MXPA00012592A - Aryl alkanoylpyridazines - Google Patents

Abstract

The invention relates to aryl alkanoylpyridazine derivatives of the formula (I) and their physiologically compatible salts and solvates, where R1, R2, Q and B have the meanings given in claim 1. Said compounds have a phosphodiesterase-IV inhibiting action and can be used in the treatment of allergic disorders, asthma, chronic bronchitis, atopic dermatitis, psoriasis and other skin diseases, inflammatory diseases, auto-immune diseases such as rheumatoid arthritis, multiple sclerosis, Crohn's disease, diabetes mellitus or ulcerative colitis, osteoporosis, transplant rejection reactions, cachexia, tumour growth or tumour metastases, sepsis, memory disturbances, atherosclerosis and AIDS.

Description

ARILA CANOILPIRIDAZINAS DESCRIPTION OF THE INVENTION The invention relates to the arylalkanoyl pyridazine derivatives of formula I wherein B represents phenyl unsubstituted or mono- or poly-substituted with R3, is absent or represents alkylene of 1 to 4 carbon atoms, R 'independently represents -OR4, -S-R4, -SO-R4, -S02-R4, or Hai, R1 and R2, together, also represent -0-CH2-0-, R3 represents R4, Hai, OH, OR4, OPh, N02, NHR4, N (R) 2, NHCOR4, NHS02R4 or NHCOOR4, R4 represents A, cycloalkyl of 3 to 7 carbon atoms, alkylenecycloalkyl of 5 to 10 carbon atoms or alkenyl of 2 to 8 carbon atoms, Ref: 124858 A represents alkyl of 1 to 10 C atoms which may be substituted with 1 to 5 atoms of F and / or Cl and Hai represents F, Cl, Br or I, to their physiologically acceptable salts and its solvates. J. Med. Chem 38, 4878 (1995) describes, for example, the 1-benzoyl-tetrahydropyridazines as ligands of the progesterone receptor. In the German document No. 196 32 549 Al similar compounds are also described. The aim of the invention was to discover new compounds with valuable properties, in particular compounds that can be used to make medicines. It was found that the compounds of formula I and their salts and solvates possess very valuable pharmacological properties and are well tolerated. In particular, these compounds selectively inhibit phosphodiesterase IV, which is related to an intracellular increase in cAMP (N.

Sommer et al., Nature Medicine, 1, p. 244 to 248 nineteen ninety five) ) . The inhibition of EDF IV can be determined, for example, analogously to that described by C.W, Davis in Biochem. Biophys. Acta 797, pgs. 354 to 362 (1984). The compounds of the invention can be used for the treatment of asthmatic diseases. The anti-asthmatic effect of PDE IV inhibitors is described, for example, by T.J.Torphy And c ° l in Thorax, 46, p. 512 523 (1991) and can be determined, for example, according to the method of T. Olsson, Acta aliergologica, 26, p. 439-447 (1971). Since cAMP inhibits the cells responsible for bone degradation and stimulates those of bone regeneration (S. Kasugai et al., M681 and K. Miyamoto, M 682, in Abstract der American Society for Bone and Mineral Research, th annmeeting , nineteen ninety six! The compounds of the invention can also be used for the treatment of osteoporosis. In addition, the compounds show an antagonistic effect on the production of TNF (tumor necrosis factor) and, therefore, are suitable for the treatment of allergic and inflammatory diseases, of autoimmune deficiency diseases such as, for example, rheumatoid arthritis, multiple sclerosis, Morbus Crohn, diabetes mellitus or ulcerative olitis, reactions of rejection to transplants, cachexia and sepsis.

The anti-inflammatory effect of the compounds of the invention and the efficacy thereof for the treatment, for example, of autoimmune diseases such as multiple sclerosis or rheumatoid arthritis can be determined analogously to the methods of N. N. Sommer et al., Nature Medicine, 1, p. 244 to 248 (1995), or of L. Sekut et al., Clin. Exp. Immunol. , 10 0, pgs. 126 to 132 (1995). The compounds can be used for the treatment of cachexia. The anti-cachectic effect can be evaluated in CTN-dependent caquexia models (P. Cos telli et al., J. Clin.Invest.95, pp. 2367 and if followed (1995); JM Argües et al. , Med. Res. Rev. 17, pp. 477 et seq. (1997)). The inhibitors of FDE IV can also inhibit the growth of tumor cells, so that they are suitable for the therapy of tumors (D. Marko et al., Ce 11 Biochem. Biophys., 28, pp. 75 et seq. 1998)). The effect of inhibitors of PDE IV during the treatment of tumors is described, for example, in the world patents no. 95 35 281, 95 17 399 or 96 00 215. Injectors of FDE IV can prevent mortality in models for sepsis, which is why they are suitable for the therapy of sepsis (W. Fischer et al., Biochem, Pharmacol., 45, pp. 2399 et seq. (1993)). They can also be used for the treatment of memory disorders, atherosclerosis, atopic dermatitis and acquired immunodeficiency syndrome (AIDS). The effect of inhibitors of PDE IV in the treatment of asthma, inflammatory diseases, diabetes mellitus, atopic dermatitis, psoriasis, AIDS, cachexia, growth or tumor metastasis is described, for example , in the European patent no. 77 92 91. The compounds of formula I can be used in medicine and veterinary medicine as active substances of drugs. They can also be used as intermediate products to prepare other active substances of medicines. Accordingly, the subject of the present invention are the compounds of formula I and also a process for preparing the compounds of Formula I, according to claim 1, and their salts and solvates, characterized in that a compound of formula II is reacted wherein R1 and R2 have the indicated meanings, with a compound of formula III wherein B and Q have the indicated meanings and L represents Cl, Br, OH or an esterified and reactive OH group, or because a compound of formula IV is reacted wherein P1, R2 and Q have the indicated meanings, with a compound of formula V B-CO-L (V), wherein B has the indicated meaning and L represents Cl, Br, OH or an esterified reactive OH group, and / or a basic compound of formula I is converted into one of its salts by treatment with an acid. Solvates of the compounds of formula I are understood to be the additions of the molecules of the inert solvent to the compounds of formula I, which is produced as a result of their mutual attraction. Solvates are, for example, mono or dihydrates or alkoxides. The residues R1, R2, B, Q and L indicated in this text have the meanings indicated for formulas I, II, III, IV and V, unless otherwise indicated. A preferably represents alkyl, more preferably alkyl substituted with 1 to 5 fluorine atoms and / or chlorine.

