EP0230942B1 — Thieno-1,4-diazepines

Claim 1

Independent Claim 1247 words

Thieno-1,4-diazepines of general formula wherein R 1 represents hydrogen, a branched or unbranched alkyl group with 1 to 4 carbon atoms which may optionally be substituted by hydroxy or halogen, a cyclopropyl group, a branched or unbranched alkoxy group with 1 to 4 carbon atoms, or a halogen, preferably chlorine or bromine; when n > 0 R 2 represents halogen, hydroxy, wherein R 4 and R s , which may be identical or different, represent hydrogen, a branched or unbranched alkyl, alkenyl or alkynyl group with 1 to 10 carbon atoms which may optionally be substituted by halogen, hydroxy or a C-linked 5-, 6- or 7-membered heterocyclic group, whilst the carbon chain may be interrupted by nitrogen, oxygen or sulphur, a branched or unbranched alkylcarbonyl group with 1 to 6 carbon atoms, optionally substituted by hydroxy or halogen, or substituted by an amino group which is optionally mono- or disubstituted by a branched or unbranched alkyl group with 1 to 6 carbon atoms, whilst the alkyl group may be substituted by halogen or hydroxy, an optionally substituted arylcarbonyl group, an optionally substituted arylsulphonyl group, an alkylsulphonyl group with 1 to 4 carbon atoms, or R 4 and R 5 together with the nitrogen atom form a saturated or unsaturated 5-, 6- or 7- membered ring optionally mono- or polysubstituted by branched or unbranched alkyl groups with 1 to 4 carbon atoms, this ring possibly containing nitrogen, oxygen or sulphur as further heteroatoms, whilst each additional nitrogen atom may optionally be substituted by a branched or unbranched alkyl group with 1 to 4 carbon atoms; R 2 represents an arylsulphonyloxy group, optionally mono- or polysubstituted by branched or unbranched alkyl and/or alkoxy groups with 1 to 4 carbon atoms; R 2 represents a branched or unbranched alkylsulphonyloxy group with 1 to 4 carbon atoms; R 2 an arylcarbonyloxy group, optionally mono- or polysubstituted by branched or unbranched alkyl and/or alkoxy groups with 1 to 4 carbon atoms; R 2 represents a branched or unbranched alkylcarbonyloxy group with 1 to 12 carbon atoms, whilst the alkyl chain may be interrupted by nitrogen, oxygen or sulphur; R 2 represents wherein R 6 represents a branched or unbranched alkyl, alkenyl or alkynyl group with 1 to 4 carbon atoms, optionally substituted by halogen, an aryl group optionally mono- or polysubstituted by branched or unbranched alkyl and/or alkoxy groups with 1 to 4 carbon atoms, R 2 represents wherein R 8 and Rg, which may be identical or different, represent a branched or unbranched alkyl group with 1 to 4 carbon atoms, or R 8 and Rg together with the nitrogen atom represent a 5-, 6- or 7-membered ring optionally mono- or polysubstituted by branched or unbranched alkyl groups with 1 to 4 carbon atoms, this group optionally containing as further heteroatoms nitrogen, oxygen or sulphur, whilst each additional nitrogen atom is substituted by an alkyl group with 1 to 4 carbon atoms; R 2 represents a branched or unbranched alkoxy group with 1 to 4 carbon atoms; an aryloxy group; R 2 represents an imido group; dioxolan, substituted dioxolan; when n is greater than or equal to 0 R 2 represents -CH = O; cyano; R 2 represents an aryloxycarbonyl group, R 2 represents a group of general formula wherein R 10 and R 11 , which may be identical or different, represent hydrogen, phenyl, substituted phenyl, a branched or unbranched alkyl, alkenyl or alkynyl group with 1 to 10 carbon atoms, which may optionally be substituted by halogen, hydroxy, nitro, amino, substituted amino or, if R 10 = hydrogen or alkyl and Y = C-Ri or Y represents nitrogen and X represents C-alkyl, R 11 may be substituted by an ester function or an acid amide of general formula wherein R' 10 and R' 11 have the same meanings as R 10 and R 11 , with the exception