What is claimed is:
1. A multi-function unit comprising:
a printer engine;
a logical copying machine carrying out a copying process with respect to a recording medium by said printer engine; and
a plurality of logical printers carrying out printing processes with respect to the recording medium by said printer engine,
said logical copying machine and said logical printers carrying out apparent parallel operations.
2. The multi-function unit as claimed in claim 1, which further comprises:
a multi-bin stacker including a plurality of bin stackers,
each of the bin stackers corresponding to said logical copying machine or one of said logical printers.
3. The multi-function unit as claimed in claim 2, wherein said multi-bin stacker includes a plurality of bin stackers corresponding to said logical copying machine.
4. The multi-function unit as claimed in claim 2, wherein said multi-bin stacker includes a plurality of bin stackers corresponding to at least one of said logical printers.
5. The multi-function unit as claimed in claim 1, wherein each of said logical printers corresponds to one print source.
6. The multi-function unit as claimed in claim 1, wherein said printer engine sets a priority of a printing order in an order of print requests received from said logical copying machine and said logical printers.
7. The multi-function unit as claimed in claim 1, wherein said printer engine sets a priority of a printing order so that a print request received from said logical copying machine has a higher priority than print requests received from said logical printers.
8. The multi-function unit as claimed in claim 1, wherein said printer engine variably sets a priority of a printing order with respect to print requests received from said logical printers.
9. The multi-function unit as claimed in claim 1, which further comprises:
a scanner engine; and
a logical scanner reading a document by said scanner engine.
10. The multi-function unit as claimed in claim 9, wherein said scanner engine and said logical scanner form a single unit.
11. The multi-function unit as claimed in claim 9, wherein said printer engine, said logical copying machine, said logical printers, said scanner engine and said logical scanner form a single unit.
12. The multi-function unit as claimed in claim 1, wherein said printer engine, said logical copying machine and said logical printers form a single unit.
13. The multi-function unit as claimed in claim 9, which further comprises:
an operation panel coupled to said logical copying machine and said logical scanner; and
an equipment state managing part, coupled to said logical copying machine, said logical scanner and said logical printers, gathering information from said logical copying machine, said logical scanner and said logical printers and managing information related to states of the multi-function unit.
14. The multi-function unit as claimed in claim 13, wherein:
said operation panel, said logical scanner, said equipment state managing part and said logical printers respectively exchange information with a server according to a panel control protocol, a scanner protocol, an operation management protocol and a print protocol, and
said server is linked to a computer which is coupled to a network and carries out a printing, document registration, facsimile communication and operation management via the network.
15. The multi-function unit as claimed in claim 14, wherein said operation panel, said logical scanner, said equipment state managing part and said logical printers are coupled to said server via a private local area network (LAN).
16. A server connectable via a network to an equipment which has at least a print function, comprising:
a print processor having a spool part in which print data are queued, and transferring the print data queued in the spool part to the equipment according to a print protocol; and
a routing information processor having a routing list which stores at least an address of the equipment or another server coupled to the network,
a transmitting destination of the print data being specified by accessing the routing list.
17. The server as claimed in claim 16, which further comprises:
a result notification processor notifying a specified notifying destination of a process result in response to a print process carried out by said print processor.
18. The server as claimed in claim 17, wherein said result notification processor notifies the specified notifying source of the process result using a mail function.
19. The server as claimed in claim 16, wherein said routing information processor automatically generates the routing list by accessing a directory service provided in the network.
20. A server connectable via a network to an equipment which has at least a scanner function, comprising:
a filing processor having a folder which stores image data read from a document by the equipment, and carrying out a document registration process by controlling input and output of the image data with respect to the folder; and
a routing information processor having a routing list which stores at least an address of the equipment or another server coupled to the network,
a transmitting destination of the print data being specified by accessing the routing list.
21. The server as claimed in claim 20, which further comprises:
a result notification processor notifying a notifying destination which is specified or set in advance of a process result in response to a document registration process carried out by said filing processor.
22. The server as claimed in claim 21, wherein said result notification processor notifies the notifying source of the process result using a mail function.
23. The server as claimed in claim 20, wherein said routing information processor automatically generates the routing list by accessing a directory service provided in the network.
24. A server connectable via a network to an equipment which has at least a scanner function, comprising:
a facsimile processor having a reception register and a transmission register which store image data, and controlling facsimile transmission and reception of the image data; and
a routing information processor having a routing list which stores at least an address of the equipment or another server coupled to the network,
said facsimile processor automatically retrieving and selecting a route having a minimum transmission cost by accessing the routing list.
25. The server as claimed in claim 24, which further comprises:
a result notification processor notifying a notifying destination which is specified or set in advance of a process result in response to a facsimile transmission and reception process carried out by said facsimile processor.
26. The server as claimed in claim 25, wherein said result notification processor notifies the notifying source of the process result using a mail function.
27. The server as claimed in claim 24, wherein said routing information processor automatically generates the routing list by accessing a directory service provided in the network.
28. A server connectable via a network to an equipment which has at least a scanner function and an operation panel, comprising:
a facsimile processor having a reception register and a transmission register which store image data, and controlling facsimile transmission and reception of the image data; and
a telephone directory processor having a telephone number list which stores telephone numbers, and controlling input and output of a telephone number used for a facsimile process,
said telephone directory processor generating a telephone directory to be displayed on the operation panel based on the telephone number list.
29. The server as claimed in claim 28, which further comprises:
a panel controller receiving the telephone directory from said telephone directory processor and displaying the telephone directory on the operation panel in response to an operation from the operation panel, so as to urge input andor selection of a destination of a facsimile transmission.
30. The server as claimed in claim 28, which further comprises:
a result notification processor notifying a notifying destination which is specified or set in advance of a process result in response to a facsimile transmission and reception process carried out by said facsimile processor.
31. The server as claimed in claim 30, wherein said result notification processor notifies the notifying source of the process result using a mail function.
32. The server as claimed in claim 30, which further comprises:
a panel controller receiving the telephone directory from said telephone directory processor and displaying the telephone directory on the operation panel in response to an operation from the operation panel, so as to urge input andor selection of a destination of a facsimile transmission.
33. The server as claimed in claim 29, wherein said panel controller transfers data of the telephone directory to the operation panel in data units displayable at one time on the operation panel.
34. The server as claimed in claim 28, wherein said telephone directory processor sorts contents of the telephone directory in a sort order which is set in advance or is specified from the operation panel.
35. The server as claimed in claim 16, which further comprises:
a panel controller exchanging information between the operation panel,
said panel controller customizing display contents on the operation panel and operations carried out by an operation made on the operation panel, in response to an operation made on the operation panel.
36. The server as claimed in claim 16, which further comprises:
a panel controller exchanging information between the operation panel,
said panel controller editing arrangements of buttons and input items and display contents on the operation panel, in response to an operation made on the operation panel, so as to define a series of operations corresponding to a selection of each button and each input item.
37. The server as claimed in claim 36, wherein said panel controller selects an item such as facsimile and document registration and specifies a processing script when defining the series of operations in response to the operation made on the operation panel.
38. The server as claimed in claim 20, which further comprises:
an optical character reader (OCR) processor automatically extracting a title from image data read from a document by the equipment or received by a facsimile transmission and setting the title as a title of the document which is formed by the image data when storing the image data in the folder.
39. The server as claimed in claim 20, which further comprises:
an optical character reader (OCR) processor automatically recognizing a character in image data read from a document by the equipment or received by a facsimile transmission when storing the image data in the folder,
said filing processor distributing the image data to a pre-defined folder part of the folder based on a recognition result of said OCR processor.
40. The server as claimed in claim 20, which further comprises:
an optical character reader (OCR) processor automatically recognizing a character in image data read from a document by the equipment or received by a facsimile transmission when storing the image data in the folder,
said filing processor carrying out a process which is specified in advance based on a recognition result of said OCR processor.
41. The server as claimed in claim 16, which further comprises:
a panel controller exchanging information between the operation panel,
said panel controller carrying out an accounting management with respect to each operation for each identification (ID) based on an ID input from the operation panel.
42. The server as claimed in claim 16, which further comprises:
an operation management processor storing state information which includes an operation state of the equipment and states of supplies at predetermined time intervals, and returning the stored state information in response to an access to the stored state information at a frequency higher than the predetermined time intervals.
43. The server as claimed in claim 20, which further comprises:
a panel controller exchanging information between the operation panel,
said panel controller customizing display contents on the operation panel and operations carried out by an operation made on the operation panel, in response to an operation made on the operation panel.
44. The server as claimed in claim 20, which further comprises:
a panel controller exchanging information between the operation panel,
said panel controller editing arrangements of buttons and input items and display contents on the operation panel, in response to an operation made on the operation panel, so as to define a series of operations corresponding to a selection of each button and each input item.
45. The server as claimed in claim 44, wherein said panel controller selects an item such as facsimile and document registration and specifies a processing script when defining the series of operations in response to the operation made on the operation panel.
46. The server as claimed in claim 20, which further comprises:
a panel controller exchanging information between the operation panel,
said panel controller carrying out an accounting management with respect to each operation for each identification (ID) based on an ID input from the operation panel.
47. The server as claimed in claim 20, which further comprises:
an operation management processor storing state information which includes an operation state of the equipment and states of supplies at predetermined time intervals, and returning the stored state information in response to an access to the stored state information at a frequency higher than the predetermined time intervals.
48. The server as claimed in claim 24, which further comprises:
a panel controller exchanging information between the operation panel,
said panel controller customizing display contents on the operation panel and operations carried out by an operation made on the operation panel, in response to an operation made on the operation panel.
