group; or a pharaiaceutically acceptable salt or solvate thereof, in the manufacture of a medicament for use in the treatment of a mycobacterial disease, in particular mberculosis. In the context of the present specification, unless otherwise stated, an alkyl (substituent) group or an alfcjd moiety in an alkoxy or alkoxycarbon>d substituent group may be linear or branched. Preferably R" in formula (I) represents a hydrogen atom, or a Ci-Cis, more preferably Cj-Cio aikyi or myrtan>i group, or a phenyl or benzjd group optionally substituted in the aromatic ring by one to four, particularly one or two, substituents selected from amino, nitro, hydrox>^, carboxyl, halogen (e.g. fluorine, chlorine or bromine), trifluoromethyl, C|-C4 alkyl {e.g. methyl, ethyl, propjd, isoprop>1 or butyl), Ci-C4 alkoxy (e.g. methoxy, ethoxy, propoxy, or butoxy), C1-C4 alkoxycarbonyl (e.g. methoxycarbonyl, ethoxycartronyl, propoxycarbonyl or butoxycarbonyl), piperidyl, piperazinyl and morpholinjd, or a group (CH2)yCONH-R^ where y is an intega" 1, 2, 3 or 4 and R represents a phenyl group optionally substituted by one to four, particularly one or two, substituents selected from amino, nitro, hydroxyl, carboxjd, halogen (e.g. fluorine, chlorine or bromine), trifluoromethyl, C1-C4 alkyl (e.g. methyl, ethyl, propyl, isopropyl or butyl), C1-C4 alkoxy (e.g. methoxy, ethoxy, propoxy, or butoxy), C1-C4 alkoxycarbonjd (e.g.methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl or butoxycarbonyl), piperidyl, piperazmyl and moipholinyl. The group R" especially represents a hydrogen atom, or a C4-C10 alkyl (e.g. butyl, pentyl, hexyl, hqjtyl, octyl, nonyl or decyl) or myrtanyl group, or a phenyl group substituted by a piperidyl substituent group, or a group (CH2)yCONH-R^ where y is 1 or 2 and R represents a phenyl group substituted by a piperidyl substituent group. Preferably R represents a hydrogen atom or a C1-C4 alkyl, particularly methyl group, or R together with R represents a carbon-carbon single bond provided that x is 0, or R together with R* represents a group =CH2. R* preferably represents a hydrogen atom or a C1-C4 alkyl group (e.g. methyl, ethyl, propjd or butyl); or a C2-C10 alkylamino group optionally substituted by a dJ(Ci-C6 alkyl)amino, especially di(Ci-C4 alkylamino, substituent group; or an aniljno group optionally substituted in the aromatic ring by one to four, particularly one or two. substituents selected from amino, nitro, hydroxyl, caiboxyl, halogen (e.g. fluorine, chlorine or bromine), trifluoromethyl, C1-C4 alky! (e.g. methyl, ethyl, propyl, isopropyl or butyl), C1-C4 alkoxy (e.g. methoxy, ethoxy, propoxy, or butoxy), C1-C4 alkoxycarbonyl (e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl or butoxycarbonyl), piperidyl, piperazinyl and morpholinyl; or a group -SCH2CH2OH, -SCH2CH2NH2, -SCH2CH2(NH2)C02H or -SCH2CH2NHCO-R^ where R^ represents a C5-Cio alkyl or Cj-Ct cycloalkyl groi^, or a phenyl group optioimlly substituted by one or more substituents selected from amino, nitro, hydroxyl, carboxyl, halogen {e.g. fluorine, chlorine or bromine), trifluoromethyl, C1-C4 alkyl (e.g. methyl, ethyl, propyl, isopropyl or butyl), C3-C6 alkoxy (e.g. propoxy, butoxy, pentoxy or hexyloxy), C[-C4 alkoxycarbonyl (e.g. methoxycariwnyl, ethoxycatbonyl, propoxycaibonyl or butoxycarbonyl), piperidyl, piperazinyl and morpholinyl; or R is linked to R as defined above. It is preferred that R^ represents a hydrogen atom, a methyl or ethyl group, a C2-C10 alkylamino group optionally substituted by a di(C2-C4 alkyl)amino substituent group, an aniline group substituted by a piperidyl substituent