PL109423B1 - Method of producing new derivatives of isoquinoline - Google Patents

Description

The invention relates to a process for the preparation of new isoquinoline derivatives of the general formula II, wherein Z1 and Z2 are the same or different and each represents a group of the formula -O-CH2-O- or 1, 2 or 3 methoxy groups, R2 and R3, the same or different, represent an alkyl group of 1-3 carbon atoms, a 2-propenyl or 2-propynyl group, R4 and R5, the same or different, represent a benzyl or phenylethyl group, in which the phenyl ring may optionally be substituted by one or more substituents such as a halogen atom, an alkoxy group of 1-3 carbon atoms and a group of the formula -O-CH2-O- (methylenedioxy). A and B, the same or different, represent an alkylene group of 1-3 carbon atoms, L represents an alkylene group of 2-12 carbon atoms or a group of the formula -L1.0.L2-, wherein L1 and L2 each represent an alkylene group of at least two carbon atoms and together contain up to 11 carbon atoms and X" represents an anion. Preferably, the substituents A and B together contain at least 4 carbon atoms. The compounds of the general formula II are used as neuromuscular blocking agents. A number of heterocyclic compounds derived from isoquinoline are known which have pharmacological properties such that they are used as neuromuscular blocking agents, or as they are often referred to, as muscle relaxants. This type of These agents cause skeletal muscle paralysis by disrupting the neurohumoral transmission process associated with acetylcholine release. Many of these agents are widely used during surgical procedures. One group of muscle relaxants acts by inhibiting or reducing the depolarization of motor endplates, while others act by inducing prolonged depolarization. Depolarizing agents have a number of disadvantages. They are not antagonized by anticholinesterase drugs, which, on the contrary, can intensify the depolarization process. They can also cause a postoperative increase in muscle pain and cramps, possibly by initiating muscle contraction or contraction induced by a single motor nerve fiber. Other blocking agents that inhibit depolarization include d-tubocurarine, gallamine, and pancuronium are among the most effective neuromuscular blocking agents. These agents are also called competitive agents because they compete with acetylcholine at the motor endplates and prevent their depolarization. The net effect of this competitive action is to maintain the muscles in a relaxed state and to maintain a relaxant contraction. Gallamine, d-tubocurarine, and pancuronium moderately prolong the state of paralysis, and the degree of relaxation is invariably slow. Anticholinesterase agents, such as neostigmine, edrophonium, and physostigmine, can be used to antagonize the paralysis induced by d-tubocurarine, pancuronium, and gallamine, and are widely used used in anesthesiology. A serious disadvantage of competitive blocking agents is their effect on the autonomic mechanism. Tubocurarine blocks autonomic ganglia, causing cardiac bradycardia and hypertension, while gallamine and pancuronium cause vagal blockade, resulting in tachycardia and hypertension. It is therefore advantageous to obtain compounds causing neuromuscular blockade, such that they combine some of the advantages of known agents of various types without having their disadvantages. In particular, it is important to separate the ability to cause neuromuscular paralysis from the effect on the autonomic mechanism. A number of isoquinoline derivatives are known that cause neuromuscular blockade. Among them is a group diesters with a structure similar to that of the compounds prepared by the method of the invention. These known compounds show, according to J. M. Z. Gladych and E. P. Taylor, X Chein. Soc., 1481—1487 (1962), "considerable variability in biological activity". One of these diesters of formula I, named γ-oxalolaudonium by R. T. Brittain et al., Brit. J. Pharmacol, 17, 116—123 (1961), seems to be worth further investigation, although it shows relatively weak activity in animals and is subsequently determined to be too weak in volunteer studies to be of any value in anaesthesia (Gladych, supra, p. 1483). The starting compounds of the general formula 4 defined below are new compounds which do not induce neuromuscular blockade. The compounds prepared by the method according to the invention have more advantageous properties than the previously known agents inducing neuromuscular blockade. These compounds induce neuromuscular paralysis by a non-depolarizing mechanism of relatively short duration and are characterized by minimal effects on the cardiovascular system and autonomic mechanism. Preferred compounds of the invention are compounds of formula 2 wherein Z1 and Z2 represent methoxy groups attached to adjacent carbon atoms, compounds wherein Z1 and Z2 represent methoxy groups attached to carbon atoms in the 6- and 7-positions, and compounds of formula 2 wherein Z1, R2 and R4 have the same meaning as Z2, R3 and R5, respectively. A preferred group of compounds of general formula 2 are compounds of general formula 3 wherein y represents an integer of 1, 2 or 3, especially 2, wherein at least one of the methoxy groups is preferably in the 3-, 4- or 5-position, especially 3 and 4, n is an integer from 2 to 8, preferably 4 to 7, and X" is a pharmaceutically acceptable anion, for example a halide, such as iodide, bromide, chloride, sulfate, or an anion of an organic acid, such as methanesulfonate, benzenesulfonate, nitrobenzenesulfonate or naphthalenesulfonates. The process according to the invention also provides non-pharmaceutically acceptable salts of compounds of formula II, which are intermediates which are converted into pharmacologically acceptable salts. Valuable compounds of general formula III include the following derivatives: N,N-dimethyl-N,N'-4,12-dioxa salts -3,13-dioxo-pentadecylene-1,15-di(tetrahydropapaverinium), [compounds of formula 3, in which n is equal to 7 and (OMe)y is a 3,4-dimethoxy group]; N,N'-dimethyl-N,N'-4,9-dioxa-3,10-dioxo-dodecylene•*.1,12-di(tetrahydropapaverinium), [compounds of formula 3, in which n is equal to 4 and (OMe)y is a 3,4-dimethoxy group]; and particularly preferably compounds such as: N,N'-dimethyl-N^N'-4,10-dioxa-3,11-dioxo-tridecylene-1,13-di(tetrahydropapaverinium), 5 [compounds of formula 3, wherein n is equal to 5 and (OMe)y denotes a 3,4-dimethoxy group] and N,N'-dimethyl-N,N'-4,11-dioxa-3,12-diketotetradecyl-1,14-di(tetrahydropapaverinium) salts [compounds of formula 3, wherein n is equal to 6 and (OMe)y denotes a 3,4-dimethoxy group]. The method for preparing new isoquinoline derivatives of general formula 2, in which all symbols have the above-mentioned meanings, according to the invention consists in quaternizing a ditertiary base of general formula 4, in which Z1, Z2, R4, Rs, AB and L have the above-mentioned meanings, or a monoquaternary derivative thereof, in which one of the groups isoquinoline esters are substituted in the 2-position by a group R2 or R3. Quaternizing agents may be reactive alcohol esters of the formula R6OH, where R6 has the meaning given for R2 or R3. Preferred quaternizing agents are compounds of the formula R6X, where R6 has the meaning given above and X is the anion of an organic or inorganic acid. When quaternizing a base, at least two molar equivalents of the quaternizing ester should be used, with a large excess being preferred. If a monoquaternary base derivative of formula 4 is quaternized, at least an equimolar amount of the ester is used. According to the invention, a tertiary amine of formula 4 containing at least six of the groups required in the desired diquaternary compound is reacted with a quaternizing agent containing the remaining groups and the optionally obtained salt is converted into a salt with a different anion. The amines of formula 4 are preferably introduced into the reaction in the form of a dioxalate salt. The reaction can be carried out without a solvent, preferably using a solvent such as an alkanol, e.g. methanol, an aromatic hydrocarbon, e.g. toluene; a halogenated hydrocarbon, e.g. chloroform; an aliphatic ketone, e.g. acetone or methyl ethyl ketone; dioxane, tetrahydrofuran, dimethylsulfoxide, acetonitrile, or dimethylformamide. The reaction is carried out at a temperature up to boiling point, optionally under increased pressure, and optionally in the absence of light. Reactive ester derivatives include halides, e.g., bromide or iodide; p-toluenesulfonate, methanesulfonate, benzenesulfonate, nitrobenzenesulfonate, or naphthalenesulfonate. If the reactive ester derivative is given by the formula R6Y, then Y is preferably selected so as to obtain the anion X" in the compound of formula 2. Otherwise, the group Y can be exchanged for the anion Xr by simple exchange methods such as double exchange, exchange, ion exchangers or other known methods. The intermediate compound of formula 4 can be prepared by reacting the compound of formula 5 with a compound of formula G.CÓ.O.L.O.CÓ.G2, in which formulas Z1, R4 and L have the same or different meanings as previously given for formula 2aG I.OV, denoting a group of formula -O (J*).