TETRACYCLIC DERIVATIVES. PROCESS OF PREPARATION AND USE— This invention relates to a series of tetracyclic derivatives, to processes for their preparation, pharmaceutical compositions containing them, and their use as therapeutic agents. In particular, the invention relates to tetracyclic derivatives which are potent and selective inhibitors of cyclic guanosine 3',5'- monophosphate specific phosphodiesterase (cGMP specific PDE) having utility in a variety of therapeutic areas where such inhibition is thought to be beneficial, including the treatment of cardiovascular disorders. Thus, according to a first aspect, the present invention provides compounds of formula (I) (Figure removed) and salts and solvates (e.g. hydrates) thereof, in which: R° represents hydrogen, halogen or C1-6 alkyl; R1 represents hydrogen, C1-6alkyl, C2-6alkenyI, C2-6 alkynyl, haloC1-6alkyl, C3-8cycloalkyl, C3-8cycloalkylC1-3alkyl, arylC1-3alkyl or heteroarylOC1-3alkyl; R2 represents an optionally substituted monocyclic aromatic ring selected from benzene, thiophene, furan and pyridine or an optionally substituted bicyclic ring ^^ attached to the rest of the molecule via one of the benzene ring carbon atoms and wherein the fused ring A is a 5- or 6-membered ring which may be saturated or partially or fully unsaturated and comprises carbon atoms and optionally one or two heteroatoms selected from oxygen, sulphur and nitrogen; and R3 represents hydrogen or d.3 alkyl, or R1 and R3 together represent a 3- or 4- membered alkyl or alkenyl chain. There is further provided by the present invention a subgroup of compounds of formula (I), the subgroup comprising compounds of formula (la) (Figure removed) and salts and solvates (e.g. hydrates) thereof, in which: R° represents hydrogen, halogen or C1-6 alkyl; R1 represents hydrogen, C1-6alky!, haloC1-6alkyl, C3-8cycloalkylC1-3alkyl, arylC1-3alkyl or heteroarylC1-3alkyl; and R2 represents an optionally substituted monocyclic aromatic ring selected from benzene, thiophene, furan and pyridine or an optionally substituted bicyclic ring (Figure removed) attached to the rest of the molecule via one of the benzene ring carbon atoms and wherein the fused ring A is a 5- or 6-membered ring which may be saturated or partially or fully unsaturated and comprises carbon atoms and optionally one or two heteroatoms selected from oxygen, sulphur and nitrogen. Within R1 above, the term "aryl" as part of an arylC1-3alkyl group means phenyl or phenyl substituted by one or more (e.g. 1, 2 or 3) substituents selected from halogen, C1-6alkyl, C1-6alkoxy and methylenedioxy. The term "heteroaryl" as part of a heteroarylC1-3alkyl group means thienyl, furyl or pyridyl each optionally substituted by one or more (e.g. 1, 2 or 3) substituents selected from halogen, C1-6 alkyl and C1-6alkoxy. The term "C3-8cycloalkyl" as a group or part of a C3-8cycloalkylC1-3alkyl group means a monocyclic ring comprising three to-eight carbon atoms. Examples of suitable cycloalkyl rings include the C3-6cycloalkyl rings cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. Within R2 above, optional benzene ring substituents are selected from one or more (e.g. 1, 2 or 3) atoms or groups comprising halogen, hydroxy, C1-6alky!, C-i^alkoxy, -CO2Rb, haloC1-6alkyl, haloC1-6alkoxy, cyano, nitro and NRaRb, where Ra and Rb are each hydrogen or C1-6alky!, or Ra may also represent C2-7alkanoyl or C1-6alkylsulphonyl. Optional substituents for the remaining ring systems are selected from one or more (e.g. 1, 2 or 3) atoms or groups comprising halogen, C1-6alkyl, C1-6alkoxy and arylC1-3alkyl as defined above. The bicyclic ring (Figure removed) may, for example, represent naphthalene, a heterocycle such as benzoxazole, benzothiazole, benzisoxazole, benzimidazole, quinoline, indole, benzothiophene or benzofuran or Y (where n is an integer 1 or 2 and X and Y may each represent CH2, 0, S or NH), In the above definitions, the term "alky!" as a group or part of a group means a straight chain or, where available, a branched chain alkyl moiety. For example, it may represent a C1-4alkyl function as represented by methyl, ethyl, n-propyl, i-propyl, n-butyl, s-butyl and t-butyl. The term 'alkenyl' as used herein includes straight-chained and branched alkenyl groups, such as vinyl and allyl groups. The term 'alkynyl' as used herein includes straight-chained and branched alkynyl groups, suitably acetylene. The term "halogen" herein means a fluorine, chlorine, bromine or iodine atom. The term "haloC1-6alkyl" means an alkyl group as defined above comprising one to six carbon atoms substituted at one or more carbon atoms by one or more (e.g. 1, 2 or 3) halogen atoms. Similarly, a haloC1-6alkoxy group is a haloC1-6alkyl group as defined above linked to the R2 benzene ring via an oxygen atom. Examples of haloC1-6alkyl groups include trifluoromethyl and 2,2,2-trifluoroethyl. An example of a haloC1-6alkoxy group is trifluoromethoxy. The term "C2-7alkanoyl" means a C1-6alkylcarbonyl group where the C1-6alkyl portion is as defined above. An example of a suitable C2-7alkanoyl group is the C2alkanoyl group acetyl. It will be appreciated that when R° is a halogen atom or a C1-6alkyl group this substituent may be sited at any available position on the phenyl portion of the tetracyclic ring. However, a particular site of attachment is the ring 10- position. The compounds of formula (I) may contain two or more asymmetric centres and thus can exist as enantiomers or diastereoisomers. In particular, in formula (I) above two ring chiral centres are denoted with asterisks. It is to be understood that the invention includes both mixtures and separate individual isomers of the compounds of formula (I). The compounds of formula (I) may also exist in tautomeric forms and the invention includes both mixtures and separate individual tautomers thereof. The pharmaceutically acceptable salts of the compounds of formula (I) which contain a basic centre are acid addition salts formed with pharmaceutically acceptable acids. Examples include the hydrochloride, hydrobromide, sulphate or bisulphate, phosphate or hydrogen phosphate, acetate, benzoate, succinate, fumarate, maleate, lactate, citrate, tartrate, gluconate, methanesulphonate, b,enzenesulphonate and p-toluenesulphonate salts. Compounds of the formula (Figure removed) can also provide pharmaceutically acceptable metal salts, in particular alkali metal salts, with bases. Examples include the sodium and potassium salts. A particular group of compounds of the invention are those compounds of formula (I) in which R° is hydrogen or halogen (e.g. fluorine), especially hydrogen. Another particular group of compounds of the invention are those compounds of formula (I) in which R1 represents hydrogen, C1-4alkyl, haloC1-4alkyl,, C3-6cycloalkyl, C3-6cycloalkylmethyl, pyridylC1-3alkyl, furylC1-6alkyl or optionally substituted benzyl. Within this particular group of compounds, examples of C1-4alkyl groups are methyl, ethyl, n-propyl, i-propyl and n-butyl. Examples of C3-6cycloalkylmethyl groups are cyclopropylmethyl and cyclohexylmethyl. Examples of optionally substituted, benzyl groups include benzyl and halobenzyl (e.g. fluorobenzyl). A further particular group of compounds of the invention are those compounds of formula (I) in which R2 represents an optionally substituted benzene, thiophene, furan, pyridine or naphthalene ring or an optionally substituted bicyclic ring v Y (where n is 1 or 2 and X and Y are each CH2 or O). Within this particular group of compounds, examples of substituted benzene groups are benzene substituted by one of halogen (e.g. chlorine), hydroxy, C1-3alkyl (e.g. methyl, ethyl or i-propyl), C1-6alkoxy (e.g. methoxy or ethoxy), -CO2Rb, halomethyl (e.g. trifluoromethyl), halomethoxy (e.g. trifluoromethoxy), cyano, nitro or NRaRb where Ra and Rb are each hydrogen or methyl or Ra is acetyl; or benzene substituted by dihalo (e.g. dichloro) or by C1-3alkoxy (e.g. methoxy) and one of halogen (e.g. chlorine) and hydroxy. An example of a substituted thiophene ring is a halo (e.g. bromo) substituent thiophene ring. A still further particular group of compounds of formula I are those wherein R3 represents hydrogen or R1 and R3 together represent a 3-membered alkyl chain. A preferred group of compounds of the invention are the cis isomers of formula (I) represented by formula (Ib) and mixtures thereof with their cis optical enantiomers, including racemic mixtures, and salts and solvates (e.g. hydrates) of these compounds in which R° is hydrogen or halogen (e.g. fluorine), especially hydrogen and R1, R and R3 are as defined previously. The single isomers represented by formula (Ib), i.e. the 6R, 12aR isomers, are particularly preferred. Within the above definitions R may preferably represent C1-4alkyl (e.g. methyl, ethyl, i-propyl and n-butyl), C3-6cycloalkyl (e.g. cyclopentyl) or C3-6cycloalkylmethyl (e.g. cyclopropylmethyl). R2 may preferably represent a substituted benzene ring such as benzene substituted by C1-3alkoxy (e.g. methoxy) or by C1-3alkoxy (e.g. methoxy) and halogen (e.g. chlorine), particularly 4-methoxyphenyl or 3-chloro-4- methoxyphenyl, or R2 may preferably represent 3,4-methylenedioxyphenyl. It is to be understood that the present invention covers all appropriate combinations of particular and preferred groupings hereinabove. Particular individual compounds of the invention include: Cis-2,3,6,7, 1 2, 1 2a-hexahydro-2-(4-pyridylmethyl)-6-(3,4- methylenedioxyphenyl)-pyrazino[2', 1' : 6, 1]pyrido[3,4-b]indole-1 ,4-dione; Cis-2,3,6,7, 12,1 2a-hexahydro-6-(2,3-dihydrobenzo[b]furan-5-yl)-2-methylpyrazino[ 2', 1 ':6, 1 ]pyrido[3,4-b]indole -1 ,4-dione; Cis-2,3,6,7, 12,1 2a-hexahydro-6-(5-bromo-2-thienyl)-2-methylpyrazino[ 2', 1 ':6, 1 ]pyrido[3,4-b]indole -1 ,4-dione; pyrazino[2', 1 '.6,1 ]pyrido[3,4-b]indole -1 ,4-dione; (6R, 1 2aR)-2, 3,6,7 , 1 2, 1 2a-Hexahydro-2-isopropyl-6-(3,4- methylenedioxyphenyl)-pyrazino[2', 1 ':6, 1 ]pyrido[3,4-b]indole -1 ,4-dione; (6R, 1 2aR)-2,3,6.7, 1 2, 1 2a-Hexahydro-2-cyclopentyl-6-(3,4- methylenedioxyphenyO-pyrazino'.l'iG.ljpyridoIS-bJindole -1,4-dione; (6R, 1 2aR)-2,3,6,7,1 2, 12a-Hexahydro-2-cydopropylmethyl-6-(4-methoxyphenyl)- pyrazino[2', 1 ':6, 1 ]pyrido[3,4-b]indole -1 ,4-dione; (6R, 1 2aR)-2,3,6,7,1 2, 1 2a-Hexahydro-6-(3-chloro-4-methoxyphenyl)-2-methyl- -1 ,4-dione; pyrazino[2', 1 ':6, 1 ]pyrido[3,4-b]indole-1 ,4-dione; ( 6 R , a R . S . e . . a - H e x a h y d r o - e - C S pyrazino[2', 1' : 6,1] pyrido [3,4-b] indole-1 ,4-dione; (5aR, 12R, 14aS)-1, 2,3,5,6, 11,1 2, 14a-Octahydro-12-(3,4- methylenedioxyphenyl)-pyrrolo[1",2" : 4' ,5']pyraz\r\o[2' ,V : 6,1]pyrido[3,4- b]indole-5-1 ,4-dione; and physiologically acceptable salts and solvates (e.g. hydrates) thereof. A specific compound of the invention is: (6R, 1 2aR)-2,3,6,7, 1 2, 1 2a-hexahydro-2-methyl-6-(3,4-methylenedioxyphenyl)- pyrazino[2',1':6,1]pyrido[3,4-b]indole -1,4-dione; and physiologically acceptable salts and solvates (e.g. hydrates) thereof. It has been shown that compounds of the present invention are potent and selective inhibitors of cGMP specific PDE. Thus, compounds of formula- (I) are of interest for use in therapy, specifically for the treatment of a variety of conditions where inhibition of cGMP specific PDE is