group,-SCH2CH20H,-SCH2CH2NH2,-SCH2CH2(NH2)C02H, -SCH2CH2NHCO-R^ where R^ represents a C7 alkyl, cyclopropyl, cyclopaityl or cyclohexj^ group or a phenyl group substituted by a nitro, C1-C4 alkyl or C3-C6 alkoxy substituent group, or R is linked to R^ as defined above. Particularly preferred compotmds of formula (I) include: l-Decylpyrrolidine-2,5-dione, l-((6,6-Dimethylbicyclo[3,l,l]hept-3-yl)methyl)-3-methyl-3-pyrroline-2,5-dione, 3-Meth>i-l-nonyl-3-pyrroline-2,5-dione, 5 3-Meth>1ene-l -nonylpyrroUdine-2,5-dione, 3-Methyl-l-octyl-3-pyrroline-2,5-dioiie, 3-Meth>iene-l -octjipyirolidine-2,5-dione, (4-(3-methyl-2,5-dioxo-3-pyrrolinyl)phenyl)piperidine, 1 -Oc^-3-pyrroline-2,5-dione, l-Decyi-3-pyrroline-2,5-dione, 1 -Nonyl-3-pyrroline-2,5-dione, 1 -BotyJ-3-pyiioIiiie-2,5-dione, l-Hexyl-3-pyrroluie-2,5-dione, l-(4-Piperidylphenyl)-3-pyiToline-2,5-dione, HOctyl-3-(octyiainmo)-pyrroUdine"2,5-dione, l-Decyl-3-(decylamino)pyrrolidine"2,5-diDn6, 3-(Octylammo)-3-pyrrolidine-2,5-dione, 3-(Heptylaniino)-l -nonyi pyiTolidme-2,5-dione, 1 -Noii)4-3-(nonylamino) pyrToIidine-2,5-dione, l-Noii)d-3-(octylamino) pynx)lidme-2,5-dione, 2-Amino-3-(3-methyl-l -nonyl-2,5-dioxo-pyiTolidin-3-ylthio)propanoic acid, 2-Aniino-3-{3-methyl-l-octyl-2,5-dioxo-pyiTolidm-3-ylthio)propanoicacid, 2-Amino-3-(l -octyl-2,5-dioxo-pyrrolidm-3-ylthio)propanoic acid, 3-Metiiyl-l -octyipyiroli(Mne-2,5-dione, 3-Meth>4-l -M>nylpyiiolidJne-2,5-dione, 2-(2,5-DioxopyrroUdiuyl)-N-(4-piperidylphenyl)ethanaiiude, 2-(2,5-DioxopyiTolidinyl)-N-(4-piperidylphenyl)propanamide, 3-Ethyl-l -nony lpyiTolidine-2,5-dione, 3-{2-Aminoethjdthio)-! -nonyipyrrolidine-2,5-dione, 2-Ethyl-N-(2-( 1 -nonyi-2,5-dioxopyrrolidin-3->dthio)ediyi)hexanamide, Cyclopropyl-N-{2-(l-nonyI-2,5-dioxopyrrolidin-3-ylthio)ethyl)formamide, {4-But)dphenyl)-N- (2-(l-iion>i-2, 5-dioxopyrroIidin-3-ylthio)ethyl)formamide, {4-Hexyloxyphenyl)-N-(2-(l-non>i-2,5-dioxopyrroUdiii-3-jdthio)ethyl)fonnarmde, (4"Methylpbenyl)-N-(2-(l-nonyI-2,5-dioxt^yrrolidin-3-yltluo)ethyl)fora\amide, 4-(tert-Butyl)pheDjl-N-(2-( 1 -noii>i-2^-dioxopyiTOEdin-3-ylduo)etb>i)foimamide, Cyclopentyl-N-(2-( 1 -nonyl-2,5-dioxopyiTolidin-3-ylthio)ethyl)fonnamide, ethane, Cyclohexyl-N-{2-{l-nonyl-2,5-dioxopyrrolidin-3-ylthio)ethyl)formaimde, {4-Nitrophenyl)-N-(2-(l-noEyI-2,5-dioxopyrrolidin-3-ylthio)ethyI)formamide, 3-({2-{I>ibut>damino)ethyl)anmio)-l -non>ipyrroUdine-2,5-diotte, 3-((2-(Diediy lamino)eth>i)amino)-l -nony lpyrrolidine-2,5-dione, l-Nonjd-3-((4~piperidtnylpbenyl)amino)pyrrolidine-2,5-dione, j-i,nyuroxyemyitnio;-j-meUiyi-l-nonylpyrrolidine-2,5-dione, 3-(2-Aminoethylthio)-3-methyl-l -nonylpyrroUdine-2,5-dione, and 3-Methyl-l -octyl-3-(oct)4amino)pyrrolidine-2,5-dione. The compounds of fonnula (I) are known compounds or may be preparwi using techniques conventional in the art. The compoimds of formula (0 may, if desired, be converted to a phannaceutically-acceptable salt or solvate thereof, preferably an acid addition salt such as a hydrochloride, hydrobromide, phosphate, acetate, fiimarate, maleate, tartrate, citrate, oxalate, methanesulphonate oip-toluenesulphonate, or an alkali metal salt such as a sodium or potassium salt. Certain compounds of formula (I) are capable of existing in stereoisomeric forms. It will be understood that the invention encompasses all geometric and optical isomers of the confounds of fonnula (!) and mixtures thereof including racemates. Tautomers and mixtures thereof also form an aspect of the present invention. The compounds of fonnula (I) are advantageous in that they possess bactericidal activity against mycobacteria, particularly pathogenic mycobacteria such