SEPARATING ELEMENT FOR SEPARATING SOLID PARTICLES, SUSPENDED IN A GASEOUS CURRENT, BY CENTRIFUGAL FORCE IN A CYLINDRICAL WHIRL CHAMBER

Abstract: 1. A separator element (2) for separating solid matter suspended in a gas stream, by means of centrifugal force, having a plurality of parallel flow channels (4) and a plurality of cylindrical swirl chambers (6) which adjoin the flow channels with a flow-away edge and an approach flow edge in each case and, between these, are open to the flow channel over a portion of their wall surface, and having two clean-gas outlet pipes (8) in each of the swirl chambers, which are arranged coaxially in the swirl chambers and extend towards one another from the end walls in each case, the cross-section of the flow channel being so reduced from chamber to chamber in the direction of flow that the entering velocity of the gas stream into each of the swirl chambers is substantially the same, and wherein the inlets of all the flow channels are arranged in an entry plane (14) which lies substantially transversely to the flow channels, and the flow channels lead into a residual-air channel (12) behind the last swirl chamber in the flow direction in each case, characterised in that the residual-air channel (12) is taken back, inside the separator element (2), lying parallel to the flow channels (4), to the entry plane (14) of the separator element (2) and opens, in this plane, at a distance from the inlets (10) of the flow passages, into an attachment flange and/or sealing flange (18) adjoining the entry plane.

Description: COMPOUNDS HAVING ANTIPLATELET AGGREGATION ACTIVITY, A PROCESS FOR THE PREPARATION THEREOF AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM The present invention relates to compounds of general formula (I) EMI1.1 wherein: m rn is zero or 1; n n is zero, 1, 2; 3 or 4; A A is a 3,7-dimethylxanthine-1-yl or 1,3-dimethylxan- thine-7-yl residue; and pharmaceutically acceptable salts thereof with inorganic or organic acids. Preferred compounds of the invention are the following: N-[1-keto-5-(3,7-dimethylxanthine-1-yl)pentyl]-4,5,6,7-te trahydro-thieno[3,2-c]pyridine; N-[2-keto-5-(3,7-dimethylxanthine-1-yl)pentyl]-4,5,6,7-te trahydro-thienoL3,2--pyridine; N-[2-keto-4-(3,7-dimethylxanthine-1-yl)butyl]-4,5,6,7-tetra hydro-thieno/3,2-c/pyridine; N-Z2-keto-3-(3,7-dimethylxanthine-1-yl)propylS-4,5,6,7-te- trahydro-thieno[3,2-c]pyridine; N-[2-keto-6-(1,3-dimethylxanthine-7-yl)hexyl]-4,5,6,7-tetra hydro-thienoL3,2-c7pyridine; N-[1-keto-5-(1,3-dimethylxanthine-7-yl)pentyl]-4,5,6,7-te trahydro-thieno[3,2-c]pyridine; N-[2-keto-5-(1,3-dimethylxanthine-7-yl)pentyl]-4,5,6,7-te trahydro-thienog,2-c7pyridine; N-/2-keto-4-(1,3-dimethylxanthine-7-yl)butyl/-4,5,6,7-tetra hydro-thieno[3,2-c]pyridine; ; N-L2-keto-3-(1,3-dimethylxanthine-7-yl)propylS-4,5,6,7-te- trahydro-thieno/3,2-cSpyridine. The present invention also relates to a process for the preparation of cmppunds (I), comprising reacting 4,5,6,7-tetrahydrothieno[3,2-c]pyridine (II) with theobromine or theophylline haloderivatives of formula (III), according to the following scheme: EMI2.1 wherein m, n and A have the above mentioned meanings, whilst X represents a halogen atom, preferably chlorine or bromine. More particularly, X preferably represents chlorine when m is zero, and bromine when m = 1. The reaction is preferably carried out in the presence of acid-binding agents, preferably tertiary bases such as triethylamine, pyridine and the like, in inert solvents such as acetonitrile, aromatic