thought to be beneficial. As a consequence of the selective PDE V inhibition exhibited by compounds of the present invention, cGMP levels are elevated, which in turn can give rise to beneficial anti-platelet, anti-neutrophil, anti-vasospastic, vasodilatory, natriuretic and diuretic activities as well as potentiation of the effects of endothelium-derived relaxing factor (EDRF), nitrovasodilators, atrial natriuretic factor (ANF), brain natriuretic peptide (BMP), C-type natriuretic peptide (CNP) and endothelium-dependent relaxing agents such as bradykinin, acetylcholine and 5-HT.,. The compounds of formula (I) therefore have utility in the treatment of a number of disorders, including stable, unstable and variant (Prinzmetal) angina, hypertension, pulmonary hypertension, congestive heart failure, renal failure, atherosclerosis, conditions of reduced blood vessel patency (e.g. postpercutaneous transluminal coronary angioplasty), peripheral vascular disease, vascular disorders such as Raynaud's disease, inflammatory diseases, stroke, bronchitis, chronic asthma, allergic asthma, allergic rhinitis, glaucoma and diseases characterised by disorders of gut motility (e.g. irritable bowel syndrome). It will be appreciated that references herein to treatment extend to prophylaxis as well as treatment of established conditions. It will also be appreciated that 'a compound of formula (I),' or a physiologically acceptable salt or solvate thereof can be administered as the raw compound, or as a pharmaceutical composition containing either entity. There is thus provided as a further aspect of the invention a compound of formula (I) for use in the treatment of stable, unstable and variant (Prinzmetal) angina, hypertension, pulmonary hypertension, chronic obstructive pulmonary disease, congestive heart failure, renal failure, atherosclerosis, conditions of reduced blood vessel patency, (e.g. post-PTCA), peripheral vascular disease, vascular disorders such as Raynaud's disease, inflammatory diseases, stroke, bronchitis, chronic asthma, allergic asthma, allergic rhinitis, glaucoma or diseases characterised by disorders of gut motility (e.g. IBS). According to another aspect of the invention, there is provided the use of a compound of formula (I) for the manufacture of a medicament for the treatment of stable, unstable and variant (Prinzmetal) angina, hypertension, pulmonary hypertension, chronic obstructive pulmonary disease, congestive heart failure, renal failure, atherosclerosis, conditions of reduced blood vessel patency, (e.g. post-PTCA), peripheral vascular disease, vascular disorders such as Raynaud's disease, inflammatory diseases, stroke, bronchitis, chronic asthma, allergic asthma, allergic rhinitis, glaucoma or diseases characterised by disorders of gut motility (e.g. IBS). In a further aspect, the invention provides a method of treating stable, unstable and variant (Prinzmetal) angina, hypertension, pulmonary hypertension, chronic obstructive pulmonary disease, congestive heart failure, renal failure, atherosclerosis, conditions of reduced blood vessel patency, (e.g. post-PTCA), peripheral vascular disease, vascular disorders such as Raynaud's disease, inflammatory diseases, stroke, bronchitis, chronic asthma, allergic asthma, allergic rhinitis, glaucoma or diseases characterised by disorders of gut motility (e.g. IBS) in a human or non-human animal body which comprises administering to said body a therapeutically effective amount of a compound with formula (I). Compounds of the invention may be administered by any suitable route, for example by oral, buccal, sub-lingual, rectal, vaginal, nasal, topical or parenteral (including intravenous, intramuscular, subcutaneous and intracoronary) administration. Oral administration is generally preferred. For administration to man in the curative or prophylactic treatment of the disorders identified above, oral dosages of a compound of formula (I) will generally be in the range of from 0.5-800mg daily for an average adult patient (70kg). Thus for a typical adult patient, individual tablets or capsules contain from 0.2-400mg of active compound, in a suitable pharmaceutically acceptable vehicle or carrier, for administration in single or multiple doses, once or several times per day. Dosages for intravenous, buccal or sublingual administration will typically be within the range of from 0.1-400 mg per single dose as required. In practice the physician will determine the actual dosing regimen which will be most suitable for an individual patient and it will vary with the age, weight and response of the particular patient. The above dosages are exemplary of the average case but there can be individual instances in which higher or lower dosage ranges may be merited, and such are within the scope of this invention. For human use, a compound of the formula (I) can be administered alone, but will generally be administered in admixture with a pharmaceutical carrier selected with regard to the intended route of administration and standard pharmaceutical practice. For example, the compound may be administered orally, buccally or sublingually, in the form of tablets containing excipients such as starch or lactose, or in capsules or ovules either alone or in admixture with excipients, or in the form of elixirs or suspensions containing flavouring or colouring agents. Such liquid preparations may be prepared with pharmaceutically acceptable additives such as suspending agents (e.g. methylcellulose, a semi-synthetic glyceride such as witepsol or mixtures of glycerides such as a mixture of apricot kernel oil and PEG-6 esters or mixtures of PEG-8 and caprylic/capric glycerides). A compound may also be injected parenterally, for example intravenously, intramuscularly, subcutaneously or intracoronarily. For parenteral administration, the compound is best used in the form of a sterile aqueous solution which may contain other substances, for example salts, or monosaccharides such as mannitol or glucose, to make the solution isotonic with blood. Thus, the invention provides in a further aspect a pharmaceutical composition comprising a compound of the formula (I) together with a pharmaceutically acceptable diluent or carrier therefor. There is further provided by the present invention a process of preparing a pharmaceutical composition comprising a compound of formula (I), which process comprises mixing a compound of formula (I) together with a pharmaceutically acceptable diluent or carrier therefor. A compound of formula (I) may also be used in combination with other therapeutic agents which may be useful in the treatment of the above-mentioned disease states. The invention thus provides, in another aspect, a combination of a compound of formula (I) together with another therapeutically active agent. The combination referred to above may conveniently be presented for use in the form of a pharmaceutical formulation and thus pharmaceutical compositions comprising a combination as defined above together with a pharmaceutically acceptable diluent or carrier comprise a further aspect of the invention. The individual components of such a combination may also be administered either sequentially or simultaneously in separate pharmaceutical formulations. Appropriate doses of known therapeutic agents for use in combination with a compound of formula (I) will be readily appreciated by those skilled in the art. Compounds of formula (I) may be prepared by any suitable method known in the art or by the following processes which form part of the present invention. In the methods below R°, R^ and R^ are as defined in formula (I) above unless otherwise indicated. Thus, a process (A) for preparing a compound of formula (I) wherein R3 represents hydrogen comprises treating a compound of formula (II) (Figure removed) (in which Alk represents C1-6alky, e.g. methyl or ethyl and Hal is a halogen atom, e.g. chlorine) with a primary amine R1NH2 in a suitable solvent such as an alcohol (e.g. methanol or ethanol) or a mixture of solvents, conveniently at a temperature of from 20°C to reflux (e.g. at about 50°C). A compound of formula (II) may conveniently be prepared by treating a compound of formula (III) (Figure removed) with a haloacetyl halide (e.g. chloroacetyl chloride) in a suitable solvent such as a halogenated hydrocarbon (e.g. trichloromethane or dichloromethane), or an ether (e.g. tetrahydrofuran), preferably in the presence of a base such as an organic amine (e.g. a trialkylamine such as triethylamine) or an alkali metal carbonate or bicarbonate (e.g. NaHCOs). The reaction may conveniently be effected at a temperature of from -20°C to +20°C (e.g. at about 0°C). A compound of formula (I) may also be prepared from a compound of formula (III) in a two-step procedure via a compound of formula (II) isolated without purification. Compounds of formula (I) may be prepared as individual enantiomers in two steps from the appropriate enantiomer of formula (III) or as mixtures (e.g. racemates) of either pairs of cis or trans isomers from the correspondong mixtures of either pairs of cis or trans isomers of formula (III). Individual enantiomers of the compounds of the invention may be prepared from racemates by resolution using methods known in the art for the separation of racemic mixtures into their constituent enantiomers, for example using HPLC (high performance liquid chromatography) on a chiral column such as Hypersil naphthylurea. A compound of formula (III) may conveniently be prepared from a tryptophan alkyl ester of formula (IV) (Figure removed) (where Alk is as previously defined) or a salt thereof (e.g. the hydrochloride salt) according to either of the following procedures (a) and (b). Procedure (b) is only suitable for preparing cis isomers of formula (III) and may be particularly suitable for preparing individual cis enantiomers of formula (III) from D- or Ltryptophan alkyl esters as appropriate. Procedure (a) This comprises a Pictet-Spengler cyclisation between a compound of formula (IV) and an aldehyde R^CHO. The reaction may conveniently be effected in a suitable solvent such as a halogenated hydrocarbon (e.g. dichloromethane) or an aromatic hydrocarbon (e.g. toluene) in the presence of an acid such as trifluoroacetic acid. The reaction may conveniently be carried out at a temperature of from -20°C to reflux to provide a compound of formula (III) in one step. The reaction may also be carried out in a solvent such as an aromatic hydrocarbon (e.g. benzene or toluene) under reflux, optionally using a Dean- Stark apparatus to trap the water produced. The reaction provides a mixture of cis and trans isomers which may be either individual enantiomers or racemates of pairs of cis or trans isomers depending upon whether racemic or enantiomerically pure tryptophan alkyl ester was used as the starting material. Individual cis or trans enantiomers may conveniently be separated from mixtures thereof by fractional crystallisation or by chromatography (e.g. flash column chromatography) using appropriate solvents and eluents. Similarly, pairs of cis and trans isomers may be separated by chromatography (e.g. flash column chromatography) using appropriate eluents. An optically pure trans isomer may also be converted to