In the preceding formulas the alkyl group preferably has a straight chain of 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 C atoms, preferably 1, 2, 3, 4, 5 or 6 C atoms, and preferably represents methyl, ethyl, trifluoromethyl, pentafluoroethyl or propyl, then preferably isopropyl, butyl, isobutyl, sec-butyl or tertbutyl, but also n-pentyl, neopentyl, isopentyl or n-hexyl. A particularly preferred meaning of the alkyl group is methyl, ethyl, trifluoromethyl, propyl, isopropyl, butyl, n-pentyl, n-hexyl or n-decyl. The cycloalkyl group preferably has 3 to 7 C atoms and preferably represents cyclopropyl and cyclobutyl, then preferably cyclopentyl or cyclohexyl, and also cycloheptyl, and more preferably cyclopentyl. The alkenyl group preferably represents allyl, 2- or 3-butenyl, isobutenyl, sec-butenyl, then preferably 4-pentenyl, isopentenyl or 5-hexenyl. The alkylene group is preferably straight chain and preferably represents methylene or ethylene, then preferably propylene or butylene.

The alkoxycycloalkyl group preferably has 5 to 10 carbon atoms and preferably represents methylene cyclopropyl, methylenecyclobutyl, then preferably methylenecyclopentyl, methylene cyclohexyl or methylene cycloheptyl. It also represents et-cyclopropyl, ethylenecyclobutyl, ethylenecyclopentyl, ethylenecyclohexyl or ethylenecycloheptyl, propylenecyclopentyl, propylenecyclohexyl, butylene cyclopentyl or butylcyclohexyl. Hai preferably represents F, Cl or Br, but also I. The radicals R1 and R2 can be the same or different and are in the 3 or 4 position of the phenyl ring. Independently of one another, they represent, for example, hydroxyl, -S-CH 3, -SO-CH 3, -S0 2 CH 3, F, Cl, Br or I, or together they represent methylenedioxy. In particular, each preferably represents methoxy, ethoxy, propoxy, cyclopentoxy, or else fluoromethoxy, difluoromethoxy, trifluoromethoxy, 1-fluoroethoxy, 2-fluoroethoxy, 1,2-difluoro-ethoxy, 2,2-difluoroethoxy, , 2, 2-t-fluoroethoxy or 2,2,2-trifluoroethoxy. In particular, R1 more preferably represents methoxy, ethoxy, cyclopentoxy or isopropoxy.

In particular, R 2 represents more preferably methoxy or ethoxy. R3 preferably represents R4, F, Cl, Br or I, hydroxyl, O-alkyl, OPh, N02, alkylamino, cycloalkylamino, dialkylamino, alkylcycloalkylamino, NHCOalkyl, NHCOcycloalkyl, NHS02alkyl, NHS02cycloalkyl, NCOO-alkyl or NHCOOcycloalkyl, wherein alkyl and cycloalkyl they have one of the meanings indicated above. A particularly preferred meaning of R3 is that of N02, methoxy, ethoxy, propoxy, isopropoxy, butoxy, pentoxy or hexyloxy or decyloxy, Cl or F, NCOOCH3, NCOOC2H5, NS02CH3, NCOCH3 or NCOCH (CH3) 2. In particular, the radical R3 is preferably in the 3 or 4 position of the phenyl ring. R 4 preferably represents alkyl, cycloalkyl, alkenyl or alkylenecycloalkyl whose meanings are those indicated above. A particularly preferred meaning of R 4 is that of alkyl or cycloalkyl. The residue B preferably represents unsubstituted phenyl or mono or polysus tyred with R3, wherein R3 has one of the meanings indicated above.

B more preferably represents phenyl, o-, m- or p-methylphenyl, o-, m- or p-et ilphenyl, o-, m- or p-propylphenyl, o-, m- or p-isopropyl-phenyl, or -, m- or p-tert butylphenyl, o-, m- or pN, N-dimethylaminophenyl, o-, m- or p-nitrophenyl, o-, m- or,., p-hydroxyphenyl, or-, m- or p-methoxyphenyl, o-, m- or p-ethoxyphenyl, o-, m- or p-isopropoxyphenyl, o-, m- or p-butoxyphenyl, o-, m- or p-pentoxyphenyl, or-, m- or p-hexyloxyphenyl, o-, m- or p-decyloxyphenyl, o-, m- or p-trifluoromethylphenyl, o-, m- or p-fluorophenyl, o-, m- or p-chlorophenyl, or-, m- or p-bromophenyl, o-, m- or p-acetylaminophenyl, o-, m- or p-isopropylcarbonylaminophenyl, o-, m- or p-methanesulfonylaminophenyl, o-, m- or p-ethanesulfonylaminophenyl, o-, m- or p-methoxycarbonylaminophenyl, o-, m- or p-ethoxycarbonylaminophenyl, also preferably 2,3-, 2,4-, 2,5-, 2,6-, 3,4- or 3, 5 -dimethyl phenyl, 2,3- 2,4-, 2,5-, 2,6-, 3,4- or 3,5-dihydroxy phenyl, 2,3-, 2,4-, 2,5-, 2,6-, 3,4- or 3,5-difluorophenyl, 2,3- , 2,4-, 2,5-, 2,6-, 3,4- or 3,5-dichlorophenyl, 2,3-, 2,4-, 2,5-, 2,6-, 3,4 - or 3, 5-dimethoxyphenyl. The residue Q is preferably absent or preferably represents alkylene with the meanings indicated above. In particular, Q is preferably absent. All the remains of the present invention that appear repeatedly can be the same or different, that is, they are independent of each other.