hydrocarbons, dimethylformamide, dimethyl sulphoxide, ethers and the like; alternatively, a tertiary base excess may be used as the solvent. The following examples illustrate the process according to the invention, without limiting it. Melting points are not corrected; H-NMR spectra were registered by means of an EM-390 device, 90 MHz, TMS inner standard. TLC chromatograms were developed on silica gel plates Merck PF-254. EXAMPLE 1 a) 1-(6-Bromo-5-ketophexyl)-3,7-dimethylxanthine 50 Grams (0.18 moles) of 1-(5-keto-hexyl)-3,7-dimethylxanthine were dissolved in 490 ml of completely anhydrous methanol, at 45-500C. After cooling to room temperature, 32 g (0.20 moles) of bromine were added in one single portion with stirring. The solution decoloured in 1 hour. After 7 more hours of stirring, the resulting precipitate was pump filtered, the filtrate was concentrated under vacuum, yielding other precipitate which was joined to the first one, to obtain totally 33 g of dry product, consisting in the dimethylketal of the desired compound, m.p. 125-1350C, which was hydrolyzed at room temperature, for 10 hours, in 270 ml of a dioxane/water mixture (2:1 by volume) acidified with 25-30 drops of conc. H2S04. The mixture was left to stand overnight in the cool, the resulting precipitate was pump filtered, washed with some water, dried and crystallized from 200 ml of methanol. 28 Grams of bromoketone were obtained (43.6% of the theoric), m.p. 115-117 C, having the following analytical characteristics: TLC: methanol/methylene chloride 0.5/9.5: unitary spot with R = 0.71; Rf of the starting compound: 0.58. 1 f H-NMR (CDCl ) spectrum: 7.53 (s, 1 H, N=C); 4.016 3 (superimposed signales, 5 H, CH3 and CH2N); 3.93 #(s, 2 H, CH2-Br); 3.60(s, 3 H, CH3); 2.74 (m, 2 H, CH2CO-); 1.73 6 (m, 4 H, 2 CH2). Elementary analysis for C13H17BrN4O3: C H Br N O Calculated, % : 43.71 4.8 22.37 15.58 13.43 Found, % : 43.48 4.75 22.28 15.7 13.34. b) N-[2-Keto-6-(3,7-dimethylxanthine-1-yl)hexyl]-4,5,6,7 tetrahydro-thieno[3,2-c]pyridine EMI4.1 30 Grams (0.084 moles) of 1-(6-bromo-5-keto-hexyl)-3,6-dimethylxanthine and 210 g of acetonitrile were heated to 600C in a flask provided with condenser, stirrer and thermometer, in a thermostatized bath. A solution of 11.7 g (0.084 moles) of 4,5,6,7-tetrahydrothieno[3,2-c]py- ridine and 9.1 g (0.09 moles) of triethylamine in 80 ml of acetonitrile was quickly added thereto, keeping the inner temperature at 600C, under stirring. After 4 hours under these conditions, the mixture was cooled at room temperature, then in a refrigerator for some hours. The formed triethylammonium bromide was pump filtered and washed on the filter with acetonitrile (2 x 20 ml). The filtrate was evaporated under vacuum to dryness, and the residue was freed from the residual triethylammonium bromide by means of 3 extractions in warm with 3 x 300 ml of CHC13, which was decanted. The chloroform extracts were filtered, the filtrate was washed with 20 ml of water, then dried over Na2S04 and evaporated to dryness under vacuum at 400C and 3 mm/Hg. The oily residue (37 g, yield 90% of theoric) showed the following analytical characteristics. TLC: MeOH/methylene chloride 0.5/9.5, unitary spot, R = f 0.51. H-NMR (CDCl3) spectrum: 7.51 #(@, 1 H, N=C-H); 7.05d, 1 H, J = 4.5 Hz, S-CH=CH); 6.68 S (d, 1 H, N = 4.5 Hz, S-CH=CH); 4.1 S(superimposed signals, 5 H, CH3 = CH2); 3,67 # (s, 2 H, CH2); 3.57 #(s, 3 H, CH3) 3.40 # (s, 2 H, CH2); 2.87 # (m, 4 H, 2 CH2); 2.60 # (m, 2 H, -CO-CH2); 1.70 # (m, 4 H, 2 