of an acid amide, R 10 o or R 11 represent a saturated or unsaturated 5-, 6- or 7-membered heterocyclic ring linked by a carbon atom, optionally mono- or polysubstituted by branched or unbranched alkyl with 1 to 4 carbon atoms, R 10 o and R 11 together with the nitrogen atom represent a saturated or unsaturated 5-, 6- or 7- membered ring optionally mono- or polysubstituted by branched or unbranched alkyl groups with 1 to 4 carbon atoms and optionally containing, as further heteroatoms, nitrogen, oxygen or sulphur, whilst each additional nitrogen atom may be substituted by a branched or unbranched alkyl group with 1 to 4 carbon atoms, preferably methyl, R 2 represents a group of general formula wherein B represents oxygen, sulphur, NH or NC1-C6-alkyl D represents the group (C Re Rf)n, wherein n may be from 0 to 3, Ra represents hydrogen, alkyl with 1 to 6 carbon atoms optionally substituted by a hydroxy or amino group, C 1 to C 4 alkoxycarbonyl, dialkylaminocarbonyl, Rb, Rc, Rd, Re, Rf represent hydrogen, alkyl with 1 to 6 carbon atoms optionally substituted by a hydroxy or amino group, or phenyl; R 3 represents phenyl, wherein the phenyl ring, preferably in the 2 position, may be mono- or polysubstituted by methyl, halogen, nitro, alkoxy and/or trifluoromethyl, or R 3 may represent pyridyl; R represents hydrogen, alkyl or an acyl group with 1 to 4 carbon atoms, R' represents hydrogen, phenyl, substituted phenyl or a branched or unbranched alkyl group with 1 to 4 carbon atoms, X,Y independently of each other represent C-R i or N but cannot both simultaneously represent C-Ri, or Y represents the group C-COOR * , wherein R * = alkyl or hydrogen and X = nitrogen; Z represents a branched or unbranched alkyl or alkenyl group with n carbon atoms, wherein Z may optionally additionally be substituted by aryl or disubstituted by R 2 , whilst R 2 may be identical or different; and n represents one of the numbers 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, in the form of their racemates, enantiomers, diastereomers and mixtures thereof, as free bases or as the physiologically acceptable acid addition salts thereof, whilst as substituents one or more atoms selected from halogen, methyl, methoxy, hydroxy and trifluoromethyl may be present, and aryl represents an aromatic group having up to 10 carbon atoms, which may optionally also be mono- or polysubstituted by halogen, methyl, methoxy, hydroxy and trifluoromethyl, with the proviso that in the case of a compound of general formula la, if X and Y both represent nitrogen, Z represents an unbranched alkyl chain, n = 0 or a number from 1 to 8, R 1 represents hydrogen, a branched or unbranched C 1-4 alkyl group (optionally substituted by halogen or hydroxy), a cyclopropyl group, a C 1 - 3 alkoxy group or a halogen atom and R 2 represents a group of general formula wherein R 10 and R 11 , which may be identical or different, represent hydrogen, a branched or unbranched C, -4 alkyl or hydroxyalkyl group or R 10 and R 11 together with the nitrogen atom form a 5-, 6- or 7-membered ring which may optionally contain nitrogen, oxygen or sulphur as additional heteroatoms, whilst the second nitrogen atom may optionally be substituted by a C 1 - 4 alkyl group, R 3 does not represent phenyl or a phenyl group, which may be mono- or polysubstituted by methyl, halogen, nitro or trifluoromethyl or may represent a-pyridyl, whilst additionally the following compounds are excluded: 2-(2-chloroethyl)-4-(2-chlorophenyl)-9-methyl-6H-thieno[3,2-f][1,2,4]triazole[4,3-a][1,4]-diazepine, 2-(methylsulphonylmethyl)-4-(2-chlorophenyl)-9-methyl-6H-thieno[3,2-d][1,2,4]triazolo[4,3-a]-[1,4]-diazepine, 2-cyano-4-(2-chlorophenyl)-9-methyl-thieno[3,2-f]-[1,2,4]triazolo[4,3-a][1,4]diazepine, 2-(1-hydroxyethyl)-4-(2-chlorophenyl)-9-methyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]-diazepine.