an optically pure cis isomer using suitable epimerisation procedures. One such procedure comprises treating the trans isomer or a mixture (e.g. 1 : 1 mixture) of cis and trans isomers with methanolic or aqueous hydrogen chloride at a temperature of from 0°C to the refluxing temperature of the solution. The mixture may then be subjected to chromatography (e.g. flash column chromatography) to separate the resulting diastereoisomers, or in the procedure utilising aqueous hydrogen chloride the desired cis isomer precipitates out as the hydrochloride salt which may then be isolated by filtration. Procedure (b) This comprises a four-step procedure from a compound of formula (IV) or a salt thereof (e.g. the hydrochloride salt). The procedure is particularly suitable for preparing a 1R, 3R isomer of formula (III) from a D-tryptophan alkyl ester of formula (IV) or a salt thereof (e.g. the hydrochloride salt). Thus, a first step (i) comprises treating a compound of formula (IV) with an acid halide R^COHal (where Hal is as previously defined) in the presence of a base, e.g. an organic base such as a trialkylamine (for example triethylamine), to provide a compound of formula (V) (Figure removed) The reaction may be conveniently carried out in a suitable solvent such as a halogenated hydrocarbon (e.g. dichloromethane) or an ether (e.g. tetrahydrofuran) and at a temperature of from -20°C to +40°C. Step (ii) comprises treating a compound of formula (V) with an agent to convert the amide group to a thioamide group. Suitable sulfurating agents are well-known in the art. Thus, for example, the reaction may conveniently be effected by treating (V) with Lawesson's reagent. This reaction may conveniently be carried out in a suitable solvent such as an ether (e.g. dimethoxyethane) or an aromatic hydrocarbon (e.g. toluene) at an elevated temperature such as from 40°C to 80°C to provide a compound of formula (Figure removed) Step (iii) comprises treating a compound of formula (VI) with a suitable agent to provide a compound of formula (VII) (Figure removed) (where Hal is a halogen atom, e.g. iodine). The reaction may conveniently be effected by treating (VI) with an alkylating agent such as a methyl halide (e.g. methyl iodide) or an acylating agent such as an acetyl halide (e.g. acetyl chloride) in a suitable solvent such as a halogenated hydrocarbon (e.g. dichloromethane) at an elevated temperature (e.g. under reflux). In step (iv) the resulting iminium halide of formula (VII) may be treated with a reducing agent such as boron hydride, e.g. sodium borohydride, to provide the desired compound of formula (III). The reduction may conveniently be effected at a low temperature, e.g. within the range of -100°C to 0°C, in a suitable solvent such as an alcohol (e.g. methanol). There is further provided by the present invention a process (B) for preparing a compound of formula (I), wherein R1 and R3 together represent a 3- or 4- membered alkyl or alkenyl chain, which process (B) comprises cyclisation of a compound of formula (VIII) (Figure removed) wherein Alk represents C1-6alkyl and R1 and R3 together represent a 3- or 4- membered chain both as hereinbefore described. The cyclisation is suitably carried out in an organic solvent or solvents, such as an alcoholic solvent (e.g. methanol) and optionally an ether .solvent such as tetrahydrofuran, and in the presence of a reducing agent, aptly a palladium catalyst, such as palladium on carbon. Conveniently a compound of formula (VIII) is prepared by reaction of a compound of formula (III) as hereinbefore described with a compound of formula (Figure removed) wherein Hal represents a halogen atom as hereinbefore described, R1 and R3 together represent a 3- or 4-membered chain as hereinbefore described and R4 represents a protecting group, suitably a benzyloxycarbonyl group or the like. Typically the reaction is carried out in a chlorinated organic solvent, such as dichloromethane, and a tertiary amine, such as triethylamine or the like. According to a further aspect of the present invention, there is provided a process (C) for preparing a compound of formula (I) wherein R3 represents Ci. 3alkyl, which process comprises cyclisation of a compound of formula (X) (Figure removed) wherein Alk represents C1-6alkyI as hereinbefore described and R5 represents C2-5alkyi, substituted at C1 by a halogen atom, the halogen atom being as hereinbefore described. Suitably the cyclisation is achieved by reflux for many hours, such as 22 to 26 hours, in the presence of an ether solvent, such as tetrahydrofuran, and a suitable amine as hereinafter described in the accompanying examples. Aptly a compound of formula (X) can be prepared from a compound of formula (III) by suitable acylation techniques, such as reaction with a C1-3carboxylic acid, substituted at C2 by a halogen atom in a halogenated organic solvent, such as dichloromethane. Compounds of formula (I) may be converted to other compounds of formula (I). Thus, for example, when R2 is a substituted benzene ring it may be necessary or desirable to prepare the suitably substituted compound of formula (I) subsequent to .process (A), (B) or (C) as above. Examples of appropriate interconversions include nitro to amino or aralkyloxy to hydroxy by suitable reducing means (e.g. using a reducing agent such as SnCl2 or a palladium catalyst, such as palladium-on-carbon), or amino to substituted amino such as acylamino or sulphonylamino using standard acylating or sulphonylating conditions, In the case where R2 represents a substituted bicyclic system, suitable interconversion can involve removal of a substituent: such as by treatment with a palladium catalyst (e.g. palladium-on-carbon) whereby, for example, a benzyl substituent may be removed from a suitable bicyclic system. The pharmaceutically acceptable acid addition salts of the compounds of formula (I) which contain a basic centre may be prepared in a conventional manner. For example, a solution of the free base may be treated with a suitable acid, either neat or in a suitable solution, and the resulting salt isolated either by filtration or by evaporation under vacuum of the reaction solvent. Pharmaceutically acceptable base addition salts may be obtained in an analogous manner by treating a solution of a compound of formula (I) with a suitable base. Both types of salt may be formed or interconverted using ionexchange resin techniques. Compounds of the invention may be isolated in association with solvent molecules by crystallisation from or evaporation of an appropriate solvent. Thus, according to a further aspect of the invention, we provide a process for preparing a compound of formula (I) or a salt or solvate (e.g. hydrate) thereof which comprises process (A), (B) or (C) as hereinbefore described followed by i) an interconversion step; and/or either ii) salt formation; or iii) solvate (e.g. hydrate) formation. There is further provided by the present invention compounds of formulae (II), (VIII), (X) and further compounds of formulae (III), (V), (VI) and (VII), with the exception for compounds (III), (V), (VI) and (VII) wherein R° is hydrogen, R2 is phenyl and Alk is methyl. The synthesis of the compounds of the invention and of the intermediates for use therein are illustrated by the following, non-limiting Examples. In the Examples section hereinafter the following abbreviations are used: DMSO (dimethylsulphoxide), MeOH (methanol), EtOH (ethanol), DMF (dimethylformamide), EtOAc (ethyl acetate) and THF (tetrahydrofuran). Intermediates 1 and 2 Methyl 1,2.3,4-tetrahvdro-1 -(3.4-methvlenedioxvphenvn-9H-pyrido[3,4- b1indole-3-carbQxvlate. cis and trans isomers To a stirred solution of racemic tryptophan methyl ester (13 g) and piperonal (9.7 g) in anhydrous CH2CI2 (300 ml) cooled at 0°C was added dropwise trifluoroacetic acid (9 ml) and the solution was allowed to react at ambient temperature. After 4 days, the yellow solution was diluted with CH2CI2 (100 ml), washed with a saturated aqueous solution of NaHCOs, then with water and dried over Na2S04- The organic layer was evaporated to dryness under reduced pressure and the residue was purified by flash chromatography eluting with CH2Cl2/MeOH (99/1) to give first Intermediate 1. the cis isomer (6.5 g) m.p. : 90-93°C followed by Intermediate 2. the trans isomer (6.4 g) m.p.: 170°C. The following compounds were obtained in a similar manner: Intermediates 3 arid 4 Methyl 1,2,3.4-tetrahvdro-1-(4-methoxvphenvn-9H-pyridof3.4-b1indole-3- carboxylate, cis and trans isomers The same method but starting from racemic tryptophan methyl ester and 4- methoxybenzaldehyde gave Intermediate 3. the cis isomer as white crystals m.p.: 142°C and Intermediate 4. the trans isomer as white crystals m.p.: 209- 210°C. Intermediate 5 Methyl 1,2.3.4-tetrahvdro-1 -(3-methoxvphenvn-9H-pyridof3.4-b1indole-3- carboxylate, cis isomer The same method but starting from racemic tryptophan methyl ester and 3- methoxybenzaldehyde gave the title compound as white crystals m.p.: 146°C. Intermediates 6 and 7 Methyl 1,2.3.4-tetrahydro-1 -(4-ethoxvphenvn-9H-pyridof3.4-b1indole-3- carboxylate. cis and trans isomers The same method but starting from racemic tryptophan methyl ester and 4- ethoxybenzaldehyde gave Intermediate 6. the cis isomer as white crystals m.p.: 180°C and Intermediate 7. the trans isomer as white crystals m.p.: 196-198°C. Intermediates 8 and 9 Methyl 1.2,3.4-tetrahydro-1 -(2.3-dihydrobenzorb1furan-5-vn-9H-pyridof3.4- blindole-3-carboxylate, cis and trans isomers The same method but starting from racemic tryptophan methyl ester and 2,3- dihydrobenzo[b]furan-5- carboxaldehyde gave Intermediate 8. the cis isomer as white crystals m.p. : 106-109°C and Intermediate 9. the trans isomer as white crystals m.p : 219-222°C. Intermediates 10 and 11 Methyl 1,2.3,4-tetrahvdro-1 -(3.4-ethvlenedioxvphenvn-9H-pvridof3,4-b1indole-3- carboxylate. cis and trans isomers The same method but starting from racemic tryptophan methyl ester and 1,4- benzodioxan-6-carboxaldehyde gave Intermediate 10. the cis isomer as white crystals m.p. 104-106°C and Intermediate 11, the trans isomer as white crystals m.p. : 207-209°C. intermediate, Methyl 1.2.3.4-tetrahydro-1 -(2-chlorophenvl)-9H-pvridof3.4-b1indole-3- carboxylate. mixture of cis and trans isomers The same method but starting from racemic tryptophan methyl ester and 2- chlorobenzaldehyde gave the title compound as white crystals m.p.: 154°C. Intermediates 13 and 14 Methyl 1.2.3.4-tetrahvdro-1-(4-chlorophenvl)-9H-pvridof3.4'-b1indole-3- carboxylate. cis and trans isomers The same method but starting from racemic tryptophan methyl ester and 4- chlorobenzaldehyde gave Intermediate 13. the cis isomer as white crystals m.p. : 208-209°C and Intermediate 14. the trans isomer as white crystals m.p. : 108- 109°C. Intermediates 15 and 16 Methyl 1.2.3.4-tetrahvdro-1-(3.4-dichlorophenvn-9H-pyridof3.4-blindole-3- carboxylate. cis and trans isomers The same method but starting from racemic tryptophan methyl ester and 3,4- dichlorobenzaldehyde gave Intermediate 15, the cis isomer as a white solid ^ H NMR (CDCI3) 8 (ppm): 7.8-7 (m, 8H, H aromatic); 5.15 (brs, 1H, H-1); 3.9 - 3.8 (dd, 1H, H-3) 3.7 (s, 3H, CO2CH3) ; 3.2-3.1 (ddd, 1H, H-4) 2.9 (m, 1H, H-4) ; 2.4 (brs, 