Mycobacterium tuberculosis, M. bovis. M. avium and M. marinum. Accordingly, in another aspect, the invention provides a method of treating a patient suffering frran, or at risk of, a mycobacterial disease, which comprises administering to the patient a therapeutically effective amoimt of a compound of formula (I), or a phannaceutically-acceptable salt or solvate thereof, as defined above. The compounds of formula (I) and phannaceutically-acceptable salts and solvates thereof may be used on their own but will generally be administered in the form of a pharmaceutical composition in which the formula (I) compoimd/salt/solvaie (active ingredient) is in association with a phannaceutically-acceptable adjuvant, diluent or cairier. Depending on the mode of administration, the pharmaceutical composition will preferably comprise from 0.05 to 99 %w (per cent by wei^t), more preferably from 0.10 to 70 %w. of active ingredient, and, fix>m 1 to 99.95 %w, more preferably from 30 to 99.90 %w, of a pharmaceuticaliy-acceptable adjuvant, diluent or carrier, all percentages by weight being based on total composition. The pharmaceutical composition may additionally contain another anti-tubercular agent and/or various other ingredients known in the art, for example, a lubricant, stabilising agent, buffering agent, emulsifying agent, viscosity-regulating agent, surfactant, preservative, flavoring or colorant. The daily dosage of formula (I) compound administered will, of course, vary with the compoimd employed, the mode of administration, the treatment desired and ttie mycobacteria] disease indicated. However, in general, satisfactory results will be obtained when the compoimd of formula (!) is administCTed at a daily dosage not exceeding 1 g, e.g. in the range from 10 to 50 mg^g body weight. The compounds of fonnula (I) may be administered systemically, e.g. by oral administration in the form of tablets, c^sixles, syrups, powders or grannies, or by parenteral administration in the form of solutions or suspensions. The present invention will now be fiirther explained with reference to the following illustmtive examples. Example:! l-DecyipyrTolidme-2.5-dione Succinimide (O.l M) dissolved in dry dimethylformamide was treated with sodium hydride (0.1 M) at a temperatixre of 0° C. Nonyl bromide (0.1 M) was then added and the reaction mixture was stirred at room temperature for three hours. The reaction mixture was concentrated in vacuo and the residue extracted into ethyl acetate. The ethyl acetate layer was washed with water, dried over sodhira sulphate and concentrated in vacuo. The residue obtained was chromatographed over silica gel to afford the desired product. "HNMR: 5 0.75 {3H, t), 1.10-1.20 (12H, m), 1.35-1.45 (2H, m), 2.55 (4H, s), 3.35 (2H, dd) A solution of phthaUc anhydride (0,1 M) in pyridine (20 ml) was treated with (-)-cis-myrtanylamine (0.1 M). The reaction mixture was heated to 90°C for six hours. The reaction mixture was then concentrated in vacuo and the residue was extracted into ethyl acetate. The ethj^ acetate layer was washed with water and with cold aqueous hydrochloric acid, then dried over sodium sulphate and finally concentrated in vacuo. The residue obtained was cbromatographed over silica gel to afford the desired product. "HNMR: 5 0.85 {IH, d), 1.2 (6H,d), 1.5- 1.65 (2H, m), 1.80-2.05 (4H, m), 2.27-2.35 (IH, m), 2.45-2.60 (IH, m), 3.60-3.75 (2H, m), 7.65-7.70 (2H, m), 7.78-7.85 (2H,m) A solution of citraconic anhydride {0.1 M) in pyridine {20 ml) was treated with nonylamine 10 (0.1 M). The reaction mixture was heated to 90""C for six hours. The reaction mixture was