Claim 2

Dependent Claim 1247 words

Thieno-1,4-diazepines of general formula wherein R 1 represents hydrogen, a branched or unbranched alkyl group with 1 to 4 carbon atoms which may optionally be substituted by hydroxy or halogen, a cyclopropyl group, a branched or unbranched alkoxy group with 1 to 4 carbon atoms, or a halogen, preferably chlorine or bromine; when n > 0 R 2 represents halogen, hydroxy, wherein R 4 and R s , which may be identical or different, represent hydrogen, a branched or unbranched alkyl, alkenyl or alkynyl group with 1 to 10 carbon atoms which may optionally be substituted by halogen, hydroxy or a C-linked 5-, 6- or 7-membered heterocyclic group, whilst the carbon chain may be interrupted by nitrogen, oxygen or sulphur, a branched or unbranched alkylcarbonyl group with 1 to 6 carbon atoms, optionally substituted by hydroxy or halogen, or substituted by an amino group which is optionally mono- or disubstituted by a branched or unbranched alkyl group with 1 to 6 carbon atoms, whilst the alkyl group may be substituted by halogen or hydroxy, an optionally substituted arylcarbonyl group, an optionally substituted arylsulphonyl group, an alkylsulphonyl group with 1 to 4 carbon atoms, or R 4 and R 5 together with the nitrogen atom form a saturated or unsaturated 5-, 6- or 7- membered ring optionally mono- or polysubstituted by branched or unbranched alkyl groups with 1 to 4 carbon atoms, this ring possibly containing nitrogen, oxygen or sulphur as further heteroatoms, whilst each additional nitrogen atom may optionally be substituted by a branched or unbranched alkyl group with 1 to 4 carbon atoms; R 2 represents an arylsulphonyloxy group, optionally mono- or polysubstituted by branched or unbranched alkyl and/or alkoxy groups with 1 to 4 carbon atoms; R 2 represents a branched or unbranched alkylsulphonyloxy group with 1 to 4 carbon atoms; R 2 an arylcarbonyloxy group, optionally mono- or polysubstituted by branched or unbranched alkyl and/or alkoxy groups with 1 to 4 carbon atoms; R 2 represents a branched or unbranched alkylcarbonyloxy group with 1 to 12 carbon atoms, whilst the alkyl chain may be interrupted by nitrogen, oxygen or sulphur; R 2 represents wherein R 6 represents a branched or unbranched alkyl, alkenyl or alkynyl group with 1 to 4 carbon atoms, optionally substituted by halogen, an aryl group optionally mono- or polysubstituted by branched or unbranched alkyl and/or alkoxy groups with 1 to 4 carbon atoms, R 2 represents wherein R 8 and Rg, which may be identical or different, represent a branched or unbranched alkyl group with 1 to 4 carbon atoms, or R 8 and Rg together with the nitrogen atom represent a 5-, 6- or 7-membered ring optionally mono- or polysubstituted by branched or unbranched alkyl groups with 1 to 4 carbon atoms, this group optionally containing as further heteroatoms nitrogen, oxygen or sulphur, whilst each additional nitrogen atom is substituted by an alkyl group with 1 to 4 carbon atoms; R 2 represents a branched or unbranched alkoxy group with 1 to 4 carbon atoms; an aryloxy group; R 2 represents an imido group; dioxolan, substituted dioxolan; when n is greater than or equal to 0 R 2 represents -CH = O; cyano; R 2 represents an aryloxycarbonyl group, R 2 represents a group of general formula wherein R 10 and R 11 , which may be identical or different, represent hydrogen, phenyl, substituted phenyl, a branched or unbranched alkyl, alkenyl or alkynyl group with 1 to 10 carbon atoms, which may optionally be substituted by halogen, hydroxy, nitro, amino, substituted amino or, if R 10 = hydrogen or alkyl and Y = C-Ri or Y represents nitrogen and X represents C-alkyl, R 11 may be substituted by an ester function or an acid amide of general formula wherein R' 10 and R' 11 have the same meanings as R 10 and R 11 , with the exception of an acid