1H, NH) and Intermediate 16. the trans isomer as a white solid m.p. : 204°C. Intermediate 17 Methyl 1,2.3.4-tetrahydro-1 -(1.2.3.4-tetrahvdro-6-naphthvl)-9H-pvridof3.4- b]indole-3-carboxylate, cis isomer The same method but starting from racemic tryptophan methyl ester and 1,2,3,4- tetrahydronaphthyl-6- carboxaldehyde gave the title compound as a white solid 1H NMR (CDCi3) 6 (ppm) : 7.7-7(m, 8H, H aromatic); 5.2 (s, 1H, H-1) ; 4.0 (dd, 1H, H-3) ; 3.8 (s, 3H, CO2CH3) ; 3.2 (m, 1H, H-4) ; 3.0 (m, 1H, H-4) ; 2.7 (m, 4H, ; 1 .7 (s, 4H, Intermediates 18 and 1.9 Methyl 1 ,2,3.4-tetrahvdro-1 -(2-naphthvn-9H-pyridor3.4-b1indole-3-carboxvlate. cis and trans isomers The same method but starting from racemic tryptophan methyl ester and 2- naphthaldehyde gave Intermediate 18. the cis isomer as a white solid 1 H NMR (CDCIs) 6 (ppm) : 8-6.9 (m, 12H, H aromatic) ; 5.4 (s, 1H, H-1) ; 3.95 (dd, 1H, H- 3) ; 3.7 (s, 3H, CO2CH3) 3.2 (ddd, 1H, H-4) ; 3 (m, 1H, H-4) ; 2.5 (brs, 1H, NH) and Intermediate 19. the trans isomer as a white solid (0.6 g) m.p. : 1 19°C. Intermediates 20 and 21 Methyl 1 .2.3.4-tetrahvdro-1-(2-thienvn-9H-pvridof3.4-b1indole-3-carboxvlate. cis and trans isomers The same method but starting from racemic tryptophan methyl ester and 2- thiophenecarboxaldehyde gave Intermediate 20. the cis isomer as a pale yellow solid m.p. : 134-137°C and Intermediate 21 . the trans isomer as white crystals m.p. :169°C. Intermediates 22 and 23 Ethyl 1 .2.3.4-tetrahvdro-1-(3-thienvl)-9H-pvridof3.4-b1indole-3-carboxvlate. cis and trans isomers The same method but starting from racemic tryptophan ethyl ester and 3- thiophenecarboxaldehyde gave Intermediate 22. the cis isomer as white crystals m.p. : 130°C and Intermediate 23, the trans isomer as white crystals m.p. :182- 184°C. Intermediates 24 and 25 Methyl 1.2,3,4-tetrahydro-1-(5-bromo-2-thienvn-9H-pvridof3.4-b1indole-3- carboxylate. cis and trans isomers The same method but starting from racemic tryptophan methyl ester, and 5- bromo-2-thiophenecarboxaldehyde gave Intermediate 24, the cis isomer as a cream solid m.p.: 130°C and Intermediate 25. the trans isomer as a cream solid m.p. :205°C., Intermediates 26 and 27 Methyl 1.2.3.4-tetrahvdro-1 -(4-bromo-2-thienvm-9H-pvridor3.4-b1indole-3- carboxylate. cis and trans isomers The same method but starting from racemic tryptophan methyl ester and 4- bromo-2-thiophenecarboxaldehyde gave Intermediate 26. the cis isomer as a cream solid m.p.: 200°C and Intermediate 27. the trans isomer as a cream solid m.p. : 120°C. Intermediate 28 Methyl 1.2.3.4-tetrahvdro-1 -(3-furvn-9H-pyridof3.4-b1indole-3-carboxvlate. mixture of cis and trans isomers The same method but starting from racemic tryptophan methyl ester and 3- furaldehyde gave the title compound as a yellow solid m.p.: 130°C. Intermediates 29 and 30 Ethyl 1,2.3.4-tetrahvdro-1 -(5-methvl-2-furvl)-9H-pyridor3.4-plindole-3- carboxylate. cis and trans isomers The same method but starting from racemic tryptophan ethyl ester and 5- methylfurfural gave Intermediate 29. the cis isomer as a oily compound 1H NMR (CDCI3) 6 (ppm): 7.7 (brs, 1H, NH indole); 7.5 (d, 1H, H aromatic); 7.25-6.9 (m, 3H, H aromatic); 6.15 (d, 1H, H aromatic); 5.85 (m, 1H, H aromatic); 5.25 (brs, 1 H, H-1); 4.2 (q, 2H, CO2CH2CH3); 3.8 (dd, 1 H, H-3); 3.2 - 2.8 (m, 2H, H-4); 2.2 (s, 3H, CHs); 1.25 (t, 3H, CC^Ch^CHs) and Intermediate 30. the trans isomer as a cream solid m.p. : 152°C. Intermediates 31 and 32 Ethyl 1.2,3,4-tetrahvdro-1-(4-methvlphenvl)-9H-pyridor3,4-b1indole-3- carboxylate, cis and trans isomers The same method but starting from racemic tryptophan ethyl ester and ptolualdehyde gave Intermediate 31. the cis isomer as white crystals m.p. : 148°C and Intermediate 32, the trans isomer as white crystals m.p. : 180°C. Intermediates 33 and 34 Methyl 1,2.3.4-tetrahvdro-1 -(3-methvlphenvn-9H-pyridof3.4-b1indole-3- carboxylate. cis and trans isomers The same method but starting from racemic tryptophan methyl ester and mtolualdehyde gave Intermediate 33, the cis isomer as white crystals IH NMR (CDCIa) 6(ppm): 7.6-7 (m, 9H, H aromatic); 5.2 (brs, 1H, H-1); 4-3.9 (dd, 1H, H- 3) 3.8 (s, 3H, C02CH3) ; 3.2 - 3.1 (ddd, 1H, H-4) 3 (m, 1H, H-4) ; 2.35 (s, 3H, CHs) ; 1.7 (brs, 1H, NH) and Intermediate 34. the trans isomer as a white solid m.p. : 175°C. Intermediates 35 and 36 Methyl 1.2.3.4-tetrahydro-1 -(4-trifluoromethvlphenvl)-9H-pyridor3.4-b1indole-3- carboxylate. cis and trans isomers The same method but starting from racemic tryptophan methyl ester and 4- trifluoromethylbenzaldehyde gave Intermediate 35. the cis isomer as pale yellow crystals m.p. : 190°C and Intermediate 36. the trans isomer as pale yellow crystals m.p.: 203°C. Intermediates 37 and 38 Ethyl 1,2.3.4-tetrahvdro-1 -(4-cyanophenvn-9H-pyridof3.4-b1indole-3- carboxvlate. cis and trans isomers The same method but starting from racemic tryptophan ethyl ester and 4- cyanobenzaldehyde gave Intermediate 37. the cis isomer as white crystals m.p. : 200°C and Intermediate 38. the trans isomer as white crystals m.p.: 156°C. Intermediate 39 Methyl 1,2.3.4-tetrahvdro-1 -(4-hvdroxvphenvn-9H-pyridor3.4-b1indo!e-3- carboxylate. cis isomer The same method but starting from racemic tryptophan ethyl ester and 4- hydroxybenzaldehyde gave the title compound as pale yellow crystals 1,H NMR (DMSO) 5(ppm) : 10.3 (s, 1H, NH-indole) 9.4 (s, 1H, OH) ; 7.8 - 7.5 (m, 8H, H aromatic) ; 5.1 (brs, 1H, H-1) ; 3.9 (m, 1H, H-3) ; 3.75 (s, 3H, COaCHa) 3.1 (m, 1H, H-4); 2.8 (m, 1H, H-4). Intermediate 40 Methyl 1.2.3.4-tetrahvdro-1 -(3-hvdroxv-4-methoxyphenvn-9H-pvridof3.4- blindole-3-carboxvlate. cis isomer The same method but starting from racemic tryptophan methyl ester and 3- hydroxy-4-methoxybenzaldehyde gave the title compound as a yellow solid m.p. : 140-148°C. Intermediate 41 Methyl 1.2.3.4-tetrahvdro-1 -(4-hvdroxv-3-methoxvphenvn-9H-pyrido[3.4- blindole-3-carboxylate. cis isomer The same method but starting from racemic tryptophan methyl ester and 4- hydroxy-3-methoxybenzaldehyde gave the title compound as a cream solid m.p. : 195°C. Intermediate 42 Methyl 1.2.3.4-tetrahvdro-1 -(4-ethvlphenvl)-9H-pyridor3.4-b1indole-3- carboxvlate. cis and trans isomers The same method but starting from racemic tryptophan methyl ester and 4- ethylbenzaldehyde gave the cis and trans isomer of the title compound. Cis isomer: white solid 1H NMR (CDCIs) 8(ppm): 7.65-7.1 (m, 9H, H aromatic); 5.25 (brs, 1H, H-1); 4(dd, 1H, H-3); 3.9 (s, 3H, CO2CH3); 3.4 (ddd, 1H, H-4); 3.1 (m, 1H, H-4); 2,7 (q, 2H, CHHs) 1.4 (t, 3H, CCHa). Trans isomer: white solid m.p.: 187°C. Intermediates 43 and 44 Methyl 1.2.3.4-tetrahvdro-1-(4-isopropvlphenvl)-9H-pvridof3.4-b1indole-3- carboxylate. cis and trans isomers The same method but starting from racemic tryptophan ethyl ester and 4- isopropylbenzaldehyde gave Intermediate 43, the cis isomer as a white solid 1H NMR (DMSO) 8(ppm): 10.15 (s, 1H, NH indole); 7.3-6.7 (m, 8H, H aromatic) ; 5 (brs, 1H, H-1) ; 3.6 (m, 1H, H-3); 3.5 (s, 3H, CCCHa); 2.95-2.5 (m, 3H, H-4 + CH-(Me)2) 2.4 (brs, 1H, NH) ; 1(d, 6H, 2xCH3) and Intermediate 44. the trans isomer as a white solid m.p : 189°C. Intermediates 45 and 46 Ethyl 1,2,3.4-tetrahvdro-1 -(4-nitrophenvl)-9H-pvridof3.4-b1indole-3-carboxvlate. cis and trans isomers The same method but starting from racemic tryptophan ethyl ester and 4- nitrobenzaldehyde gave Intermediate 45. the cis isomer as yellow crystals m.p. : 168°C and Intermediate 46, the trans isomer as yellow crystals m.p.: 195°C. Intermediate 47 Ethyl 1.2.3.4-tetrahvdro-1-(4-dimethvlaminophenvn-9H-pvridof3.4-b1indole-3- carboxvlate. mixture of cis and trans isomers The same method but starting from racemic tryptophan ethyi ester and 4- dimethylaminobenzaldehyde gave the title compound as white crystals m.p. : 170°C. Intermediates 48 and 49 Ethyl 1.2.3.4-tetrahvdro-1-(3-pyridvl)-9H-pvridor3.4-b1indole-3-carboxvlate. cis and trans isomers The same method but starting from racemic tryptophan ethyl ester and 3- pyridinecarboxaldehyde gave Intermediate 48. the cis isomer as pale yellow crystals m.p. : 230-232°C and Intermediate 49t the trans isomer as white crystals m.p. :210-214°C. Intermediates 50 and 51 Methyl 1.2.3.4 tetrahvdro-6-fluoro-1-(3.4-methvlenedioxvphenvl)-9H-pyridor3.4- b|indole-3-carboxyiate. cis and trans isomers The same method but starting from racemic 5-fluoro-tryptophan methyl ester and piperonai gave Intermediate 50, the cis isomer as a cream solid m.p, :60°C and Intermediate 51. the trans isomer as a cream solid m.p.: 213°C. Intermediates 52 and 53 Methyl 1,2,3.4-tetrahvdro-6-fluoro-1-(4-methoxvphenvn-9H-pyridof3,4-b1indole- 3-carboxylate. cis and trans isomers The same method but starting from racemic 5-fluoro-tryptophan methyl ester and 4-methoxybenzaldehyde gave Intermediate 52. the cis isomer as a solid 1H NMR (CDCIs) 6 (ppm) : 7.4-6.8 (m, 8H, H aromatic) ; 5.15 (brs, 1H, H-1) ; 3.9 (dd, 1H, H-3) 3.8 (s, 3H, CO2CH3) ; 3.2-2.9 (m, 2H, H-4) and Intermediate 53. the trans isomer as a solid m.p.: 197°C. Intermediates 54 and 55 (1 R.3R)-Methyl 1.2.3.4-tetrahvdro-1-(3.4-methvlenedioxvphenvl)-9H-pvridof3.4- blindole-3-carboxylate. cis isomer and (1 S.3R)-methvl 1.2.3.4-tetrahvdro-1-(3.4-methvlenedioxvphenvl)-9H-pyrido[3,4- bTindole-3-carboxylate trans isomer To a stirred solution of D-tryptophan methyl ester (11 g) and piperonal (7.9 g) in anhydrous CH2CI2 (400 mL) cooled at 0°C was added dropwise trifluoroacetic acid (7.7 ml) and the solution was allowed to react at ambient temperature. After 4 days, the yellow solution was diluted with CH2CI2 (200 mL) and washed with a saturated aqueous solution of NaHCOs, then with water (3x200 mL) and dried over Na2SO4- The organic layer was evaporated under reduced pressure and the residue was purified by flash chromatography eluting with dichloromethane/ethyl acetate (97/3) to give first Intermediate 54, the cis isomer (6.5 g) m.p. : 154°C followed by Intermediate 55. the trans isomer (8.4 g) m.p. : 188°C. The following compounds were obtained in a similar manner: Intermediate 56 (1 S. 3S) Methvl-1.2.3.4-tetrahvdro-1-(3.4-methvlenedioxvphenvn-9H-pvridof3.4- blindole-3-carboxylate. cis isomer and (1R. 3S) methvl-1.2,3.4-tetrahvdro-1-(3,4-methvlenedioxvphenvl)-9H-pyridof3.4- blindole-3-carboxylate. trans isomer The same method but starting from L-tryptophan methyl ester and piperonal gave the cis and trans isomers of the title compound. Cis isomer: white crystals m.p. : 154°C. Trans isomer: white crystals m.p. : 187-189°C. Intermediates 57 and 58 (1 R.3R)-Methyl 1.2.3.4-tetrahvdro-1-(4-methoxvphenvl)-9H-pyrido[3,4-b1indole- 3-carboxylate, cis isomer and (1S.3R)-methvl 1.2.3.4-tetrahvdro-1-(4-methoxvphenvn-9H-pyridof3.4-b1indole- 3-carboxylate, trans isomer The same method but starting from D-tryptophan methyl ester and 4- methoxybenzaldehyde gave Intermediate 57. the cis isomer as white crystals m.p. : 124-125°C and Intermediate 58, trans isomer as white crystals m.p. : 219- 222°C. Intermediates 59 and 60 (1R. 3R)-Methvl 1.2.3.4-tetrahvdro-1-(3-chloro-4-methoxvphenvn-9H-pyridof3.4- blindole-3-carboxvlate. cis isomer and (1S. 3R)-methvl 1.2.3.4-tetrahvdro-1-(3-chloro-4-methoxyphenvn 9H-pyridof3.4- blindole-3-carboxylate. trans isomer The same method, but starting from D-tryptophan methyl ester and 3-chloro-4- methoxybenzaldehyde gave