then concentrated in vacuo and the residue was extracted into ethyl acetate. The ethyl acetate layer was washed with water and with cold aqueous hydrochloric acid, then dried over sodium sulphate and finally concentrated in vacuo. The residue obtained was chromatographed over silica gel to afford the desired product. "HNMR: 5 0.8 (3H, t), 1.15-1.30 (12H, m), 1.4-1.55 (2H, m), 2.05 (3H, s), 3.4 (2H, dd A solution of citraconic anhydride (0.1 M) in pyridine {20 ml) was treated with octjdamine (0.1 M). The reaction mixture was heated to 90""C for six hours. The reaction mixture was then concentrated in vacuo and the residue was extracted into ethyl acetate. The ethyl acetate layer was washed with water and with cold aqueous hydrochloric acid, then dried over sodium sulphate and finally concentrated in vacuo. The residue obtained was chiomatogr^hed over sihca gel to afTord the desired product. "HNMR: 6 0.85 (3H, t), 1.15-1.30 (12H, m), 1.45-1.60 (2H, m), 2.05 (2H, s), 3.45 (2H,dd),6.27(lH,s) A solution of citraconic anhydride (0.1 M) in pyridine (20 ml) was treated with 4-{l-piperidyl)aniline (0.1 M). The reaction mixture was heated to 90°C for six hours. The reaction mixture was thrai concentrated in vacuo and the residue was extracted into ethyl acetate. The ethyl acetate layer was washed with water and with cold aqueous hydrochloric acid, then dried over sodium sulphate and finally concentrated in vacuo. The residue obtained was chromatographed over silica gel to afford the desired product. "HNMR: 5 1.5-1.75 (6H, m), 2.12 (3H, s), 3.18 (4H, t), 6.4 (IH, br s), 6.95 (2H, d), 7.1(2H,d) To a solution of maleic anhydride (0.1 M) in acetone (150 ml), maintained at 0° C, was added octylamine (0.1 M) dropwise over a 15 minute period. The reaction mixture was stirred for an additional period of one hour, and the white crystalline N-octyl maleimic acid that separated was filtered and dried. A mixture of N-octyl maleimic acid (0.1 M) and sodiimi acetate (0.1 M) in acetic anhydride (150 ml) was heated on a steam bath for two hours. The acetic anhydride was removed under vacuum and the residual Uquid product was taken up in ethyl acetate, 10 washed with water, dried with sodium sulfate and concentrated to give a viscous liquid. Purification by flash chromatography (10% ethyl acetate in petroleum ether) yielded the desired product. "HNMR: 5 0.82 (3H, t), 1.15-1.4 (lOH, m), 1.48-1.6 (2H, m), 3.45 (2H, dd), 6.65 (2H, s) The procedure of Example 10 was repeated using butylamine in place of octjdamine. "HNMR: 5 0.9 (3H, t), 1.25 (2H, m), 1.6 (2H, m), 3.5 (2H, dd), 6.65 (2H, s) The procedure of Example 10 was repeated using 4-(piperidyl)aniline in place of octylamine. "HNMR: 5 1.5-1.65 (6H, m), 3.0-3.12 (4H, m), 6.80 {2H, s), 6.95 (2H, d), 7.1 (2H, d) Example: 16 l-(Octyl-3-(octylaiiiino>pyiToUdine-2,5-dione A mixture of N-decyl maleimide {0.01 M) prepared as described in Example ll above, decylamine (0.01 M), triethylamine [catalytic, 0.1 equivalent] in acetonitrile (25 ml) was stirred for 24 hours at room temperature. Acetonitrile was removed under vacuum to leave a residual liquid product which was flash chromatographed (25% ethyl acetate in petroleiun ether) to yield a white solid as the desired product. "HNMR: 5 0.8 (6H, t), 1.15-1.35 (24H. ra), 1.45-1.65 {4H, m), 1.7 (IH, s), 2.45-2.65 (3H, ra), 2.88 (IH, dd), 3.25 (2H, dd), 3.71 (IH, dd) Example: 18 3--3-pviToIidine-2.5-€iione A mixture of N-nonyl maleimide {0.01 M) prepared as described in Example 12 above, heptylamine (O.OI M), triethylamine [catalytic, 0.1 equivalent] in acetonitrile (25 ml) was stirred for 24 hours at room