= = CHj2 or a reactive ester derivative or derivative of a group of formula (I.OH), in which J is an alpha-leno group with 1-3 carbon atoms, one of the substituents J1 and J2 is a hydrogen atom and the other is a hydrogen atom or a methyl group, or G2 is a group of formula 6, in which B, R5 and Z2 are as defined in formula 2. In particular, intermediate compounds of formula 4, in which at least one of the substituents A and B is a group of formula -(CH^-), optionally substituted methyl group, can be easily prepared by a Michael reaction between an acrylic ester of formula G.CO.O.L.O.CO.G2 and a compound of formula 5, preferably at an elevated temperature, e.g. up to 100°C, or optionally in an inert solvent, such as an aromatic hydrocarbon, e.g. benzene, at the boiling point. Intermediate compounds of formula G.CO.O.L.O.CO.G2, in which G2 is a group An isoquinolinium compound can be prepared by reacting a compound of formula 5 with an excess of another compound of formula G.C.O.L.O.C.O.G.2, wherein G.C.O.L.O.C.O.G.2 is not an isoquinolinium group. The compounds of formula 2 have four asymmetric centers, one on each nitrogen atom and one in each of the isoquinolinium rings. The stereoisomerism of the compounds of formula 2 can be partially regulated by using starting compounds of formula 5 with a specific steric configuration, which can result in the DD-, LL- or meso-form of the base of formula 4. Quaternization introduces two further asymmetric centers and usually gives the compound of formula 2 as a mixture of stereoisomers. All stereoisomeric compounds of formula 2 are prepared by the process of the invention. The compounds of formula 2 is used as an active ingredient in pharmaceutical preparations for inducing neuromuscular paralysis. These preparations can be administered intravenously. In such a case, they may be aqueous solutions containing bacteriostatic agents, antioxidants, buffers, or other pharmaceutically acceptable additives. The described compounds can also be administered parenterally in other ways, in the form of solutions, emulsions, or suspensions in pharmaceutically acceptable solvents or solvent mixtures, with the addition of bacteriostatic agents, antioxidants, thickening agents. 6. Compounds of formula 2, e.g., in the form given above, can be used to induce neuromuscular blockade in animals and humans. The dose used depends on the type of compound and the type of stereoisomer, as well as the degree of paralysis the physician wishes to induce. The appropriate dose for intravenous administration is 0.1-4.0 mg, preferably 0.1-2.0 mg/kg of body weight, especially 0.25-1.0 mg/kg. Hence, the size of a single dose of the compound of formula II is 20-80 mg, preferably 40-60 mg, and the solution for 10 injections contains 1-100 mg, preferably 10-50 mg, most preferably 20-30 mg of the compound of formula II per milliliter. In some cases, an additional amount of the compound may be necessary to maintain the paralysis, depending on the duration of the surgical procedure. Due to the most advantageous method of administration, salts of the compound of formula II are preferred, the solubility in water of which is at least 20 mg/ml at room temperature. The results of a comparison of the pharmacological properties of the two compounds of formula II and the known compound, gallamine, are given in 20 in Table I. This table gives the average doses required to induce 50% (PD50) and 95% (PD95) paralysis and 50% (VD50) blockade of the vagus nerve in 4 or 5 anaesthetized cats. The lack of vagus nerve blockade by the compounds of the invention designated by numbers 1c and 6c when administered at doses inducing paralysis is illustrated by the VD50/PD95 ratio. All doses are given in mg of compound per kilogram of body weight. As can be seen from the data in the table, the compounds of the invention have better properties than the currently used neuromuscular blocking agents. Example I. Preparation of the compound of formula 7. To a solution containing 0.1 mole 1.5-pentanediol, 0.2 mol of triethylamine and 0.1 g of pyrogallol in 100 ml of anhydrous benzene, 0.2 mol of acrylyl chloride was added with stirring over a period of half an hour. Then a further 100 ml of anhydrous benzene and 10 ml of triethylamine were added and the mixture was stirred for half an hour at 50°C. The precipitated triethylamine hydrochloride was filtered off and the solvent removed under reduced pressure. The remaining yellow oil was distilled in the presence of a trace of p-methoxyphenol, protected from light. Table I Compound Gallamine Compound 1c Compound 6c No. of cats | PD50 | PD95 4 5 4 0.85 0.11 0.092 1.8 0.22 0.16 VD5„ 0.56 3.7 2.7 yD50/PD50 | 0.66 35 31 VD50/PD9S 1 0.31 17 ¦ • 17 dispersants, suspending agents or other pharmaceutically acceptable substances. Such forms are prepared in single-dose forms, such as ampoules, or multi-dose forms, such as bottles from which the appropriate doses can be administered. All such forms should be sterile. Alternatively, the compounds may be formulated as dry powders with or without diluents and then dissolved or suspended in a solvent before use. The simplest and preferred form is a solution of the compound of formula 2 in water. This is prepared by dissolving the compound in sterile and pyrogen-free water, carrying out these operations under sterile conditions and then sterilizing the solution. 55 60 65 12.9 g (61%) of pentamethylene-1,5-diacrylate are obtained, boiling point 90-95°C/0.01 mmHg. A solution of 4.43 g of tetrahydropapaverine and 1.30 g of pentamethylene-1,5-diacrylate in 15 ml of anhydrous benzene is stirred and heated under reflux for 48 hours, protected from light. The solvent is evaporated under reduced pressure and the remaining pale red oil is dissolved in 10 ml of chloroform. After adding about 400 ml of ether and then about 500 ml of saturated ethereal solution of oxalic acid, a flocculent precipitate is formed, which is filtered off, washed with ether and dried. After twice crystallization from ethanol, 3.5 g (51%) of N,N'-4,10-dioxa-3,11-dioxotridecylene-1,13-di(tetrahydropapaverine) oxalate is obtained as a white powder with a melting point of 117-121°C. The free base of N,N'-4,10-dioxa-3,11-dioxotridecylene-1,13-di(tetrahydropapaverine) (compound 1a) is obtained by alkalizing an aqueous solution of the oxalate with sodium bicarbonate solution and then extracting it with by evaporation of the solvent with toluene. The product is obtained as a colorless, viscous oil. To a solution of the thoroughly dried base (0.5 g) in 8 ml of spectrally pure acetonitrile is added 8 ml of methyl iodide and the mixture is left to stand for 22 hours. The mixture is filtered and added dropwise, with stirring, to about 450 ml of anhydrous ether. The flocculent precipitate is filtered off, washed with anhydrous ether and dried in vacuo over phosphorus pentoxide at 50°C. This gives N,N'-4,10-dioxa-3,11-dioxotridecylene-1,13-di(tetrahydropapaverinium) diiodide, melting at 143-148°C. and softening point 138°C (compound Ib). By repeating the above procedure but using methyl methanesulfonate, methyl benzenesulfonate, methyl toluenesulfonate, methyl naphthalene-1-sulfonate or methyl naphthalene-2-sulfonate instead of methyl iodide and carrying out the reaction for 48 hours instead of 22 hours, the following salts are obtained: 1c) (N,N'-dimethyl-N,N'--4,10-dioxa-3,11-dioxotridecylene-1,13-di)tetrahydropapaverinium dimethanesulfonate in the form of a white powder with a melting point of 104-112°C; 1d) N,N'-dimethyl-N,N'-di-(benzenesulfonate) - - dioxa-3,11-diox ... diketotridecylene - 1,13 - - di(tetrahydropapaverinium) in the form of a pale yellow powder with a melting point of 65-85°C; and 1g) di-(naphthalene-2-sulfonate)N,N' - dimethyl - - N,N' - 4,10 - dioxa - 3,11 - diketotridecylene - 1,13 - - di(tetrahydropapaverinium) in the form of a white powder with a melting point of 60-80°C. Examples II-XV. Using the method given in Example I, the following tertiary bases (compounds 2a-15a) are obtained via oxalates. 