CH2, CO-CH2-CH2-CH2-CH2N). Elementary analysis for C20H25N5O3S: C H N O s Calculated, % : 57.81 6.06 16.85 11.55 7.72 Found, % : 57.46 6.12 16.68 11.51 7.65. From the base, the corresponding bisulfate was obtained by dissolving 40 g (0.096 moles) of the same base, in the warm, at 350 ml of isopropanol/water 90/10 (by volume), and adding a solution of 12.25 g (0.12 moles) of conc. H2SO4 in 150 ml of isopropanol/water 90/10 (by volume), under stirring. The mixture was warm filtered with 2 g of decolouring coal, thereafter it was cooled first to room temperature, then to 50C for some hours. The crystalline precipitate was pump filtered, washed with 2 x 50 ml of cold isopropanol and dried in oven under vacuum at 700C (otherwise, operating under milder conditions, the salt may contain 2 moles of crystallization water). 44.5 Grams of C20H25N5O3S.H2SO4 (LM-PT bisulfate), m.p. 182184 C, titre 98-99%. EXAMPLE 2 a) N-(1-Bromo-5-carboxy-pentyl)-4,5,6,7-tetrahydro-thieno L3, 2qjpyridine In a 250 ml flask, 18.1 g of 5-bromovalerianic acid (0.1 moles) and 65 g of thionyl chloride (0.55 moles) were placed. 2 Drops of pyridine were added, and the mixture was stirred for 2 hours at a temperature of about 0-50C Stirring was continued overnight at room temperature. The excess thionyl chloride was evaporated off under reduced pressure at 40-500C, the residue was treated with 50 ml of anhydrous methylene chloride. 2.8 Grams of 4,5,6,7-tetra hydro-thieno/3,2-c-pyridine (0.2 moles) dissolved in 50 ml of anhydrous methylene chloride were added dropwise, under stirring, in about 1 hour, at room temperature. Stirring was continued for 3 hours at room temperature, and tetrahydrothienopyridine hydrochloride precipitated, which was filtered and washed twice with 30 ml of methylene chloride. The organic phases were pooled and washed in turn with 50 ml of a 10% aqueous solution of hydrochloric acid, 50 ml of water, 50 ml of a 5% sodium bicarbonate aqueous solution, finally with 50 ml of water. The solution was dried over anhydrous sodium sulfate, filtered and evaporated under vacuum. 26 grams (87%) of crude compound were obtained, which was directly used in the next step. b) N-[keto-5(3,7-dimethylxanthinyl-1-yl)pentyl]-4,5,6,7 tetrahydro-thienoz3,2-i7-pyridine 1.32 Grams (0.044 moles) of a 80% sodium hydride suspension in mineral oil was added to a mixture of theobromine (7.9 g; 0.04 moles) in 200 ml of anhydrous dimethylformamide, under stirring, during about 10 minutes, at a temperature of 70 C. After completion of the addition, temperature was raised to 95-100oC, and maintained for 3 hours. 12.1 Grams (0.04 moles) of the compound of step a) were added to the mixture, which was stirred for 20 hours at 95-100 C. After cooling, the resulting precipitate was filtered and washed with methylene chloride. The.pooled organic layers were evaporated at 80-9OoC, the obtained residue was taken up in 150 ml of water and 200 ml of methylene chloride, then treated with a 10% NaOH aqueous solution to pH 13. The two layers were separated, the aqueous phase was extracted with 2 x 80 ml of methylene chloride, the extracts were combined with the main organic phase, which was washed with 100 ml of water, dried over anhydrous sodium sulfate, filtered and evaporated off. 11 Grams of compound were obtained, which was triturated with diisopropylether, then crystallized from isopropanol, obtaining 8 g (50% yield) of the desired compound, melting at 176-178 C. A sample of the compound,treated with hot isopropanol, had melting point at 177-179 