temperature. Acetonitrile was removed under vacuum to leave a residual liquid product which was flash chromatographed {25% ethyl acetate in petroleum ether) to yield a white solid as the desired product. Example: 20 l-Nonyl-3-{f«ft"Y"*""""^Q^P"vrrolidine-2^dione A mixture of N-nonyl maleimide (0.01 M) prepared as described in Example 12 above, oct>iamine (0.01 M), triethylamine [catalytic, O.l eqiiivalent] in acetonitrile (25 ml) wasstirred for 24 hours at room temperature. Acetonitrile was removed under vacuum to leavea residual liquid product, which was flash chiomatographed (25% ethyl acetate in petroleumether) to yield a white solid as the desired product. "HNMR: 5 0.8-0.9 (6H, m), 1.18-1.30 (20H, m), 1.35-1.60 (4H, m), 2.5-2.6 (3H, m), is 2.7-3.0 (5H, m), 3.45 (2H, dd) The procedure according to Example 22 was repeated using the imide of Example 8 above. "HNMR: 5 0.85 (3H, t), 1.15-1.32 (lOH, m), 1.3 (3H, d), 1.4-1.52 (2H, m), 2.65-2.85 (2H, m), 3.00-3.30 (2H, m), 3.42 (2H. t), 3.85 (IH, dd) Example :24 2-Aiiiino-3-fl-octvl-2.5-dioxo-pvrrolidin-3-vlthio)propanoicacid 10% Palladium on carbon catalyst (5 wt%) was added to a stirred solution of N-nonyl citraconimide {0.02 M) prepared as described in Example 5 above in methanol {100 ml). Hydrogen gas was bubbled through this solution for three hours. The solution was then filtered over celite and concentrated in vacuo. Chromatography over silica gel gave the desired product. "HNMR: 5 0.85 {3H, t), 1.15-1.3 (lOH, m), 1.3 (3H, d), 1.47-1.60 (2H, m), 2.28 (IH, dd), 2.77-2.95 (2H, m), 3.45 (2H, dd) Example:26 3-Metfa^-l-nonylpyiTolidme-2,5-dione A solution of glycine benzyl ester hydrochloride {0.1 mM) in diethj^ ether was treated with triethylamine (0.11 mM) and then with succinic anhydride (0.11 mM). The reaction mixture was stirred at room temperature for two hours and then partitioned between 10% aqueous hydrochloric acid and ethyl acetate. The ethyl acetate layer was separated, dried over sodium sulphate and concentrated in vacuo to afford a yellow oil. This oil was dissolved in acetic anhydride{20 ml) containing sodium acetate {0.1 mM) and heated to 90°C for three hours. The reaction mixture was cooled, poured into water and extracted thrice with ethyl acetate. The ethyl acetate layer was separated, dried over sodium sulphate and concentrated in vacuo to afford a yellow oil. Chromatography over silica gel gave the succinoyl glycine benzyl ester. 10% Palladium on carbon catalyst (5 wt%) was added to a stirred solution of the succino>i benzyl ester (0.009 M) in methanol (50 ml). Hydrogen gas was bubbled through this solution for three hours. The solution was then filtered over celite and concentrated in vacuo to give the corresponding acid as a white solid. A solution of the acid (O.I mM) in dry dichloromethane was cooled to 0° Cand treated with dimethylfonnamide (0.1 mM) followed by oxalyl chloride (0.1 mM). The cooling bath was removed and the reaction mixture was refluxed for one hour. 4-(piperidyl)amline (0.1 mM) was then added to the reaction mixture and this solution was stirred for two hours at room temperature. The reaction was then diluted with dichloromethane, washed with saturated aqueous sodium bicarbonate and water. The organic layer was dried over sodium sulphate and concentrated in vacuo. The residue obtained was chromatographed to afford the desired product. "HNMR: 5 1.5-1.7 (6H, m), 2.8 (4H, s), 3.10 (4H, t), 4.3 (2H, s), 6.85 (2H, d),7.30 (2H, d), 7.42(1H, br s) The procedure according to Example 27 was repeated using instead P-alauine benzyl ester hydrochloride. "HNMR: 5 1.50-1.85 {6H, m), 2.65-2.80 (6H, m), 3.05 {4H, t), 3.9 (2H, t), 6.85 (2H, d), is 7.35 (2H,d), 7.4-7.5 (IH, br s) A solution of succinimide (15.15 mM) in tetrahydrofuran (15 ml) containing hexamethji phosphorus triamide at -78 °C was treated with a solution of lithium diisopropjdamide (30.30 mM) in tetrahydrofiiran (25 ml). This solution was stirred at -78 °C for one hour and then treated with ethyl iodide (15.90 mM). The reaction mixture was stirred at -78 °C for 30 minutes, warmed up to room temperature and quenched with saturated aqueous ammonium chloride. The organic layer was separated and the aqueous layer extracted with ethyl acetate(3 x 25 ml). The combined organic layers were washed with 10% aqueous sodium thiosulfate, brine, dried over sodium sulfate and concentrated in vacuo. Chromatography over silica gel afforded pure 3-ethyl succinimide. A solution of 3-ethyl succinimide (4.72 mM) in dimethylfonnamide (10 ml) was treated with sodiiun hydride (5.20 mM) and nonyl bromide (5.20 mM). The reaction mixture was stirred at room temperature for two hours and then quenched with saturated aqueous ammonium chloride. The organic layer was separated and the aqueous layer extracted with ethyl acetate(3 x 25 ml). The combined organic layers were washed with 10% aqueous sodium thiosulfate, brine, dried over sodium sulfate and concentrated in vacuo. Chromatography over silica gel afforded the desired product, pure 3-ethyW- nonyl succinimide. "HNMR: 5 0.8 (3H, t), 0.9 (3H, t), 1.15-1.35 (12H, m), 1.45-1.65 (3H, m), 1.80-1.95 (IH, m), 2.35 (IH, dd), 2.6-2.95 {2H, m), 3.45 (2H, dd) N-nonyl,3-niercapto ethylamino maleimide (0.5 mM) prepared as described in Example 30 above in 2ml of dichloromethane was treated with one equivalent of triethylamine and one equivalent of 2-etliylhexanoyl chloride. The reaction mixture was stirred for five hours. The dichloromethane was then evi^orated to leave a residue to which a saturated sodium bicarbonate solution (2 ml) was added with stirring for 30 minutes, followed by -ethyl acetate (2 ml) with stirring for a fiirther 30 minutes. The ethyl acetate layer was then separated and concentrated to yield the desired product. The procedure of Example 40 was rej)eated using instead 3-diethylaniino-methylpropylamine. A solution of N-nonjd citraconimide (0.5 mM) prepared as described in Example 5 above in dimethylfonnamide (10 ml) was treated with triethylamine (0.5 mM) and then 2-mercaptoethanoi (0.5 mM) was added dropwise. The progress of the reaction was monitored by thin layer chromatography and when the starting material could no longer be detected the reaction mixture was concentrated in vacuo. The residue obtained was dissolved in ethyl acetate, washed with water and dried over sodium sulfate. Purification by chromatography yielded the desired product. A solution of N-oct>i citraconimide (0.223 g, 1 mM) prepared as described in Example 7 above in acetonitrile (2 ml) was treated with triethylamlne (0.14 ml, I mM) and then octylamine (0.165 ml, 1 mM) was added dropwise. The progress of the reaction was monitored by thin layer chromatography and when the starting material could no longer be detected the reaction mixture was concentrated in vacuo. The residue obtained was dissolved in ethyl acetate, washed with water and dried over sodium sulfate. Purification by chromatography yielded the desired product. "HNMR: 8 0.8 (6H, t). 