Intermediate 59. the cis isomer isolated as the hydrochloride salt as white crystals m.p. : 200°C and Intermediate 60. the trans isomer as white crystals m.p.: 164°C. Intermediates 61 and 62 (1 R.3R)-Methyl 1.2.3.4-tetrahvdro-1-(2.3-dihvdrobenzofb1furan-5-vn-9Hpyrido[ 3.4-b]indole-3-carboxvlate. cis isomer and (1 S.3R)-methvl 1.2.3.4-tetrahydro-1 -(5-(2.3-dihydrobenzofblfuran))-9Hpyrido[ 3.4-b]indole-3-carboxylate. trans isomer The same method but starting from D-tryptophan methyl ester and 2,3- dihydrobenzo[b]furan-5-carboxaldehyde gave Intermediate 61. the cis isomer as white crystals m.p. : 282°C and Intermediate 62. the trans isomer as white crystals m.p. : 204°C, Intermediates 63 and 64 (1 R,3R)-Methyl 1,2,3.4-tetrahvdro-1-(5-indanvlV9H-pyrido[3.4-b1indole-3- carboxvlate cis isomer and (1S.3R)-methyl 1.2,3,4-tetrahydro-1-(5-indanvn-9H-pyridof3.4-b]indole-3- carboxylate trans isomer The same method but starting from D-tryptophan methyl ester and indan-5- carboxaldehyde gave Intermediate 63. the cis isomer as white crystals m.p. : 130-131 °C and Intermediate 64. the trans isomer as white crystals m.p.: 196°C. Intermediate 65 Ethyl 1.2.3,4-tetrahvdro-1-(4-trifluoromethoxvphenvl)-9H-pyrido[3.4-blindole-3- carboxylate, cis and trans isomers The same method but starting from racemic tryptophan ethyl ester and 4- trifluoromethoxybenzaldehyde gave cis and trans isomers of the title compound. Cis isomer: white crystals m.p.: 88°C. Trans isomer: white crystals m.p.: 152°C. Intermediate 66 Methyl 1.2.3.4-tetrahvdro-1-(5-methvl-2-thienvn-9H-pyrido r3.4-b1indole-3- carboxvlate. cis and trans isomers The same method but starting from racemic tryptophan methyl ester and 5- methyl-2-thiophenecarboxaldehyde gave the cis and trans isomers of the title compound. Cis isomer: oily compound 1H NMR (CDCIa) 8 (ppm): 8.4 (brs, 1H, NH-indole); 7.7 - 6.6 (m, 6H, H aromatic); 5.5 (brs, 1H, H-1); 3.9 (dd, 1H, H-3); 3.85 (s, 3H, CO2CH3); 3.3 - 2.9 (m, 2H, H-4); 2.5 (s, 3H, CH3). Trans isomer: white crystals m.p.: 194°C. Intermediates 67 and 68 (1 S.3R)-Methvl 1.2.3.4-tetrahvdro-1 -(3.4-methvlenedioxyphenvn-9H-pvridof3.4- blindole-3-carboxvlate and (1 R.3R)-methvl 1.2.3.4-tetrahvdro-1 -(3.4-methvlenedioxyphenvl)-9H-pvridof3.4- blindole-3-carboxylate To a stirred solution of D-tryptophan methyl ester (obtained by treating the corresponding hydrochloride salt in water with saturated aqueous NaHCOs solution and extraction with CH2CI2) (25.7g) and piperonal (19.4g) in anhydrous dichloromethane (700ml) cooled to 0°C was added dropwise trifluoroacetic acid (18.1ml) and the solution was allowed to react at 4°C. After 5 days, the yellow solution was diluted with dichloromethane (500ml). The organic layer was washed with a saturated aqueous solution of NaHCOs, then with water (3 x 500ml) until the pH was neutral and dried over N32SO4- The organic layer was evaporated under reduced pressure to a volume of about 500ml. The transisomer, which crystallised, was filtered and the filtrate was reduced to 200ml. Another fraction of the trans-isomer crystallised. The fractions of trans-isomer were combined to give the (1S.3R) isomer, Intermediate 67. as white crystals (11.4g). mp: 188°C 20° [x]p = +32.4° (c = 1.03, CHC!3). The filtrate containing mainly the cis-isomer was reduced to 100ml and isopropyl ether (200ml) was added. Upon cooling, the (1R.3R) isomer, Intermediate 68. crystallised as a white solid (17.4g). mp: 154-155°C 20° [ap = + 24.4° (c = 1.03, CHCy. Intermediate 69 (1 R.3R)-Methvi 1,2.3.4-tetrahvdro-1-(3.4-methvlenedioxyphenvl)-9H-pvridof3.4- bjindole-3-carboxylate Method A Intermediate 67 (S.Og) was dissolved in methanol (150ml). Hydrogen chloride was bubbled into the solution for several minutes at 0°C and the resulting yellow solution was refluxed for 24 hours. The solvent was removed under reduced pressure and the residue was basified with a saturated aqueous solution of NaHCOs and extracted with dichloromethane. The organic layer was washed with water, dried over Na2SO4 and purified by flash chromatography eluting with dichloromethane/methanol (99/1) to give the title compound (2.3g) corresponding to an authentic sample of Intermediate 68. Method B Intermediate 67 (25g) was heated in 1N hydrochloric acid (78.5m!) and water (400ml) at 60°C for 36 hours. From the initial pale yellow solution, a white solid precipitated. The mixture was then allowed to cool to 0°C and the solid filtered. The sofid was then washed with diisopropyl ether (3 x 200ml) and dried to give the hvdrochloride salt of the title compound (20g) as a white solid. mp(dec.):209-212°C Method C A 1 : 1 mixture of the cis and trans isomers of Intermediates 54 and 55 (2g) was heated in 1N hydrochloric acid (6.8ml) and water (15ml) at 50°C for 72 hours. A similar work-up as described in Method B above gave the hydrochloride salt of the title compound (1.7g) as a white solid. Intermediate 70 (R)-Na-(3.4-Methvlenedioxvphenvlcarbonvn-trvptophan methyl ester To a suspension of D-tryptophan methyl ester hydrochloride (10.2g) in anhydrous CH2CI2 (150ml) cooled at 0°C was added dropwise triethylamine (12.3ml). To the resulting solution solid piperonyloyl chloride (8.16g) was added portionwise at the same temperature, and the mixture was stirred at room temperature for 2 h. The mixture was washed successively with water, 0.5N hydrochloric acid, water, a saturated aqueous solution of NaHCOs and again with water. After drying over Na2SO4 and evaporation of the solvent under reduced presure, the resulting oil on trituration from hot cyclohexane afforded the title compound as a white solid (14.7g). mp: 123-124°C 70° [a]p = - 84.4° (c = 1.04, CHCIg). Intermediate 71 (R)-N-(3.4-Methvlenedioxyphenvlthiocarbonvn-trvptophan methyl ester A mixture of Intermediate 70 (14g) and Lawesson's reagent (9.28g) in dimethoxyethane (280ml) was heated at 60°C under N2 for 16 hours with stirring. The reaction mixture was evaporated to dryness and the resulting oil was dissolved in ethyl acetate, then washed successively with an aqueous saturated solution of NaHCOs and water and dried over Na2S04- The oily residue obtained after evaporation under reduced pressure gave, on trituration from cyclohexane, a yellow powder which was filtered and washed with cooled methanol to afford the title compound (9.74g). mp: 129-130°C 200 [a]p =-186.8° (c= 1.14, CHCI3). Intermediate 72 (1 R.3R)-Methvl 1.2.3.4-tetrahvdro-1 -(3.4-methvlenediowphenvl V9H-pyridof3.4- blindole-3-carboxylate A solution of Intermediate 71 (9g) and methyl iodide (10ml) in anhydrous dichloromethane (200ml) was heated at reflux under an argon atmosphere with protection from light. After 24 hours, the solvent was removed under reduced pressure to give an orange oil which on trituration from hexane gave a solid which was washed with ether and used without further purification in the next step. This compound (13.11g) was dissolved in methanol (250ml) and the solution was cooled to -78°C. NaBH4 (0.99g) was then added by portions and the mixture was stirred at the same temperature for 1 hour. The reaction was quenched by addition of acetone (10ml) and the solvent was removed under reduced pressure. The residue was dissolved in CH2CI2, washed with water and then with brine and dried over N32SO4. After evaporation of the solvent, the orange oil gave on trituration from a hot mixture of diethyl ether/cyclohexane an orange powder which was recrystallised from diethyl ether/pentane to afford the title compound as a pale yellow solid (5.15g) corresponding to an authentic sample of Intermediate 68. Intermediate 73 (1 R.3R)-Methvl 1.2.3.4-tetrahydrO'2-chloroacetvl-(3.4-methvlenedioxvphenvngH- pyridofS^-blindole-S-carboxylate Method A To a stirred solution of Intermediate 72 (9.7g) and NaHCOs (2.79g) in anhydrous CHCI3 (200ml) was added dropwise chloroacetyl chloride (5.3ml) at 0°C under N2- The resulting mixture was stirred for 1 hour at the same temperature and diluted with CHCI3 (100ml). Water (100ml) was then added dropwise with stirring to the mixture, followed by a saturated aqueous solution of NaHCO3 The organic layer was washed with water until neutrality and dried over Na2SO4 After evaporation of the solvent under reduced pressure, the oily compound obtained was crystallised from ether to give the title compound as a pale yellow solid (9.95g). mp : 233°C 90° [a]p =-125.4° (c= 1.17, CHCIg). Method B Chloroacetyl chloride (4ml) was added dropwide to a solution of Intermediate 72 (16.1g) and triethylamine (7ml) in anhydrous CH2CI2 (200ml) at 0°C under N2- The solution was stirred at 0°C for 30 minutes, then diluted with CH2CI2 (300ml). The solution was washed with water (200ml), a saturated aqueous solution of NaHCOs (300ml) and brine (400ml). After drying over Na2SO4 and evaporation under reduced pressure, the resulting solid was washed with ether (300ml) to give the title compound as a pale yellow solid (18.3g). Intermediate 74 Methyl -1- S-tetrahydro-S-methyl-l -(3.4-methvlenedioxvphenvl)-9H-pvridof3.4- blindole-3-carboxylate. cis and trans isomers The cis and trans isomers of the title compound were prepared using the method described in Intermediate 1 but starting from racemic 5-methyltryptophan methyl ester and piperonal. Cis isomer: yellow solid m.p.: 85°C. Trans isomer: yellow solid m.p.: 185°C. Intermediates 75 and 76 (1R. 3R)-Methvl 1.2.3.4-tetrahvdro-1 -(7-(4-methyl-3.4-dihydro-2Hbenzo[ 1.41oxazinvl))-9H-pyrjdo[3.4-b1indole-3-carboxvlate. cis isomer and (18, 3R)-Methvl 1.2.3.4-tetrahvdro-1-(7-(4-methvl-3.4-dihvdro-2Hbenzof 1,41oxazinvn)-9H-pvridof3.4-b1indole-3-carboxvlate. trans isomer The same method, as described for intermediates 54 and 55, but starting from D-tryptophan methyl ester and 4-methyl-3,4-dihydro-2H-benzo[1,4]oxazine-7- carboxaldehyde gave Intermediate 75 the cis isomer as an oily compound 1H NMR (CDCI3) 6 (ppm): 7.6-7.1 (m, 5H); 6.9-6.6 (m, 3H); 5.15 (br s, 1H) ; 4.3 (t, 2H) ; 4 (dd, 1 H); 3.8 (s, 3H); 3.3 (t, 2H); 3.3-2.95 (m, 2H); 2.9 (s, 3H); 1.6 (br s) and intermediate 76, the trans isomer as white crystals m.p. : 119-121 °C. Intermediate 77 Methyl 1,2.3.4-tetrahvdro-1 -(S-(N-benzvlindolinvn)-9H-pyridor3,4-b1indole-3- carboxvlate. mixture of (1R. 3R) and (1S. 3R) isomers The same method, as described for intermediates 54 and 55, but starting from D-tryptophan methyl ester and N-benzylindoline-5-carboxaldehyde gave intermediate 77 as an oily compound. Intermediates 78 and 79 (1R. 3R)-Methvl 1.2.3.4-tetrahvdro-1-(4-carbomethoxvphenvn-9H-pyridor3.4- blindole-3-carboxvlate. cis isomer and (1S. 3R)-methvl 1.2.3.4-tetrahvdro-1-(4- carbomethoxvphenvl)-9H-pyrido[3.4-b1indole-3-carboxvlate. trans isomer The same method, as described for intermediates 54 and 55, but starting from D-tryptophan methyl ester and methyl 4-formylbenzoate gave Intermediate 78, the cis isomer as white crystals m.p. : 157-160°C and Intermediate 79, the trans isomer as pale yellow crystals m.p.: 124-126°C. Intermediate 80 (1R. 3R)-Methvl 1.2.3.4-tetrahvdro-2-f2-(benzvloxvcarbonvn-R-prolvn-1-(3.4- methvlenedioxvphenvn-9H-pvrido[3.4-b1indole-3-carboxylate A solution of N-(benzyloxycarbonyl)-D-proline acid chloride (0.64 g, 2.4 mmol) in anhydrous dichloromethane (10 ml) was added dropwise to a stirred solution of intermediate 54 (0.7 g, 2 mmol) and