49. The server as claimed in claim 24, which further comprises:
a panel controller exchanging information between the operation panel,
said panel controller editing arrangements of buttons and input items and display contents on the operation panel, in response to an operation made on the operation panel, so as to define a series of operations corresponding to a selection of each button and each input item.
50. The server as claimed in claim 49, wherein said panel controller selects an item such as facsimile and document registration and specifies a processing script when defining the series of operations in response to the operation made on the operation panel.
51. The server as claimed in claim 24, which further comprises:
a panel controller exchanging information between the operation panel,
said panel controller carrying out an accounting management with respect to each operation for each identification (ID) based on an ID input from the operation panel.
52. The server as claimed in claim 24, which further comprises:
an operation management processor storing state information which includes an operation state of the equipment and states of supplies at predetermined time intervals, and returning the stored state information in response to an access to the stored state information at a frequency higher than the predetermined time intervals.
53. The server as claimed in claim 28, which further comprises:
a panel controller exchanging information between the operation panel,
said panel controller customizing display contents on the operation panel and operations carried out by an operation made on the operation panel, in response to an operation made on the operation panel.
54. The server as claimed in claim 28, which further comprises:
a panel controller exchanging information between the operation panel,
said panel controller editing arrangements of buttons an d input items and display contents on the operation panel, in response to an operation made on the operation panel, so as to define a series of operations corresponding to a selection of each button and each input item.
55. The server as claimed in claim 54, wherein said panel controller selects an item such as facsimile and document registration and specifies a processing script when defining the series of operations in response to the operation made on the operation panel.
56. The server as claimed in claim 28, which further comprises:
a panel controller exchanging information between the operation panel,
said panel controller carrying out an accounting management with respect to each operation for each identification (ID) based on an ID input from the operation panel.
57. The server as claimed in claim 28, which further comprises:
an operation management processor storing state information which includes an operation state of the equipment and states of supplies at predetermined time intervals, and returning the stored state information in response to an access to the stored state information at a frequency higher than the predetermined time intervals.
58. A network system comprising:
at least one computer;
at least one multi-function unit comprising:
a printer engine;
a logical copying machine carrying out a copying process with respect to a recording medium by said printer engine; and
a plurality of logical printers carrying out printing processes with respect to the recording medium by said printer engine,
said logical copying machine and said logical printers carrying out apparent parallel operations; and
one or a plurality of networks coupling said computer and said multi-function unit.
59. The network system as claimed in claim 58, which further comprises:
a server coupled to said multi-function unit according to a protocol and controlling said multi-function unit,
said server linking to said computer which is coupled to said one or plurality of networks and carrying out at least one of a printing, document registration, facsimile communication and operation management via said one or plurality of networks.
60. The network system as claimed in claim 59, wherein said multi-function unit and said server are coupled via a private local area network (LAN).
61. The network system as claimed in claim 58, wherein said one or plurality of networks include first, second and third networks, at least one multi-function unit and at least one server being coupled to said first network, at least one multi-function unit and at least one server being coupled to said second network, said first network and said second network being coupled via said third network.
62. The network system as claimed in claim 58, wherein said server comprises:
a print processor having a spool part in which print data are queued, and transferring the print data queued in the spool part to said multi-function unit according to a print protocol; and
a routing information processor having a routing list which stores at least an address of said multi-function unit or another server coupled to the network,
a transmitting destination of the print data being specified by accessing the routing list.
63. The network system as claimed in claim 62, wherein said one or plurality of networks include first, second and third networks, at least one multi-function unit and at least one server being coupled to said first network, at least one multi-function unit and at least one server being coupled to said second network, said first network and said second network being coupled via said third network.
64. The network system as claimed in claim 58, wherein said server comprises:
a filing processor having a folder which stores image data read from a document by said multi-function unit, and carrying out a document registration process by controlling input and output of the image data with respect to the folder; and
a routing information processor having a routing list which stores at least an address of said multi-function unit or another server coupled to the network,
a transmitting destination of the print data being specified by accessing the routing list.
65. The network system as claimed in claim 64, wherein said one or plurality of networks include first, second and third networks, at least one multi-function unit and at least one server being coupled to said first network, at least one multi-function unit and at least one server being coupled to said second network, said first network and said second network being coupled via said third network.
66. The network system as claimed in claim 58, wherein said server comprises:
a facsimile processor having a reception register and a transmission register which store image data, and controlling facsimile transmission and reception of the image data; and
a routing information processor having a routing list which stores at least an address of said multi-function unit or another server coupled to the network,
said facsimile processor automatically retrieving and selecting a route having a minimum transmission cost by accessing the routing list.
67. The network system as claimed in claim 66, wherein said one or plurality of networks include first, second and third networks, at least one multi-function unit and at least one server being coupled to said first network, at least one multi-function unit and at least one server being coupled to said second network, said first network and said second network being coupled via said third network.
68. The network system as claimed in claim 58, wherein said server comprises:
a facsimile processor having a reception register and a transmission register which store image data, and controlling facsimile transmission and reception of the image data; and
a telephone directory processor having a telephone number list which stores telephone numbers, and controlling input and output of a telephone number used for a facsimile process,
said telephone directory processor generating a telephone directory to be displayed on an operation panel of said multi-function unit based on the telephone number list.
69. The network system as claimed in claim 68, wherein said one or plurality of networks include first, second and third networks, at least one multi-function unit and at least one server being coupled to said first network, at least one multi-function unit and at least one server being coupled to said second network, said first network and said second network being coupled via said third network.
70. The network system as claimed in claim 58, which further comprises:
a directory provided by the network system,
said server comprising:
a routing information processor having a routing list which stores an address of each multi-function unit and each server coupled within the network system,
said routing informatoin processor automatically generating the routing list by accessing said directory provided by the network system.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. Pharmaceutical formulation comprising at least one compound of the formula I
49
in which
R1 and R2 are each, independently of one another, H, A, OH, OA or Hal,
R1 and R2 together are alternatively alkylene having 3-5 carbon atoms, OCH2CH2, CH2OCH2, OCH2O or OCH2CH2O,
R3 and R4 are each, independently of one another, H or A,
X is R5, R6 or R7, each of which is monosubstituted by R8,
R5 is linear or branched alkylene having 1-10 carbon atoms, in which one or two CH2 groups may be replaced by CHCH groups, O, S or SO,
R6 is cycloalkyl or cycloalkylalkylene having 5-12 carbon atoms,
R7 is phenyl or phenylmethyl,
R8 is COOH, COOA, CONH2, CONHA, CON(A)2 or CN,
A is alkyl having from 1 to 6 carbon atoms, and
Hal is F, Cl, Br or I,
andor physiologically acceptable salts andor solvates thereof and at least one endothelin receptor antagonist.
2. Pharmaceutical formulation according to claim 1, comprising at least one compound of the formula I according to claim 1 in which
X is R5, phenyl or phenylmethyl, each of which is substituted by COOH, COOA, CONH2, CONA2, CONHA or CN;
andor physiologically acceptable salts andor solvates thereof and at least one endothelin receptor antagonist.
3. Pharmaceutical formulation according to claim 1, comprising at least one compound of the formula I according to claim 1 in which
R1 and R2 together are alkylene having 3-5 carbon atoms, OCH2CH2, OCH2O or OCH2CH2O,
X is R5, phenyl or phenylmethyl, each of which is substituted by COOH, COOA, CONH2, CONA2, CONHA or CN;
andor physiologically acceptable salts andor solvates thereof and at least one endothelin receptor antagonist.
4. Pharmaceutical formulation according to claim 1, comprising at least one compound of the formula I according to claim 1 in which
R1 and R2 are each, independently of one another, H, A, OH, OA or Hal,
R1 and R2 together are alternatively alkylene having 3-5 carbon atoms, OCH2CH2, OCH2O or OCH2CH2O,
X is R6, phenyl or phenylmethyl, each of which is substituted by COOH, COOA, CONH2, CONA2, CONHA or CN;
andor physiologically acceptable salts andor solvates thereof and at least one endothelin receptor antagonist.
5. Pharmaceutical formulation according to claim 1, comprising at least one compound of the formula I according to claim i in which
R1 and R2 are each, independently of one another, H, A, OH, OA or Hal,
R1 and R2 together are alternatively alkylene having 3-5 carbon atoms, OCH2CH2, OCH2O or OCH2CH2O,
X is alkylene having 2-5 carbon atoms, cyclohexyl, phenyl or phenylmethyl, each of which is monosubstituted by R1,
R3 is alkyl having 1-6 carbon atoms,
R4 is alkyl having 1-6 carbon atoms,
R8 is COOH or COOA,
A is alkyl having from 1 to 6 carbon atoms,
Hal is F, Cl, Br or l;
andor physiologically acceptable salts andor solvates thereof and at least one endothelin receptor antagonist.
6. Pharmaceutical formulation according to claim 1, comprising at least one compound of the formula I according to claim 1 in which
R1 and R2 are each, independently of one another, H, A, OH, OA or Hal,
R1 and R2 together are alternatively alkylene having 3-5 carbon atoms, OCH2CH2, OCH2O or OCH2CH2O,
R3 is alkyl having 1-6 carbon atoms,
R4 is alkyl having 1-6 carbon atoms,
X is (CH2)2, R8, in which one CH2 group may be replaced by O, or is 4-W-cyclohexyl, 4-R8-phenyl or 4-(R8-methyl)phenyl,
R8 is COOH or COOA;
andor physiologically acceptable salts andor solvates thereof and at least one endothelin receptor antagonist.