amide, R 10 o or R 11 represent a saturated or unsaturated 5-, 6- or 7-membered heterocyclic ring linked by a carbon atom, optionally mono- or polysubstituted by branched or unbranched alkyl with 1 to 4 carbon atoms, R 10 o and R 11 together with the nitrogen atom represent a saturated or unsaturated 5-, 6- or 7- membered ring optionally mono- or polysubstituted by branched or unbranched alkyl groups with 1 to 4 carbon atoms and optionally containing, as further heteroatoms, nitrogen, oxygen or sulphur, whilst each additional nitrogen atom may be substituted by a branched or unbranched alkyl group with 1 to 4 carbon atoms, preferably methyl, R 2 represents a group of general formula wherein B represents oxygen, sulphur, NH or NC1-C6-alkyl D represents the group (C Re Rf)n, wherein n may be from 0 to 3, Ra represents hydrogen, alkyl with 1 to 6 carbon atoms optionally substituted by a hydroxy or amino group, C 1 to C 4 alkoxycarbonyl, dialkylaminocarbonyl, Rb, Rc, Rd, Re, Rf represent hydrogen, alkyl with 1 to 6 carbon atoms optionally substituted by a hydroxy or amino group, or phenyl; R 3 represents phenyl, wherein the phenyl ring, preferably in the 2 position, may be mono- or polysubstituted by methyl, halogen, nitro, alkoxy and/or trifluoromethyl, or R 3 may represent pyridyl; R represents hydrogen, alkyl or an acyl group with 1 to 4 carbon atoms, R' represents hydrogen, phenyl, substituted phenyl or a branched or unbranched alkyl group with 1 to 4 carbon atoms, X,Y independently of each other represent C-R i or N but cannot both simultaneously represent C-Ri, or Y represents the group C-COOR * , wherein R * = alkyl or hydrogen and X = nitrogen; Z represents a branched or unbranched alkyl or alkenyl group with n carbon atoms, wherein Z may optionally additionally be substituted by aryl or disubstituted by R 2 , whilst R 2 may be identical or different; and n represents one of the numbers 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, in the form of their racemates, enantiomers, diastereomers and mixtures thereof, as free bases or as the physiologically acceptable acid addition salts thereof, whilst as substituents one or more atoms selected from halogen, methyl, methoxy, hydroxy and trifluoromethyl may be present, and aryl represents an aromatic group having up to 10 carbon atoms, which may optionally also be mono- or polysubstituted by halogen, methyl, methoxy, hydroxy and trifluoromethyl, with the proviso that in the case of a compound of general formula la, if X and Y both represent nitrogen, Z represents an unbranched alkyl chain, n = 0 or a number from 1 to 8, R 1 represents hydrogen, a branched or unbranched C 1-4 alkyl group (optionally substituted by halogen or hydroxy), a cyclopropyl group, a C 1 - 3 alkoxy group or a halogen atom and R 2 represents a group of general formula wherein R 10 and R 11 , which may be identical or different, represent hydrogen, a branched or unbranched C, -4 alkyl or hydroxyalkyl group or R 10 and R 11 together with the nitrogen atom form a 5-, 6- or 7-membered ring which may optionally contain nitrogen, oxygen or sulphur as additional heteroatoms, whilst the second nitrogen atom may optionally be substituted by a C 1 - 4 alkyl group, R 3 does not represent phenyl or a phenyl group, which may be mono- or polysubstituted by methyl, halogen, nitro or trifluoromethyl or may represent a-pyridyl, whilst additionally the following compounds are excluded: 2-(2-chloroethyl)-4-(2-chlorophenyl)-9-methyl-6H-thieno[3,2-f][1,2,4]triazole[4,3-a][1,4]-diazepine, 2-(methylsulphonylmethyl)-4-(2-chlorophenyl)-9-methyl-6H-thieno[3,2-d][1,2,4]triazolo[4,3-a]-[1,4]-diazepine, 2-cyano-4-(2-chlorophenyl)-9-methyl-thieno[3,2-f]-[1,2,4]triazolo[4,3-a][1,4]diazepine, 2-(1-hydroxyethyl)-4-(2-chlorophenyl)-9-methyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]-diazepine.