C, and the following characteristics: TLC (thin layer of silica gel; eluent: CH2C1 /MeOH, 95:5): 22 unitary spot, Rf 0.55. ÚH-NMR (CDCl2) spectrum: 7.42 # (s, 1 H, N=C-H); 6.97 3 # (d, 1 H, S-CH=CH); 6.58 # (d, 1 H, S-CH=CH); 4.103.20 6(superimposed signals, 12 H, 2 CH3 + 3 CH2); 3.002.73 # (superimposed signals, 4 H, 2 CH2); 2.56 # (t, 2 H, -CH2 C=O); 2.7-1.75 (quintet, 2 H, -CH2-C¯2-CH2-). Elementary anaysis for C19H23N5O3S (M.W. 401.49): C H N Calculated, % : 56.84 5.77 17.45 Fand, % : 56.65 5.79 17.46. EXAMPLE 3 The same compound of Example 2 may alternatively be obtained starting ¯from 1- ( 5-carboxymethyl ) -pentyl-3, 7-di- methylxanthine, obtained by reacting theobromine and methyl 5-bromovalerianate, in the presence of sodium hydride. 1.47 Grams (0.005 moles) of the xanthinic intermediate, 2.07 g (0.015 moles) of 4,5,6,7-tetrahydro-thieno/3,2-c/-pyridine and 0.66 g (0.0025 moles) of rhodium trihydrate chloride were heated at 100ob for 3 days. After cooling, 15 ml of methylene chloride, then 12.5 ml of a 1N hydrochloric acid solution, were added. The precipitate was filtered and the organic phase was separated, washed with 10 ml of water, dried on anhydrous sodium sulfate, filtered and evaporated off. 2.2 Grams of crude compound were obtained, which was purified by chromatography on silica gel, to obtain 0.78 g of the compound of Example 2, melting at 176-178 C and having the same analytical characteristics of the compound of Example 2. EXAMPLE 4 a) 1-(2-Keto-5-pentyl)-3, 7-dimethylxanthine A suspension of 80% sodium hydride in mineral oil (3 g; 0.1 moles) was added in small portions during 10 minutes', to a suspension of 18 g (0.1 moles) of theobromine in 400 ml of anhydrous dimethylformamide. The reaction mixture was heated to 95-100 C for 3 hours. Then 13.26 g (0.11 moles) of 5-chloro-2-pentanone were added, and the reaction mixture was maintained at 95-100 C for 20 hours more. After filtration, the filtrate was evaporated under reduced pressure, the residue was treated with 150 ml of water and the pH was adjusted to 13-14 with a 10% NaOH aqueous solution. The mixture was extracted with 3 x 80 ml of methylene chloride, the combined organic extracts were washed with 3 x 50 ml of water, dried over anhydrous sodium sulfate, filtered and evaporated under vacuum. 2.95 Grams (11.2%) of the title compound were obtained, melting at 109-111 C, which was directly used in the next step. The 1H-NMR spectrum was consistent with the formula. b) l-(l-Bromo-2-keto-5-pentyl)-3,7-dimethylxanthine 4.93 Grams (0.031 moles) of bromine were added to a solution of 7.3 g (0.0276 moles) of compound a) in 100 ml of methanol, at 1000. After stirring for 15 hours at room temperature, the reaction mixture volume was concentrated to 30 ml under reduced pressure, then 60 ml of water, and 3 drops of conc. sulphuric acid were added. The mixture was stirred at room temperature for 4 hours, in order to hydrolyze any dimethylketals formed by reaction with methanol. After dilution with 50 ml of water, the pH of the mixture was adjusted to 8-9, by addition of a 10% sodium bicarbonate aqueous solution, the mixture was extracted with 3 x 50 ml of methylene chloride, washed with water, dried on anhydrous sodium sulfate, filtered and evaporated under vacuum. 