7. Pharmaceutical formulation according to claim 1, comprising at least one compound of the formula I according to claim 1 selected from the group consisting of
(a) 5-7-(3-chloro-4-methoxybenzylamino)-1-methyl-3-propyl-1H-pyrazolo4,3dpyrimidin-5-ylpentanoic acid;
(b) 4-7-(3-chloro-4-methoxybenzylamino)-1-methyl-3-propyl-1H-pyrazolo4,3-dpyrimidin-5-y)benzoic acid;
(c) 4-7-(3,4-methylenedioxybenzylamino)-1-methyl-3-propyl-1H-pyrazolo4,3-dpyrimidin-5-ylbutyric acid;
(d) 5-(7-(benzylamino)-1-methyl-3-propyl-1H-pyrazolo4,3-d-pyrimidin-5-ylpentanoic acid;
(e) 7-(3-chloro-4-methoxybenzylamino)-1-methyl-3-propyl-1H-pyrazolo4,3-dpyrimidin-5-ylmethoxyacetic acid;
andor physiologically acceptable salts andor solvates thereof and at least one endothelin receptor antagonist.
8. Pharmaceutical formulation according to claim 1, comprising at least 7-(3-chloro-4-methoxybenzylamino)-1-methyl-3-propyl-1H-pyrazolo-4,3-dpyrimidin-5-ylmethoxyacetic acid andor physiologically acceptable salts andor solvates thereof and at least one endothelin receptor antagonist.
9. Pharmaceutical formulation according to claims 1 to 8, in which the endothelin receptor antagonist is selected from the group consisting of bosentan, tezosentan and sitaxentan.
10. Pharmaceutical formulation according to claims 1 to 8, in which the endothelin receptor antagonist is selected from the group consisting of
a) BMS-193884 (EP 558258),
b) BMS-207940 (Pharmaprojects (13.06.97)),
c) BQ-123 (Exp.Opin.Invest.Drugs, 1997, 6, No.5, 475487),
d) SB-209670 (Exp.Opin.Invest.Drugs, 1997, 6, No.5, 475487),
e) SB-217242 (Exp.Opin.Invest.Drugs, 1997, 6, No.5, 475487),
f) SB-209598 (Trends in Pharmacol. Sci., 17, 177-81,1996),
g) TAK(-044 (Exp.Opin.Invest.Drugs, 1997, 6, No.5, 475A487),
h) Bosentan (Trends in Pharmacol. Sci., 18, 408-12, 1997),
i) PD-156707 (J.Med.Chem., 40, No.7, 1063-74,1997),
j) L-749329 (Bioorg.Med.Chem.Lett., 7, No.3, 275-280,1997),
k) L-754142 (Exp.Opin.Invest.Drugs, 1997, 6, No.5, 475-487),
l) ABT627 (J.Med.Chem., 40, No.20, 3217-27,1997),
m) A-127772 (J.Med.Chem., 39, No.5, 1039-1048, 1996),
n) A-206377 (213th American Chemical Society National Meeting, San Francisco, Calif., USA, 13-17 April 1997, Poster, MEDI 193),
o) A-182086 (J.Med.Chem., 40, No.20, 3217-27, 1997),
p) EMD-93246 (211th American Chemical Society National Meeting, New Orleans, USA, 1996, Poster, MEDI 143),
q) EMD-122801 (Bioorg.Med.Chem.Lett., 8, No.1, 17-22,1998),
r) ZD-1611 (Trends in Pharmacol. Sci., 18, 408-12, 1997),
s) AC-610612 (R&D Focus Drug News (18.05.98)),
t) T-0201 (70th Annual Meeting of the Japanese Pharmacological Society, Chiba, Japan, 22-15 March 1997, Lecture, 0-133),
u) J-104132 (R&D Focus Drug News (15.12.97)),
50
11. Pharmaceutical formulation according to claims 1 to 8, in which the endothelin receptor antagonist is selected from
a) the compounds of the formula (described in EP 0733626
51
in which
-AB-CD- is a CHCHCHCH group in which 1 or 2 CH has (have) been replaced by N,
Ar is Ph or naphthyl, each of which is unsubstituted or monosubstituted, disubstituted or trisubstituted by H, Hal, A, alkenyl having up to 6 carbon atoms, Ph, OPh, NO2, NR4R5, NHCORW, CF3, OCF3, CN, OR4, COOR4, (CH2)nCOOR4, (CH2),NR4R5, NCO or NHCONR4R5,
R1, R2
and R3 are each, independently of one another, absent, H, Hal, A, CF3, NO2, NR4R5, CN, COOR4, NHCOR4,
R4 and R5 are each, independently of one another, H or A, or together are alternatively CH2(CH2), CH2,
A is alkyl having from 1 to 6 carbon atoms,
Ph is phenyl,
X is or S,
Hal is F, Cl, Br or 1,
n is 1, 2 or 3,
and their salts, with the exception of
4-methyl-N-(2,1,3-benzothiadiazol-4-yl)benzenesulfonamide,
4-methyl-N-(2,1,3-benzothiadiazol-5-yl)benzenesulfonamide, 4-nitro-N-(2,1,3-benzothiadiazol-4-yl)benzenesulfonamide, 4-nitro-N-(2, 1,3-benzothiadiazol-5-yl)benzenesulfonamide, 4-amino-N-(2,1,3-benzo-thiadiazol-4-yl)benzenesulfonamide and 4-amino-N-(2,1,3-benzothiadiazol-5-yl)benzenesulfonamide;
b) the compounds of the formula I described in EP 0733626
52
in which
X is a saturated, partially unsaturated or completely unsaturated 3- to 4-membered alkylene chain, in which from 1 to 3 carbon atoms may be replaced by N andor from 1 to 2 carbon atoms may be replaced by 1-2 O atoms andor 1-2 S atoms, but where at most up to 3 carbon atoms may be replaced and where, in addition, a single, double or triple substitution of the alkylene chain andor of a nitrogen located therein by A, R andor NR4R4 may occur, and where furthermore one CH2 group in the alkylene chain may also be replaced by a CO group,
A is alkyl having 1-6 carbon atoms, in which one or two CH2 groups may be replaced by O or S atoms or by CR4CR4 groups and in addition 1-7H atoms may be replaced by F,
R1 is H or A,
R2 is COOR4, CN, 1H-tetrazol-5-yl or CONHSO2R8,
R3 is Ar,
R4 and R4 are each, independently of one another, H, alkyl having from 1 to 6 carbon atoms or benzyl,
Ar is phenyl or naphthyl, each of which is unsubstituted or monosubstituted, disubstituted or trisubstituted by R5, R6 or R7, or is a
53
which is unsubstituted or monosubstituted or disubstituted in the phenyl part by R1 or R6,
R5, R6
and R7 are each, independently of one another, R4, OR4, Hal, CF3, OCF3, OCHF2, OCH2F, NO2, NR4R4, NHCOR4,
CN,NHSO2R4, COOR4, COR4, CONHSO2R8, O(CH2)nR2, OPh, O(CH2)nOR4 or S(O)mR4,
R8 is phenyl or naphthyl, each of which is unsubstituted or monosubstituted, disubstituted or trisubstituted by A, OR1, NR4R4 or Hal,
E is CH2, or 0,
D is carbonyl or C(R4R4)1,
Hal is F, Cl, Br or I,
m is 0, 1 or 2,
n is 0 or 2,
and their salts;
c) the compounds of the formula I described in EP 0755934
54
in which
Y-Z- is NRWCO, NC(OR7) or NCR8,
R1 is Ar,
R2 is COOR6, CN, 1H-tetrazol-5-yl or CONHSO2Ar,
R3, R4
and R5 are each, independently of one another, R6, OR6, S(O)mR6, Hal, NO2, NR6R6, NHCOR6, NHSO2R6, OCOR6, COOR6 or CN,
R6 and R6 are each, independently of one another, H, alkyl having from 1 to 6 carbon atoms, benzyl or phenyl,
R7 is (CH2)nAr,
R3 is Ar or OAr,
Ar is phenyl which is unsubstituted or monosubstituted, disubstituted or trisubstituted by R9, R10 or W11, or is unsubstituted naphthyl or a
55
which is unsubstituted or monosubstituted or disubstituted in the phenyl part by R9 or R10, or is a
56
which is unsubstituted or monosubstituted or disubstituted in the cyclohexadienyl part by R9 or R10,
R9, R10
and R11 are each, independently of one another, R6, OR6, Hal, CF3, OCF3, OCHF2, OCH2F, NO2, NR6R6, NHCOR6, CN, NHSO2R6, COOR6, COR6, CONHSO2Ar, O(CH2)nR2, O(CH2),OR6 or S(O),R6,
E is CH2, S or O,
D is carbonyl or C(R6R6),
Hal is F, Cl, Br or 1,
X is O or S,
m is 0, 1 or 2,
n is 1 or 2,
and their salts;
d) the compounds of the formula I described in EP 0757039
57
in which
Y-Z- is NR7CO, NC(OR7) or NCR8,
R1 is Ar,
R2 is COOR6, (CH2)nCOOR6, CN, 1H-tetrazol-5-yl or CONHSO2Ar,
R3, R4
and R5 are each, independently of one another, R8, OR6, S(O)mR6, Hal, NO2, NR6R6, NHCOR6, NHSO2R6, OCOR6, COR6, COOR6 or CN, where R3 and R4 together may alternatively be an O(CH2),O group,
R6 and R6 are each, independently of one another, H, alkyl having from 1 to 6 carbon atoms, benzyl or phenyl,
R7 is (CHO2)nAr,
R8 is Ar or OAr,
Ar is phenyl which is unsubstituted or monosubstituted, disubstituted or trisubstituted by R9, R10 or R11, or is unsubstituted naphthyl or a
58