Therefore, a particular object of the invention are those compounds of formula I in which at least one of the mentioned moieties has one of the preferred meanings indicated above. Some preferred groups of compounds may be represented by the partial formulas indicated below, which correspond to formula I and in which the moieties which are not expressly detailed have the meanings indicated for formula I, namely: in R1 and R2 independently represent OA, Q is absent and B represents phenyl unsubstituted or substituted with R3; in Ib R1 and R2 independently represent OA, Q represents methylene and B represents phenyl unsubstituted or substituted with R3; in R R11 and RR22 together represent -0-CH2-0-, Q Q is absent and B represents phenyl not substituted or substituted with R3. In general, both the compounds of formula I and the starting materials for their preparation are prepared according to known methods, such as those described in the literature (for example, in certain works such as Houben-Weyl, " Methoden der organischen Chemie "(Methods of Organic Chemistry), Georg-Thieme-See lag, Stuttgart) and under reaction conditions that are known and suitable for the reactions mentioned. You can also make use of the known variants of these methods that are not detailed in this text. In the compounds of formulas II and IV, the radicals R1 and R2 have the meanings indicated above, in particular the preferred meanings. In the compounds of formulas III and IV, Q is preferably absent or represents methylene or ethylene, then preferably propylene or butylene. In the compounds of formulas III and V, B has the preferred meanings indicated above, while L represents Cl, Br, OH or a group of reactive and esterified OH. When L represents a group of reactive and esterified OH, it is preferably a group of alkylsulfonyloxy of 1 to 6 carbon atoms (preferably methylsulfonyloxy) or arylsulfonyloxy of 6 to 10 carbon atoms (preferably phenylsulfonyloxy) or p-tolylsulfonyloxy, then also 2-naphthalenesulfonyloxy).

If desired, the starting materials can be prepared in themselves, but in such a way that instead of isolating them from the reaction mixture they are left to react directly to form the compounds of formula I. On the contrary, it is also possible to carry out the reaction in stages. The compounds of formula I can be obtained preferably by reaction of compounds of formula II with compounds of formula III. As usual, the starting substances of formulas II and III are known, otherwise they can be obtained by known methods. In particular, the reaction of the compounds of formula II with the compounds of formula III is carried out both in the presence and in the absence of an inert solvent, at temperatures between about -20 ° and about 150 °, preferably between 20 and 100. °. Suitable inert solvents include, for example, hydrocarbons such as hexane, petroleum ether, benzene, toluene or xylene; chlorinated hydrocarbons such as trichlorethylene, 1,2-dichloroethane, carbon tetrachloride, chloroform or dichloromethane; alcohols such as methanol, ethanol, isopropanol, n-propanol, n-butanol or tert-butanol; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran (THF) or dioxane; glycol ethers such as ethylene glycol monomethyl ether or ethylene glycol monoethyl ether (methyl glycol or ethyl glycol), ethylene glycol dimethyl ether (diglyme); ketones such as acetone or butanone; amides such as acetamide, dimethylacetamide or dimethylformamide (DMF); nitriles such as acetonitrile; sulfoxides such as dimethyl sulfoxide (DMSO); nitro compounds such as nitromethane or nitrobenzene; esters such as ethyl acetate, or mixtures of these solvents. The compounds of formula I can also be obtained by reacting compounds of formula IV with compounds of formula V. The starting substances of formulas IV and V are usually known. The compounds of formula IV are disclosed, for example, in German patent no. 196 32 549. If these starting substances are not known, then they can be obtained by known methods. Thus, the preparation of 1-benzoyl-tetrahydro-pyridazine is described, for example, in J. Med. Chem., 38, 4878 (1995).

The -CO-L moiety of the compounds of formula V represents a previously activated carboxylic acid, preferably a carboxylic acid halide. The reaction conditions of the compounds of formula IV with the compounds of formula V are similar, with respect to the reaction time, at the temperature and the solvent, to those described for the reaction of the compounds of formula II with the compounds of formula III. A base of formula I can be converted into its salt by the addition of an acid, for example, by reacting equivalent amounts of the base and the acid in an inert solvent such as ethanol, and then concentrating by evaporation. Acids which form acceptable salts from the physiological point of view are suitable for this reaction. Therefore, it is possible to use Inorganic acids, such as, for example, sulfuric acid, nitric acid, hydrocides such as hydrochloric or hydrobromic acid, phosphoric acids such as orthophosphoric acid, sulfamic acid, and also organic acids. , in particular the aliphatic, alicyclic, araliphatic, aromatic or heterocyclic monobasic or polybasic carboxylic, sulphonic or sulfuric acids such as, for example, formic, acetic, propionic, pivalic, diethylacetic, malonic, succinic, pimelic, fumaric, maleic, lactic, tartaric, malic, citric, gluconic, ascorbic, nicotinic, isonicotonic, methanesulfonic or eosulonic, ethanedisulfonic, 2-hydroxyethane-sulphonic, benzenesulfonic, p-toluenesulfonic, naphthalene-sulfonic, naphthalenedisulfonic and lauryl-sulfuric. Salts of acids which are not physiologically acceptable, for example picrates, can be used to isolate and / or purify the compounds of formula I. If desired, the bases of formula I can be released from their salts by treatment with bases (for example, with sodium or potassium hydroxide, or with sodium or potassium carbonate). The object of the invention is constituted by the compounds of formula I and their physiologically acceptable salts and solvates which are used as medicaments. Also object of the invention are the compounds of formula I and their physiologically acceptable salts and solvates which act as phosphodiesterase IV inhibitors. Another object of the invention is the use of the compounds of formula I and / or their salts and / or solvates 1 physiologically acceptable to prepare pharmaceutical preparations, in particular by a non-chemical route. These compounds can be brought into a suitable dosage form together with at least one excipient or auxiliary solid, liquid and / or semi-liquid product and optionally in combination with one or more additional active substances. Another object of the invention are pharmaceutical preparations containing at least one compound of formula I and / or one of its physiologically acceptable salts and / or solvates. These preparations can be used in medicine and in veterinary medicine as medicines. Among the excipients there may be mentioned organic or inorganic substances which are suitable for enteral administration (eg orally), parenterally or for topical application, and which do not react with the new compounds. Examples of these excipients are water, vegetable oils, benzyl alcohols, alkylene glycols, polyethylene glycols, glycerin triacetate, gelatin, carbohydrates such as lactose or starch, magnesium stearate, talc, petrolatum. For oral administration, tablets, pills, dragees, capsules, powders, granules, syrups, juices or drops are used in particular; for rectal application, suppositories are used; for parenteral administration the solutions, preferably the solutions, preferably the oily or aqueous solutions, and also the suspensions, emulsions or implant; and for topical application ointments, creams or powders. The new compounds can also be lyophilized and the resulting lyophilized products can be used, for example, for the preparation of injectable preparations. The aforementioned preparations can be sterilized and / or contain auxiliary substances such as lubricants, preservatives, stabilizers and / or wetting agents, emulsifying agents, salts for influencing the osmotic pressure, pH regulating substances, dyes, flavors and / or one or more substances additional active substances, for example, one or several vitamins. The compounds of formula I and their physiologically acceptable salts and solvates can be used to combat diseases in which an increase in the level of cAMP (cyclic adenosine monophosphate) inhibits or prevents inflammation and leads to muscle relaxation. In particular, the FDE IV inhibitors of the invention can be used in the treatment of allergies, asthma, chronic bronchitis, atopic dermatitis, psoriasis and other skin diseases, inflammatory diseases, autoimmunodeficiencies such as, for example, rheumatoid arthritis, multiple sclerosis, Morbus Crohn, diabetes roellitus and ulcerative colitis, osteoporosis, rejection reactions to transplants, cachexia, growth or metastasis of tumors, sepsis, memory disorders, atherosclerosis and AIDS. In general, the substances of the invention are administered in a manner similar to Rolipram, preferably in doses between 1 and 500 mg, in particular between 5 and 100 mg per dosage unit. The daily dose is preferably comprised between ca. 0.02 and 10 mg / kg of body wt. However, the individual dose of each patient depends on different factors, for example, the effectiveness of the special compound used, age, body wt, general health, sex, diet, timing and the manner of administration, the rate of excretion, the combination of medications and the severity of the disease to which the therapy is applied. Oral administration is preferred. The temperatures indicated in this text are given in ° C. In the examples that follow, the expression "one works (or treats) in a usual manner" means the following: if necessary, water is added, the pH is adjusted between 2 and 10 according to the constitution of the final product, it is extracted with acetate. ethyl or dichloromethane, the phases are separated, the organic phase is dried over sodium sulfate, concentrated by evaporation and purified by chromatography on silica gel and / or by recrystallization.