triethylamine (0.33 mL, 2.4 mmol) in dichloromethane (15 ml) at - 10°C. The mixture was stirred for 2 h at - 10°C after which it was diluted with dichloromethane (50 mL), washed with hydrochloric acid (1N), water, a saturated solution of NaHC03, a saturated NaCI solution and dried over Na2S04. Evaporation of the solvent and recrystallisation of the crude product from methanol gave the title compound as pale yellow crystals (0.75 g) m.p. : 268-270°C. Intermediate 81 (1 R. 3R)-Methvl 1.2.3.4-tetrahvdro-2-f2-(benzyloxvcarbonvn-S-prolvn-1-(3.4- methvlenedioxyphenvn-9H-pvridor3.4-b1indole-3-carboxvlate A solution of N-(benzyloxycarbonyl)-L-proline acid chloride (0.86 g, 3.2 mmol) in anhydrous dichloromethane (10 mL) was added dropwise to a stirred solution of intermediate 54 (0.91 g, 2.6 mmol) and triethylamine (0.44 ml, 3.2 mmol) in dichloromethane (20 mL) at - 10°C. The mixture was stirred for 2 hours at - 10°C after which it was diluted with dichloromethane (60 mL), washed with hydrochloric acid (1N), water , .a saturated solution of NaHC03, a saturated NaCI solution and dried over Na2SO4. Evaporation of the solvent and recrystallisation of the crude product from methanol/water gave the title compound as pale yellow crystals (0.8 g) m.p. : 115-120°C. Intermediate 82 (1R. 3R)-Methvl 1.2.3.4-tetrahydro-2-(2-chloropropionvn-1-(3.4- methvlenedioxyphenvn-9H-pyridof3.4-b1indole-3-carboxvlate To a solution of (S)-(-)-2-chloropropionic acid (87 ul, 1 mmol) in anhydrous dichloromethane (15 ml), was added dicyclohexylcarbodiimide (0.23 g, 1.1 mmol). Intermediate 54 (0,35 g, 1 mrnol) was then added and the mixture was stirred at room temperature for 20 hours. The formed precipitate of dicyclohexylurea was removed by filtration, the filtrate was evaporated iavacuo and the crude product was purified by flash chromatography eluting with toluene/ethyl acetate : 95/5. The oily compound obtained was then crystallised from ether/hexane to give the title compound as pale yellow crystals (0.31 g) m.p. : 125-127°C. Intermediate 83 (1 R. 3R)-Methvl 1 .2.3,4-tetrahvdro-2-(2-chloropropionyl)-1-(3.4- methvlenedioxyphenyl)-9H-pyrido[3.4-b1indole-3-carboxvlate To a solution of (R)-(+)-2-chloropropionic acid (191 ul, 2.2 mmol) in anhydrous dichloromethane (30 mL), was added dicyclohexylcarbodiimide (0.45 g, 2.2. mol). Intermediate 54 (0,7 g, 2 mmol) was then added and the mixture was stirred at room temperature for 20 hours. The formed precipitate of dicyclohexylurea was removed by filtration, the filtrate was evaporated in vacuo and the crude product was purified by flash chromatography eluting with toluene/ethyl acetate : 95/5. The oily compound obtained was then crystallised from ether/hexane to give the title compound as pale yellow crystals (0.74 g) m.p. : 126-128°C Intermediates 84 and 85 (1 R, 3R)-Methyl 1 ^.S blindole-3-carboxvlate cis isomer and (1S. SRVmethvl 1.2.3.4-tetrahvdro-1-(3.4- dibenzvloxvphenvh-9H-Pvrido f3.4-b1indole-3-carboxvlate trans isomer The same method as described for intermediates 54 and 55 but starting from Dtryptophan methyl ester and 3,4-dibenzyloxybenzaldehyde gave intermediate 84, the cis isomer as an oily compound 1H NMR (CDCI3) 5(ppm): 7.5 - 6.95 (m, 15H) ; 6.85 (s, 1H) ; 6.75 (s, 2H) ; 5.1 (s, 2H) ; 5 (br s, 1H) ; 4.95 (d, 2H) 3.85 (dd, 1H) ; 3.7 (s, 3H); 3.2-2.8 (m, 2H); 2.3 (br s, 1H) and intermediate 85, the trans isomer as an oily compound 1HNMR (CDCI3) 8 (ppm) 7.6-7 (m, 15H); 6.9- 6.7 (m, 3H) ; 5.2 (br s, 1H) ; 5,1 (s, 2H) ; 5 (s, 2H) ; 3.8 (t, 1H) ; 3.65 (s, 3H) ; 3.3-3 (m, 2H); 2.25 (br s, 1H). Intermediate 86 (6R. 12aR)-2.3.67.12.12a-Hexahvdro-6-(3.4-dibenzvloxyphenvn-2-methvlpyrazino[ 2'. 1': 6.npyridof3.4-bTmdole-1.4-dione The same two step procedure but starting from intermediate 84 and methylamine gave, after recrystallisation from dichloromethane/ether, the title compound as white crystals m.p. : 158-160°C, [cc]20°D = + 11.7° (c = 1.23 ; CHCI3). Intermediate 87 Methyl 1.2.3.4-tetrahvdro-1 -(5-(2-methvlisoindolinvn)-9H-pvrido[3.4-b1indole-3- carboxvlate. mixture of (1R.3R) and (1S.3R) isomers The same method, as described for intermediates 54 and 55, but starting from D-tryptophan methyl ester and N-methylisoindoline-5-carboxaldehyde gave intermediate 87 as an oily compound. Example 1 Cis-2.3.6,7,12.12a-hexahvdro-2-methvl-6-(3.4-methvlenedioxvphenvn- Pvrazino[2'.1':6Jlpvridof3.4-blindole -1.4-dione a) To a stirred solution of intermediate 1 (2 g) and NaHCOs (0.6 g) in anhydrous CHCI3 (40 ml) was added dropwise chloroacetyl chloride (1.1 ml_) at 0°C. The resulting mixture was stirred for 1 hour at the same temperature and diluted with CHCI3. Water (20 ml) was then added dropwise with stirring to the mixture, followed by a saturated solution of NaHCOs- The organic layer was washed with water until neutrality and dried over N32SO4. After evaporation of the solvent under reduced pressure, cis-methvl 1.2.3.4- tetrahvdro-2-chloroacetvl-1-(3.4-methvlenedioxvphenvl)-9H-pyridof3.4- blindole-3-carboxvlate was obtained as an oil which was crystallised from ether (2 g, m.p. : 215-218°C) and was used without further purification in the next step. b) To a stirred suspension of the chloroacetyl intermediate (0.34 g) in MeOH (20 mL) was added at ambient temperature a solution of methylamine (33% in EtOH) (0.37 mL) and the resulting mixture was heated at 50°C under N2 for 1 4 hours. The solvent was removed under reduced pressure and the residue was dissolved in CH2CI2 (50 mL). After washing with water (3x30 mL), drying over Na2S04 and evaporating to dryness, the residue was purified by flash chromatography eluting with CH2Cl2/MeOH (99/1) and recrystallised from MeOH to give the title compound as white crystals (0.19 g) m.p. : 253-255°C. Analysis for Calculated:CJ67.86;H,4.92;N,10.79; Found:C,67.53;H,4.99;N,10.62%. The following compounds were obtained in a similar manner : Example 2 Cis-2. 3, 6. 7, 12. 12a-hexahvdro-2-butvl-10-fluoro-6-(4-methoxvphenvl)- pyrazinof2'. 1' ; 6.1lpyridof3.4-b1indole-1,4-dione The same two step procedure but starting from butylamine and intermediate 52 gave, after recrystallisation from ethanol, the title compound as white crystals m.p. : 182°C. Analysis for C25H26FN303 (0.1 H2O): Calculated : C, 68,67 ; H, 6.04 ; N, 9.61; Found : C, 68.38 ; H, 6.11 ; N, 9.53%. Example 3 Trans^.S.ej.^.^a-hexahydro^-methvl-e-OX-methvlenedioxyphenyi)- pyrazino[2'J;6l1lpyridof3.4-b|indole -1 ,4-dione The same two step procedure but starting from methylamine and intermediate 2 gave, after recrystallisation from toluene, the title compound as white crystals m.p. : 301-303°C. Analysis for 022H9O04 Calculated: C,67.86;H,4.92;N, 10.79; Found:C,67.98;H,4.98;N,10.73%. Example 4 Cis-2.3.6,7.12.12a-hexahvdro-6-(3.4-methvlenedioxvphenvl)- pyrazinof2'. 1 ':6.1 ]pvridof3.4-b1indole -1.4-dione The same two step procedure but starting from ammonia and intermediate 1 gave, after recrystallisation from methanol, the title compound as white crystals m.p. : 283-285°C. Analysis for C21H 17^04- Calculated: C.67.19;H,4.56;N, 11.19; Found:C,67.04;H,4.49;Nl11.10%. Example 5 Cis-2.3.6.7.12.12a-hexahydro-10-fluoro-6-(4-methoxvphenvl)-2-(2,2.2- trifluoroethvl)-pyrazinof2M': S.npyrido f3.4-b1indole-1.4-dione The same two step procedure but starting from 2,2,2-trifluoroethylamine and intermediate 52 gave, after recrystallisation from ethanol/diisopropyl ether, the title compound as white crystals m.p.: 190°C. Analysis for C 2 s H - 4 0 ) 3 : Calculated : C, 59.87 ; H, 4.15 ; N, 9.11; Found : C, 59.81 ; H, 4.18 ; N, 9.21%. Example 6 Cis-2.3,6,7,12.12a-hexahvdro-10-fluoro-2-methvl-6-(3.4-methvlenedioxyphenvl)- pyrazinof2',1' : 6,1 |pyridof3,4-b1indole-1.4-dione The same two step procedure but starting from methylamine and intermediate 50 gave, after recrystallisation from ethanol, the title compound as white crystals m.p. : 292°C. Analysis for C22H- 8 3 0 4 - Calculated : C, 64.86 ; H, 4.45 ; N, 10.31; Found : C, 64.66 ; H, 4.60; N, 10.21%. Example 7 (6R. 12aS)-2.3.6.7.12.12a-hexahvdro-2-methvl-6-(3.4-methvlenedioxyphenvnpyrazinof2'. 1': 6.11pvridof3.4-blindole-1.4-dione The same two step procedure but starting from methylamine and the trans isomer of intermediate 56 gave, after recrystallisation from toluene, the title compound as white crystals m.p. :287-289°C. Analysis for 622^19^04 (0.25 toluene): Calculated : C, 69.16 ; H, 5.13 ; N, 10.19; Found : C.69.09 ; H, 5.14 ; N, 10.19%. 20° [ot]D = -293.4° (C=1.28; CHCy. Example 8 (6S. 12aR V-2.3.6.7.12.12a-hexahvdro-2-methvl-6-(3.4-methvlenedioxvphenvl )- pyrazinof2'. 1': 6.npvridof3.4-b1ind6le-1.4-dione The same two step procedure but starting from methylamine and intermediate 55 gave, after recrystallisation from toluene, the title compound as white crystals m.p. : 287°C. Analysis for C22Hi 9 0 4 (0.3 toluene): Calculated : C, 69.41 ; H, 5.17 ; N, 10.08; Found : C, 69.56 ; H.5.24; N, 10.08%. 20° [a]D = + 297.9° (C=1.21; CHCy. Example 9 Cis-2. 3. 6. 7. 12. 12a-hexahydro-2-r2-(2-pyridvn-ethvn-6-(3.4- methvlenedioxyphenvn-pvrazinofZ.I'-e.npvridofS^-blindole-l^-dione The same two step procedure but starting from 2-(2-pyridyl)ethylamine and intermediate 1 gave, after recrystallisation from 2-propanol, the title compound as white crystals m.p.: 218-222°C. Analysis for C28H24N4O4: Calculated : C, 69.99 ; H, 5.03 ; N, 11.66; Found : C, 69.92 ; H, 5,16 ; N, 11.48%. Example 10 Cis-2.3.6.7.12.12a-hexahvdro-2-(2-pyridvlmethvn-6-(3.4- methylenedioxvphenvn-pvrazinof2'. 1': 6.npyridof3.4-b1indole-1.4-dione The same two step procedure but starting from 2-pyridylmethylamine and intermediate 1 gave, after recrystallisation from DMF/water, the title compound as cream crystals m.p : 285-286°C. Analysis for C27H20N4 (0.4 FO): Calculated : C, 68.46 ; H.4.85 ; N, 11.83; Found : C, 68.58 ; H, 4.88 ; N, 11.90%. Example 11 Cis-2.3.6.7.12.12a-hexahvdro-2-(3-pyridvlmethvn-6-(3.4- methvlenedioxvphenvn-pyrazinof2'. 1': 6.npvridof3.4-b1indole-1.4-dione The same two step procedure but starting from 3-pyridylmethylamine and intermediate 1 gave, after recrystallisation from CH2Cl2/MeOH, the title compound as cream crystals m.p.: 292-293°C. Analysis: 027^2^04: Calculated : C, 69.52 ; H, 4.75 ; N, 12.01; Found : C, 69.27 ; H, 4.74 ; N, 11.37%. Example 12 Cis-2.3.6.7.12.12a-hexahvdro-2-(4-pvridvlmethvn-6-(3.4- methvlenedioxvphenvn-pvrazinof2'. 1': 6.npyridor3.4-b1indole-1.4-dione The same two step procedure but starting from 4-pyridylmethylamine and intermediate 1 gave, after recrystallisation from MeOH, the title compound as pale yellow crystals m.p. : 273-274°C. Analysis for C27H22N4260°C. Analysis for C2iH-j7Cl2NsO2 (0.5 hO): Calculated: C,59.39;H,4.29;N,9.93; Found:C,59.32;H,4.16;N,9.99%. Example 44 Cis-2.3.6.7. 1 2. 1 2a-hexahvdro-2-butvl-6-phenvl-pyrazinof2'. 1 ':6. 1 1pyridor3.4- b]indole -1 . 4-dione The same two step procedure but starting from butylamine and cis-methyl 1 .S-tetrahydro-l-phenyl-gH-pyridofS-indole-S-carboxylate1 gave, after recrystallisation from methanol/water, the title compound as white crystals m.p. : 243-245°C. Analysis for C24H25N3O2: Calculated: C,74.39;H,6.50;N,10.84; Found:C,74.54;H,6.51;N,10.86%. 