which is unsubstituted or monosubstituted or disubstituted in the phenyl part by R9 or R10, or is
59
which is unsubstituted or monosubstituted or disubstituted in the cyclohexadienyl part by R9 or R10,
R9, R10
and R11 are each, independently of one another, R6, ORW, Hal, CF3, OCF3, OCHF2, OCH2F, NO2, NR6R6, NHCOR8, CN, NHSO2R6, COOR6, COR6, CONHSO2Ar, O(CH2)nR2, O(CH2),OR6 or S(O)mR6,
E is CH2,S or O,
D is carbonyl or C(R6R6)n,
X is O or S,
Hal is F, Cl, Br or 1,
m is 0, 1 or 2,
n is 1 or 2,
and their salts;
e) the compounds of the formula I described in EP 0796250
60
in which
Y is C(R4R4)C(R4R4), CR4CR4 or C(R4R4)S,
R1 is Het, Ar, RW or R4,
R2 is Ar or a
61
which is unsubstituted or monosubstituted or disubstituted in the phenyl part by A, R3, OR4, NH2, NHA, NA2, NO2, CN, Hal, NHCOR4, NHSO2R4, COOR4, COR4, CONHSO2RW, O(CH)nR3, OPh, O(CH2),OR4 or S(O)mR4, or a
62
which is unsubstituted or monosubstituted or disubstituted in the cyclohexadienyl part by A, R3, OR4, NH2, NHA, NA2, NO2, CN, Hal, NHCOR4, NHSO2R4, COOR4, COR4, CONHSO2RG, O(CH2),R3, OPh, O(CH2),OR4 or S(O)mR4,
R3 is CN, COOH, COOA, CONHSO2R5 or I H-tetrazol-5-yl,
R4 and R4 are each, independently of one another, H, A, or phenyl or benzyl, each of which is unsubstituted or monosubstituted by alkoxy,
R5 is A or Ar,
R6 is phenyl or naphthyl, each of which is unsubstituted or monosubstituted, disubstituted or trisubstituted by A, OR5, NH2, NHA, NA2, NO2, CN or Hal,
A is, alkyl having 1-6 carbon atoms, in which one or two CH2 groups may be replaced by O or S atoms or by CR4CR4-groups and in addition 1-7H atoms may be replaced by F, or benzyl,
Ar is phenyl or naphthyl, each of which is unsubstituted or monosubstituted, disubstituted or trisubstituted by A, OR4, NH2, NHA, NA2, NO2, CN, Hal, NHCOR4, NHSO2R4, COOR4, COR4, CONHSO2R6, O(CH2),R3,
OPh, O(CHD2)nOR4 or S(O)mR4,
Het is a monocyclic or bicyclic, saturated, unsaturated or aromatic heterocyclic radical having from 1 to 4 N, O andor S atoms, bonded via N or C, which may be unsubstituted or monosubstituted, disubstituted or trisubstituted by Hal, A, R3, NH2, NHA, NA2, CN, NO2 andor carbonyl oxygen,
D is carbonyl or C(R4R4)n,
E is CH2, S or O,
Hal is F. Cl, Br or I,
X is O or S,
m is 0, 1 or 2,
n is 1 or 2,
and their salts;
f) the compounds of the formula I described in WO 9719077
63
in which
R is
64
X is O or S,
R1 is H, Hal, OH, OA, A, alkylene-O-A, NO2, NH2, NH-acyl, SO2NH2, SO3-A, SO2NHA, CN or formyl,
R2 is H or A,
R9, R5, R6
R7 and R8 are each, independently of one another, H, Hal, OH, OA, O-alkylene-R4, A, S-A, NO2, NH2, NHA, NA2, NH-acyl, NHSO2A, NHSO2R4, NASO2A, NASO2R4, NH(CO)NH2, NH(CO)NHA, formyl, NH(CO)NH-phenyl, NHCOOA, NA-acyl, NHR4, NHCOOR4, NHCOO-benzyl, NHSO2-benzyl, NHCOO-alkylene-OA, NH(CO)NA2, N-piperidinyl-CONH, N-pyrrolidinyl-CONH, O(CH2)nCOOR2, O(CH2)nOR2, CH2OH or CH2OA,
R3 and R4 together are alternatively OCH2O, OCH2CH2O, OCH2CH2, OCF2O or OCF2CF2O,
R4 is phenyl which is unsubstituted or monosubstituted or polysubstituted by R3 andor R6,
A is alkyl having 1-6 carbon atoms,
Hal is fluorine, chlorine, bromine or iodine,
n is 1 or 2, and their salts;
g) the compounds of the formula I described in WO 9730982
65
in which
R is
66
X is O or S,
R1 is H, Hal, OH, OA, A, alkylene-O-A, NO2, NH2, NH-acyl, SO2NH2, SO3-A, SO2NHA, CN or formyl,
R2, R3
and R4 are each, independently of one another, a phenyl group which is unsubstituted or monosubstituted or polysubstituted by Hal, OH, OA, O-alkylene-Rr, A, S-A, SOA, SO2A, SOR5, SO2R5, NO2, NH2, NHA, NA21 NH-acyl, NHSO2A, NHSO2R5, NAS02A, NASO2R8, NH(CO)NH2, NH(CO)NHA, formyl, NH(CO)NHR6, NHCOOA, NA-acyl, NHCOOCH2R5, NHSO2CH2R5, NHCOO-alkylene-OA, NH(CO)NA2, 1-piperidinyl-CONH, 1-pyrrolidinyl-CONH, O(CH2),COOA, O(CH2)nCOOH, O(CH2)nOH, O(CH2),OA, CH2OH, CH2OA, COOH, COOA, CH2COOH or CH2COOA,
or is a
67
group or a
68
group, where
R2 is additionally A or cycloalkyl,
R5 is a phenyl group which is unsubstituted or monosubstituted or polysubstituted by Hal, OH, OA, A, S-A, NO2, NH2, NHA, NA2, NH-acyl, NHSO2A, NASO2A, NH(CO)NH2, NH(CO)NHA, formyl, NHCOOA, NA-acyl, NHCOO-alkylene-OA, NH(CO)NA2, N-piperidinyl-CONH, N-pyrrolidinyl-CONH, O(CHJNCOOA, O(CH2)nCOOH, O(CH2)nOH, O(CH2)nOA, CH2OH, CH2OA, COOH, COOA, CH2COOH or CH2COOA,
A is alkyl having 1-6 carbon atoms, in which one or two CH2 groups may be replaced by O or S atoms or by CR6CR6-groups andor 1-7H atoms may be replaced by F,
D is carbonyl or C(R6R6)m,
E is CH2, S or O,
Y is O or S,
R1 and R6 are each, independently of one another, H, F or A,
Hal is fluorine, chlorine, bromine or iodine,
n is 1 or 2, and
m is 1 or 2,
or a tautomeric cyclised form, and the (E)-isomers and the salts of all isomers;
h) the compounds of the formula I described in WO 9730996
69
in which
-AB-CD- is a CHCHCHCH group, in which, in addition, 1 or 2 CH may be replaced by N,
Het is a monocyclic or bicyclic, saturated, unsaturated or aromatic heterocyclic radical having from 1 to 4 N, O andor S atoms which is unsubstituted or substituted by -Z-R6,
R1,R2
and R3 are each, independently of one another, absent, H, Hal, A, CF3, NO2, NR4R5, CN, COOR4 or NHCOR4,
R4 and R5 are each, independently of one another, H or A, or together are alternatively CH2(CH2)nCH2,
R6 is a phenyl radical, benzothiadiazol-5-yl or benzoxadiazol-5-yl radical, each of which is unsubstituted or monosubstituted, disubstituted or trisubstituted by R7, R8 andor R9,
R1, R8
and R9 are each, independently of one another, A, O-A, CN, COOH, COOA, Hal, formyl, CO-A, and R7 and R8 are alternatively O(CH2)mO,
A is alkyl having from 1 to 6 carbon atoms,
X is O or S,
z is CO, CONH, CO(CH2)n, CHCH, (CH2)n, CONHCO, NHCONH, NHCOO, OCONH, COO or OCO,
Hal is F, Cl, Br or I,
m is 1 or 2, and
n is 1, 2 or 3,
and their salts; i) the compounds of the formula I described in DE 19609597
70
in which
Ar is naphthyl which is monosubstituted by NH2, NHA or NA2, and
A is alkyl having from 1 to 6 carbon atoms,
and their physiologically acceptable salts;
j) the compounds of the formula I described in DE 19612101
71
in which
Y-Z- is NR4CO or NCR5,
R1 is Ar,
R2 is H, alkyl having 1-6 carbon atoms which is unsubstituted or monosubstituted, disubstituted or trisubstituted by OR3 or Hal, or (CH2)mPh or (CH2)m-cycloalkyl, each of which is unsubstituted or monosubstituted, disubstituted or trisubstituted by RW, ORW or Hal,
R3 and R3 are each, independently of one another, H, alkyl having 1-6 carbon atoms or benzyl,
R4 is CH2Ar,
R5 is OCH2Ar,
Ar is phenyl which is unsubstituted or monosubstituted, disubstituted or trisubstituted by R6, R7 or R8, or a
72
which is unsubstituted or monosubstituted in the phenyl part by R6, or a
73
which is unsubstituted or monosubstituted in the cyclohexadienyl part by R8,
E is CH2 or 0,
D is carbonyl or (CH2)n,
E and D together are alternatively CHCR9,
R6, R are each, independently of one another, R3, R3 or Hal,
R7 is R3, OR3, Hal, NO2, NH2, NHR3, NR3R3, NHCOR3, COOR3, O(CH2)nR3 or O(CH2),OR3,
R8 is Ph which is unsubstituted or monosubstituted, disubstituted or trisubstituted by R3, OR3, Hal, NO2, NH2, NHR6, NR6R6, NHCOR3 or COOR3,
R9 is H, OH, CH2OH or COOR3,
Hal is F, Cl, Br or 1,
Ph is phenyl,
m is 0 or 1,
n is 1 or 2,
and their salts;
k) the compounds of the formula I described in WO 9827091
74
in which