8.3 Grams of compound were obtained, which, by TLC and NMR analysis, showed to be impure by the presence of the l-(3-bromo-2-keto-5-pentyl)-3,7-dimethylxan- thine regioisomer. The crude compound was directly used for the next step. c) N-[2-keto-5-(3,7-dimethylxanthinyl-1-yl)pentyl] 4,5,6,7-tetrahydro-thienog3,2-c-pyridine 2.85 Grams (0.02 moles) of tetrahydro-thieno/3,2 cg-pyridine and a solution of 2.43 g of triethylamine in 30 ml of acetonitrile were added to a solution of the crude product from step a) in 60m1 of acetonitrile, at 600C. The mixture was stirred for 6 hours at 65-700C, then solvent was evaporated under reduced pressure, the residue was treated with 50 ml of methylene chloride and 50 ml of water and the phases were separated. The aqueous phase was extracted with 2 x 30 ml of methylene chloride. The combined organic phases were washed with 2 x 30 ml of water, dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure. 8.4 Grams of crude compound were obtained, which was purified by chromatography on silica gel, using as the eluent firstly methylene chloride, then methylene chloride:methanol mixtures from 99:1 to 98:2. 4.2 Grams of the title compound were obtained, corresponding to a total yield of 38%. The obtained compound was pure by TLC analysis and had the following H-NMR spectrum, which was consistent with the desired structure: ÚH-NMR (CDCl3) spectrum: 7.42 # (s, 1 H, N=C-H); 6.94 #(d, 1 H S-CH=CH); 6,58 # (d, 1 H, -S-CH=CH); 4.10- 3.20 S(superimposed signals, 12 H, 2 CH3 + 3 CH2); 3.002.73 # (superimposed signals, 4 H, 2 CH2); 2.56 g(t, 2 H, -CH2-C=0-); 2.17-1.75 5 (quintet, 2 H, -CH2CH2-CH2-). d) Bisulfate salt of compound c) Compound from step c) was dissolved in hot methanol and 1.03 g of 96% conc. sulphuric acid were added dropwi se, under stirring, to the solution. The mixture was refluxed for 10 minutes under stirring, and evaporated under reduced pressure. The gummy residue was dissolved at ebollition in 45 ml of an isopropanol/water 9:1 mixture, then it was cooled to room temperature, left to stand for 20 hours and the precipitated compound was filtered, washed with 3 x 150 ml of isopropanol and dried under vacuum at 750C, to obtain 3.3 g (65.2%) of the title compound, having softening point at 2000 and melting point at 215 C, with decomposition. The compound showed unitary spot by TLC, and the following analytical characteristics: Acid-base titre: more than 99% Elementary analysis for C H N O S , M.W. 499.57 19-25-5-7-2- C H N Calculated, % : 45.68 5.04 14.02 Found, % : 45.85 5.12 13.98. EXAMPLE 5 a) 7- ( 6-Bromo-5-keto-hexyl) -1, 3-dimethylxanthine 9.7 Grams (0.06 moles) of bromine were added to a solution of 15 g (0.054 moles) of 7-(5-keto-hexyl)-1,3-dimethylxanthine in 100 ml of anhydrous methanol, at 1000 with stirring. After 30 minutes at the same temperature, stirring was continued for 7 more hours at room temperature. The mixture was then concentrated under reduced pressure till a residual volume of 30 ml, diluted with 30 ml of water, added with 3 drops of 96% sulphuric acid and stirred for 4 hours at room temperature, to hydrolyze any dimethylketal formed, then diluted with 100 ml of water and alkalized with a 10% sodium bicarbonate aqueous solu tion. The mixture was extracted with 2 x 80 ml of methylene chloride, the organic phase was washed with water, dried and evaporated under reduced pressure. The residue was dissolved in 30 ml of ethyl acetate, cooled and crystallized at 5-100C. 7.5 Grams (40%) of the title compound were obtained, melting at 106-1090C, which was directly used in the next step. b) N-[2-Keto-6-(1,3-dimethylxanthine-1-yl)-hexyl]-4,5,6,7 tetrahydro-thieno[3,2-c]-pyridine A solution of 2.78 g of thienopyridine in 20 ml of acetonitrile was added to a solution of 6.9 