Example 1 A solution of 1.1 g of l- (3-amino-benzoyl) -3-83-ethoxy-4-methoxyphenyl) -1,4,5,6,6-tetrahydro-pyridazine, m.p. 180 ° [obtained by catalytic hydrogenation at room temperature of 1- (3-nor trobenzoyl) -3- (3-ethoxy-4-methoxyphenyl) -1,4,5,6,6-tetrahydro-pyridazine, m.p. 173 °, in 150 ml of tetrahydrofuran and in the presence of 3.5 g of Raney nickel] and 0.6 ml of pyridine in 50 ml of acetonitrile with 0.5 g of 4-chlorobenzoyl chloride and stir for two hours. The solvent is removed and the mixture is worked in the usual manner. After recrystallization, N- (3- (3-ethoxy-4-methoxy phenyl) -1,4,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -4-chlorobenzoyl-3-carboxamide is obtained, pf 236 °. By analogous reaction of 1- (3-aminobenzoyl) -3- (3-ethoxy-4-methoxy phenyl) -1,4,5,6-tetrahydro-pyridazine with 3-nitrobenzoyl chloride the N- (3- (3-ethoxy-4-methoxy phenyl) -1,4,5,6-tet-rahydro-p-ridazin-1-ylcarbonyl) -phenyl) -3-nitrobenzoyl-3-carboxamide, mp 160 °; with 4-nit robenzoyl chloride, the N- (3- (3-ethoxy-4-methoxyphenyl) -1,4,5,6-tet rahydro-p? r? dazin-1-ylcarbonyl) -phenyl) - is obtained 4-nitrobenzoyl-3-carboxamide, mp 255 °; With 4-methoxybenzoyl chloride, N- (3- (3-ethoxy-4-methoxy phenyl) -1,4,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -4-methoxybenzoyl-3 is obtained. -carboxamide, mp 206 °; with 4-methybenzoyl chloride, N- (3- (3-ethoxy-4-methoxy phenyl) -1,4,5,6-tetrahydro-p-ridazin-1-ylcarbonyl) -phenyl) is obtained. 4-methybenzoyl-3-carboxamide, mp 219 °; with benzoyl chloride, N- (3- (3-ethoxy-4-methoxy phenyl) -1,4,5,6-tetrahydro-p-ridazin-1-ylcarbonyl) -phenyl) -benzoyl-3-carboxamide is obtained. , pf 203 A with 3,4-dichlorobenzoyl chloride gives N- (3- (3-ethoxy-4-methoxy phenyl) -1,4,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -3 , 4-dichlorobenzoyl-3-carboxamide, mp 111 °; with 4-trifluoromethylbenzoyl chloride, N- (3- (3-ethoxy-4-methoxy phenyl) -1,4,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -4-tri fluoromet ilbenzoi is obtained. 1-3-carboxamide, mp 207 °; with 3-chlorobenzoyl chloride, N- (3- (3-ethoxy-4-methoxyphenyl) -1,4,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -3-chlorobenzoyl-3 is obtained carboxamide, mp 121 °; with 4-fluorobenzoyl chloride, N- (3- (3-ethoxy-4-methoxyphenyl) -1,4,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -4-fluorobenzoyl-3 is obtained. carboxamide, mp 236 °; With 4-butoxybenzoyl chloride, N- (3- (3-ethoxy-4-methoxy-phenyl) -1,4,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -4-butoxybenzoyl-3 is obtained. -carboxamide, mp 123 °; With 4-pent oxybenzoyl chloride, N- (3- (3-ethoxy-4-methoxy phenyl) -1,4,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -4-pentoxybenzoyl- is obtained. 3-carboxamide, mp 145 °; With 4-ethoxybenzoyl chloride, N- (3- (3-ethoxy-4-methoxy phenyl) -1,4,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -4-ethoxybenzoyl-3 is obtained. -carboxamide, mp 174 °; with 3-4-dimethoxybenzoyl chloride, N- (3- (3-ethoxy-4-methoxy phenyl) -1,4,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -3,4 is obtained -dimethoxybenzoyl-3-carboxamide, mp 160 °; With 3-meth ilbenzoyl chloride, N- (3- (3-ethoxy-4-methoxyphenyl) -1,4,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -3-methybenzoyl- is obtained. 3-carboxamide, mp 115 °; With 3-methoxybenzoyl chloride, N- (3- (3-ethoxy-4-methoxyphenyl) -1,4,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -3-methoxybenzoyl-3 is obtained. carboxamide, mp 161 °.