R is phenyl which is unsubstituted or monosubstituted, disubstituted or trisubstituted by R3, R4 or R6, or 2,1,3-benzothiadiazolyl which is unsubstituted or mono-substituted by R2,
R1 is A, in which 1-7H atoms may be replaced by F,is S-A, O-A, is phenyl or -alkylene-phenyl, each of which is unsubstituted or monosubstituted by R3, or is thienyl which is unsubstituted or monosubstituted by R3,
R2 is A, F, Cl, Br or O-A,
R3, R4
and R5 are each, independently of one another, A, O-A, S-A, O-alkylene-COOH, -alkylene-COOH or COOH,
R3 and R4 together are alternatively OCH2O, and
A is alkyl having 1-7 carbon atoms,
and their salts;
l) the compounds of the formula I described in WO 9827077
75
in which
R is
76
X is O or S,
R1 is H, Hat, OH, OA, A, alkylene-O-A, NO2, NH2, NH-acyl, SO2NH2, SO3-A, SO2NHA, CN or formyl,
R2, R3
and R4 are each, independently of one another, a phenyl group which is unsubstituted or monosubstituted or poly-substituted by R7, where R2 is additionally A or cycloalkyl, or are
77
with the proviso that at least one of the radicals R2, R3 or R4 is an R8 radical which is unsubstituted or monosubstituted or polysubstituted by R7,
R5 is a phenyl group which is unsubstituted or monosubstituted or polysubstituted by Hal, OH, OA, A, S-A, NO2, NH2, NHA, NA2, NH-acyl, NHSO2A, NASO2A, NH(CO)NH2, NH(CO)NHA, formyl, NHCOOA, NA-acyl, NHCOO-alkylene-OA, NH(CO)NA2, N-piperidinyl-CONH, N-pyrrolidinyl-CONH, O(CH2)COOA, O(CHONCOOH, O(CH2),OH, O(CH2)nOA, CH2OH, CH2OA, COOH, COOA, CH2COOH or CH2COOA,
A is alkyl having 1-6 carbon atoms, in which one or two CH2 groups may be replaced by O or S atoms or by CR6CR6-groups andor 1-7H atoms may be replaced by F,
D is carbonyl or C(R6R6)m,
E is sCH2, S or O,
Y is O or S,
R6 and R6 are each, independently of one another, H, F or A,
R7 is Hal, OH, OA, O-alkylene-R5, A, S-A, S-OA, SO2A, SOR5, SO2R5, NO2, NH2, NHA, NA2, NH-acyl, NHSO2A, NHSO2R5, NASO2A, NASO2R5, NH(CO)NH2, NH(CO)NHA, formyl, NH(CO)NHR5, NHCOOA, NA-acyl, NHCOOCH2R5, NHSO2CH2R5, NHCOO-alkylene-OA, NH(CO)NA2, 1-piperidinyl-CONH, 1-pyrrolidinyl-CONH, O(CH2)nCOOA, O(CH2)nCOOH, O(CH2)nOH, O(CH2)nOA, CH2OH, CH2OA, COOH, COOA, CH2COOH or CH2COOA,
R8 is a 5-7-membered heterocyclic radical having 1-4 N, O andor S atoms or is
78
G and Z are each, independently of one another, CH, N, O or S,
L is CH, CHCH or CH2CH2CH2,
Hal is fluorine, chlorine, bromine or iodine,
n is 0, 1 or 2, and
m is 1 or 2,
or a tautomeric cyclised form, and the (E)-isomers and the salts of all isomers;
m) the compounds of the formula I described in WO 9841515
79
in which
X is O or S,
R1 is H, Hal, OH, OA, A, NO2, NH2, NHA, NAA, NHCOR4, NHCOR6, NHSO2R4, NHSO2R6, S(O)mR6, SO3H, SO2NR4R4 or formyl,
R2 and R2 are each, independently of one another, A, (CH2)nAr, (CHO2)nHet, CH2COAr, CH2COHet or OAr,
R2 is additionally also H,
R3 is COOR4, CN, 1H-tetrazol-5-yl or CONHSO2R5,
R4 and R4 are each, independently of one another, H or A,
R5 is A or Ar,
R6 is phenyl or naphthyl, each of which is unsubstituted or monosubstituted, disubstituted or trisubstituted by A, NH2, NHA, NAA, NO2, CN or Hal,
R7 and R7 are each, independently of one another, H or alkyl having 1-6 carbon atoms,
A and A are each, independently of one another, alkyl having 1-6 carbon atoms, in which one or two CH2 groups may be replaced by O or S atoms or by CR7CR7-groups andor 1-7H atoms may be replaced by F, or benzyl,
Ar is phenyl or naphthyl, each of which is unsubstituted or monosubstituted, disubstituted or trisubstituted by A, OR4, NH2, NHA, NAA, NO2, CN, Hal, NHCOR4, NHCOR6, NHSO2R4, NHSO2R4, COOR4, OPh, CONH2, CONHA, CONAA, COR4, CONHSO2R4, CONHSO2R6, O(CH2)nCOOR4, O(CH2)OR4, SO3H, SO2NR4R4, S(O)mR6 or S(O)mR4,
Het is a monocyclic or bicyclic, saturated, unsaturated or aromatic heterocyclic radical having 1-4 N, O andor S atoms, bonded via N or C, which may be unsubstituted or monosubstituted, disubstituted or trisubstituted by Hal, A, R3, NH2, NHA, NAA, NO2 andor O,
Hal is fluorine, chlorine, bromine or iodine,
m is 0, 1 or 2, and
n is 1 or 2,
where, if R2 is CH2COAr and R1 is H, R3 is not COOA, and salts thereof;
n) the compounds of the formula I described in WO 9841521
80
in which
Z is a single or double bond,
R1 is a
81
which is unsubstituted or monosubstituted in the phenyl part by R7, or is a
82
which is unsubstituted or monosubstituted in the cyclohexadienyl part by R7,
R2 is A, Ar-(CH2)m, cycloalkyl-(CH2)m, Het-(CH2)m or R1-(CH2)m,
R3 and R3 are each, independently of one another, OR4, NHSO2R5, NH2, NHA or NAA,
R3 and R3 together are alternatively O, forming a cyclic anhydride,
R4 and R4 are each, independently of one another, H or A,
R5 is A or Ar,
R6 is phenyl or naphthyl, each of which is unsubstituted or monosubstituted, disubstituted or trisubstituted by A, NH2, NHA, NAA, NO2, CN or Hal,
R7 is A, COOR4, CN, 1H-tetrazol-5-yl, CON HSO2R5, Hal, OR4, NO2, NH2, NHA, NAA, NHCOR4, NHCOR6, NHSO2R4, NHSO2R6, S(O)kR4, S(O)kR4, SO2NR4R4 or formyl,
R8 and R5 are each, independently of one another, H or alkyl having 1-6 carbon atoms,
E is CH2 or O,
D is carbonyl or (CR4R4)n,
E and D together are alternatively CR4R4,
X is S or O,
A and A are each, independently of one another, alkyl having 1-6 carbon atoms, in which one or two CH2 groups may be replaced by O or S atoms or by CR8CR8 groups andor 1-7H atoms may be replaced by F, or benzyl,
Ar is phenyl or naphthyl, each of which is unsubstituted or monosubstituted, disubstituted or trisubstituted by A, OR4, NH2, NHA, NAA, NO2, CN, Hal, NHCOR4, NHCOR6, NHSO2R4, NHSO2R6, COOR4, OPh, CONH2, CONHA, CONAA, COR4, CONHSO2R4, CONHSO2R6, O(CH2),COOR4, O(CH2)nOR4, SO2NR4R4, S(O)kR6 or S(O)kR4,
Het is a monocyclic or bicyclic, saturated, unsaturated or aromatic heterocyclic radical having 1-4 N, O andor S atoms, bonded via N or C, which may be unsubstituted, monosubstituted or disubstituted or trisubstituted by Hal, A, COOR4, CN, 1H-tetrazol-5-yl, CONHSO2R5, NH2, NHA, NAA, NO2 andor O,
Hal is fluorine, chlorine, bromine or iodine,
k is 0, 1 or 2,
m is 0, 1 or 2, and
n is 1 or 2,
and the (Z)- and (E)-isomers and the salts of all isomers;
o) the compounds of the formula I described in WO 9842702
83
in which
R
84
X and Y are each, independently of one another, O or S,
R1 is H, Hal, OH, OA, A, alkylene-O-A, NO2, NH2, NH-acyl, SO2NH21 SO2A, SO2N HA, ON or formyl,
R2, R3
and R4 are each, independently of one another, a phenyl group which is unsubstituted or monosubstituted or polysubstituted by Hal, OH, OA, O-alkylene-R1, A, S-A, S-OA, SO2A, SOR5, SO2R5, NO2, NH2, NHA, NA2, NH-acyl, NHSO2A, NHSO2R5, NASO2A, NASO2R5, NH(CO)NH2, NH(CO)NHA, formyl, NH(CO)NHR5, NHCOOA, NA-acyl, NHCOOCH2R5, NHSO2CH2R5, NHCOO-alkylene-OA, NH(CO)NA2, 1-piperidinyl-CONH, 1-pyrrolidinyl-CONH, O(CH2),COOA, O(CH2),COOH, O(CH2),OH, O(CH2),OA, CH2OH, CH2OA, COOH, COOA, CH2COOH or CH2COOA,
85
R2 is additionally A or cycloalkyl,
R5 is a phenyl group which is unsubstituted or monosubstituted or polysubstituted by Hal, OH, OA, A, S-A, NO2, NH2, NHA, NA2, NH-acyl, NHSO2A, NASO2A, NH(CO)NH2, NH(CO)NHA, formyl, NHCOOA, NA-acyl, NHCOO-alkylene-OA, NH(CO)NA2, N-piperidinyl-CONH, N-pyrrolidinyl-CONH, O(CH2),COOA, O(CH2),COOH, O(CH2)nOH, O(CH2),OA, CH2OH, CH2OA, COOH, COOA, CH2COOH or CH2COOA,
A is alkyl having 1-6 carbon atoms, in which one or two CH, groups may be replaced by O or S atoms or by CR6CR6-groups andor 1-7H atoms may be replaced by F,