2a) N,N' - 4,10 - dioxa - 3,11 - diketotridecylene - - 1,3 - di(-D-) - (-tetrahydropapaverine) in the form of a colorless, viscous oil with a specific rotation [α]23.5 = —53.62° (c = 1.408, chloroform); 3a) N,N' - 4.10 - dioxa - 3.11 - diketotridecylene - - 1.13 - di - (L-) + (-tetrahydropapaverine) in the form of a colorless, viscous oil with a specific rotation [α] = +62.65° (c = 0.961, chloroform); 4a) N,N' - 7 - methyl - 4.10 - dioxa - 3.11 - diketotridecylene - 1.13 - di(-tetrahydropapaverine); 5a) N,N' - 4.10 - dioxa - 3,11-diketotridecylene* - 1,13-di-{1',2',3',4'-tetrahydro- 6'7'-dimethoxy- 1-[2'-(3",4"-dimethoxyphenyl)ethyl]isoquinoline} in the form of a colourless oil; 8 6a) N,N - 4,11-dioxa- 3,10-diketetradecylene - - 1,14-di-(tetrahydropapaverine); 7a) N,N' - 4,9-dioxa- 3,10-diketododecylene - - 1,12-di-(tetrahydropapaverine) in the form of a colourless precipitate with a melting point of 44-46°C; 8a) N,N' - 4,9-dioxa- 3,10- diketododecylene - 1,12 - - di - (D-) — (-tetrahydropapaverine) in the form of a colourless precipitate with a melting point of 47-49°C and a specific rotation [α]2° =—70,6° (c = 0,395, chloroform); 9a) N,N' - 4,9 - dioxa - 3,10 - diketododecylene - 1,12 - - di - (L-) + (-tetrahydropapaverine) in the form of a colourless precipitate with a melting point of 48-50 °C and a specific rotation [α]2° = +71,2° (c = 1,215, chloroform); 10a) N,N' - 4,8 - dioxa - 3,9 - diketoundecylene - 1,11 - - di - (tetrahydropapaverine) in the form of a colourless precipitate with a melting point of 46-46 °C; 11a) N,N' - 4,7 - dioxa - 3,8 - diketodecyl - 1,10 - - di fl',2',3',4' - tetrahydro - 6',7' - dimethoxy - 1 - - (3",4",5" - trimethoxybenzyl)isoquinoline] in the form of a colourless precipitate with a melting point of 46-47 °C; 12a) N,N' - 4,7 - dioxa - 3,8 - diketodecylene - 1,10 - - di - [1',2',3',4' - tetrahydro - 6',7' - dimethoxy - 1 - - (2" - bromo - 4",5" - dimethoxybenzyl)isoquinoline] in the form of a colourless precipitate with a melting point of 65-67°C; 13a) N,N' - 4,7 - dioxa - 3,8 - diketodecylene - 1,10 - - di - [1',2',3',4' - tetrahydro - 6',7', - dimethoxy - 1 - - (3",4" - methylenedioxybenzyl)isoquinoline] in the form of a colourless precipitate with a melting point of 44-46°C; 14a) N,N' - 4,7 - dioxa - 3,8 - diketodecylene - 1,10 - - di - 1',2',3',4' - tetrahydro - 6',7' - dimethoxy - 1 - - (3,1,4,1 - dichlorobenzyl)isoquinoline] in the form of a colourless precipitate with a melting point of 45-48°C; 15a) N,N' - 4,7 - dioxa - 3,8 - diketodecylene - 1,10 - - di - [1',2',3',4' - tetrahydro- 6',7' - dimethoxy - - 1 - (2",5" - dimethoxybenzyl)isoquinoline] in the form of a colourless precipitate with a melting point of 11-16°C; From the above compounds the following salts of formula 2 are prepared (compounds 2b—15b): 2b) di-(methanesulfonateJNiN7 - dimethyl - N,N' - - 4,10 - dioxa - 3,11 - diketotridecylene - 1,13 - di- - (D-) — (-tetrahydropapaverinium) with a melting point of 110—114°C, softening point of 95—97°C, and specific rotation [a]2*5 = 41—,67° (c = 1,323, chloroform); 3b) di-(methanesulfonate)N,N' - dimethyl - N,N' - - 4,10 - dioxa - 3,11 - diketotridecylene - 1,13 - di- - (L-) + (-tetrahydropapaverinium) with a melting point of 110-114°C, softening point 95-97°C and specific rotation [a]2£ = +40.26°C (c = 1.016, chloroform); 4b) N^' - dimethyl - N,N' - 7 - methyl - 4,10 - dioxa - 3,11 - diketotridecylene - 1,13 - di- (tetrahydropaperinium) di- (methanesulfonate) in the form of a white powder with a melting point of 100.5-109 °C; 5b) N,N' - dimethyl - N*N' - 4,10 - dioxa - 3,11 - diketotridecylene - 1,13 - di- - {1',2',3',4' - tetrahydro - 6',7'-dimethoxy-1-[2--(3",4"-dimethoxyphenyl)ethyl]isoquinolinium}, melting point 98-105°C; 10 15 20 25 30 35 40 45 50 55 60109 423 9 6b) N,N'-dimethyl-N,N'-4,11-dioxa-3,12-dioxotetradecylene-1,4-di-(tetrahydropapaverinium)diiodide, melting point 132-138°C; 6c) N,N'-dimethyl-N,N'-4,11-dioxa-3,12-dioxotetradecylene-1,14-di-(methanesulfonate)di- (tetrahydropapaverinium) in the form of a white powder with a melting point of 109-118 °C; 7c) N,N' - dimethyl - N,N' - - 4,9 - dioxa - 3,10 - diketododecylene - 1,12 - di - - ((+) - tetrahydropapaverinium) di - (methanesulfonate) with a melting point of 91-115 °C; 8b) N,N' - dimethyl - N,N' - - 4,9 - dioxa - 3,10 - diketododecylene - 1,12 - di - - (D-) — (- tetrahydropapaverinium) di - (methanesulfonate) with a melting point of 105-115 °C and a specific rotation [a] ^ = = —51,18 ° (c = 1,105, chloroform); 9b) N,N/-dimethyl - N,N'-diketododecylene - 1,12-dimethyl - (methanesulfonate) with a melting point of 102-113°C and a specific rotation of [α]^ = = +50,28° (c — 1,095, chloroform); 10b) N,N'-dimethyl - N,N'-diketoundecyl - 1,11-dimethyl - (methanesulfonate) in the form of a white precipitate with a melting point of 96-120°C; 11b) N,N'-dimethyl - (methanesulfonate) with a melting point of 96-120°C; N,N' - - 4,7 - dioxa - 3,8 - diketodecyl - 1,10 - di - [1',2',3',4' - tetrahydro - 6',7' - dimethoxy - 1 - (3",4",5" - - trimethoxybenzyl)isoquinolinium] di - (methanesulfonate) N,N' - - 4,7 - dioxa - 3,8 - diketodecyl - 1,10 - di - [1',2',3',4' - tetrahydro - 6',7' - dimethoxy - 1 - (2 - bromo - - 4//,5// - dimethoxybenzyl)isoquinolinium] di - (methanesulfonate) 13b) N,N'-dimethyl-N,N'-di-(methanesulfonate)-4,7-dioxa-3,8-dioxodecylene-1,10-di-[1',2',3',4'-tetrahydro-6',7'-dimethoxy-1-(3",4"-methylenedioxybenzyl)isoquinolinium]-dimethyl-(methanesulfonate)-4,7-dioxa-3,8-dioxo ... 14b) N,N'-dimethyl-N,N'-di-(methanesulfonate)-4,7-dioxa-3,8-dioxodecylene-1,10-di-[1',2',3',4'-tetrahydro-6',7'-dimethoxy-1-(3",4"-dichlorobenzyl)isoquinolinium]-di-(methanesulfonate)-4,7-dioxa-3,8-dioxo ... and 15b) N,N'-dimethyl-N,N'-di-(methanesulfonate)-4,7-dioxa-3,8-dioxodecylene-1,10-di-[1',2',3',4'-tetrahydro-6',7'-dimethoxy-1-(2,n,3,n-di-methoxybenzyl)isoquinolinium] di-(methanesulfonate)-melting point 86-95°C. Example XVI. By the method described in Example 1, N,N'-4,12-dioxa-3,13-dioxopentadecylene-1,15-di-(tetrahydropapaverine) was prepared in the form of a viscous oil (compound 16a). To a thoroughly dried 0.5 g of the compound obtained in 10 ml of chloroform was added 10 ml of methyl iodide and the mixture was left to stand for 22 hours at room temperature. After filtration, the mixture was added dropwise, with stirring, to 450 ml of filtered anhydrous ether. The flocculated white precipitate was filtered off, washed with anhydrous ether and dried in vacuo over P2O2 at 50°C. N,N'-4,12-dioxa-3,13-dioxopentadecylene-1,5-di-(tetrahydropapaverine) diiodide is obtained, melting at 114-123°C (compound 16b). Examples XVII-XXIII. Using the method given in Example XVI, compounds 17a-23a are prepared; 17a) N,N'-4,13-dioxa-3,14-dioxohexadecylene-1,16-di-(tetrahydropapaverine) in the form of a viscous oil; 18a) N,N' - 4,7 - dioxa - 3,8 - diketodecylene - 1,10 - - di - ((+) - tetrahydropapaverine) in the form of a colourless precipitate with a melting point of 47-49°C; 19a) N,N' - 4,7 - dioxa - 3,8 - diketodecylene - 1,10 - - di - [1',2',3',4' - tetrahydro - 1' - (3",4" - dimethoxybenzyl) - 6' - 7' - methylenedioxoisoquinoline] in the form of a colourless precipitate with a melting point of 49-50°C; 20a) N,N' - 4,10 - dioxa - 3,11 - diketotridecylene - - 1,13 - di - [1,,2,,3,,4/ - tetrahydro - 1' - (3",4" - - dimethoxybenzyl) - 6',7' - methylenedioxyisoquinoline] in the form of a colourless, viscous oil; 21a) N,N - 4,7 - dioxa - 3,8 - diketodecylene - 1,10 - - di - [r,2',3',4' - tetrahydro - 6',7' - dimethoxy - - r - benzylisoquinoline] in the form of a colourless oil; 22a) N,N' - 4,7 - dioxa - 3,8 - diketodecyl - 1,10 - - di - [1',2',3',4' - tetrahydro - 6',7' - dimethoxy - 25 - I' - (4" - methoxybenzyl)isoquinoline] in the form of a colorless, viscous oil; 23a) N,N' - 4,7,10 - trioxa - 3,11 - diketotridecyl - 1,13 - di - (tetrahydropapaverine) in the form of a