Example 2 A solution of 1.1 g of 1- (4-amino-benzoyl) -3- (3-ethoxy-4-methoxy phenyl) -1,4,5,6, -tetrahydro-pyridazine, m.p. 154 ° [obtained by catalytic hydrogenation at room temperature of 1- (4-nitrobenzoyl) -3- (3-ethoxy-4-methoxy-phenyl) -1,4,5,6-tetrahydro-pyridazine, m.p. 159 °, in 150 ml of tetrahydrofuran and in the presence of 3.5 g of nickel-Raney] and 0.6 ml of pyridine in 50 ml of acetonitrile with 0.5 g of 4-nor trobenzoyl chloride and stir for two hours. The solvent is removed and the mixture is worked in the usual manner. After recrystallization, N- (3- (3-ethoxy-4-methoxyphenyl) -l is obtained., 4,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -4 -nit-robenzoyl-4-carboxamide, m.p. 233 °. By analogous reaction of 1- (4-aminobenzoyl) -3- (3-ethoxy-4-methoxy phenyl) -1,4,5,6-tetrahydro-pyridazine with 4-methoxybenzoyl chloride the N- (3-) is obtained (3-ethoxy-4-methoxy phenyl) -1,4,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -4-methoxybenzoyl- -carboxamide, mp 201 °; With 4-fluorobenzoyl chloride, N- (3- (3-ethoxy-4-methoxyphenyl) -1,4,5,6-tet -hydro-pyridazin-1-ylcarbonyl) -phenyl) -4-fluorobenzoyl-4 is obtained. -carboxamide, mp 193 °; with benzoyl chloride, N- (3- (3-ethoxy-4-methoxy phenyl) -1,4,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -benzoyl-4-carboxamide, m.p. 186 °; with 4-chlorobenzoyl chloride, N- (3- (3-ethoxy-methoxy-phenyl) -1,4,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -4-chlorobenzoyl-4 is obtained. carboxamide, mp 200; With 3-nitrobenzoyl chloride, N- (3- (3-ethoxy-4-methoxy phenyl) -1,4,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -3-nitrobenzoyl-4 is obtained. -carboxamide, mp 233 °.

EXAMPLE 3 A suspension of 4.70 g of 3- (3,4-dimethoxyphenyl) -1,4,5,6-tet ahydropyridazine in 150 ml of THF is mixed with 2.24 g of potassium terbutylate and stirred for 30 minutes. 5.44 g of 3-benzoylaminobenzoyl chloride are added and stirred for 10 hours at room temperature. The solvent is removed and the mixture is worked in the usual manner. The N- (3- (3,4-dimethoxyphenyl) -1,4,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -3-benzoyl-3-carboxamide, m.p. 196 °. By analogous reaction of 3- (3,4-dimethoxyphenyl) -1,4,5,6-tetrahydropyridazine with 3- (3,4-dimethoxybenzoyl) -aminobenzoyl chloride, the N- (3- (3, 4- dimethoxyphenyl) - 1, 4, 5, 6-tet rahydro-pyridazin-1-i-Icarboni 1) -phenyl) -3,4-dimethoxybenzoyl-3-carboxamide, mp 183 °; with 3- (3-methybenzoyl) -aminobenzoyl chloride, N- (3- (3,4-dimethoxyphenyl) -1,4,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -3 is obtained. -met-ilbenzoyl -3-carboxamide, mp 171 °; with 3- (3-chlorobenzoyl) -aminobenzoyl chloride, N- (3- (3,4-dimethoxyphenyl) -l, 4,5,6-tetrahydro-p-ridazin-1-ylcarbonyl) -phenyl) is obtained. 3-chlorobenzoyl-3-carboxamide, mp 172 °; with 3- (4-methoxybenzoyl) -aminobenzoyl chloride there is obtained N- (3- (3,4-dimethoxyphenyl) -1,4,5,6-tetrahydro-pyridazin-1-ylcarboni 1) -phenyl) - 4-methoxybenzoyl-3-carboxamide, mp 203 °.

Example 4 By analogous reaction to that of Example 2 of 1- (4-aminobenzoyl) -3- (3-isopropoxy-4-methoxy phenyl) -1,4,5,6-tetrahydropyridazine with 4-butoxybenzoyl chloride, the N- (3- (3-isopropoxy-4-methoxyphenyl) -1,4,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -4-butoxy-benzoyl-4-carboxamide, mp 161 °; With 4-ethoxybenzoyl chloride there is obtained N- (3- (3-isopropoxy-4-methoxyphenyl) -1,4,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -4-ethoxy-benzoyl- 4-carboxamide, 171 °; with benzoyl chloride, N- (3- (3-isopropoxy-4-methoxy phenyl) -1,4,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -benzoyl-4-carboxamide, m.p. 220 °; with 3-meth ilbenzoyl chloride, N- (3- (3-isopropoxy-4-methoxyphenyl) -l, 4,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -3-methyl-benzoyl is obtained. -4 -carboxamide, mp 196 °; with 4-cyclopentyloxybenzoyl chloride, N- (3- (3-isopropoxy-4-methoxyphenyl) -l, 4,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -4-cyclo-pentyloxybenzoyl is obtained. -4-carboxamide, mp 163 °; with 4-isopropoxybenzoyl chloride, N- (3- (3-isopro-oxy-4-methoxyphenyl) -l, 4,5,6-tetrahydro-pyridazin-1-icarboni-1-phenyl) -4- is obtained. iso-propoxybenzoyl-4-carboxamide, mp 183 °, 4-propoxybenzoyl chloride yields N- (3- (3-isopropoxy-4-methoxy phenyl) -1,4,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) - 4 - propoxy-benzoyl-4-carboxamide, mp 171 °.