D is carbonyl or C(R6R6)m,
E is CH2, S or O,
R6 and R6 are each, independently of one another, H, F or A,
R7 is OC(Y)-NHR8,
R8 is alkyl having 1-10 carbon atoms which is unsubstituted or monosubstituted or disubstituted by R8 and in which 1-2 carbon atoms may be replaced by O andor S, andor may be substituted by O, or cycloalkyl, in which 1-2 carbon atoms may be replaced by N, O andor S,
R9 is phenyl which is unsubstituted or monosubstituted or disubstituted by Hal, or is naphthyl, A-OC(O) or Hal,
Hal is fluorine, chlorine, bromine or iodine,
n is 0, 1 or 2, and
m is 1 or 2,
and salts thereof;
p) the compounds of the formula I described in WO 9842709
86
in which
X is NR3, O or S,
R is 2,1,3-benzothiadiazol-4- or 5-yl or 2,1-benzoiso-thiazol-5- or 6-yl, each of which is unsubstituted or monosubstituted or disubstituted by R2 andor R2, or phenyl which is unsubstituted or monosubstituted, disubstituted or trisubstituted by R2 andor R2,
R1 is H or A,
R2 and R2 are each, independently of one another, H, A, OH, OA, Hal, OCF3, OCHF2, OCO-A, O-alkylene-COOR1, O-alkylene-CH2OR1, or OCH2-phenyl or OCO-phenyl, each of which is unsubstituted or monosubstituted or disubstituted in the phenyl part by R4 andor R4,
R2 and R2 together are alternatively OCH2O, OCH2CH2O or OCH2CH2,
R3 is H, A, alkylene-O-A, CO-OA, or alkylene-phenyl which is unsubstituted or mono-substituted or disubstituted in the phenyl part by R4 andor R4,
R4 and R4 are each, independently of one another, H, A, OH, OA, Hal, COOR1 or CH2OR1,
A is alkyl having 1-6 carbon atoms,
Hal is fluorine, chlorine, bromine or iodine,
and their salts;
q) the compounds of the formula I described in WO 9905132
87
in which
R
88
X is O or S,
R1 is H, Hal, OA or A,
R2, R3, R5,
and R6 are each, independently of one another, H, Hal, A, OA or R4,
R4 is O(CH2)n-Cy,
Cy is cycloalkyl having 3-8 carbon atoms;
A is alkyl having 1-6 carbon atoms, in which one or two CH2 groups may be replaced by O or S atoms or by CR5CR5 groups andor 1-7H atoms may be replaced by F,
R5 and R5 are each, independently of one another, H, F or A,
Hal is fluorine, chlorine, bromine or iodine,
n is 0, 1 or 2,
or a tautomeric cyclised form, and the (E)-isomers and the salts of all isomers.
12. Pharmaceutical formulation according to one of the preceding claims, comprising one or more excipients andor assistants.
13. Use of a pharmaceutical preparation according to one of claims 1 to 12 for the preparation of a medicament for the treatment of angina, high blood pressure, high pulmonary pressure, congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), cor pulmonale, dextrocardiac insufficiency, atherosclerosis, conditions of reduced patency of the heart vessels, peripheral vascular diseases, strokes, bronchitis, allergic asthma, chronic asthma, allergic rhinitis, glaucoma, irritable bowel syndrome, tumours, renal insufficiency, liver cirrhosis, erectile dysfunction and for the treatment of female sexual disorders.
14. Use according to claim 13 for the preparation of a medicament for the treatment of high pulmonary pressure, congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), cor pulmonale andor dextrocardiac insufficiency.
15. Set (kit) consisting of separate packs of (a) an effective amount
of 7-(3-chloro-4-methoxybenzylamino)-1-methyl-3-propyl-1H-pyrazolo4,3-dpyrimidin-5-ylmethoxyacetic acid andor physiologically acceptable salts andor solvates thereof and
(b) an effective amount of an endothelin receptor antagonist.
16. Pharmaceutical formulation comprising at least one compound of the formula I-I
89
in which
R1 and R2 are each, independently of one another, H, A, OA, OH or Hal,
R1 and R2 together are alternatively alkylene having 3-5 carbon atoms, OCH2CH2, CH2OCH2, OCH2O or OCH2CH2O,
X is R4, R5 or R5, each of which is monosubstituted by R7,
R4 is linear or branched alkylene having 1-10 carbon atoms, in which one or two CH2 groups may be replaced by CHCH groups,
R5 is cycloalkyl or cycloalkylalkylene having 5-12 carbon atoms,
R6 is phenyl or phenylmethyl,
R7 is COOH, COOA, CONH2, CONHA, CON(A)2 or CN,
A is alkyl having from 1 to 6 carbon atoms, and
Hal is F, Cl, Br or 1,
andor physiologically acceptable salts andor solvates thereof and at least one endothelin receptor antagonist.
17. Pharmaceutical formulation according to claim 16, comprising at least one compound of the formula I-II according to claim 16 in which X is R4, phenyl or phenylmethyl, each of which is substituted by COOH, COOA, CONH2, CONA2, CONHA or CN.
18. Pharmaceutical formulation according to claim 16, comprising at (east one compound of the formula I-II according to claim 16 in which R1 and R2 together are alkylene having 3-5 carbon atoms,
OCH2CH2, OCH2O or OCH2CH2O,
X is R4, phenyl or phenylmethyl, each of which is substituted by COOH, COOA, CONH2, CONA2, CONHA or CN.
19. Pharmaceutical formulation according to claim 16, comprising at (east one compound of the formula I-II according to claim 16 in which
R1 and R2 are each, independently of one another, H, A, OA or Hal,
R1 and R2 together are alkylene having 3-5 carbon atoms, OCH2CH2, OCH2O or OCH27CH2O,
X is R4, phenyl or phenylmethyl, each of which is substituted by COOH, COOA, CONH2, CONA2, CONHA or CN.
20. Pharmaceutical formulation according to claim 16, comprising at least one compound of the formula I-II according to claim 16 in which
R1 and R2 are each, independently of one another, H, A, OA or Hal,
R1 and R2 together are alternatively alkylene having 3-5 carbon atoms, OCH2CH2, OCH2O or OCH2CH2O,
X is alkylene having 2-5 carbon atoms, cyclohexyl, phenyl or phenylmethyl, each of which is monosubstituted by R7
R7 is COOH or COOA,
A is alkyl having from 1 to 6 carbon atoms,
Hal is F, Cl, Br or I.
21. Pharmaceutical formulation according to claim 16, comprising at least one compound of the formula I-II according to claim 16 in which
R1 and R2 are each, independently of one another, H, A, OA or Hal,
R1 and R2 together are alternatively alkylene having 3-5 carbon atoms, OCH2CH2, OCH2O or OCH2CH2O,
X is alkylene having 2-5 carbon atoms, cyclohexyl, phenyl or phenylmethyl, each of which is monosubstituted by R7,
R7 is COOH or COOA,
A is alkyl having from 1 to 6 carbon atoms,
Hal is F. Cl, Br or I.
22. Pharmaceutical formulation according to claim 16, comprising at least one compound of the formula I-II according to claim 16, selected from the group consisting of
(a) 34-(3-chloro-4-methoxybenzylamino)benzo4,5thieno2,3-d-pyrimidin-2-ylpropionic acid;
(b) 4-4-(3,4-methylenedioxybenzylamino)benzo4,5thienol-2,3-d)-pyrimidin-2-ylbutyric acid;
(c) 7-4-(3,4-methylenedioxybenzylamino)benzo4,5thieno2,3-d-pyrimidin-2-ylheptanoic acid;
(d) 7-4-(3-chloro-4-methoxybenzylamino)benzo4,5thieno2,3-d-pyrimidin-2-ylheptanoic acid;
(e) 5-4-(3-chloro-4-methoxybenzylamino)benzo4,5thieno2,3-dpyrimidin-2-ylvaleric acid;
(f) 2-4-4-(3-chloro-4-methoxybenzylamino)benzo4,5thieno-2,3-dpyrimidin-2-ylcyclohexyl-1-ylacetic acid;
(g) 4-4-(3,4-methylenedioxybenzylamino)benzo4,5thieno2,3-d-pyrimidin-2-ylcyclohexanecarboxylic acid;
(h) 4-4-(3,4-methylenedioxybenzylamino)benzo4,5thieno2,3-d-pyrimidin-2-ylbenzoic acid;
(i) 4-4-(3,4-methylenedioxybenzylamino)benzo4,5thieno2,3-d-pyrimidin-2-ylphenylacetic acid;
(j) 4-4-(3-chloro-4-methoxybenzylamino)benzothieno2,3-d-pyrimidin-2-ylcyclohexanecarboxylic acid.