Claim 3

Dependent Claim 397 words

Compounds of general formula la or Ib as claimed in claim 1, wherein R 1 represents methyl, ethyl, methoxy, ethoxy, chlorine or bromine; R 2 represents chlorine, bromine, iodine or hydroxy, wherein R 4 and R s , which may be identical or different, represent hydrogen, a branched or unbranched alkyl group with 1 to 6, more particularly 1 to 4, carbon atoms, whilst the carbon chain may be interrupted by nitrogen, a branched or unbranched alkylcarbonyl group with 1 to 4 carbon atoms, optionally substituted by a dimethylamino group, a phenylcarbonyl group, when R 5 = hydrogen, R 2 may also represent a phenylsulphonyl group optionally substituted by acylamino, particularly acetylamino, amino, alkylamino or dialkylamino, or R 4 and R 5 together with the nitrogen atom form a piperidine, pyrrolidine, N'-methylpiperazine, an optionally dimethyl-substituted morpholine ring, a pyrrole, pyrazole, imidazole or triazole ring; R 2 represents -CH = O; -COOH; a A 2- imidazoline, -oxazoline, -thiazoline optionally mono- or polysubstituted by methyl; a tolylsulphonyloxy group; a methylsulphonyloxy group; a phenylcarbonyloxy group; a branched or unbranched alkylcarbonyloxy group with 1 to 5 carbon atoms; a methoxy- or ethoxycarbonyl group; R 2 represents wherein R 6 represents a branched or unbranched alkyl group with 1 to 4 carbon atoms; R 2 represents wherein R 8 and Rg, which may be identical or different, represent a methyl, ethyl, propyl or isopropyl group or R 8 and Rg together with the nitrogen atom represent an N'-methylpiperazine or morpholine ring; R 2 represents R 3 represents phenyl, whilst the phenyl ring may be substituted by chlorine in the 2 position; R represents hydrogen, methyl or acetyl; R' represents hydrogen; X,Y independently of each other represent C-R 1 or N but cannot both simultaneously represent C-Ri, (Ri preferably represents hydrogen), or Y represents the group C-COOR*, wherein R * = alkyl or hydrogen and X = nitrogen; Z is defined as hereinbefore and preferably represents -(CH 2 ) n -, optionally substituted by phenyl or disubstituted by R 2 , whilst R 2 may also be different, or -CH 2 -CHR 2 -CH 2 -R 2 , -CH 2 -CHR 2 R 2 , -CH 2 CHR 2 -CH 2 -C 6 H 5 ; and n represents one of the numbers 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, and optionally the physiologically acceptable acid addition salts thereof.

Claim 4

Dependent Claim 63 words

Compounds of general formula la as claimed in claim 1 or 2, wherein R 2 is as hereinbefore defined and R 1 represents methyl or methoxy, R 3 represents o-chlorophenyl, R' represents hydrogen, X and Y both represent nitrogen or X represents C-H and Y represents nitrogen, Z represents -(CH 2 ) n -, and n represents the number 2, 3 or 7.

Claim 5

Dependent Claim 200 words

Process for preparing compounds of general formula la as claimed in claim 1, 2 or 3, wherein Ri, R 3 , R', Z, X, Y and n are as hereinbefore defined, R 2 represents -COOR*, where R * = alkyl, or R 2 represents hydroxy, alkylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, dioxolan, substituted dioxolan or R 8 Rg NS0 2 , characterised in that a corresponding compound of general formula A) if X and Y represent nitrogen a) is reacted with an acid hydrazide of general formula b) or is converted with hydrazine into a compound of general formula and is then reacted with an acid halide of general formula or with an orthoester of general formula wherein R' represents a lower alkyl group, or B) if X represents C-H and Y represents nitrogen a) is reacted with an aminoalkyne of general formula wherein R 11 represents hydrogen or a lower alkyl group, or b) is reacted with an a-aminoaldehyde-alkylacetal or a-aminoketone-alkylketal of general formula wherein R 1 represents a lower alkyl group or cyclopropyl group, or C) if X represents nitrogen and Y represents C-H, a compound of general formula is decarboxylated, and optionally converted into the harmless acid addition salts thereof.