Example 5 By analogous reaction to that of example 1 of 1- (3-aminobenzoyl) -3- (3-cyclopentyloxy-4-methoxyphenyl) -1,4,5,6-tetrahydropyridazine with 3-methybenzoyl chloride, the N- (3- (3-cyclopentyloxy-4-methoxyphenyl) -1,4,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -3-methyl-benzoyl-3-carboxamide, mp 144 °; with 4-methoxybenzoyl chloride, N- (3- (3-cyclopentyloxy-4-methoxy-phenyl) -1,4,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -4-methoxy-benzoyl is obtained -3-carboxamide, mp 194 °; With 4-phenylbenzoyl chloride, N- (3- (3-cyclopentyloxy-4-methoxyphenyl) - 1,4,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -4-phenyl-benzoyl- is obtained. 3-carboxamide, mp 140 °.

Example 6 By analogous reaction to that of example 1 of 1- (3-aminobenzoyl) -3- (3,4-di ethoxy phenyl) -1,4,5,6-tetrahydro-pyridazine with 4-chlorobenzoyl chloride is obtained N- (3- (3, 4-diethoxyphenyl) -1,4,5,6-tet, rahydro-pyridazin-1-ylcarbonyl) -phenyl) -4-chlorobenzoyl-3-carboxamide, mp 152 °; with 3-nit robenzoyl chloride, N- (3- (3,4-diethoxy-phenyl) -l, 4,5,6-tetrahydro-pi-ridazin-1-ylcarbonyl) -phenyl) -3-nitrobenzoyl-3 is obtained carboxamide, mp 105 °; with 4-butoxybenzoyl chloride, N- (3- (3,4-diethoxyphenyl) -l, 4,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -4-butoxybenzoyl-3-carboxamide is obtained, pf 103 °; with 4-ethoxybenzoyl chloride, N- (3- (3,4-diethoxy-phenyl) -l, 4,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -4-ethoxybenzoyl-3-carboxamide is obtained, pf 181 °.

Example 7 By analogous reaction to that of example 2 of 1- (4-aminobenzoyl) -3- (3,4 -dietoxyphenyl) -1,4,5,6-tetrahydro-pyridazine with 4-chlorobenzoyl chloride, the N is obtained. - (3- (3,4-diethoxyphenyl) -l, 4,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -4-chlorobenzoyl-4-carboxamide, mp 195 °; with 3-nit robenzoyl chloride, N- (3- (3,4-diethoxyphenyl) -1,4,5-6-tet -hydro-pyridazin-1-ylcarbonyl) -phenyl) -3-nitrobenzoyl-4- is obtained carboxamide, mp 218 °; With 4-butoxybenzoyl chloride, N- (3- (3,4-diethoxyphenyl) -1,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -4-butoxybenzoyl-4-carboxamide is obtained. pf 103 °; with 4-ethoxybenzoyl chloride, N- (3- (3,4-diethoxyphenyl) -l, 5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -4-ethoxybenzoyl-4-carboxamide, m.p. 176 °; With 4-methoxybenzoyl chloride, N- (3- (3,4-diethoxyphenyl) -1,4,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -4-methoxybenzoyl-4-carboxamide is obtained. pf 192 °.

Example 8 By analogous reaction to that of example 1 of 1- (3-aminobenzoyl) -3- (3-isopropoxy-4-methoxyphenyl) -1,4,5,6-tetrahydropyridazine with 4-ethoxybenzoyl chloride, the N is obtained. - (3- (3-isopropoxy-4-methoxyphenyl) -1,4,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -4-ethoxybenzoyl-3-carboxamide, mp 160 °; with 4-butoxybenzoyl chloride, N- (3- (3-isopropoxy-4-methoxyphenyl) -1,4,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -4-butoxybenzoyl-3- is obtained. carboxamide, mp 160 °; With 4-methoxybenzoyl chloride, N- (3- (3-isopropoxy-4-methoxyphenyl) -1,4,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -4-methoxybenzoyl-3 is obtained. carboxamide, mp 161 °; with 4-isopropoxybenzoyl chloride, N- (3- (3-isopropoxy-4-methoxyphenyl) -1,5,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -4-isopropoxybenzoyl-3-carboxamide is obtained. , pf 168 °; with 3-nitrobenzoyl chloride, N- (3- (3-isopropoxy-4-methoxyphenyl) -1,4,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -3-nitrobenzoyl-3 is obtained carboxamide, mp 194 Example 9 By analogous reaction to that of Example 1 of 1- (3-aminobenzoyl) -3- (3,4-dimethoxyphenyl) -1,4,5,6-tetrahydro-pyridazine with 4-ethoxybenzoyl chloride the N is obtained. - (3- (3,4-dimethoxy phenyl) -1,4,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -4-ethoxybenzoyl-3-carboxamide, mp 176 °; with 4-butoxybenzoyl chloride there is obtained N- (3- (3,4-dimethoxyphenyl) -1,4,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -4-butoxybenzoyl-3-carboxamide, pf 143 °; With 4-pentoxybenzoyl chloride, N- (3- (3,4-dimethoxy phenyl) -1,4,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -4-pentoxybenzoyl-3-carboxamide is obtained. , pf 140 °; With 3-propoxybenzoyl chloride, N- (3- (3,4-dimethoxyphenyl) -1,4,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -3-isopropoxybenzoyl-3-carboxamide is obtained. pf 153 °; with 4-hexyloxybenzoyl chloride, N- (3- (3,4-dimethoxy phenyl) -1,4,5,6-tetrahydro-pyridazin-1-ylcarboni 1) -phenyl) -4-hexyloxybenzoyl-3 is obtained. -carboxamide, mp 162 °; With 4-decyloxybenzoyl chloride, N- (3- (3,4-dimethoxy phenyl) -1,4,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -4-decyloxybenzoyl-3-carboxamide is obtained. , pf 130 °; Example 10 By analogous reaction to that of example 1 of 1- (3-aminobenzoyl) -3- (3-ethoxy-4-methoxy phenyl) -1,4,5,6-tetrahydropyridazine with 4-isopropoxybenzoyl chloride, the N- (3- (3-ethoxy-4-methoxyphenyl) -1,4,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -4-isopropoxybenzoyl-3-carboxamide, mp 108 °; With 3-ethoxybenzoyl chloride, N- (3- (3-ethoxy-4-methoxyphenyl) -l, 4,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -3-ethoxybenzoyl-3 is obtained. carboxamide, mp 142 °; with 3-butoxybenzoyl chloride, N- (3- (3-ethoxy-4-methoxyphenyl) -l, 4,5,6-tet, rahydro-pyridazin-1-ylcarbonyl) -phenyl) -3-butoxybenzoyl-3 is obtained. -carboxamide, mp 144 °; with 3-hexyloxybenzoyl chloride, N- (3- (3-ethoxy-4-methoxyphenyl) -1,4,5,6-tetrahydro-p-ridazin-1-ylcarbonyl) -phenyl) -3-hexyloxybenzoyl- is obtained. 3-carboxamide, mp 137 °; With 4-decyloxybenzoyl chloride, N- (3- (3-ethoxy-4-methoxy phenyl) -1,4,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -4-decyloxybenzoyl-3 is obtained. -carboxamide, mp 123 °; with 3-methoxycarbonylaminophenylbenzoyl chloride, N- (3- (3-ethoxy-4-methoxy phenyl) -1,4,5,6-tetrahydro-pyridazin-1-ylcarboni-1-phenyl) -3-methoxycarbonylamino is obtained. -phenylobenzoyl-3-carboxamide, mp 193 °; With 3-ethoxycarbonylaminophenylbenzoyl chloride, N- (3- (3-ethoxy-4-methoxyphenyl) -1,4,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -3-ethoxycarbonylamino-phenylbenzoyl is obtained. 3-carboxamide, mp 221 °; With 3-methanesulfonylaminobenzoyl chloride, N- (3- (3-ethoxy-4-methoxyphenyl) -1,4,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -3-methanesulfonylamino-benzoyl- is obtained. 3-carboxamide, mp 174 °; With 4-methoxycarbonylaminophenylbenzoyl chloride, the N- (3- (3-ethoxy-4-methoxy phenyl) -1,4,5,6-tethydro-pyridazin-1-ylcarbonyl) -phenyl) -4-methoxycarbonylamino- phenylbenzoyl-3-carboxamide, mp 2. 3. 4; With 4-ethoxycarbonylaminophenylbenzoyl chloride, N- (3- (3-ethoxy-4-methoxyphenyl) -l, 4,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -4-ethoxycarbonylamino-phenylbenzoyl is obtained. 3-carboxamide, mp 221 °; with 4-acetylaminobenzoyl chloride, N- (3- (3-ethoxy-4-methoxyphenyl) -l, 5,6-tetrahydro-pyridazin-1-ylcarboni-1-phenyl) -4-acetylaminobenzoyl-3 is obtained. -carboxamide, mp 244 °.