23. Pharmaceutical formulation according to claim 16, comprising at least 4-4-(3-chloro-4-methyloxybenzylamino)benzothieno2,3-d-pyrimidin-2-ylcyclohexanecarboxylic acid, ethanolamine salt.
24. Pharmaceutical formulation according to claims 16 to 23, in which the endothelin receptor antagonist is selected from the group consisting of bosentan, tezosentan and sitaxentan.
25. Pharmaceutical formulation according to claims 16 to 23, in which the endothelin receptor antagonist is selected from the group consisting of
a) BMS-193884 (EP 558258),
b) BMS-207940 (Pharmaprojects (13.06.97)),
c) BQ-123 (Exp.Opin.Invest.Drugs, 1997, 6, No.5, 475487),
d) SB-209670 (Exp.Opin.Invest.Drugs, 1997, 6, No.5, 475-487),
e) SB-217242 (Exp.Opin.Invest.Drugs, 1997, 6, No.5, 475487),
f) SB-209598 (Trends in Pharmacol. Sci., 17, 177-81,1996),
g) TAK-044 (Exp.Opin.Invest.Drugs, 1997, 6, No.5, 475487),
h) Bosentan (Trends in Pharmacol. Sci., 18, 408-12, 1997),
i) PD-156707 (J.Med.Chem., 40, No.7,1063-74,1997),
j) L-749329 (Bioorg.Med.Chem.Lett., 7, No.3, 275-280,1997),
k) L-754142 (Exp.Opin.Invest.Drugs, 1997, 6, No.5, 475487),
l) ABT-627 (J.Med.Chem., 40, No.20, 3217-27,1997),
m) A-127772 (J.Med.Chem., 39, No.5,1039-1048,1996),
n) A-206377 (213th American Chemical Society National Meeting, San Francisco, Calif., USA, 13-17 April 1997, Poster, MEDI 193),
o) A-182086 (J.Med.Chem., 40, No.20, 3217-27, 1997),
p) EMD-93246 (211 American Chemical Society National Meeting, New Orleans, USA, 1996, Poster, MEDI 143),
q) EMD-122801 (Bioorg.Med.Chem.Lett., 8, No.1, 17-22,1998),
r) ZD-1611 (Trends in Pharmacol. Sci., 18, 408-12, 1997),
s) AC-610612 (R&D Focus Drug News (18.05.98)),
t) T-0201 (70th Annual Meeting of the Japanese Pharmacological Society, Chiba, Japan, 22-15 March 1997, Lecture, 0-133),
u) J-104132 (R&D Focus Drug News (15.12.97)),
90
26. Pharmaceutical formulation according to claims 16 to 23, in which the endothelin receptor antagonist is selected from
a) the compounds of the formula I described in EP 0733626
91
in which
-AB-CD- is a CHCHCHCH group in which 1 or 2 CH has (have) been replaced by N.
Ar is Ph or naphthyl, each of which is unsubstituted or monosubstituted, disubstituted or trisubstituted by H, Hal, A, alkenyl having up to 6 carbon atoms, Ph, OPh, NO2, NR4R5, NHCOR4, CF3, OCF3, CN, OR4, COOR4, (CH2),COORW, (CH2),NR4R5, NCO or NHCONR4R5,
R1, R2
and R3 are each, independently of one another, absent, H, Hal, A, CF3, NO2, NR4R5, CN, COOR4, NHCOR4,
R4 and R5 are each, independently of one another, H or A, or together are alternatively CH2(CH2), CH2,
A is alkyl having from 1 to 6 carbon atoms,
Ph is phenyl,
X is O or S,
Hal is F, Cl, Br or 1,
n is 1, 2 or 3,
and their salts, with the exception of
4-methyl-N-(2,1,3-benzothiadiazol-4-yl)benzenesulfonamide,
4-methyl-N-(2,1,3-benzothiadiazol-5-yl)benzenesulfonamide, 4-nitro-N-(2,1,3-benzothiadiazol-4-yl)benzenesulfonamide, 4-nitro-N-(2, 1,3-benzothiadiazol-5-yl)benzenesulfonamide, 4-amino-N-(2,1,3-benzo-thiadiazol-4-yl)benzenesulfonamide and 4-amino-N-(2,1,3-benzothia-diazol-5-yl)benzenesulfonamide;
b) the compounds of the formula I described in EP 0733626
92
in which
X is a saturated, partially unsaturated or completely unsaturated 3- to 4-membered alkylene chain, in which from 1 to 3 carbon atoms may be replaced by N andor from 1 to 2 carbon atoms may be replaced by 1-20 atoms andor 1-2 S atoms, but where at most up to 3 carbon atoms may be replaced and where, in addition, a single, double or triple substitution of the alkylene chain andor of a nitrogen located therein by A, R1 andor NR4R4 may occur, and where furthermore one CH2 group in the alkylene chain may also be replaced by a CO group,
A is alkyl having 1-6 carbon atoms, in which one or two CH2 groups may be replaced by O or S atoms or by CR4CR4-groups and in addition 1-7H atoms may be replaced by F,
R1 is H or A,
R2 is COOR4, CN, 1H-tetrazol-5-yl or CONHSO2R8,
R3 is Ar,
R4 and R4 are each, independently of one another, H, alkyl having from 1 to 6 carbon atoms or benzyl,
Ar is phenyl or naphthyl, each of which is unsubstituted or monosubstituted, disubstituted or trisubstituted by R5, R6 or R7, or is a
93
which is unsubstituted or monosubstituted or disubstituted in the phenyl part by R5 or R5,
R5, R6
and R7 are each, independently of one another, R4, OR4, Hal, CF3, OCF3, OCHF2, OCH2F, NO2, NR4R4, NHCOR4, CN,NHSO2R4, COOR4, COR4, CONHSO2R4, O(CH2)R2,
OPh, O(CH2),OR4 or S(O)mR4,
R8 is phenyl or naphthyl, each of which is unsubstituted or monosubstituted, disubstituted or trisubstituted by A, OR1, NR4R4 or Hal,
E is CH2 or O,
D is carbonyl or C(R4R4)n,
Hal is F, Cl, Br or I,
m is 0, 1 or 2,
n is 1 or 2,
and their salts;
c) the compounds of the formula I described in EP 0755934
94
in which
Y-Z- is NR7CO, NC(OR7) or NCR8,
R1 is Ar,
R2 is COOR6, CN, 1H-tetrazol-5-yl or CONHSO2Ar,
R3, R4
and R5 are each, independently of one another, R6, OR6, S(O)mR8, Hal, NO2, NR6R6, NHCOR6, NHSO2R6, OCOR6, COOR6 or CN,
R6 and R6 are each, independently of one another, H, alkyl having from 1 to 6 carbon atoms, benzyl or phenyl,
R7 is (CH2)nAr,
R8 is Ar or OAr,
Ar is phenyl which is unsubstituted or monosubstituted, disubstituted or trisubstituted by R9, R10 or R1, or is unsubstituted naphthyl or a
95
which is unsubstituted or monosubstituted or disubstituted in the phenyl part by R9 or R10, or is a
96
which is unsubstituted or monosubstituted or disubstituted in the cyclohexadienyl part by R9 or R10,
R9, R10
and R11 are each, independently of one another, R6, OR6, Hal, CF3, OCF3, OCHF2, OCH2F, NO2, NR6R6, NHCOR6, CN, NHSO2R6, COORW, COR6, CONHSO2Ar, O(CH2),R2, O(CH2),OR6 or S(O)mR6,
E is CH2, S or O,
D is carbonyl or C(R6R6))n,
Hal is F, Cl, Br or I,
X is O or S,
m is 0, 1 or 2,
n is 1 or 2,
and their salts;
d) the compounds of the formula I described in EP 0757039
97
in which Y-Z- is NR7CO, NC(OR7) or NCR9,
R1 is Ar,
R2 is COOR6, (CH2)nCOOR6, CN, 1H-tetrazol-5-yl or CONHSO2Ar,
R3, R4
and R5 are each, independently of one another, R6, OR6, S(O)mR6, Hal, NO2, NR6R6, NHCOR6, NHSO2R4, OCOR6, COR6, COOR8 or CN, where R3 and R4 together may alternatively be an O(CH2),O group,
R6 and R6 are each, independently of one another, H, alkyl having from 1 to 6 carbon atoms, benzyl or phenyl,
R7 is (CH2),Ar,
R8 is Ar or OAr,
Ar is phenyl which is unsubstituted or monosubstituted, disubstituted or trisubstituted by R9, R10 or R10, or is unsubstituted naphthyl or a
98
which is unsubstituted or monosubstituted or disubstituted in the phenyl part by R9 or R10, or is a
99
which is unsubstituted or monosubstituted or disubstituted in the cyclohexadienyl part by R9 or R10,
R9, R10
and R11 are each, independently of one another, R1, OR6, Hal, CF3, OCF3, OCHF2, OCH2F, NO2, NR6RW, NHCOR6, CN, NHSO2R6, COOR8, COR8, CONHSO2Ar, O(CH2)nR2, O(CH2)nOR6 or S(O)mR6,
E is CH2, S or O,
D is carbonyl or C(R6R6),
X is O or S,
Hal is F, Cl, Br or I,
m is 0, 1 or 2,
n is 1 or 2,