Claim 6

Dependent Claim 805 words

Process for preparing compounds of general formula according to one of claims 1, 2 or 3, characterised in that, as starting compound, a compound of general formula I wherein R 1 = hydrogen, alkyl, cycloalkyl; Z, X, Y, R', n and R 3 are defined as hereinbefore and R represents a lower alkyl group, is reacted as follows: (1) compounds of general formula la wherein are obtained by saponification of compounds of formula I; (2) compounds of general formula la wherein are obtained by reacting la wherein with an amine of formula for example in the presence of sulphonyldiimidazole or carbonyldiimidazole; (3) compounds of general formula la wherein are obtained by selective reduction of I, e.g. with lithium alanate or sodium borohydride; or by hydrolysis of a compound of general formula la wherein R 2 represents an alkylcarbonyloxy group; (4) compounds of general formula la wherein are obtained by reacting the alcohol, e.g. prepared according to 3), with an isocyanate of general formula (5) compounds of general formula la wherein R 2 = alkyl or arylcarbonyloxy are obtained by reacting the alcohol, e.g. prepared according to 3), with an acid equivalent of a carboxylic acid of formula wherein R represents an aryl group or a branched or unbranched alkyl with 1 to 8 carbon atoms, whilst the carbon chain may be interrupted by nitrogen, oxygen or sulphur; (6) compounds of general formula la wherein R 2 = alkylsulphonyloxy or arylsulphonyloxy are obtained by reacting the alcohol prepared, for example, according to 3), with an alkyl- or arylsulphonyl halide, with the addition of an acid binding agent; (7) compounds of general formula la wherein or an imido group, are obtained by reacting the mesylate, e.g. prepared according to (6), with an amine of formula or an imide; (8) compounds of general formula la wherein are obtained, for example, by cleaving the phthalimide, or from the corresponding isocyanates, wherein R 2 is N = C = O, by hydrolysis; (9) compounds of general formula la wherein where R 4 or R 5 represents alkyl- or arylcarbonyl are obtained by reacting a primary or secondary amine, e.g. prepared according to 7) or 8), with a carboxylic acid equivalent derived from a carboxylic acid of formula (10) compounds of general formula la wherein are obtained by oxidation of the alcohol, e.g. prepared according to 3), with shortening of the chain from n to n-1; (11) compounds of general formula la wherein R 2 represents a group of general formula are obtained by reacting a compound of general formula la wherein with an amine of general formula wherein R a , R b , R e , R d , D and B have the meanings given hereinbefore, in the presence of triphenylphosphine, CC1 4 and a base; (11 a) Compounds of general formula la wherein R 2 is an optionally substituted thiazoline group are obtained from the corresponding oxazolines, e.g. prepared according to (11) by sulphurisa- tion, e.g. with phosphorus pentasulphide or Lawesson's reagent®; (12) compounds of general formula la wherein are obtained by reacting compounds of general formula la wherein with phosphorus oxychloride; (13) compounds of general formula la wherein R 2 is a 2-imidazoline optionally substituted by branched or unbranched alkyl groups, are obtained by reacting compounds of general formula la wherein a) with ethanolic HCI, b) reacting the resulting imidoethyl ester with an ethylenediamine optionally substituted by branched or unbranched alkyl groups, c) and optionally the free N-H function is alkylated with known alkylating agents; (14) compounds of general formula la wherein R 2 is an aryloxy or alkyloxy group are obtained, for example, by reacting the mesylate, prepared according to 6), for example, with the corresponding alkoxides; (15) compounds of general formula la, wherein R 2 = alkyl- or aryloxycarbonyl, are obtained by reacting an acid equivalent of I (R 2 = COOH) with the corresponding alcohols; (16) compounds of general formula la wherein R 2 = halogen, are obtained by reacting the tosylate, e.g. prepared according to 6), with a halogenating agent; and subsequently, if desired, the resulting compounds la wherein R 1 = hydrogen are reacted in the presence of a base with a halogenating agent such as chlorine or bromine to form a compound of general formula la wherein R 1 = halogen, e.g. chlorine or bromine; and subsequently, if desired, the halogen compound is converted into a compound of general formula la wherein R 1 = alkoxy with 1 to 4 carbon atoms by reacting with the corresponding alkoxide; and subsequently, if desired, a compound of general formula la is selectively reduced to give a compound of general formula Ib wherein R = = hydrogen, and subsequently, if desired, it is alkylated or acylated; and optionally the resulting compounds la or Ib are converted into the harmless acid addition salts thereof.

Claim 7

Dependent Claim 70 words

Process for preparing compounds of general formula la as claimed in claim 4, wherein R 1 is halogen or alkoxy, characterised in that a compound of general formula la wherein R 1 is hydrogen a) is halogenated with a halogenating agent such as chlorine or bromine and subsequently, if desired, b) the halogen compound is reacted with the corresponding alkoxide and optionally converted into a harmless acid addition salt thereof.