1.10-1.28 (20H, m), 1.3 (3H, s), 1.32-1.58 (4H, m), 2.25-2.48 (2H, m), 2.50 & 2.80 (2H, ABq), 3.42 (2H, dd) Example 46 Each of the compounds of Examples 1 to 45 was assessed for bactericidal activity against M. tuberculosis by measuring its minimum inhibitory concentration (MIC) in the "BACTEC" (trade mark) system developed by Becton-Dickinson Diagnostic Instrument Systems, Sparks, U.S.A., which is based on a radiometric principle whereby carbon dioxide released by the catabolism of C-palmitate is spectrophotometrically detected and quantitated in arbitrary units of measurement referred to as growth index (GI) units. Thus, "BACTEC" vials were inoculated with 0.1 ml of M. tuberculosis (final bacterial concentration, 1 x 10^ colony forming units per ml) and 0.1 ml oftest compound in a range of concentrations. GI values were monitored until a value of ^ 30 was achieved for the 1:100 dilution control. For the purpose of this test, MIC is defined as the minimum concentration of test compound that effects a >95% inhibition of the culture in comparison to the undiluted control, when the control reaches a GI value of 999. Endpoint determination (>99% inhibition) is based on a conventional t % resistance cutHDfF, wherein the organism is considered resistant to a particular concentration of test compound if growth of greater than 1 % of the bacterial population is observed. Thus, a comparison is made between growth of the organism in the presence of a pre¬determined concentration oftest compound and growth of the same organism diluted 1:100 in the absence of any test con^round. The change in the GI values (AGI)isused to determine the endpoint susceptibility of the organism to the test compound. If the AGI of the 1:100 control isgreata-thanthe AGI in the presence of the test compound, then the concentration of test con^und used is considered to be bactericidal (>99% inhibition) for the organism. The MIC of the compounds of Examples 1 to 46 were determined for the following strains of M. tuberculosis: H37RV, H37Ra, 1 clinical isolate susceptible to isoniazid, rifampicin, ethambutol and streptomycin [E: 22/95; Estonia], 1 clinical isolate resistant to isomazid [H: 997/94; Honduras], 1 clinical isolate resistant to isoniazid and ethambutol [E:5/94; Estonia], 1 clinical isolate resistant to isomazid and rifampicin [H: 44/95; Honduras], 1 clinical isolate resistant to isomazid and streptomycin [S: 150/96; Sweden], 1 clinical isolate resistant to isoniazid, rifampicin and streptomycin [AA:063; Ethiopia], 3 clinical isolates resistant to isoniazid, rifampicin, streptomycin and ethambutol [P:24/95; Estonia, S: 39/95; Nepal, S:42/95; China, H: 1005/94; Honduras], and were found in all cases to be less than or equal to 20 fig/ml. Therefore, the compounds of Examples 1 to 46 demonstrate effective bactericidal activity against the above strains of M. tuberculosis which include single- and multiple-drug resistant strains. WE CLAIM: 1. A medicament comprising pyrroline-dione or pyrrolidine-dione compounds of genera! formula trifluoromethyl, Cj-Ce aikyi, Ci-Ce alkoxy, Ci-Ce alkoxycarbonyl, piperidyl, piperazinyl and morpholinyl;or R* is linked to R^ as defined above; OTR"^ , R^ and R* together represent a phenyl group; with the provisos that: (i) R" , R^, R^ and R^ do not each simultaneously represent a hydrogen atom, (ii) when x is 0, R represents a 4-fluorophenyl group and R represents a hydrogen atom, then R and R do not together represent a carbon"carbon single bond, and (iii) when x is 0, R represents a 4-fluorophenyl group and R and R both represent a4 hydrogen atom, then R does not represent an anilino, 4-chloroanilino, 2,6-dichloroanilino,3,4-dichloroOTilino, 2,5-dichloroanilino, 3-chloro-4-fluoroani!ino or 4-fluoroanilino group; or a pharmaceutically acceptable salt or solvate thereof. 