1. D. Soerens et al.. J. Org. Chem. 44, 535 - 545 (1979). Example 45 Cis-2.3.6.7.12.12a-hexahvdro-2-benzvl-6-phenvl-pyrazinor2'.1 ':6.11pyridof3.4- blindole -1,4-dione The same two step procedure but starting from benzylamine and cis-methyl- 1,2,3,4-tetrahydro-1-phenyl-9H-pyrido[3,4-b]indole-3-carboxylate gave, after recrystallisation from methanol, the title compound as white crystals m.p.: 193- 195°C. Analysis for C27H23N3O2: Calculated: C,76.94;H,5.50;N,9.97; Found:C,77.23;H,5.54;N,9.97%. Example 46 Trans-2.3.6.7.12.12a-hexahvdro-2-benzvl-€-phenvl-pyrazinof2'. 1 ':6.11pyridof3.4- blindole -1,4-djone The same two step procedure but starting from benzylamine and cis-methyl- 1 -S-tetrahydro-l-phenyl-gH-pyridop^-bjindole-S-carboxyiate gave, after recrystallisation from methanol, the title compound as white crystals m.p. : 284°C. Analysis for C2yH23N302: Calculated: C,76.94;H,5.50;N,9.97; Found:C,76.88;H,5.45;N,9.89%. Example 47 Cis-2.3.6.7.12.12a-hexahvdro-2-methvl-6-(1.2.3.4-tetrahvdro-6-naphthvl)- pyrazinof2'.1':6,npvridof3.4-blindole -1,4-dione The same two step procedure but starting from methylamine and intermediate 17 gave, after recrystallisation from methanol, the title compound as white crystals m.p.: >260°C. Analysis for C25H25N302: Calculated: C,75.16;H,6.31;N,10.52; Found:C,74.93;H,6.43;N,10.63%. Example 48 Cis-2.3.6.7.12.12a-hexahvdro-2-isopropvl-6-(1.2.3.4-tetrahvdro-6-naphthvl)- Pvrazinof2'.1':6.1lpyridof3.4-b1indole -1.4-dione The same two step procedure but starting from isopropylamine and intermediate 17 gave, after recrystallisation from the title compound as off-white crystals m.p.: 244-246°C. Analysis for C27H9N02 (0.25H2O): Calculated: C,75.06;H,6.88;N,9.73; Found:C,75.00;H,6.83;N,9.69%. Example 49 Cis-2.3.6.7.12.12a-hexahvdro-2-cvclopropvlmethvl-6-(1.2.3.4-tetrahvdro-6- naphthvn)H3vrazinof2'.1':6.1lpyridor3.4-b1indole -1,4-dione The same two step procedure but starting from cyclopropylmethylamine and intermediate 17 gave, after recrystallisation from ethanol/pentane, the title compound as white crystals m.p.: 125°C. Analysis for C28H29N3O2 (0.25 H2O): Calculated: C,75.73;H,6.70;N,9.46; Found:C,75.45;H,6.86;N,9.14%. Example 50 Cis-2.3.6.7.12.12a-hexahvdro-2-methvl-6-(2-naphthvl)- pyrazinof2'.1':6.11pvridof3.4-b1indole -1,4-dione The same two step procedure but starting from methylamine and intermediate 18 gave, after recrystallisation from dichloromethane/methanol, the title compound as white crystals m.p. : >260°C. Analysis for C25H2iN302 (0.25H2O): Calculated: C,75.08;H,5.42;N, 10.51; Found:C,75.35;H,5 42;N,10.49%. Example 51 Cis-2.3.6.7.12.12a-hexahydro-2-butvl-6-(2-thienvl)-pvrazinor2'. 1 ':6,11pyridor3.4- blindole -1.4-dione The same two step procedure but starting from butylamine and intermediate 20 gave, after recrystallisation from ethanol, the title compound as white crystals m.p.: 226°C. Analysis for 022H3N02S: Calculated: C,67.15;H,5.89;N,10.68; Found:C,67.39;H,5.88;N,10.77%. Example 52 Cis-2.3.6.7.12.12a-hexahvdro-6-f 5-bromo-2-thienvn-2-methvlpvrazinof2'. 1':6.npyridor3.4-b1indole -1.4-dione The same two step procedure but starting from methylamine and intermediate 24 gave, after recrystallisation from ethanol, the title compound as a cream powder m.p.: 258°C. Analysis for C-igH-ieBrNaOS: Calculated: C,53.03;H,3.75;N,9.76; Found:C,53.01 ;H,3.78;N,9.69%. Example 53 Cis-2.3.6.7.12.12a-hexahvdro-6-(4-bromo-2-thienvn-2-methvlpyrazinof2', 1 ':6.11pyridof3.4-blindole -1,4-dione The same two . step procedure but starting from methylamine and intermediate 26 gave, after recrystallisation from ethanol, the title compound as white crystals mp. : 292°C. Analysis for CigH-ieBrNaC2S (0.25H20): Calculated: C,52.48;H,3.82;N,9.66; Found:C,52.46;H,3.81;N,9.60%. Example 54 Cis-2.3.6.7.12.12a-hexahvdro-6-(5-bromo-2-thienvn-2-cvclopropylmethvlpvrazinof2'. 1':6.npvridof3.4-blindole-1.4-dione The same two step procedure but starting from cyclopropylmethylamine and intermediate 24 gave, after recrystallisation from ethanol, the title compound as white crystals m.p. : 190°C. Analysis for C22H2oBrN3O2S Calculated: C,56.18;H,4.29;N,8.93; 9 Found:C,55.92;H,4.28;N,8.74%. Example 55 Cis-2.3.6.7.12.12a-hexahvdro-6-(5-bromo-2-thienvl)-2-cvclopentvlpvrazinof2'. 1':6.npyridor3.4-b1indole-1.4-dione The same two step procedure but starting from cyclopentylamine and intermediate 24 gave, after recrystallisation from ethanol, the title compound as white crystals m.p.: 252°C. Analysis for 023283028: Calculated: C,57.03;H,4.58;N,8.67; Found:C,56.87;H,4.66;N,8.68%. Example 56 Cis-2.3.6.7.12.12a-hexahvdro-2-methvl-6-(5-methvl-2-thienvl)- pyrazinor2'.1':6.11pvridof3.4-b1indole -1,4-dione The same two step procedure but starting from methylamine and the cis isomer of intermediate 66 gave, after recrystallisation from ethanol, the title compound as white crystals m.p.: 282°C. Analysis for C2oHigN3O2S (0.25H2O): Calculated: C,64.93;H,5.31;N, 11.36; Found:C,64.84;H,5.28;N,10.81 %. Example 57 Cis-2.3.6.7.12.12a-hexahvdro-2-methvl-6-f 3-thienvOpyrazinof2'. 1':6.npvridof3.4-b1indole -1.4-dione The same two step procedure but starting from methylamine and intermediate 22 gave, after recrystallisation from acetone, the title compound as white crystals m.p. : 290-295°C. Analysis for C-igH-i/NsOS: Calculated: C,64.94;H,4.88;N,11.96; Found: C, 64.81 ; H.4.95 ; N,11.68%. Example 58 Cis-2.3.6.7.12.12a-hexahvdro-2-butvl-6-(3-thienvn-pyrazinof2'. 1 ':6.11pyrido[3.4- blindole -1,4-dione The same two step procedure but starting from butylamine and intermediate 22 gave, after recrystallisation from methanol, the title compound as white crystals m.p.: 236-239°C. Analysis for C22H23N302S: Calculated: C,67.15;H,5.89;N,10.68;S,8.15; Found:C,67.42;HI5.76;N,10.57;S,8.01%. Example 59 Cis-2.3.6.7.12.12a-hexahvdro-2-methvl-6-f3-furvn-pyrazinof2'.1 ':6.11pyridor3.4- b]indole-1,4-dione The same two step procedure but starting from methylamine and the cis isomer of intermediate 28 gave, after recrystallisation from ether, the title compound as a white solid m.p.: 250°C. Analysis for C-jgH-jyNsOa (0.5H2O): Calculated: C,66.27;H,5.27;N,12.20; Found:C,66.33;H,5.48;N,12.02%. Example 60 Cis-2.3.6.7.12.12a-hexahvdro-2-methvl-6-(5-methvl-2-furvl)- pvrazinof2'.1':6.npyridof3.4-b1indole -1,4-dione The same two step procedure but starting from methylamine and intermediate 29 gave, after recrystallisation from ethanol, the title compound as a cream powder m.p.: 303°C. Analysis for C2oHigN303 (0.25H2O): Calculated: C,67.88;H,5.55;N,11.87; Found:C,67.90;H,5.50;N,11.98%. Example 61 Cis-2.3.6.7.12.12a-hexahydro-2-methvl-6-(4-methvlphenyl)- pvrazinof2'.1':6.1l|pvridof3.4-bTmdole -1,4-dione The same two step procedure but starting from methylamine and intermediate 31 gave, after recrystallisation from ethanol, the title compound as white crystals m.p :>260°C. Analysis for C22H21 N3O2 (0.25 H2O): Calculated: C,72.61;H,5.95;N,11.55; Found:C,72.73;H,5.96;N,11.59%. Example 62 Cis-2.3.67.12.12a-hexahvdro-2-isopropvl-6-(4-methvlphenvnpyrazinof2'. 1 ':6.11pyridof3.4-b1indole -1.4-dione The same two step procedure but starting from isopropylamine and intermediate 31 gave, after recrystallisation from the title compound as white crystals m.p. : 170°C. Analysis for 624H5N02 (0.5H20): Calculated: C,72.70;H,6.61;N, 10.60; Found:C,73.06;H,6.43;N,9.66%. Example 63 Cis-2.3.6.7.12.12a-hexahvdro-2-butvl-6~(4-methvlphenvnpvrazinof2', 1':6.11pyridof3,4-b1indole -1,4-dione The same two step procedure but starting from butylamine and intermediate 31 gave, after recrystallisation from methanol, the title compound as white crystals m.p.: 194°C. Analysis for 625H7N02 (0.5H2O): Calculated: C,73.15;H,6.87;N, 10.24; Found:C,73.01 ;H,6.84.N, 10.26%. Example 64 Cis-2.3.6.7.12.12a-hexahvdro-2-cvclopropylmethvl-6-(4-methvlphenvnpvrazinof2'. 1 ':6.11pvridof3.4-b1indole -1.4-dione The same two step procedure but starting from cyclopropylmethylamine and intermediate 31 gave, after recrystallisation from methanol/water, the title compound as white crystals m.p.: 194°C. Analysis for 025H5N02 (1.1H2O): Calculated: C.71.61 ;H,6.54;N, 10.02; Found:C,71.42.H,607;N,9.95%. Example 65 Cis-2.3.6.7.12.12a-hexahvdro-2-methvl-€-(3-methvlphenvl)- pvrazinof2'.1':6.11pvridof3.4-b1indole-1.4-dione The same two step procedure but starting from methylamine and intermediate 33 gave, after recrystallisation from ethanol, the title compound as white crystals m.p.: >260°C. Analysis for C22H21 N3O2: Calculated: C,73.52;H,5.89;N,11.69; Found:C,73.60;H,5.97;N,11.66%. Example 66 Cis-2.3.6.7.12.12a-hexahvdro-2-butvl-6-(4-trifluQromethvlphenvl)- pvrazinof2'.1':6.1 I|pvrido|'3.4-b1indole -1,4-dione The same two step procedure but starting from butylamine and intermediate 35 gave, after recrystallisation from methanol/water, the title compound as white crystals m.p. : 155°C. Analysis for C25H24F3N3O2 (0.5H2O): Calculated: C,64.65;H,5.43;N,9.05; Found:C,64.78;H,5.40;N,9.01 %. Example 67 Cis-2.3.6.7.12.12a-hexahvdro-2-methvl-6-(4-trifluoromethoxvphenvnpvrazinof2', 1':6.npvridof3.4-b]indole-1.4-dione The same two step procedure but starting from methylamine and the cis isomer of intermediate 65 gave, after recrystallisation from methanol, the title compound as white crystals m.p. : 174-180°C. Analysis for C22H 18N303 (0.5H2O): Calculated: C,60.27;H,4.37;N,9.58; Found:C,60.24;H,4.28;N,9.50%. Example 68 Cis-2.3.6.7.12.12a-hexahvdro-2-methyl-6-(4-hvdroxvphenvn- Pvrazinof2'.1':6.npyridof3.4-blindole -1,4-dione The same two step procedure but starting from methylamine and intermediate 39 gave, after recrystallisation from methanol, the title compound as yellow crystals m.p. :179-180°C. Analysis for C2iH19N303(1.25H20): Calculated: C,65.70;H,5.64;N, 10.94; Found:C,65.46;H,5.45;N,10.92%. Example 69 Cis-2.3.6.7.12.12a-hexahvdro-6-(3-hvdroxv-4-methoxvphenvl)-2-methvlpyrazinof2'. 1':6.npvridof3.4-b1indole -1.4-dione The same two step procedure but starting from methylamine and intermediate 40 gave, after recrystallisation from ethanol, the title compound as white crystals m.p. :320°C. Analysis for C22H21 N3O4(0.25H2O): Calculated: C,66.74;H,5.47;N, 10.61; Found:C,66.72;H,5.46;N,10.53%. Example 70 Cis-2.3.6.7.12.12a-hexahvdro-6-f4-hvdroxv-3-methoxvphenvl)-2-methylpyrazinof2'. 1':6.1lpvridor3.4-b1indole -1.4-dione The same two step procedure but starting from methylamine and intermediate 41 gave, after recrystallisation from dichloromethane/ethanol, the title compound as yellow crystals m.p. :264-265°C. Analysis for C22H21 N64: Calculated: C,67.51;H,5.41;N, 10.74; Found:C,67.05;H,5.41;N, 10.62%. Example 71 Cis-2.3.6.7.12.12a-hexahvdro-2-butvl-6-(4-cyanophenvnpvrazino[ 2', 1 ':6.11pyridof3.4-b1indole -1,4-dione The same two step procedure but starting from butylamine and intermediate 37 gave, after recrystallisation from methanol/water, the title compound as white crystals m.p : 246°C. Analysis for C25H24N402 (1H2O): Calculated: C,69.75;H,6.09;N, 13.01; Found:C,69.50;H,5.96;N,12.86°/cK Example 72 Cis-2.3.6.7.12.12a-hexahvdro-6-(4-ethvlphenvn-2-isopropylpyrazinof2'. 1 ':6.11pyridof3.4-b1indole -1.4-dione The same two step procedure but starting from isopropylamine and the cis isomer of intermediate 42 gave, after recrystallisation from n-pentane, the title compound as white crystals m.p.: 130°C. Analysis for C25H27N3O2 (0-5H2O): Calculated: C,73.15;H,6.87;N, 10.24; Found:C,73.39;H,7.08;N,9.81 %. Example 73 Cis-2.3.6.7.12.12a-hexahvdro-6-(4-ethvlphenvn-2-cvclopropvlmethvlpvrazinof2'. 