colorless, semi-solid substance. The following salts of formula 2 are prepared from the above compounds: 17b) N,N - dimethyl - N,N' - 4,13 - dioxa - 3,4 - diketohexadecyl - 1,16 - diiodide 18b) N,N' - dimethyl - N,N' - 4,7 - dioxa - - 3,8 - diketodecyl - 1,10 - di- ((+) - tetrahydropapaverinium) diiodide, melting point 120-130°C; 18c) N,N' - dimethyl - N,N' - 4,7 - dioxa - 3,8 - diketodecyl - 1,10 - di- ((+) - tetrahydropapaverinium) diiodide, melting point 99-108°C (obtained according to Example 1); 19b) N,N' - dimethyl - N,N' - 4,7 - dioxa - 3,8 - diketodecyl - 1,10 - di- ((+) - 40 - tetrahydropapaverinium) diiodide, melting point 99-108°C (obtained according to Example 1); - dioxa - - 3,8 - diketodecyl - 1,10 - di - [1',2',3',4' - tetrahydro - 1' - (3",4" - dimethoxybenzyl) - 6',7' - methylenedioxyisoquinolinium] with a melting point of 144-148°C; 20b) N,N' - dimethyl - N,N' - 4,10 - dioxa - - 3,11 - diketotridecyl - 1,13 - di - [1',2',3',4' - - tetrahydro - 1' - (3",4" - dimethoxybenzyl) - 6',7' - methylenedioxyisoquinolinium] with a melting point of 122-129°C; 21b) N,N' - diiodide dimethyl - N,N' - 4,7 - dioxa - - 3,8 - diketodecyl - 1,10 - di - [1',2',3',4' - tetrahydro - 6',7' - dimethoxy - 1' - benzylisoquinolinium] 55 , melting point 141-145°C; 22b) N,N' - dimethyl - N,N' - 4,7 - dioxa - - 3,8 - diketodecyl - 1,10 - di - (1',2',3',4' - tetrahydro - 6',7' - dimethoxy - V -)4" - methoxybenzyl- - (isoquinolinium) diiodide, melting point 143-150°C; and 60 23b) N,N' - dimethyl - N,N' - 4,7,10 - - trioxa - 3,11 - diketotridecylene - 1,13 - di - (tetrahydrofapaverinium) diiodide with a melting point of 119-128°C. Example XXIV. Using the procedure described in Example 1, N,N'-4,7-dioxa-3,8-dike-109,423,11-todecylene-1,10-di[D-(—)-tetrahydropapaverine] is prepared as a free base in the form of a colourless precipitate with a melting point of 47-49°C and a specific rotation of [α]2*f = -58.2° (c = 1.323, chloroform) (compound 24a), and then the di-(methanesulfonate) of this base (compound 24b) with a melting point of 105-113°C and a specific rotation of [α]2*f = -55.9° (c = 0.948, chloroform). 0.58 g of the free base and 5 ml of redistilled methyl iodide were heated to reflux in 10 ml of anhydrous benzene for 6 hours. The precipitate was dissolved in methanol, and the solution was added dropwise, with stirring, to 500 ml of filtered anhydrous ether. The flocculent white precipitate was filtered off, washed with anhydrous ether, and dried in vacuo over P2O. N,N,-dimethyl-N,N,-4,7-dioxa-3,8-dioxa-1,10-di-(D-(-tetrahydropapaverine)-diiodide is obtained, melting point 122-125°C and specific rotation [α]2g = -^48.9° (c = 1.208, chloroform) (compound 24c). Example XXV. Using the procedure described in Example XXIV, the following is obtained: 25a) N,N'-4,7-dioxa-3,8-dioxa-1,10-di-(L-(+)-tetrahydropapaverine) in the form of a colorless precipitate, melting point 48-50°C and specific rotation [α]2g = -^48.9°C (c = 1.208, chloroform) [a]2^5 = +58.9° (c = 1.021, chloroform); 25b) N,N' - dimethyl - N,N' - - 4,7 - dioxa - 3,8 - diketodecyl - 1,10 - di - (L - - (+) - tetrahydropapaverinium) di-(methanesulfonate) with a melting point of 105-114°C and a specific rotation of [a]2**5 = = +56.4° (c = 1.140, chloroform); and 25c) N,N'-dimethyl-N,N'-4,7-dioxa--3,8-dioxodecylene-1,10-di-(L-(+)-tetrahydropapaverinium) diiodide, melting point 122-126°C and specific rotation [d\2g = +48.1° (c = = 1.105, chloroform). Example XXVI. Preparation of the compound of formula 8. To 7.66 g of pentamethylene-1,5-diacrylate in anhydrous benzene are added dropwise 2.07 g of D-(+)-tetrahydropapaverin and the mixture is heated at reflux for 4 hours. The solvent is evaporated under reduced pressure and the residue is washed three times with petroleum ether (bp 40-60°C). The oily residue is dissolved in benzene and petroleum ether is added to precipitate the oil. These operations are repeated twice more and D-(—)-1-tetrahydro-2-papaverinyl-4,10-dioxa-3,11-dioxotridecene-12 is obtained with a specific rotation [α]2^5 = —41.17° (c = = 1.388, chloroform). Thin-layer chromatography on "Polygran Sil G" plates, using UV254 radiation for development and developing with a mixture of ethanol and ethyl acetate (1:1), shows the presence of one spot with Rf = 0.56. Infrared spectrum: 1740 cm-1 (c = 0 ester) and 165001*-1 (C-CHa group). 1.38 g of the above product and 0.847 g of L-(—)-tetrahydropapaverine are heated at boiling point in anhydrous benzene, with constant stirring, for 48 hours. The solvent is evaporated, the residue is dissolved in chloroform and a saturated solution of acetic acid in anhydrous ether is added to the solution. The precipitate is recrystallized from ethanol to obtain meso-N,N'-4,10-dioxa-3,11-dioxotride-12-cylene-1,13-di-(tetrahydropapaverine) disoxalate as a colorless solid with a melting point of 103-107°C and a specific rotation [α]2* = ±0° (c = 1.183, water). Using the method described in Example 1, the free base of meso-N,N'-4,7-dioxa-5,11-tridecylene-1,13-di-(tetrahydropapaverine) is obtained as a colorless solid. viscous oil with a specific rotation [α]22*5 = ±0° (c = 1.018, chloroform), and meso-NiN^dimethyl-N^N^j10-dioxa^11-dioxo-tridecyl-1,13-di-(tetrahydropapaverinium) di-(methanesulfonate) with a melting point of 102-107°C and a softening point of 97-99°C and a specific rotation [α]2!* = ±0° (c = 0.935, chloroform). The free base and salt 15 are compounds 26a and 26b, respectively. Example XXVII. Using the method described in Example XXVI, the following compounds are obtained: 27a) meso - N,N' - 4,7 - dioxa - 3,8 - diketodecyl - 1,10 - di-(tetrahydropapaverin) in the form of a gummy precipitate; and 27b) meso - N,N - dimethyl - N,N' - 4,7 - dioxa - 3,8 - diketodecyl - 1,10 - di-(tetrahydropapaverinium) di-(methanesulfonate) having a melting point of 110-112°C and a specific rotation [α]2* = 25 = ±0° (c = 0.409, chloroform). Example XXVIII. A mixture of 36 g of γ-butyrolactone and 15.2 g of 1,3-propanediol is saturated with hydrogen bromide at 0° C for two hours and then left at 0° C for 24 hours. The mixture is then added to 300 ml of water and extracted with 2 x 100 ml of dibromoethane. The combined extracts are washed with water, dried over sodium sulfate, and the solvent is evaporated. The remaining oily product is distilled to obtain about 50 g of 3-bromo-1-propyl-4-bromopropanecarboxylate as the main product, boiling at 106-140° C/0.05 mmHg. The thick distillation residue was extracted with 3 x 150 ml of petroleum ether (boiling 60-80°C). The combined extracts were evaporated to give a colorless oil, which, according to infrared and NMR analysis, was propane-1,3-di-(4-bromopropanecarboxylate). To a solution of 1.8 g of the above compound in 10 ml of boiling anhydrous toluene, was added dropwise over half an hour 4 g (6.8 g) of tetrahydropapaverine in 50 ml of toluene. The mixture was heated under reflux for 18 hours, cooled, and the tetrahydropapaverine hydrobromide was filtered off. The filtrate was evaporated under reduced pressure, and the oily residue was dissolved in chloroform (10 ml), and about 500 ml of ether and then about 500 ml of a saturated ethereal solution of oxalic acid were added. The flocculent precipitate was filtered off, washed with ether, and dried. After two recrystallizations from ethanol, N,N'-5,9-dioxa-4,10-dioxotridecylene-1,13-di-(tetrahydropapaverinium) disoxalate is obtained in the form of a white powder with a melting point of 107-115°C. Using the method described in Example 1, the free base of N,N'-5,9-dioxa-4,10-dioxotridecylene-1,13-di-(tetrahydropapaverinium) is obtained in the form of a colorless, viscous oil (compound 28a) and its di-(methanesulfonate) is obtained in the form of a white precipitate with a melting point of 95-102°C (compound 28b). 