Example 11 By analogous reaction to Example 2 of 1- (4-aminobenzoyl) -3- (3-ethoxy-4-methoxyphenyl) -1,4,5,6-tetrahydropyridazine with 4-acetylaminobenzoyl chloride, the N- (3- (3-ethoxy-4-methoxyphenyl) -1,4,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -4-acetylaminobenzoyl-4-carboxamide, mp > 266 °; with 4-isopropoxybenzoyl chloride, N- (3- (3-ethoxy-4-methoxyphenyl) -l, 4,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -4-isopropoxybenzoyl-4- is obtained. carboxamide, mp > 260 °; with 4-methoxycarbonylaminophenylbenzoyl chloride, the N- (3- (3-ethoxy-4-methoxy phenyl) -l, 4,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -4-methoxycarbonyl lamino is obtained -phenylobenzoyl-4-carboxamide, mp 275 °; with 4-ethoxycarbonylaminophenylbenzoyl chloride, N- (3- (3-ethoxy-4-methoxy phenyl) -1,4,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -4-ethoxycarbonylamino-phenylbenzoyl is obtained. -4-carboxamide, mp 246 °; With 4-methanesulfonylaminobenzoyl chloride, N- (3- (3-ethoxy-4-methoxyphenyl) -1,4,5,6-tetrahydro-pyridazin-1-ycarbonyl-1-phenyl) -4-methanesulfonylamino- is obtained. benzoyl-4-carboxamide, mp > 260 °.

Example 12 By analogous reaction to that of example 1 of 1- (3-aminobenzoyl) -3- (3,4-diethoxyphenyl) -1,4,5,6-tetrahydro-pyridazine with 4-pentoxybenzoyl chloride, the N is obtained. - (3- (3,4-diethoxyphenyl) -l, 4,5,6-tetrahydro-, pyridazin-1-ylcarbonyl) -phenyl) -4-pentoxybenzoyl-3-carboxamide, mp 145 °; with 3-propoxybenzoyl chloride, N- (3- (3,4-diethoxyphenyl) -1,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -3-propoxybenzoyl-3-carboxamide is obtained. pf 112 °; with 3-butoxybenzoyl chloride, N- (3- (3,4-diethoxyphenyl) -1,4,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -3-butoxybenzoyl-3-carboxamide is obtained. pf 120 °; with 3-hexyloxybenzoyl chloride, N- (3- (3,4-diethoxyphenyl) -1,5,6-tetrahydro-pyridazin-1-ylcarbonyl) -phenyl) -3-hexyloxybenzoyl-3-carboxamide is obtained. pf 151 °; with 3-ethoxybenzoyl chloride, N- (3- (3,4-diethoxyphenyl) -l, 4,5,6-tetrahydro-pyridin-1-ylcarbonyl) -phenyl) -3-ethoxybenzoyl-3-carboxamide is obtained. , pf 141 °. The following examples refer to pharmaceutical preparations: Example A: Injection bottles The pH of a solution of 100 g of an active substance of formula I and 5 g of disodium hydrogen phosphate in 3 1 of bidistilled water is adjusted to 6.5 with 2N hydrochloric acid, then filtered under sterile conditions , fill the jars with the solution, lyophilize and close the jars in MáM- ^ Wá-. sterile conditions. Each bottle for injection contains 5 mg of the active substance.