2. The medicament as claimed in claim I, wherein R" represents a hydrogen atom, or a C4-Cio alkyl or myrtanyl group, or a group (CH2) yCONH-R^ where y is 1 or 2 and R represents a phenyl group substituted by a piperidyl substituent group. 3. The medicament as claimed in claim 1 or claim 2, wherein R^ represents a hydrogen atom or a methyl group, or R^ together with R^ represents a carbon-carbon single bond provided that X is 0, or R^ together with R"* represents a group =CH2. 4. The medicament as claimed in any one of claims I to 3, wherein R"" represents a hydrogen atom, a methyl or ethyl group, a C2-C|o alkylamino group optionally substituted by a dJ(C2-C4 alkyl)amino substituent group, an anilino group substituted by a piperidyl substituent group, -SCH2CH2OH, -SCH2CH2NH2, -SCH2CH2(NH2)C02H, -SCH2CH2NHCO-R^ whert: R* represents a C? alkyl, cyclopropyl, cyclopentyl or cyclohexyl group or a phenyl group substituted by a nitro, C1-C4 alkyl or C3-C6alkoxy substituent group, or R"* is linked to R as defined in claim 1. 5. The medicament as claimed in claim 1 wherein the compound of formula (I) is selected trom: I -DecylpyrraIidine-2,5-dione, i-((6,6-Dimethy!bicycIo[3,l,l]hept-3-yl)methyl)-3-methyl-3-pyrroUne-2,5-dione, 3-M ethyl-1 -nonyl-3-pyrroline-2,5-dione, 3-Methylene-l-nonyipyrrolidme-2,5-dione, 3-Methyl-l-octyi-3-pyrToline-2,5-dione, 3-Methylene-1 -octy lpyrroiidine-2,5-dione, (4-(3-methyl-2,5-dioxo-3-pyrrolinyl)phenyl)piperidine, l-Octyl-3 -pyrroline-2,5 -dione, l-Decyl-3-pyrroIine-2,5-dione, 1 -Nonyl-3-pyrro]me-2,5-dione, l-Butyi-3-pyrroline-2,5-dione, 1 -Hexy!-3-pyrroline-2,5-dione, l-(4-Piperidylphenyl)-3-pyrroline-2,5-dione, l-(Octyl-3-(octylamino)-pyrrolidine-2,5-dione, l-Decyl-3-(decylamino)pyTrolidine-2,5-dione, 3-(Octylamino)-3-pyrrolidine-2,5-dione, 3-(Heptylamino)-l-nonylpyiTolidine-2,5-dione, i-Nonyl-3-{nonylamino)pyrrolidine-2,5-dione, l-Nonyl-3-{octylamino)pyrrolidine-2,5-dione, 2-Amino-3-(3-methyl-l-nonyl-2,5-dioxo-pyrTolidin-3-ylthio)propanoicacid, 2-Amino-3-(3-methyl-1 -octyl-2,5-dioxo-pyrrolidin-3-ylthio)propanoicacid, 2-Amino-3-(l-octyl-2,5-dioxo-p>Trolidin-3-ylthio)propanoicacid, 3-Methyl-l-octylpyrrolidine-2,5-dione, 3-Methyl-1 -nonylpyiToUdine-2,5-dione, 2-(2,5-Dioxopyrrolidinyl)-N-(4-piperidylphenyl)ethanamide, 2-(2,5-Dioxopyrrolidinyl)-N-(4-piperidylphenyl)propanamide, 3-Ethyl-l-nonylpyrrolidine-2,5-dione, 3-(2-Aminoethylthio)-l-nonylpyrrolidine-2,5-dione, 2-Ethyl-N-(2-(!-nonyl-2,5-dioxopyrrolidin-3-ylthio)ethyl)hexanamide, £:yclopropyl-N-(2-(l-nonyl-2,5-dioxopyTrolidin-3-ylthio)ethyl)formamide, (4-Butylphenyl)-N-(2-(l-nonyl-2,5-dioxopyrrolidin-3-ylthio)ethyl)fonnamide, (4-Hexyloxyphenyl)-N-(2-(l-nonyl-2,5-dioxopyrrolidin-3-ylthio)ethyl)formamide, (4-Melhylphenyl)-N-(2-(l-nonyl-2,5-dioxopyrn>lidin-3-ylthio)ethyl)formamide, (4-(tert-Butyl)phenyl-N-(2-(l-nonyI-2,5-dioxopyrrolidin-3-ylthio)ethyI)formamide Cyciopentyl-N-(2-(l-nonyl-2,5-dioxopyrrolidin-3-ylthio)ethyl)formamide,ethane, Cyclohexyl-N-(2-(l-nonyl-2,5- (4-Nitrophenyl)-N-(2-(l-nonyl-2,5-dioxopyrrolidin-3-ylthio)ethyl)formamide, 3-({2-(Dibutylamino)ethyl)amino)-l-nonylpytTolidine-2,5-dione, 3-((2-Diethylamino)ethy!)amino)-l -nonylpyrrolidine-2,5-dione, l-Nonyl-3-((4-piperidinylphenyl)amino)pyrrolidine-2,5-dione, 3-(HydroxyethyIthio)-3-methyl-l-nonylpyrrolidine-2,5-dione, 3-{2-Aminoethylthio)-3-methyl-l -nonylpyiTolidine-2,5-dione, and 3-Melhy !-t-octy 1-3-(octylammo)pyrrolidine-2,5-dione. 6. The medic^nent as claimed in any one of the preceding claims which is used for the treatment of mycobacterial disease such as M. tuberculosis, M. bovis, M. avium and particularly tuberculosis.

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