1':6.1lpvridof3.4-blindole -1,4-dione The same two step procedure but starting from cyclopropylmethylamine and the cis isomer of intermediate 42 gave, after recrystallisation from ethanol, the title compound as white crystals m.p.: 160°C. Analysis for C26H7N3O2: Calculated: C,75.52;H,6.58;N, 10.16; Found:C,75.54;H,6.62;N,10.08%. Example 74 Cis-2.3.6.7.12.12a-hexahvdro-6-(4-isopropylphenvl)-2-methvlpvrazinof2'. 1':6.11pvridof3.4-blindole -1,4-dione The same two step procedure but starting from methylamine and intermediate 43 gave, after recrystallisation from ethanol, the title compound as white crystals m.p. : 244°C. Analysis for 024H5N02: Calculated: C,74.39;H,6.50;N,10.84; Found:C,74.27;H,6.53;N, 11.05%. Example 75 Cis-2.3.6.7,12.12a-hexahvdro-2-butvl-6-(4-nitrophenvn- Pvrazinof2'.1':6,npyridof3.4-b1indole -1,4-dione The same two step procedure but starting from butylamine and intermediate 45 gave, after recrystallisation from methanol, the title compound as white crystals m.p. : 182°C. Analysis for C2H24N04 (0.25H2O): Calculated: C,65.97;H,5.65;N,12.82; Found:C,65.92;H,5.62;N,12.96%. Example 76 Cis-2.3.6.7.12.12a-hexahvdro-6-f4-dimethvlaminophenvl)-2-methvlpyrazinof2'. 1':6.npvridof3.4-b1indole-1.4-dione The same two step procedure but starting from methylamine and the cis isomer of intermediate 47 gave after recrystallisation from methanol, the title compound as white crystals m.p.: 266°C. Analysis for C23H24N402: Calculated: 0,71.11 ;H,6.23;N, 14.42; Found:C, 71.19 ; H, 6.24; N, 14.34%. Example 77 Cis-2.3.6.7.12.12a-hexahvdro-2-methvl-6-(3-pyridvnpyrazinof2'. 1 ':6.11pyridof3.4-blindole -1,4-dione The same two step procedure but starting from methylamine and intermediate 48 gave after recrystallisation from chloroform, the title compound as white crystals m.p.: 312°C. Analysis for C2oH1 8N402: Calculated: C,69.35;H,5.24;N,16.17; Found:C,69.08;H,5.20;N,16.19%. Example 78 (6R. 12aR)-2.3.6.7.12.12a-Hexahvdro-2-methvl-6-(3.4-methvlenedioxyphenvnpyrazinor2'. 1 ':6.11pyridof3.4-b1indole -1.4-dione a) To a stirred solution of intermediate 54 (0.5 g) and NaHCOs (0.14 g) in anhydrous CHCI3 (20 ml) was added dropwise chloroacetyl chloride (0.27 mL) at 0°C. The resulting mixture was stirred for 1 hour at the same temperature and diluted with CHCIs (20 ml). Water (10 ml) was then added dropwise with stirring to the mixture, followed by a saturated solution of NaHCOs. The organic layer was washed with water until neutrality and dried over Na2SO4. After evaporation of the solvent under reduced pressure, (6R. 12aRVmethvl 1.2.3.4-tetrahvdro-2-chloroacetvl-1 -(3.4- methvlenedioxvphenvl)-9H-pyrido[3.4-b1indole-3-carboxvlate was obtained as an oil which was crystallised from ether to give a solid (0.38 g, m.p. : 233°C) which was used without further purification in the next step. b) To a stirred suspension of the chloroacetyl intermediate (0.37 g) in.MeOH (20 mL) was added at room temperature a solution of methylamine (33% in EtOH) (0.4 mL) and the resulting mixture was heated at 50°C under N2 for 16 hours. The solvent was removed under reduced pressure and the residue was dissolved in CH2CI2 (50 mL). After washing with water (3x20 mL), drying over Na2SO4 and evaporating to dryness, the residue was purified by flash chromatography eluting with CH2d2/MeOH (99/1) and recrystallised from-2- propanol to give the title compound as white crystals (0.22 g) m.p. : 302- 303°C. Analysis for C22H 19^04: Calculated:C,67.86;H,4.92;N, 10.79; Found:C,67.77;H,4.92;N,10.74%. 20° [x]D = +71.0° (C=1.00; CHCI3). The following compounds were obtained in a similar manner: Example 79 (6R, 12aR)-2.3.6.7.12.12a-Hexahvdro-2-isopropyl-6-(3.4- methvlenedioxvphenvl)-pyrazinof2'.1':6.npvridof3.4-b1indole-1.4-dione The same two step procedure but starting from isopropylamine and intermediate 54 gave, after recrystallisation from methanol, the title compound as white crystals rn.p. : 290-293°C. Analysis for 024^3^04: Calculated: C,69.05;H,5,55;N,10.07; Found:C,69.06;H,5.49;N,10.12%. 20° [u]D = +52.6° (C=1 14; CHCIg). Example 80 (6R. 12aFO-2.3.6.7.12.12a-Hexahvdro-2-butvl-6~f 3.4-methvlenedioxvphenyl pvrazinof2'.1 ':6.11pyridof3.4-b1indolei-1 .4-dione The same two step procedure but starting from butylamine and intermediate 54 gave, after recrystallisation from toluene/hexane, the title compound as white crystals m.p.: 209-210°C. Analysis for C25H25N304: Calculated: C,69.59;H,5.84;N19.74; Found:C,69.70;H,5.93;N,9.74%. 20° [a]D = +50.2° (0=0.53; CHCI3). Example 81 (6R. 12aR)-2.3.6.7.12.12a-HexahvdrQ-2-isobutvl-6-f 3.4-methvlenedioxyphenvnpyrazinof2'. 1 ':6.11pvridof3.4-b1indole -1.4-dione The same two step procedure but starting from isobutylamine and intermediate 54 gave, after recrystallisation from methanol, the fltle compound as white crystals m.p.: 227-228°C. Analysis for 02550,4: Calculated: C,69.59;H,5.84;N,9.74; Found:C169.52;H,5.87;N,9.74%. 20° [oc]D = +45° (C=1.04; CHCy. Example 82 (6R.12aR)-2.3.6.7.12.12a-Hexahvdro-2-cvclopentvl-§-(3.4- methylenedioxvphenyl)-pvrazino[2'.1':6,1]pyridof3.4-bTmdole-1.4-dione The same two step procedure but starting from cyclopentylamine and intermediate 54 gave, after recrystaltisation from ether, the title compound as white crystals m.p. : 237-239X. Analysis for C26H25N3O4: Calculated: C.70.41 ;H,5.68;N,9.47; Found:C,70.13.H,5 67.N,9.42%. 20° [a]D = +36.6° (C=0.98; CHCI3). Example 83 (6R. 1 2aR)-2.3.6.7. 1 2. 1 2a-Hexahvdro-6-(3.4-fnethvlenedioxvphenvn-2- cvclohexvlmethvl-pyrazinof2'.1':6 1 1pyrtdof3.4-blindole -1 .4-dione The same two step procedure but starting from cyclohexyjmethylamine and the cis isomer of intermediate 56 gave, after recrystallisation from 2-propanol the title compound as white crystals m.p. : 209°C. Analysis for 023H9N04: Calculated: C,71 .32;H,6.20;N,8.91 ; Found:C,71.30;H,6.29;N,8.74%. 20° [a]D = +40.0° (O0.99; CHCy. Example 84 (6R.12aR)-2.3.6<7.12.12a"Hexahvdro-2-cvclOPropylmethvl-6-(4-methoxvphenvl)- pvrazinof2'. 1 ':6. 1 1pvridof3.4-blindo|e -1 .4-dione The same two step procedure but starting from cyclopropylmethylamine and intermediate 57 gave, after recrystallisation from methanol, the title compound as white crystals m.p. : 204-205°C. Calculated: C,70.74;H,6.17;N,9.90; Found:C,70.98;H,6.09;N,9.92%. 20° [a]D = +54.1° (C=1.03; CHCI3). Example 85 (6R. 1 2aR)-2.3.6.7. 1 2. 1 2a-Hexahydro-2-butvl-6-(4-methoxyphenvnpyrazinof2'. 1 ':6. 1 ]pyridof3.4-bTindole -1 .4-dione The same two step procedure but starting from buyJamine and intermediate 57 gave, after recrystallisation from 2-propanol, the title compound as white crystals m.p. : 183-184°C. Analysis for C25H27N3O3(0.5H20): Calculated: C,70.40;H,6.62;NI9.85; Found:C,70.55;H,6.64;N19.92%. 20° [6-(3.4-metrivlenedioxvphenvnpyrazinof2'. 1': 6.11 pyrido f3.4-b] indole-1,4-dione The same two step procedure but starting from ammonia and intermediate 54 gave, after recrystallisation from methanol, the title compound as white crystals m.p. : 285-290°C. Analysis for C2iH17N3O4: Calculated : C, 67.19 ; H, 4.56 ; N, 11.19 ; Found : C, 67.30 ; H, 4.66 ; N, 11.11 %. [apo°D = + 88° (C = o.48 ; pyridine). Example 102 (6R, 12aR)-2.3.6.7.12,12a-Hexahydro-6-(3.4-methvlenedioxyphenvn-2-(2- propynvO-pyrazino [2'. 1': 6.11 pvrido [3.4-bl indole-1,4-dione The same two step procedure but starting from propargylamine and intermediate 54 gave, after recrystallisation from acetone, the title compound as white crystals m.p. : 271 °C. Analysis for C24HigN3O4 : Calculated : C, 69.72 ; H, 4.63 ; N, 10.16 ; Found : C, 69.95 ; H, 4.66 ; N, 10.06 %. [a]20°D = + 51.7° (c = 0.49 ; CHCI3). Example 103 (6R. 12aR)-2.3.6.7.12.12a-Hexahvdro-2-f3.4-methvlendioxvbenzvl)-6-(3.4- methvlenedioxvphenvl)-pvrazinof2'. 1': 6.1] pyrido (3.4-bl indole-1,4-dione The same two step procedure but starting from piperonylamine and intermediate 54 gave, after recrystallisation from methanol, the title compound as white crystals m.p. : 204-2060C. Analysis for C29H23N3O6: Calculated : C, 68.36 ; H, 4.55 ; N, 8.25 ; Found : C, 68.25 ; H, 4.49; N, 8.41. [a]20°D = + 430 (c = 1 01 ; CHCI3). Example 104 (6R. 12aR)-2.3.6.7.12.12a-Hexahvdro-2-(3.4-dimethoxvphenethvn-6-(3.4- methvlenedioxvphenvn-pyrazino 12'. 1': 6.11 pyrido f3.4-b1 indole-1,4-dione The same two step procedure but starting from 3,4-dimethoxyphenethylamine and intermediate 54 gave, after recrystallisation from dichloromethane/ether, the title compound as white crystals m.p.: 265-266°C. Analysis for C31H29N306: Calculated : C, 69.00 ; H, 5,42 ; N, 7.79 ; Found : C, 68.68 ; H, 5.35 ; N, 7.78 %. [a]20°D = + 38.3° (c = 1.12 ; CHCI3). Example 105 (6R. 12aR)-2.3.6.7.12.12a-Hexahvdro-2-furfurvl-6-(3.4-methvlenedioxvphenvl)- pyrazino 12', V : 6.11 pvrido f3.4-b] indole-1,4-dione The same two step procedure but starting from furfurylamine and intermediate 54 gave, after recrystallisation from methanol, the title compound as white crystals m.p.: 219°C. Analysis for C26H2i N3O5 : Calculated : C, 68.56 ; H, 4.65; N, 9.23 ; Found : C, 68.16 ; H, 4.63; N, 9.15 %. [a]20°D = + 58.1° (c = 1.2 ; CHCI3) Example 106 (6R. 12aR)-2.3.6.7.12.12a-Hexahvdro-6-(3.4-methvlenedioxyphenvn-2-(2- thienylmethvD-pyrazino f2'. 1': 6.1] pyrido f3.4-b1 indole-1,4-dione The same two step procedure but starting from 2-thiophenemethylamine and intermediate 54 gave, after recrystallisation from methanol/water, the title compound as white crystals m.p.: 155-157°C. Analysis for C26H2iN3O4S: Calculated : C, 66.23 ; H, 4.49; N, 8.91 ; S, 6.8 ; Found: C, 66.13 ; H, 4.54; N, 9.12 ; S, 6.78%. [a]20°D = + 70.4° (c = 1.03 ; CHCI3). Example 107 (6R. 12aR)-2.3.6.7.12.12a-Hexahvdro-6-(4-methoxvphenvn-2-methvl-pvrazino f2'. 1': 6.11 pvrido [3.4-bl indole-1.4-dione The same two step procedure but starting from methylamine and intermediate 57 gave, after recrystallisation from methanol, the title compound as white crystals m.p.: 285-288°C. Analysis for C22H2i N3O3: Calculated : C, 70.38 ; H, 5.64 ; N, 11.19 ; Found : C, 70.31 , H, 5.69 ; N, 11.29 %. [apo°D = + 59° (c = 1.19 ; CHCI3). Example 108 (6R. 12aR)-2.3.6.7.12.12a-Hexahvdro-2-ethvl-6-(4-methoxyphenvl)-pvrazino 12'. 1': 6.11pyrido f3.4-bl indole-1.4-dione The same two step procedure but starting from ethylamine and intermediate 57 gave, after recrystallisation from methanol, the title compound as white crystals m.p.: 277°C. Analysis for 02303: Calculated : C, 70.93 ; H, 5.95 ; N, 10.79 ; Found : C, 70.90 ; H, 5.96 ; N, 10.54 %. N20°D = + 52° (c = 1-28 ; CHCI3). Example 109 (6R. 12aR)-2.3.6.7.12.12a-hexahvdro-6-f7-(4-methvl-3.4-dihvdro-2HbenzoM. 41oxa2invl))-2-methvl-Pvrazinof2'.1': 6.1lpyridof3.4-b1 indole-1,4-dione The same two step procedure but starting from intermediate 75 and methylamine gave, after recrystallisation from ethanol, the title compound as white crystals m.p.: 285-288°C. Analysis for 024^4^03 (0.5 H20): Calculated : C, 67.75; H, 5.92 ; N, 13.17 ; Found : C, 68.02 ; H, 6.00 ; N, 13.18 %. (a]2°°D = + 71.7° (c = 1, pyridine). Example 110 (6R. 12aR)-2.3.6.7.12.12a-Hexahvdro-6-(5-(N-benzvnndolinvl))-2-methvlpyrazinof2'. 1': 6.npyridof3.4-b|indole-1.4-dione The same two step procedure but starting from intermediate 77 and methylamine gave, after recrystallisation from dichloromethane/methanol, the title compound as white crystals m.p.: 223-225°C. Analysis for CQ242: Calculated : C, 75.61 ; H, 5.92 ; N, 11.76 ; Found : C, 75.2 ; H, 5,78 ; N, 11.67 %. [a]20