g of the compound from the previous step in 50 ml of acetonitrile, under stirring, at 60 C. The reaction was continued for 7 hours at 60-650C, the solvent was evaporated off and the residue was dissolved in 100 ml of methylene chloride. After dilution with 50 ml of water, the organic phase was separated, washed again with 50 ml of water, dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure. 7.1 Grams (88.57%) of the title compound were obtained, having the following analytical characteri stics: TLC: (silica gel thyn layer; eluent: M3OH/methylene chloride 0.5:9.5): unitary spot, Rf 0.55. H-NMR (CDCl3) spectrum: 7.54 6 (s, 1 H, N=C-H); 7.04 # (d, 1 H, S-CH=CH); 6.68 (d, 1 H, S-CH=CH); 4.29 2 2 H, -N=CH-N-CH2); 3.70-3.30 ä (superimposed signals, 10 H, 2 CH3 + 2 CH2); 3.09-2.80 (5 (superimposed signals, 4 H, 2 CH2); 2.60 S(t, 2 H, -CH2-C-O); 2.10-1.35 4 H, -CH2-CH2-CH2-CH2-). c) Bisulfate salt 1.64 grams of 96% sulphuric acid were added to a solution of the compound from step b), in 50 ml of methanol. An oily precipitate was obtained, which was heated under reflux for 15 minutes. An oily precipitate formed, which solidified by treatment under reflux for 15 minutes. After cooling, the precipitate was filtered and redissolved in 40 ml of hot isopropanol, left to cool for 3 hours at 10 C, filtered again and dried. 5.9 Grams of compound, melting at 178-1800C, .were obtained. After drying under high vacuum at 750C for 2 hours, 5.7 g of compound were obtained, softening at about 1800C and melting at 213 C, having the following analytical characteristics: Acid-base titre: more than 99% H-NMR spectrum: according to the desired structure. Elementary analysis for C20H25N5O3S.H2SO4, (M.W. 513.6) C H N O S Calculated, % : 46.77 5.30 13.63 21.81 12.49 Found, % : 46.25 5.99 13.63 21.84 12.55. EXAMPLE 6 a) N-[2-Keto-5-(1,3-dimethylxanthine-1-yl)pentyl]-4,5,6,7 tetrahydro-thieno[3,2-c]-pyridine The title compound was obtained according to the same procedure of Example 4, replacing theobromine with theophylline. The final compound and its bisulfate salt showed the following characteristics: ÚH-NMR (CDCl3) spectrum: 7.54 # (s, 1 H, N=C-H); 7.04 # (d, 1 H, S-CH=CH); 6.68 # (d, 1 H, S-CH=CH); 4.29 (t, 2 H, -N=CH-N-CH2); 3.70-3.30 J (superimposed signals, 10 H, 2 CH3 + 2 CH2); 3.00-2.80 6 (superimposed signals, 4 H, 2 CH2); 2.605(t, 2 H, -CH2-CO-); 2.10-1.35 6 (m, 4 H, CH2- CH2-CH2-CH2-). b) Bisulfate salt of the final compound: ClgH25N507S2: M.W. 499.57 TLC: unitary spot. M.p.: softening at 194 C. Melting with dec. at: 21600. As already stated, the compounds according to the invention show a marked antiplatelet aggregation activity. Moreover, their toxicity is very low. For example, the acute toxicity of the salt above referred by LM-PT bisulfate, was evaluated in the mouse orally and intravenously. The LD50 were about 400 mg/kg and about 100 mg/kg, respectively. The DPPV (disaggregating power percentage value) was evaluated for LM-PT bisulfate, by the ADP induced aggregation test ex vivo in the rat, orally. For a single dose of 100 mg/kg, the DPPV-was 92-96%. The present invention refers also to all of the industrially applicable aspects of compounds of formula I, as agents inhibiting platelet aggregation. Therefore, a primary object of the present invention comprises pharmaceutical compositions containing compounds I as active ingredients, optionally combined with conventional excipients. The compounds of the invention may be administered orally, at a daily dose comprised from 1 to 100 mg.