Claim 8

Dependent Claim 54 words

Process for preparing compounds of general formula Ib as claimed in claim 1, 2 or 3, characterised in that a compound of general formula la is selectively reduced and, if desired, the resulting compound Ib wherein R represents hydrogen is alkylated or acylated and optionally converted into a pharmacologically acceptable acid addition salt thereof.

Claim 9

Dependent Claim 20 words

Pharmaceutical preparations containing as active substances compounds of general formula la or Ib in conjunction with conventional excipients and/or carriers.

Claim 10

Dependent Claim 20 words

Pharmaceutical preparations containing as active substances compounds of general formula la or Ib in conjunction with conventional excipients and/or carriers.

Claim 11

Dependent Claim 35 words

Process for preparing pharmaceutical preparations as claimed in claim 8, characterised in that compounds of general formula la or Ib are processed with conventional galenic excipients and/or carriers to form conventional pharmaceutical forms for administration.

Claim 12

Dependent Claim 26 words

Compounds of general formula la or Ib as claimed in claim 1, 2 or 3 for use in the manufacture of pharmaceuticals with a PAF-antagonistic activity.

Claim 13

Dependent Claim 33 words

Process for producing pharmaceutical compositions, containing compounds of general formula la or Ib as claimed in one of claims 1, 2 or 3, for the treatment of diseases in which PAF is implicated.

Claim 14

Dependent Claim 217 words

As new intermediates, compounds of general formula wherein R' represents hydrogen, phenyl, substituted phenyl or a branched or unbranched C 1 - 4 alkyl group, R 3 represents phenyl, whilst the phenyl ring may be mono- or polysubstituted, preferably in the 2 position, by methyl, preferably halogen, more especially chlorine or bromine, nitro, alkoxy, preferably methoxy and/or trifluoromethyl, or pyridyl; Z represents a branched or unbranched alkyl or alkenyl group having n carbon atoms, whilst Z may optionally also be substituted by aryl or disubstituted by R 2 , and the R 2 substituents may be identical or different; n represents one of the numbers 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; R 2 represents hydroxy, alkylcarbonyloxy, dioxolan, substituted dioxolan or wherein R 8 and Rg, which may be identical or different, represent a straight-chained or branched C 1 - 4 alkyl group, or R 8 and Rg together with the nitrogen atom represent a 5-, 6- or 7-membered ring, optionally mono- or polysubstituted by a branched or unbranched C, - 4 alkyl, and optionally containing nitrogen, oxygen or sulphur as further heteroatoms, each additional nitrogen atom being substituted by a C 1 - 4 alkyl group, preferably methyl; or if R' does not represent hydrogen R 2 may also represent alkoxycarbonyl.

Claim 15

Dependent Claim 217 words

As new intermediates, compounds of general formula wherein R' represents hydrogen, phenyl, substituted phenyl or a branched or unbranched C 1 - 4 alkyl group, R 3 represents phenyl, whilst the phenyl ring may be mono- or polysubstituted, preferably in the 2 position, by methyl, preferably halogen, more especially chlorine or bromine, nitro, alkoxy, preferably methoxy and/or trifluoromethyl, or pyridyl; Z represents a branched or unbranched alkyl or alkenyl group having n carbon atoms, whilst Z may optionally also be substituted by aryl or disubstituted by R 2 , and the R 2 substituents may be identical or different; n represents one of the numbers 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; R 2 represents hydroxy, alkylcarbonyloxy, dioxolan, substituted dioxolan or wherein R 8 and Rg, which may be identical or different, represent a straight-chained or branched C 1 - 4 alkyl group, or R 8 and Rg together with the nitrogen atom represent a 5-, 6- or 7-membered ring, optionally mono- or polysubstituted by a branched or unbranched C, - 4 alkyl, and optionally containing nitrogen, oxygen or sulphur as further heteroatoms, each additional nitrogen atom being substituted by a C 1 - 4 alkyl group, preferably methyl; or if R' does not represent hydrogen R 2 may also represent alkoxycarbonyl.

Thieno-1,4-diazepines

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