1 ad XXIX. Preparation of 3-methylpentanediol-65-1.5, a compound used in the synthesis of compound 4a.;109 423 13 To a suspension of 20 g of lithium aluminium hydride in 150 ml of anhydrous ether, a solution of 25 g of methylglutaric anhydride in 200 ml of a 1:1 mixture of anhydrous ether and tetrahydrofuran is added dropwise over 0.5 hour at 0.5°C, with stirring. The mixture was heated at reflux for 6 hours, then cooled to 0.5°C. The complex and excess hydride were then decomposed by the careful addition of 25 ml of water, 18.5 ml of 5N sodium hydroxide solution, and another 87.5 ml of water. The inorganic salts were filtered off, and the solvent was evaporated under reduced pressure. The oily residue was distilled to give 3-methylpentadiol-1,5, boiling at 110-112.5°C/0.7 mm Hg. ID 14. Further characteristics of the compounds discussed are given in the appropriate tables. Compounds designated by a numerical symbol alone are oxalates of the corresponding bases designated by a number and the letter "a", e.g. compound 1 is N,N'-4,10-dioxa-3,11-dioxotridecylene-1,13-di-(tetrahydropapaverinium) disoxalate. Table II gives the results of elemental analysis, Table III the infrared spectra and Table IV the NMR spectra and Rf values during thin-layer chromatography carried out on "Pogram Sil/G" coated plates, developed with a 1:1 mixture of ethanol and ethyl acetate and developed with UV254 radiation and iodoplatinate spraying. Table U Elemental analysis 1 Compound No. 1 1 1 Ib lc Id le lf Ig 2 1 2b 3 1 3b i 4b 1 1 5b 6b 1 6c 1 7c 8 1 8b 1 9 1 9b 1 | 1Ob | 1 11b 1 12b | 1 13b 1 1 14b 1 1 15b 1 1 16b 1 1 17b 1 18 18b 1 18c 1 19b 20b | _ 21b | 22b | Empirical formula .2 C$5H70N3O20 C53H72I2N2012 C55H78N2018S2.2H20 C65H82N2018S2.H20 C^H^NA^^O C^H^O^^O C^H^O^S^H.O C55H70N2O20.2H2O O^H^O^^O C55H70N2O20.2H2O C55H78N2018S2.2HaO C56H80N2O18S3.2H2O C57H82N2018S2.3H20 C54H74l2N20u.2H20 C^H^O^.l^O C54H76N3018S2.4H20 C^H^O^AO C^H^NjOwSa .2HaO C54H68N2O20.H2O CS4H76N2018S2.2H20 C53H74N2018S2.H20 O^H^O^-l-SI^O C52H70Br2N2O18S2.2H2O CsoH^N^A.LSH.O C^H^aaNaO^S, .0.5HaO Cj^jNaO^Sa .2.5H2O C^H^I^O^ C^H^^O^ C^H^Oao^O 0.0^^20.2 Q,H72N2018S2.3H20 OoH^I^O,, C^H^^O^ O.H.AN20..H20 OiHtt^NaPioAO Calculated % C 3 61.22 53.80 57.8 61.9 61.7 62.75 63.55 59.24 57.19 59.24 57.19 58.43 57.00 52.60 58.43 55.1 59.88 1 56.84 59.88 56.81 57.40 55.72 49.13 , 56.02 52.22 55.66 54.54 | 54.90 | 58.21 52.63 55.22 | 51.99 | 53.22 | 53.18 | 52.46 | H 4 6.49 6.09 7.10 6.7 6.95 6.6 6.55 6.64 7.11 6.64 7.11 7.13 7.33 6.33 7.13 7.1 6.47 7.02 6.47 7.02 6.86 6.80 5.83 6.26 | 5.53 6.86 | 6.28 | 6.37 | 6.34 5.98 6.90 | 5.27 | 5.57 5.78 | 5.85 | N 5 2.60 2.37 2.43 ' 2.2 2.14 2.0 2.03 2.51 2.43 2.51 2.43 2.43 2.33 2.77 2.43 2.38 2.59 2.46 2.59 2.46 2.53 2.40 2.20 2.6 2.54 2.50 2.29 | 2.29 | 2.61 2.45 2.48 | 2.53 | 2.43 | 2.70 1 2.55 | Found % C 6 61.13 53.87 57.03 62.35 61.76 63.29 63.31 59.05 57.34 59.08 57.44 58.03 57.12 52.53 58.07 55.41 60.28 56.68 59.88 56.43 57.41 55.80 49.04 56.05 52.33 55.74 | 55.07 | 55.39 58.29 52.41 55.00 | 51.72 | 53.54 | 53.62 | 52.38 | H 7 6.27 6.18 6.80 6.73 7.04 6.21 6.44 6.31 6.88 6.35 6.90 7.37 7.10 6.44 6.87 6.61 6.35 6.79 6.34 6.88 6.68 7.03 5.76 6.58 5.57 7.23 6.46 6.49 | 5.98 6.04 6.59 | 5.25 | 5.49 | 5.74 5.73 | N 8 2.49 2.12 2.56 2.20 2.06 1.77 1.95 2.69 2.18 | 2.32 2.40 | 2.17 1 2.12 | 2.20 2.25 1 238 1 2.45 234 | 2.48 2.33 | 2.54 1 2^2 j 2.15 | 2.59 | 2.61 1 2.40 | 2.29 1 2.25 | 2.58 2.6 2.26 j 2.25 1 2.20 1 '2.48 1 2.37 !109 423 15 16 table II (continued) 1 1 | 23b 24 24b 24c 25 25b 25c 26 26b 27 ' 27b 28 2 C52H70I2N2O13 C52H64N202.H20 C52H72N2018S2 .3H20 C50H66N2I2 C52H64N202 .H20 C52H72N2018S2 .3H20 C50H66I2N2O12 C55H70N2O2 .N20 CS5H78N203S2.2H20 C52H64N2O20.H2O C52H72N2018S2 .3H20 C55H78N201SS2.3H20 3 52.70 59.2 55.22 52.63 59.2 55.22 52.6 60.22 57.19 59.20 55.22 56.33 4 5.91 6.26 6.9 5.79 6.26 6.9 5.79 6.57 7.11 6.26 6.9 7.16 5 | 6 | 7 2.38 2.66 2.48 2.45 2.66 2.48 2.45 2.55 2.43 2.66 2.48 52.99 58.9 54.8 52.37 58.9 55.56 52.46 60.54 57.06 59.67 55.43 56.08 6.1 6.27 6.53 6.12 6.27 6.58 6.04 6.52 7.54 6.01 6.72 7.18 8 | 2.36 | 2.86 2.36 2.32 | 2.86 2.32 2.28 | 2.54 2.47 | 2.84 2.37 | Table III Infrared spectra 1 Compound No. 1 1 la 1 lb 4 4a 1 4b 5 5a 1 5b 6 6a | 6b 7 1 7a 10 lOa | lOb 11 lla | llb 12 12a 1 12b 13 13a 13b 14 14a 14b | Absorption bands in cm-1 1 2 2950, 2840, 2610—2300, 1745, 1690, 1610, 1595, 1510 3010, 2940, 2860, 1740, 1610, 1595, 1510 2980, 2940, 2830, 1740, 1620, 1600, 1510 2950, 2850, 2630—2340, 1745, 1705, 1605, 1590, 1515 2900, 2810, 1740, 1610, 1590, 1505 2930, 2850, 1745, 1620, 1600, 1515 2940, 2850, 2630—2330, 1745, 1700, 1610, 1595, 1510 2930, 2820, 1735, 1605, 1595 2900, 2820, 1745, 1610, 1600, 1515 2940, 2860, 2630—2300, 1750, 1700, 1610, 1590, 1510 3000, 2950, 2850, 1740, 1610, 1600, 1510 2980, 2940, 2830, 1745, 1610, 1600, 1510 2940, 2850, 2640—2330, 1745, 1680, 1610, 1600, 1510 3000, 2940, 2870, 1745, 1610, 1600, 1510 3000, 2870, 2650—2400, 1755, 1690, 1620, 1600, 1515 3000, 2940, 2860, 1745, 1610, 1600, 1510 3000, 2950, 2830, 1740, 1620, 1600, 1510 2940, 2850, 2630—2310, 1745, 1705, 1605, 1595, 1510 2940, 2840, 1745, 1605, 1600, 1510 2940, 2850, 1745, 1610, 1510 2940, 2850, 2620—2330, 1750, 1705, 1610, 1595, 1515 2940, 2850, 1750, 1610, 1505 3000, 2940, 2850, 1743, 1610, 1510 | 2940, 2840, 2640—2340, 1745, 1705, 1610, 1595, 1505 2900, 2820, 1745, 1610, 1510, 1500 3000, 2940, 2850, 1745, 1610, 1510, 1500 | 2950, 2840, 2630-2300, 1745, 1705, 1 1610, 1595, 1510 2920, 2800, 1745, 1610, 1510 2990, 2940, 2850, 1745, 1610, 1510 | 20 35 45 55 60 table III (continued) i and | 2 15 15a | 15b 16 16a 16b 17 17a 1 17b 18 18a 18b 18c 19 | 19b 20 20a 20b 21 21a 21b 22 22a 22b 23 23a 28 28a 28b ' 2950, 2840, 2600-2280, 1745, 1705, 1605, 1595, 1510 2990, 2940, 2800, 1745, 1610, 1595, 1505, 1500 3000, 2940, 2850, 1745, 1610, 1510, 1505 2940, 2860, 2650-2340, 1750, 1710, 1615, 1590, 1515 2980, 2900, 1745, 1615, 1600, 1510 2970, 2880, 1750, 1615, 1600, 1515 2940, 2850, 2640—2310, 1750, 1715, 1615, 1595, 1515 2980, 2900, 1745, 1610, 1600, 1510 2950, 2870, 1745, 1610, 1510 2970, 2900, 2800, 2650—2330, 1745, 1705, 1610, 1590, 1500 2920, 2900, 2800, 1740, 1610, 1590, 1505 3000, 2900, 2810, 1740, 1610, 1505 3010, 2900, 2800, 1610, 1595, 1505 3460, 3000, 2960, 2850, 2630—2330, 1760, 1715, 1600, 1590, 1510, 1490 2990, 2940, 2860, 1755, 1600, 1510, 1490 3430, 2930, 2850, 2640—2330, 1750, 1710, 1600, 1590, 1490 3010, 2940, 2850, 1750, 1610, 1600, 1515, 1490 3000, 2950, 2870, 1750, 1600, 1510, 1490 2940, 2850, 2650—2300, 1740, 1705, 1610, 1590 2950, 2850, 1755, 1610, 1515 3000, 2950, 2850, 1745, 1610, 1510 2940, 2850, 2640—2320, 1745, 1705, 1605, 1595, 1510 3010, 2940, 2850, 1750, 1610, 1595, 1510 3000, 2940, 2850, 1745, 1610, 1505 3450, 3000, 2950, 2860, 2650—2350, 1760, 1720, 1650, 1595, 1520 2960, 2860, 1755, 1615, 1600, 1515 | 2940, 2880, 2650-1330, 1745, 1700, 1610, 1590, 1510 3000, 2880, 1740, 1615, 1600, 1520 2940, 2810, 1745, 1610, 1600, 1515 |109 423 18 table IV (continued) | f 2 | 3 13a 14a 15a 16a 17a 18a 19a 0.6 0.6 0.6 0.6 0.6 0.54 0.6 x ArOCH3), 3.87 (12H, s, 4 xArOCH3), 3.58—3, 90(2H, dd, 2xArCH.N), 4.17 (4H, s, 2xCOOCH2), 6.31 (2H, s, C8Ar-H), 6.56—6.60 (4H, 2s, Ar-H), 7.08 (2H, s, Ar-H). (5(CHC13): 2.25—3.45 (20H, m, 4x xArCH2), (4xCH2.N, 2xCH2COO), 1 3.70 (6H, m, 2 x C7ArOCH3), 3.85 (6H, s, 2 x C6ArOCH3), 3.60—3.91 (2H, dd, 2 x ArCH .N), 4.25 (4H, s, 2 x COOCH2), 5.94 (4H, s, 2 C7ArOCH3), 3.87 (6H, s, 2 x C6ArOCH3), 3.63—3.90 (2H, dd, 2 X ArCH .N), 4.22 (4H, s, 2 (6H, m, Ar-H). <5(CHC13): 2.28—3.43 (20H, m, 4x xArCH2, 4xCH2.N, 2xCH2COO), 3.62 (6H, s, 2 X C7ArOCH3), 3.71 (6H, s, 2xArOCH3), 3.81 (6H, s, 2xArO- CH3), 3.86 (6H, s, 2xArOCH3), 3.59—3.88 (2H, dd, 2 5_), 2.35—3.38 (20H, m, 4xArCH2, 4x x CH2 .N, 2 x CH2COO-), 3.67 (6H, s, 2 ArOCH3), 3.59—3.96 (2H, dd, ArCH..N), 4.04^4.19 (4H, m, 2X COOCH2-), 6.16 (2H, s, 2xC8Ar-H), 6.60—6.86 (8H, m, Ar-H). 