Example B: suppositories A mixture composed of 20 g of an active substance of formula I, 100 g of soya lecithin and 1400 g of cocoa butter is melted, then the melt is poured into the molds and allowed to cool. Each suppository contains 20 mg of active substance.

Example C: solution A solution is prepared with 1 g of an active substance of formula I, 9.38 g of NaH2P04 x 2H20, 28.48 g of Na2HP04 x 12 H20, 0.1 g of benzalkonium chloride and 940 ml of bidistilled water. The pH is adjusted to 6.8, brought to 1 1 volume and sterilized by irradiation. This solution can be used in the form of eye drops.

Example E: Tablets A mixture composed of 1 kg of an active substance of formula I, 4 kg of lactose, 1.2 kg of potato starch, 0.2 kg of talc and 0.1 kg of magnesium stearate is compressed in the form of tablets, so such that each tablet contains 10 mg of the active substance.

Example F: Dragees The tablets are formed analogously to that described in Example E and are then coated in a usual manner with a bath of sucrose, potato starch, talc, tragacanth and dye.

Example 6: capsules With 2 kg of an active substance of formula I, hard gelatin capsules are filled, such that each capsule contains 20 mg of the active substance.

Example H: ampoules A solution of 1 kg of an active substance of formula I in 60 1 of bidistilled water is filtered under sterile conditions. The ampoules are filled with this solution and then lyophilized and closed under sterile conditions. Each ampoule contains 10 mg of the active substance.

Example I: aerosol inhalant solution 14 g of an active substance of formula I are dissolved in 10 1 of isotonic NaCl solution. With this solution, commercial containers that have a vaporizing mechanism are filled. The solution can be inhaled through the mouth or nose. Each spray (approximately 0.1 ml) corresponds to a dose of approximately 0.14 mg.

It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention.

Claims (10)

CLAIMS Having described the invention as above, the content of the following claims is claimed as property:

1. Compounds of formula I (I), characterized in that B represents phenyl unsubstituted or mono- or poly-substituted with R3, Q is absent or represents alkylene of 1 to 4 C atoms, R1, R 'independently represent -OR4, -S-R4, -SO-R4, - S02-R4, or Hai, R and R, together, also represent -0-CH2-0-, R represents R4, Hai, OH, OR4, OPh, N02, NHR4, N (R4) 2, NHCOR4, NHS02R4 or NHCOOR4 , R represents A, cycloalkyl of 3 to 7 carbon atoms, alkylenecycloalkyl of 5 to 10 carbon atoms or alkenyl of 2 to 8 carbon atoms, A represents alkyl of 1 to 10 carbon atoms which may be substituted with 1 to 5 carbon atoms. atoms of F and / or Cl and Hai represent F, Cl, Br or I, and their physiologically acceptable salts and solvates.

2. Compounds, characterized in that they are of formula I, according to claim 1 (a) N- (3- (3-ethoxy-4-methoxyphenyl) -1,4,5,6-tetrahydropyridazin-1-ylcarbonyl) - phenyl) -4-chlorobenzoyl-3-carboxamide; (b) N- (3- (3-ethoxy-4-methoxy phenyl) -1,4,5,6-tetrahydropyridazin-1-ylcarbonyl) -phenyl) -4-pentoxybenzoyl-3-carboxamide; (c) N- (3- (3-ethoxy-4-methoxy phenyl) -1,4,5,6-tetrahydropyridazin-1-ylcarbonyl) -phenyl) -4-methoxybenzoyl-3-carboxamide; (d) N- (3- (3-ethoxy-4-methoxy phenyl) -1,4,5,6-tetrahydropyridazin-1-ylcarbonyl) -phenyl) -3-chlorobenzoyl-3-carboxamide.

3. Process for preparing the compounds of formula I, according to claim 1, and their salts, characterized in that a compound of formula II is reacted wherein R1 and R2 have the indicated meanings, with a compound of formula III wherein B and Q have the indicated meanings and L represents Cl, Br, OH or an esterified and reactive OH group, or because a compound of formula IV is reacted wherein R1, R2 and Q have the indicated meanings, with a compound of formula V B-CO-L (V), wherein B has the indicated meaning and L represents Cl, Br, OH or an esterified and reactive OH group, and / or because a basic compound of formula I is converted into one of its salts by treatment with an acid.

4. Compounds, characterized in that they are of formula I, according to claim 1, and their physiologically acceptable salts and their solvates, which act as medicaments.

5. Compounds, characterized in that they are of formula I, according to claim 1, and their physiologically acceptable salts and their solvates, which act as inhibitors of phosphodiesterase IV.

6. Pharmaceutical preparation, characterized in that it contains at least one compound of formula I, according to claim 1, and / or one of its physiologically acceptable salts and / or one of its solvates.

7. Process for obtaining pharmaceutical preparations, characterized in that a compound of formula I, according to claim 1, and / or one of its physiologically acceptable salts and / or one of its solvates is brought into a suitable dosage form , together with at least one excipient or solid, liquid or semi-liquid auxiliary product.

8. Compounds, characterized in that they are of formula I, according to claim 1, and their physiologically acceptable salts and solvates, to combat allergies, asthma, chronic bronchitis, atopic dermatitis, psoriasis and others skin diseases, inflammatory diseases, autoimmunodeficiencies such as, for example, rheumatoid arthritis, multiple sclerosis, Morbus Crohn, diabetes mellitus and ulcerative colitis, osteoporosis, rejection reactions to transplants, cachexia, the growth or metastasis of tumors, sepsis, memory disorders, atherosclerosis and AIDS.

9. Use of the compounds of formula I, according to claim 1, and / or its physiologically acceptable salts or solvates, for preparing a medicament for the control of allergies, asthma, chronic bronchitis, atopic dermatitis, psoriasis and others. skin diseases, inflammatory diseases, autoimmunodeficiencies such as, for example, rheumatoid arthritis, multiple sclerosis, Morbus Crohn, diabetes mellitus and ulcerative colitis, osteoporosis, rejection reactions to transplants, cachexia, the growth or metastasis of tumors, sepsis, memory disorders, atherosclerosis and AIDS.

10. Use of the compounds of formula I, according to claim 1, and / or their physiologically acceptable salts and / or solvates, to combat diseases.