Claims: CLAIMS for the Contracting States: BE, CH, DE, FR, GB, IT, LI, LU, NL, SE 1. Compounds of general formula (I) EMI15.1 wherein: m 1 is zero or 1; n 1 is zero, 1, 2, 3 or 4; A @ is a 3,7-dimethylxanthine-1-yl or 1,3-dimethylxan- thine-7-yl residue; and pharmaceutically acceptable inorganic or organic acid addition salts thereof. 2. As a compound according to claim 1, the N-Z-keto-6- (3,7-dimethylxanthine-1-yl)hexyl]-4,5,6,7-tetrahydro-thieno[3,2-c]-pyridine. 3. As a compound according to claim 1, the N-Z-keto-5- (3,7-dimethylxanthine-1-yl)pentyl]-4,5,6,7-tetrahydro-thieno[3,2-c]-pyridine. 4. As a compound according to claim 1, the N-2-keto-5- (3,7-dimethylxanthine-1-yl)pentyl]-4,5,6,7-tetrahydro-thieno[3,2-c]-pyridine. 5. As a compound according to claim 1, the N-A2-keto-4- (3,7-dimethylxanthine-1-yl)butyl]-4,5,6,7-tetrahydro-thie noz3,2-c7pyridine. 6. As a compound according to claim 1, the N-g2-keto-3- (3,7-dimethylxanthine-1-yl)propyl]-4,5,6,7-tetrahydro-thieno[3,2-c]-pyridine. 7. As a compound according to claim 1, the N-2-keto-6- (1,3-dimethylxanthine-7-yl)hexyl]-4,5,6,7-tetrahydro-thieno[3,2-c]-pyridine. 8. As a compound according to claim 1, the N-l-keto-5- (1,3-dimethylxanthine-7-yl)pentyl]-4,5,6,7-tetrahydro-thie not3, 2-pyridine. 9. As a compound according to claim 1, the N-[2-keto-5- (1,3-dimethylxanthine-7-yl)penthyl]-4,5,6,7-tetrahydro-thieno[3,2-c]-pyridine. 10. As a compound according to claim 1, the N-[2-keto-4- (1,3-dimethylxanthine-7-yl)butyl]-4,5,6,7-tetrahydro-thieno[3,2-c]-pyridine. 11. As acompound according to claim 1, the N-Z2-keto-3- (1,3-dimethylxanthine-4-yl)]-4,5,6,7-tetrahydro-thieno[3,2-c]-pyridine. 12. A process for preparing compounds ofclaiml, wherein 4,5,6,7-tetrahydrothieno[3,2-c]-pyridine (II) is reacted with theobromine or theophylline haloderivatives, of formula (III), according to the following scheme: EMI16.1 wherein m, n and A have the above defined meanings, and X is a halogen atom. 13. A process according to claim 12, wherein, when m = zero, X is preferably chlorine. 14. A process according to claim 12, wherein when m = 1, X is preferably bromine. 15. A process according to claims 12-14, wherein the reaction is carried out in the presence of acid binding agents. 16. Pharmaceutical compositions having anti-platelet aggregation activity, containing as the active ingredient one or more compounds of claims 1-12. CLAIMS for AT: 1. A process for preparing compounds of general formula (I) EMI18.1 wherein: m m is zero or 1; n n is zero, 1, 2, 3 or 4; A A is a 3,7-dimethylxanthine-1-yl or 1,3-dimethylxan- thine-7-yl residue; wherein 4,5,6,7-tetrahydrothieno[3,2-c]-pyridine (II) is reacted with theobromine or theophylline haloderivatives, of formula (III), according to the following scheme: EMI18.2 wherein m, n and A have the above defined meanings, and X is a halogen atom. 2. A process according to claim 1, wherein, when m = zero, X is preferably chlorine. 3. A process according to claim 1, wherein when m = 1, X is preferably bromine. 4. A process according to claims 1-3, wherein the reaction is carried out in the presence of acid binding agents.

Inventors: MUELLER, FRIEDRICH-ERNST, DIPL.-ING., NOTHDURFT, JUERGEN, Müller, Friedrich-Ernst, Dipl.-Ing., Nothdurft, Jürgen
Applicants: ANTON PILLER GMBH & CO. KG
Application year: 1986
Main classification: B01D45
IPC codes: B01D45, B04C3