6_), 2.31—3.33 (20H, m, 4xArCH2-, 4xCH2.N, 2xCH2COO), 3.64 (6H, s, 2 X C7ArOCH3), 3.83 (6H, s, 2 s, 2xArOCH3), 3.60—3.94 (2H, dd, 2x xArCH.N), 3.96—4.18 (4H, m, 2X xCOOCH2), 6.14 (2H, s, C8Ar-H), 6.56—6.84 (8H, m, Ar-H). | <5(CHC13): 2.30—3.50 (20H, m, 4x xArCH2-, 4xCH2N, 2xCH2COO), 3.64 (6H, s, 2xC7ArOCH3), 3.85 (18H, s, 6xArOCH3), 3.70—4.11 (2H, dd, 2 x ArCH .N), 4.22 (4H, s, 2 x COOCH2), 6.13 (2H, s, 2xC8Ar-H), 6.54^6.80 (8H, m, Ar-H). | <5(CDC13): 2.18—3.28 (20H, m, 4x xArCH2-, 4xCH2N, 2xCH2COO), 3.83 (6H, s, ArOCH3), 3.86 (6H, s, ArOCH3), 3.65—3.91, (2H, dd, 2 x X ArCH .N), 4.17 (4H, s, 2x-COOCH2), 5.87 (4H, s, 2xOCH2O), 6.34 (2H, s, 2xC8ArH), 6.53—6.84 (8H, m, Ar-H). [ 1 Union No. | 1 la 4a 5a 6a 7a lOa lla 12a Rf 2 0.6 0.6 0.6 0.6 0.6 0.6 0.6 0.6 NMR spectrum (ppm) 3 | 2.26—3.44 (20H, m, 4xArCH2-, 4x xCH2.N, 2xCH2.COO), 3.62 (6H, s, 2xC7ArOCH3), 3.87 (18H, s, 6x xArOCH3), 3.58—3.93 (2H, dd, 2x xArCH.N), 3.97—4.16 (4H, m, 2x xCOOCH2), 6.16 (2H, s, C8Ar-H), 6.60—6.85 (8H, m, Ar-H). ó (CDC13): 0.90 (3H, d, CH3-CH), 1.32— —1.91 (5H, m), (CH2-CH-CH2), 2.23— —3.39 (20H, m, 4xArCH2, 4xN-CH2, 2xCN2COO), 3.56 (6H, s, 2xC7Ar- OCH3), 4.05 (4H, t, 2xCH2COO), ca 4.31 (2H, dd, 2 x CH-N), 6.07 (2H, s, 2 x C8Ar-H), 6.54^6.77 (8H, m, Ar-H). (2xCH-CH2, 4xAr-CH2, 4x-N-CH2, 2 x CH2COO), 3.88 (6H, s, 2 x ArO-CH3), 3.90 (12H, s, 4xArO-CH3), 3.92 (6H, s, 2xArO-CH3), 3.58—4.21 (6H, m, 2 x CH-N, 2xCO-0-CH2), 6.56 (2H, s, Ar-H), 6.63 (2H, s, Ar-H), 6.85 (6H, s, Ar-H). | 2.31—3.36 (20H, m, 4xArOH2-, 4x dd, 2xArCH,N), 3.98—4.14 (4H, m, 2xCOOCH2), 6.14 (2H, s, C8Ar-H), 6.61—6.84 (8H, m, Ar-H). | ^(CDC13): 1.50—1.83 (4H, m, - (CH2)2-), 2.25—3.45 (20H, m, 4xArCH2-, 4x 3.58—3.91 (2H, dd, ArCHN), 3.96—4.24 (4H, m, 2xCOOCH2-) 6.17 (2H, s, C8Ar-H), 6.59—6.87 (8H, m, Ar-H). —3.46 (20H, m, 4xAr-CH2-, 4xCH2..N-, 2xCH2COO), 3.65 (6H, s, 2xC7ArOCH3), 3.89 (18H, s, 6xArO- CH3), 3.61—3.94 (2H, dd, ArCH.N), 4.14 (2H, t, 2 X COOCH2-), 6.16 (2H, s, 2xC8Ar-H), 6.59—6.88 (8H, m, Ar-H). | (5(CDC13): 2.30—3.50 (20H, m, 4x xArCH2, 4xCH2.N, 2xCH2COO), 3.54 (6H, s, 2 X C7ArOCH3), 3.85 (24H, s, 8xArOCH3): 3.63—3.90 (2H, dd, ArCH.N), 4.25 (4H, s, 2xCOOCH2), 6.14 (2H, s, 2xC8ArH), 6.38 (4H, s, Ar-H), 6.62 (2H, s, Ar-H), 3.68 (6H, s, 2C7ArOCH3), 3.78 (6H, s, 2x |109 423 1? Table IV (continued) 1 20a 20 characterized in that a ditertiary base of general formula 4, in which A, B, L, R4, R5, Z1 and Z2 have the above-mentioned meaning, is quaternized with a quaternizing agent introducing both groups R2 and R3 and optionally the resulting compound is converted into the desired salt of formula 2. 2. A method according to claim 1, characterized in that a ditertiary base of general formula 4, in which Z1 and Z2 are the same or different and each of them represents a group of the formula -O-CH2-O- or 1, 2 or 3 methoxy groups, R4 and R5, the same or different, represent a benzyl or phenylethyl group, in which the phenyl ring is optionally substituted with one or more substituents such as a halogen atom, an alkoxy group of 1-3 carbon atoms or a methylenedioxy group, A and B, the same or different, are an alkylene group of 1-3 carbon atoms, L is an alkylene group of 2-12 carbon atoms or a group of the formula -IAO.L2-, wherein L1 and L3 are each an alkylene group of at least two carbon atoms and together contain up to 11 carbon atoms, is reacted with a quaternizing agent of the formula R6X, wherein R6 is an alkyl group of 1-3 carbon atoms, a 2-propenyl or 2-propynyl group and X is an anion of an organic or inorganic acid. 3. A method according to claim 1, characterized in that the base of formula 4, in which A and R each represent a group of formula -CH2.CH2-, R4 and R5 each represent a 3,4-dimethoxybenzyl group, Z1 and Z2 each represent a 6,7-dimethoxy group, and L represents a simple alkylene group of 2-8 carbon atoms, a 3-methylpentylene or 3-oxapentylene group, is reacted with a quaternizing agent of formula R6X, in which R6 represents a methyl group and X represents an anion. 4. A method according to claim 1, characterized in that a base of formula 4, in which A and B each represent a group of formula -CH.CH2-, Z1 and Z2 each represent a 6,7-dimethoxy group, both R4 and R5 represent a group 5. A method according to claim 1, characterized in that the base of formula 4, wherein L is an alkylene group of 2-12 carbon atoms or a group of formula -IAO.L2-, wherein L1 and L2 are each alkylene groups of at least two carbon atoms and together contain up to 11 carbon atoms, is reacted with a quaternizing agent of formula R6X, wherein R6 is a methyl group and X is an anion. wherein A and B each represent a group of the formula -CH2.CH2-, R4 and R5 each represent a 3,4-dimethoxybenzyl group, Z1 and Z2 each represent a 6,7-dimethoxy group and L represents a simple alkylene group with 2-5 carbon atoms is reacted with a quaternizing agent of the formula R6X, wherein R6 represents a methyl group and X represents an anion. 6. A method according to claim 1, characterized in that a base of the formula 4, wherein A and B each represent a group of the formula -CH2.CH2-, R4 and R5 each represent a 3,4-dimethoxyphenylethyl group, Z1 and Z2 each represent a 6,7-dimethoxy group and L represents a simple pentylene group is reacted with a quaternizing agent of the formula R6X, wherein R6 is a methyl group and X is an anion. 7. A method according to claim 1, characterized in that the base of formula 4, in which A, B and L each represent a group of the formula -CH2.CH2,CH2-, R4 and R5 each represent a 3,4-dime- 21a 22a 23a 25a 0.6 0.6 0.6 0.65 (4H, s, OCH2O), 6.38 (2H, s, 2x xC8ArH), 6.60-6.82 (8H, m, ArH). | (5(CDC13): 2.37-3.40 (20H, m, 4x xArCH2, 4xCH2.N, 2xCH2COO), 3.57 (6H, s, 2xC7ArOCH3), 3.82 (6H, s, 2xC6ArOCH3), 3.82 (6H, s, 2x xC6ArOCH3), 3.47—3.79 (2H, dd, 2 x ArCH .N), 4.10 (4H, s, 2 x COOCH2), 6.07 (2H, s, CgAr-H), 6.57 (2H, s, C5-Ar-H), 7.12-7.32 (10H, m, Ar-H). | C(CDC13): 2.29—3.45 (20H, m, 4x x ArCH2, 4 x CH2 .N, 2 x CH2COO), 3.62 (6Hm, s, 2 x C^ArOCHs), 3.78 (6H, s, 2xArOCH3), 3.86 (6H, s, 2x xArOCH3), 3.54—3.86 (2H, dd, ArCH.N), 4.23 (4H, s, 2xCOOCH2), 6.11 (2H, s, 2xCeAr-H), 6.60 (2H, s, 2x C5Ar-H), 6.75—7.15 (8H, m, Ar-H). | xArCH2-, 4xCH2.N, 2xCH2COO), 3.59—3.85 (4H, m, 2x-CH2O), 3.67 (6H, s, CjArOCH,), 3.86 (6H, s, 2x xArOCH3), 3.88 (6H, s, 2xArOCH3), 3.91 (6H, s, 2xArOCH3), 3.70—3.98 (2H, dd, ArCH.N), 4.15-^1.41 (4H, m, 2xCH2OCO), 6.19 (2H, s, QAr-H), 6.61—6.85 (8H, m, Ar-H). | <5(CDC13): 1.60—3.22 (26H, m, 4x xArCH2, 4xN-CH2, 4xN-CH2, 3x xCH2-CH2-CH2, 2xCH2-CO-0), 3.65 (6H, s, 2xC7Ar-0-CH3), 3.86 (18H, 6xAr-0-CH3), 3.77—4.26 (6H, m, 2xCO-0-CH2, 2xAr-CH-N), 6.14 (2H, s, 2xC8Ar-H), 6.56-6.80 (8H, m, Ar-H). | 10 15 20 25 30 35 40 45 Patent Claims 1. A process for the preparation of new isoquinoline derivatives of the general formula II, wherein Z1 and Z2 are the same or different and each of them represents a group of the formula -O-CH2-O or 1, 2 or 3 methoxy groups, R2 and R3, the same or different, represent an alkyl group with 1-3 carbon atoms, a 2-propenyl or 2-propynyl group, R* and R5, the same or different, represent a benzyl or phenylethyl group, wherein the phenyl ring is optionally substituted with one or more substituents such as a halogen atom, an alkoxy group of 1-3 carbon atoms and a methylenedioxy group, A and B, the same or different, represent an alkylene group of 1-3 carbon atoms, L represents an alkylene group of 2-12 carbon atoms, or a group of the formula -IAO.L2-, wherein L1 and L2 each represent an alkylene group of at least two carbon atoms and together contain up to 11 carbon atoms, and X" represents an anion, i.e. 50 55 60 65 1 2 0.6 0.6 0.6 0.6 0.65 1 3 <5(CDC13): 1.27-1.78 (6H, m, -(CH2)- 3_), 2.29-3.25 (20H, m, 4xArCH2-, 4xCH2.N, 2xCH2COO), 3.87 (6H, s, ArOCH3), 3.90 (6H, s, ArOCH3), 3.68— —3.88 (2H, dd, 2xArCH.N), 3.90— —4.20 (4H, m, 2xCOOCH2), 5.91 (4H, s, OCH2O), 6.38 (2H, s, 2x xC8ArH), 6.60—6.82 (8H, m, ArH). (5(CDC13): 2.37—3.40 (20H, m, 4x xArCH2, 4xCH2.N, 2xCH2COO), 3.57 (6H, s, 2xC7ArOCH3), 3.82 (6H, s, 2xC6ArOCH3), 3.82 (6H, s, 2x xC6ArOCH3), 3.47—3.79 (2H, dd, 2 x ArCH .N), 4.10 (4H, s, 2 x COOCH2), 6.07 (2H, s, CgAr-H), 6.57 (2H, s, C5- -Ar-H), 7.12—7.32 (10H, m, Ar-H).C(CDC13): 2.29—3.45 (20H, m, 4x xArCH2, 4xCH2.N, 2xCH2COO), 3.62 (6Hm, s, 2xC7ArOCH3), 3.78 (6H, s, 2xArOCH3), 3.86 (6H, s, 2x xArOCH3), 3.54—3.86 (2H, dd, ArCH.N), 4.23 (4H, s, 2xCOOCH2), 6.11 (2H, s, 2xCeAr-H), 6.60 (2H, s, 2x C5Ar-H), 6.75—7.15 (8H, m, Ar-H). x ArCH2-, 4 x CH2 .N, 2 x CH2COO), 3.59—3.85 (4H, m, 2x-CH2O), 3.67 (6H, s, C^ArOCH,), 3.86 (6H, s, 2x xArOCH3), 3.88 (6H, s, 2xArOCH3), 3.91 (6H, s, 2xArOCH3), 3.70-3.98 (2H, dd, ArCH 2 N), 4.15-1.41 (4H, m, 2xCH 2 OCO), 6.19 (2H, s, QAr-H), 6.61-6.85 (8H, m, Ar-H). <5(CDC13): 1.60-3.22 (26H, m, 4x109 423 21 22 oxybenzite, wherein Z 1 and Z 2 each represent a 6,7-dimethyloxybenzyl group, is reacted with a quaternizing agent of formula R*X, wherein R 6 is a methyl group and X is an anion. 8. The method according to claim 3, characterized in that a base of formula 4, wherein each A and B represents a group of formula -CH2.CH3-, R4 and R5 each represent a 3,4-dimethoxybenzyl group, Z1 and Z2 each represent a 6,7-dimethoxy group, and L represents a simple pentylene group, is reacted with a quaternizing agent of the formula R6X, wherein R6 represents an alkyl group of 1-3 carbon atoms, a 2-propenyl or 2-propynyl group, and X represents an anion of an organic or inorganic acid. 9. A method according to claim 1, characterized in that a base of the formula 4, in which Z1 and Z2 are the same or different and each represents a group of the formula -O-CH2-O- or 1, 2 or 3 methoxy groups, R4 and R5, the same or different, represent a benzyl or phenylethyl group, in which 10. A process according to claim 9, wherein A and B, which may be the same or different, represent an alkylene group of 1-3 carbon atoms, L represents an alkylene group of 2-12 carbon atoms or a group of the formula -IAG.L2-, wherein L1 and L2 each represent an alkylene group of at least two carbon atoms and together contain up to 11 carbon atoms, is reacted with a quaternizing agent of the formula R6X, wherein R6 represents an alkyl group of 1-3 carbon atoms, 2-propenyl or 2-propynyl, and X represents a pharmacologically acceptable anion. that a base of formula 4, in which Z1 and Z2 are the same or different and each of them represents a group of formula -O-CH2-O- or 1, 2 or 3 methoxy groups, R4 and R5, the same or different, represent a benzyl or phenylethyl group, in which the phenyl ring is optionally substituted by one or more substituents such as a halogen atom, an alkoxy group of 1-3 carbon atoms or a methylenedioxy group, A and B, the same or different, represent an alkylene group of 1-3 carbon atoms, L represents an alkylene group of 2-12 carbon atoms or a group of formula -IAO.L2-, in which each L1 and L2 represents an alkylene group of at least two carbon atoms and together contain up to 11 carbon atoms, is subjected to 11. A method according to claim 9, characterized in that a base of formula 4, wherein Z1 and Z2 are the same or different and each of them is a group of the formula -O-CH2-O- or 1, 2 or 3 methoxy groups, R4 and R5, the same or different, are benzyl or phenylethyl, in which the phenyl ring is optionally substituted by one or more substituents such as a halogen atom, an alkoxy group of 1-3 carbon atoms or a methylenedithioxy group, A and B, the same or different, are 12. A method according to claim 1, characterized in that a base of formula 4, in which each Z1 and Z2 is a 6,7-dimethoxy group, L is a simple pentylene group, each A and B is a group of formula -CH2.CH2-, and each R4 and R5 is a 3,4-dimethoxybenzyl group is reacted with a quaternizing agent of the formula R6X, in which R6 is a methyl group and X is an anion of an organic or inorganic acid. 13. The method according to claim 12, characterized in that a base of the formula 4, in which Z1 and Z2 are each a 6,7-dimethoxy group, L is a simple pentylene group, A and B are each a group of the formula -CH2.CH2-, and R4 and R5 are each a 3,4-dimethoxybenzyl group is reacted with methyl benzenesulfonate. 14. The method according to claim 1, characterized in that a base of the formula 4, in which Z1 and Z2 are the same or different and each is a group of the formula -O-CH2-O- or 1, 2 or 3 methoxy groups, R4 and R5, the same or different, are benzyl or phenylethyl, the phenyl ring being optionally substituted by one or more halogen, alkoxy of 1-3 carbon atoms or methylenedioxy, A and B, the same or different, are alkylene of 1-3 carbon atoms, L is alkylene of 2-12 carbon atoms or a group of formula -IAO.L2-, wherein L1 and L2 each represent an alkylene group of at least two carbon atoms and together contain up to 11 carbon atoms, are reacted with a quaternizing agent of formula R6X, wherein R6 is an alkyl group of 15. A method according to claim 1, characterized in that the base of formula 4, wherein Z1 and Z2 are the same or different and each of them represents a group of the formula -O-CH2-O- or 1, 2 or 3 methoxy groups, R4 and R5, the same or different, represent a benzyl or phenylethyl group, wherein the phenyl ring is optionally substituted by one or more substituents such as a halogen atom, an alkoxy group of 1-3 carbon atoms or a methylenedioxy group, A and B, the same or different, represent an alkylene group with 1-3 carbon atoms, L is an alkylene group with 2-12 carbon atoms or a group of the formula -L1.O.L2-, wherein L1 and L2 each represent an alkylene group of at least two carbon atoms and together contain up to 11 carbon atoms, is reacted with a reactive ester derivative of an alcohol of the formula R6OH, wherein R6 is an alkyl group with 1-3 carbon atoms, a 2-propenyl or 2-propynyl group. 16. A method according to claim 15, characterized in that the base b of formula 4, in which Z1 and Z2 are the same or different and each of them represents a group of the formula -O-CH2-O-, or 1, 2 or 3 methoxy groups, R4 and R5, the same or different, represent a group benzyl or phenylethyl, wherein the phenyl ring is optionally substituted with one or more substituents such as a halogen atom, an alkoxy group having 1-3 carbon atoms or a methylenedioxy group, A and B, the same or different, represent an alkylene group having 1-3 carbon atoms, L represents an alkylene group having 2-12 carbon atoms or a group of the formula -L1.O.L2-, wherein each L1 and L2 represents an alkylene group having at least two carbon atoms and together containing up to 11 carbon atoms, is reacted with a reactive ester derivative of hydrogen chloride, hydrogen bromide or hydrogen iodide. characterized in that a base of formula 4, in which Z1 and Z2 are the same or different and each represents a group of formula -O-CH2-O- or 1, 2 or 3 methoxy groups, R4 and R5, the same or different, represent a benzyl or phenylethyl group, the phenyl ring being optionally substituted by one or more substituents such as a halogen atom, an alkoxy group having 1-3 carbon atoms or a methylenedioxy group, A and B, the same or different, represent an alkylene group having 1-3 carbon atoms, L represents an alkylene group having 2-12 carbon atoms or a group of formula -IAO.L2-, in which L1 and L2 each represent an alkylene group having at least two carbon atoms and together containing up to 11 carbon atoms, is reacted with 18. A method according to claim 15, characterized in that the base of formula 4, wherein Z1 and Z2 are the same or different and each represents a group of the formula -O-CH2-O- or 1, 2 or 3 methoxy groups, R4 and R5, the same or different, represent a benzyl or phenylethyl group, in which the phenyl ring is optionally substituted by one or more substituents such as a halogen atom, an alkoxy group of 1-3 carbon atoms or a methylenedioxy group, A and B, the same or different, represent an alkylene group of 1-3 carbon atoms, L is an alkylene group having p2-12 carbon atoms or a group of the formula -IAO.L2-, wherein X1 and L2 each represent an alkylene group having at least two carbon atoms and together containing up to 11 carbon atoms, is reacted with a derivative of p-toluenesulfonic acid, naphthalene-1-sulfonic acid or naphthalene-2-sulfonic acid. 19. The process of claim 1, wherein a molar excess of the quaternizing agent is used. 20. The process of claim 1, wherein the reaction is carried out in the presence of a solvent. 21. The process of claim 20, wherein the solvent is an alkanol, an aromatic hydrocarbon, a halogenated hydrocarbon or an aliphatic ketone. 22. The process of claim 23, wherein 23. A process according to claim 1, characterized in that the reaction is carried out at room temperature. 24. A process according to claim 1, characterized in that the reaction is carried out by heating to the boiling point of the reaction mixture. 25. A process according to claim 1, characterized in that the reaction is carried out in the absence of light. 26. A process according to claim 1, characterized in that the reaction is carried out under increased pressure. 27. A process for the preparation of new isoquinoline derivatives of the general formula II, wherein Z1 and Z2 are the same as R2 and R3, the same or different, represent an alkyl group of 1-3 carbon atoms, a 2-propenyl group or a 2-propynyl group, R4 and R5, the same or different, represent a benzyl or phenylethyl group, the phenyl ring being optionally substituted by one or more halogen atoms, an alkoxy group of 1-3 carbon atoms and a methylenedioxy group, A and B, the same or different, represent an alkylene group of 1-3 carbon atoms, L represents an alkylene group of 2-12 carbon atoms, or a group of the formula -IAO.L2-, wherein L1 and L2 each represent a group alkylene group having at least two carbon atoms and containing up to 11 carbon atoms in total, and X" is an anion, characterized in that a monoquaternary derivative of a base of general formula 4, in which A, B, L, R4, R5, Z1 and Z2 have the above-mentioned meanings, and furthermore one of the isoquinoline groups is substituted in position 2 by a group R2 or R3, is quaternized with a quaternizing agent introducing one of the groups R2 and R3, and optionally the obtained compound is converted into the desired salt of formula 2. 28. A method according to claim 27, characterized in that a monoquaternary derivative of a base of general formula 4, in which one of the isoquinoline groups is substituted in position 2 by a group R2 or R3 representing a methyl group, Z1 and Z2 are such the same or different and each of them represents a group of the formula -O-CH2-O- or 1, 2 or 3, the methoxy groups, R4 and R5, the same or different, represent a benzyl or phenylethyl group, the phenyl ring of which is optionally substituted by one or more substituents such as a halogen atom, an alkoxy group of 1-3 carbon atoms or a methylenedioxy group, A and B, the same or different, represent an alkylene group of 1-3 carbon atoms, L represents an alkylene group of 2-12 carbon atoms or a group of the formula -IAO.L2-, wherein each L1 and L2 represents an alkylene group of at least two carbon atoms and together contain up to 11 carbon atoms, are reacted with a quaternizing agent of 29. A method according to claim 27, characterized in that a monoquaternary derivative of a base of formula 4, in which A and B each represent a group of the formula -CH2.CH2-, R4 and R5 each represent a 3,4-dimethoxybenzyl group, Z1 and Z2 each represent a 6,7-dimethoxy group, and L represents a simple alkylene group of 2-8 carbon atoms, a 3-methylpentylene or 3-oxapentylene group, and in which one of the isoquinoline groups is substituted in position 2 by a group R2 or R3 representing a group 30. A method according to claim 27, characterized in that the monoquaternary base derivative of formula 4, wherein each of A and B is a group of the formula -CH.CH2-, each of Z1 and Z2 is a 6,7-dimethoxy group, each of R4 and R5 is a benzyl, 4-methoxybenzyl, 3,4-dimethoxybenzyl, 3,4-dimethoxy-6-bromobenzyl, 30. A process according to claim 1 wherein the isoquinoline group is substituted in the 2-position by a group R2 or R3 representing a methyl group, is reacted with a quaternizing agent of the formula R6X, wherein R6 is a methyl group and X is an anion. 32. A method according to claim 27, characterized in that a monoquaternary derivative of a base of formula 4, in which A and B each represent a group of formula -CH2.CH2-, R4 and R5 each represent a 3,4-dimethoxybenzyl group, Z1 and Z2 each represent a 6,7-dimethoxy group, and L represents a simple alkylene group of 2-5 carbon atoms, and in which one of the isoquinoline groups is substituted in position 2 by a group R2 or R3 representing a methyl group, is reacted with a quaternizing agent of formula R6X, in which R6 represents a methyl group and X represents an anion. 32. A method according to claim 27, characterized in that a monoquaternary derivative of a base of formula 4, in which A and B each represent a group of formula -CH2.CH2-, R4 and R5 each represent a 3,4-dimethoxyphenylethyl group, Z1 and Z2 each represent a 6,7-dimethoxy group, and L represents a simple pentylene group, and in which one of the isoquinoline groups is substituted in position 2 by a group R2 or R3 representing a methyl group, is reacted with a quaternizing agent of formula R6X, in which R6 represents a methyl group and X represents an anion. 33. A method according to claim 27, characterized in that a monoquaternary derivative of a base of formula 4, in which A, B and L each represent a group of formula -CH2.CH2.CH2-, R4 and R5 each represent a 3,4-dimethoxybenzyl group and Z1 and Z2 each represent a 6,7-dimethoxy group and in which one of the isoquinoline groups is substituted in position 2 by a group R2 or R3 representing a methyl group, is reacted with a quaternizing agent of formula R6X, in which R6 represents a methyl group and X represents an anion. 34. A method according to claim 29, characterized in that a monoquaternary derivative of a base of formula 4, in which A and B each represent a group of formula -CH2.CH2-, R4 and R5 each represent a 3,4-dimethoxybenzyl group, Z1 and Z2 each represent a 6,7-dimethoxy group, and L represents a simple pentylene group, and in which one of the isoquinoline groups is substituted in position 2 by a group R2 or R3 representing a methyl group, is reacted with a quaternizing agent of formula R6X, in which R6 represents an alkyl group of 1-3 carbon atoms, a 2-propenyl or 2-propynyl group, and X represents an anion. A process according to claim 27, characterized in that a monoquaternary derivative of a base of formula 4, in which one of the isoquinoline groups is substituted in position 2 by a group R2 or R3 representing a methyl group, Z1 and Z2 being the same or different and each of them representing a group of the formula -O-CH2-O- or 1, 2 or 3 methoxy groups, R4 and R5, the same or different, representing a benzyl or phenylethyl group, in which the phenyl ring is optionally substituted by one or more substituents such as a halogen atom, an alkoxy group of 1-3 carbon atoms or a methylenedioxy group, A and B, the same or different, representing an alkylene group of 1-3 carbon atoms, L representing an alkylene group of 2-12 carbon atoms or a group of formula -IAO.L2-, wherein L1 and L2 each represent an alkylene group of at least two carbon atoms and together contain up to 11 carbon atoms, is reacted with a quaternizing agent of formula R6X, wherein R6 represents an alkyl group of 1-3 carbon atoms, a 2-propenyl or 2-propynyl group and X represents a pharmacologically acceptable anion. 27, characterized in that a monoquaternary derivative of the base of formula 4, in which one of the isoquinoline groups is substituted in position 2 by a group R2 or R3 denoting a methyl group, Z1 and Z2 being the same or different and each of them denoting a group of the formula -O-CH2-O- or 1, 2 or 3 methoxy groups, R4 and R5 being the same or different, denoting a benzyl or phenylethyl group, in which the phenyl ring is optionally substituted by one or more substituents such as a halogen atom, an alkoxy group of 1-3 carbon atoms or a methylenedioxy group, A and B being the same or different, denoting an alkylene group of 1-3 carbon atoms, L being an alkylene group of 2-12 carbon atoms or a group of formula -IAO.L2-, in which L1 and L2 each represent an alkylene group of at least two carbon atoms and together contain up to 11 carbon atoms, is reacted with a quaternizing agent of formula R6X, in which R6 represents an alkyl group of 1-3 carbon atoms, a 2-propenyl or 2-propynyl group, and X represents an organic acid radical. 37. The method according to claim A process according to claim 27, characterized in that a monoquaternary derivative of a base of formula 4, in which one of the isoquinoline groups is substituted in position 2 by a group R2 or R3 representing a methyl group, Z1 and Z2 are the same or different and each of them represents a group of the formula -O-CH2-O- or 1, 2 or 3 methoxy groups, R4 and R5, the same or different, represent a benzyl or phenylethyl group, in which the phenyl ring is optionally substituted by one or more substituents such as a halogen atom, an alkoxy group of 1-3 carbon atoms or a methylenedioxy group, A and B, the same or different, represent an alkylene group of 1-3 carbon atoms, L represents an alkylene group of 2-12 carbon atoms or a group of the formula -IAO.L2-, in which L1 and L2 each represent an alkylene group having at least two carbon atoms and together containing up to 11 carbon atoms, is reacted with a quaternizing agent of the formula R6X, in which R6 represents an alkyl group having 1-3 carbon atoms, a 2-propenyl or 2-propynyl group, and X represents an anion ensuring the water solubility of the product is at least 20 mg/ /ml at room temperature. 10 15 20 25 30 35 40 45109 423 2'3 CH3CW -CH3 CH2 OCH, (CH,)v0.C0.C0.0.(CH7) OCH: OCH, OCH, OCH3 OCH, 2X' Formula 1 -A.CO.O.L.O.CO. B R* " " R5 k R R Formula 2 /ICH2)2-CO.O.(CH2)n.O.CO.[CH2)2 2X_ (OCH3) • A.CO.O.L.O.CO-B-N Formula U109 423 ^ NH Formula 5 -B-N (CH2)2-C0 • 0. (CH2)5 -0 • CO. (CH^ OCH, CH,0 OCH, CH3/ CH£ 2X" Formula 7 ~CHO. ! cH,a (CH2)2.C0.O(CH2)5.0.C0.(CH2) OCH, CHO OCH, CH30 2X' IN Formula 8 PL PL PL PL PL PL PL PL PL PL

Claims (1)

1.