and their salts;
e) the compounds of the formula I described in EP 0796250
100
in which
Y is C(R4R4)C(R4R4), CR4CR4- or C(R4R4)S,
R1 is Het, Ar, R3 or R4,
R2 is Ar or a
101
which is unsubstituted or monosubstituted or disubstituted in the phenyl part by A, R3, OR4, NH2, NHA, NA2, NO2, CN, Hal, NHCOR4, NHSO2R4, COOR4, COR4, CONHSO2R3, O(CH2),R3, OPh, O(CH2)nOR4 or S(O)mR4, or a
102
which is unsubstituted or monosubstituted or disubstituted in the cyclohexadienyl part by A, R, OR4, NH2, NHA, NA2, NO2, CN, Hal, NHCORW, NHSO2R4, COOR4, COR4, CONHSO2R6, O(CH2),R3, OPh, O(CH2),ORW or S(O)mR4,
R3 is CN, COOH, COOA, CONHSO2R6 or 1H-tetrazol-5-yl,
R4 and R4 are each, independently of one another, H, A, or phenyl or benzyl, each of which is unsubstituted or monosubstituted by alkoxy,
R5 is A or Ar,
R6 is phenyl or naphthyl, each of which is unsubstituted or monosubstituted, disubstituted or trisubstituted by A, OR5, NH2, NHA, NA2, NO2, CN or Hal,
A is alkyl having 1-6 carbon atoms, in which one or two CH2 groups may be replaced by O or S atoms or by CR4CR4-groups and in addition 1-7H atoms may be replaced by F, or benzyl,
Ar is phenyl or naphthyl, each of which is unsubstituted or monosubstituted, disubstituted or trisubstituted by A, OR4, NH2, NHA, NA2, NO2, CN, Hal, NHCOR4, NHSO2R4, COOR4, COR4, CONHSO2R6, O(CH2)nR3, OPh, O(CH2)nOR4 or S(O)mFR4,
Het is a monocyclic or bicyclic, saturated, unsaturated or aromatic heterocyclic radical having from 1 to 4 N, O andor S atoms, bonded via N or C, which may be unsubstituted or monosubstituted, disubstituted or trisubstituted by Hal, A, R3, NH2, NHA, NA2, CN, NO2 andor carbonyl oxygen,
D is carbonyl or C(R4R4)n,
E is CH2, S or O,
Hal is F, Cl, Br or I,
X is O or S,
m is 0, 1 or 2,
n is 1 or 2,
and their salts;
f) the compounds of the formula I described in WO 9719077
103
in which
R
104
X is O or S,
R1 is H, Hal, OH, OA, A, alkylene-O-A, NO2, NH2, NH-acyl, SO2NH2, SO3-A, SO2NHA, ON or formyl,
R2 is H or A,
R3, R5, R6
R7 and R8 are each, independently of one another, H. Hal, OH, OA, O-alkylene-R4, A, S-A, NO2, NH2, NHA, NA2, NH-acyl, NHSOA, NHSO2R4, NASOA, NASO2R4, NH(CO)NH2, NH(CO)NHA, formyl, NH(CO)NH-phenyl, NHCOOA, NA-acyl, NHR4, NHCOOR4, NHCOO-benzyl, NHSO2-benzyl, NHCOO-alkylene-OA, NH(CO)NA2, N-piperidinyl-CONH, N-pyrrolidinyl-CONH, O(CH2)nCOOR2, O(CH2)nOR2, CH2OH or CH2OA,
R3 and R3 together are alternatively OCH2OOCH2CH2O, OCH2CH2, OCF2O or OCF2CF2O,
R4 is phenyl which is unsubstituted or monosubstituted or polysubstituted by R3 andor R6,
A is alkyl having 1-6 carbon atoms,
Hal is fluorine, chlorine, bromine or iodine,
n is 1 or 2,
and their salts;
g) the compounds of the formula I described in WO 9730982
105
in which
R
106
X is O or S,
R1 is H, Hal, OH, OA, A, alkylene-O-A, NO2, NH2, NH-acyl, SO2NH2, SO3-A, SO2NHA, CN or formyl,
R2, R3
and R4 are each, independently of one another, a phenyl group which is unsubstituted or monosubstituted or polysubstituted by Hal, OH, OA, O-alkylene-R5, A, S-A, SOA, SO2A, SOR5, SO2R5, NO2, NH2, NHA, NA2, NH-acyl, NHSO2A, NHSO2R5, NASO2A, NASO2-Rr, NH(CO)NH2, NH(CO)NHA, formyl, NH(CO)NHR5, NHCOOA, NA-acyl, NHCOOCH2R5, NHSO2CH2R5, NHCOO-alkylene-OA, NH(CO)NA2, 1-piperidinyl-CONH, 1-pyrrolidinyl-CONH, O(CH2)nCOOA, O(CH2)nCOOH, O(CHO,OH, O(CH2)nOA, CH2OH, CH2OA, COOH, COOA, CH2COOH or CH2COOA,
107
R2 is additionally A or cycloalkyl,
R5 is a phenyl group which is unsubstituted or monosubstituted or polysubstituted by Hal, OH, OA, A, S-A, NO2, NH2, NHA, NA2, NH-acyl, NHSO2A, NASO2A, NH(CO)NH2, NH(CO)NHA, formyl, NHCOOA, NA-acyl, NHCOO-alkylene-OA, NH(CO)NA2, N-piperidinyl-CONH, N-pyrrolidinyl-CONH, O(CH2)nCOOA, O(CH2)nCOOH, O(CH2)nOH, O(CH2)nOA, CH2OH, CH2OA, COOH, COOA, CH2COOH or CH2COOA,
A is alkyl having 1-6 carbon atoms, in which one or two CH2 groups may be replaced by O or S atoms or by CR6CR6 groups andor 1-7H atoms may be replaced by F,
D is carbonyl or C(R6R6)m,
E is CH2, S or O,
Y is O or S, W6 and R6 are each, independently of one another, H, F or A,
Hal is fluorine, chlorine, bromine or iodine,
n is 1 or 2, and
m is 1 or 2,
or a tautomeric cyclised form, and the (E)-isomers and the salts of all isomers;
h) the compounds of the formula I described in WO 9730996
108
in which
-AB-CD- is a CHCHCHCH group, in which, in addition, 1 or 2 CH may be replaced by N,
Het is a monocyclic or bicyclic, saturated, unsaturated or aromatic heterocyclic radical having from 1 to 4 N, O andor S atoms which is unsubstituted or substituted by -Z-R6,
R1, R2
and R3 are each, independently of one another, absent, H, Hal, A, CF3, NO2, NR4R5, CN, COOR4 or NHCOR4,
R4 and R5 are each, independently of one another, H or A, or together are alternatively CH2(CH2)nCH2, R6 is a phenyl radical, benzothiadiazol-5-yl or benzoxa-diazol-5-yl radical, each of which is unsubstituted or monosubstituted, disubstituted or trisubstituted by R7, R8 andor R1,
R1, R8
and R9 are each, independently of one another, A, O-A, CN, COOH, COOA, Hal, formyl, CO-A, and R7 and R8 are alternatively O (CH2)mO,
A is alkyl having from 1 to 6 carbon atoms,
X is O or S,
Z is CO, CONH, CO(CH2)n, CHCH, (CH2)nCONHCO, NHCONH, NHCOO, OCONH, COO or OCO,
Hal is F, Cl, Br or I,
m is 1 or 2, and
n is 1, 2 or 3,
and their salts;
i) the compounds of the formula I described in DE 19609597
109
in which
Ar is naphthyl which is monosubstituted by NH2, NHA or NA2, and
A is alkyl having from 1 to 6 carbon atoms, and their physiologically acceptable salts;
j) the compounds of the formula I described in DE 19612101
110
in which
Y-Z- is NR4CO or NCR5,
R1 is Ar,
R2 is H, alkyl having 1-6 carbon atoms which is unsubstituted or monosubstituted, disubstituted or trisubstituted by OR3 or Hal, or (CH2)mPh or (CH2)m-cycloalkyl, each of which is unsubstituted or monosubstituted, disubstituted or trisubstituted by R3, OR3 or Hal,
R3 and R3 are each, independently of one another, H, alkyl having 1-6 carbon atoms or benzyl,
R4 is CH2Ar,
R5 is OCH2Ar,
Ar is phenyl which is unsubstituted or monosubstituted, disubstituted or trisubstituted by R6, R7 or R8, or a
111
which is unsubstituted or monosubstituted in the phenyl part by R6, or a
112
which is unsubstituted or monosubstituted in the cyclo-hexadienyl part by R6,
E is CH2 or O,
D is carbonyl or (CH2)n,
E and D together are alternatively CHCR9,
R6, R6 are each, independently of one another, R3, OR3 or Hal,
R7 is R3, OR3, Hal, NO2, NH2, NHR3, NR3R3, NHCOR3, COOR3, O(CH2),R3 or O(CH2)nOR3,
R3 is Ph which is unsubstituted or monosubstituted, disubstituted or trisubstituted by R3, OR3, Hal, NO2, NH2, NHR6, NR6R6, NHCOR3 or COOR3,
R9 is H, OH, CH2OH or COOR3,
Hal is F, Cl, Br or I, Ph is phenyl,
m is 0 or 1,
n is 0 or 2,
and their salts;
k) the compounds of the formula I described in WO 9827091
113
in which
R is phenyl which is unsubstituted or monosubstituted, disubstituted or trisubstituted by R3, R4 or R5, or 2,1,3-benzothiadiazolyl which is unsubstituted or monosubstituted by R2,
R1 is A, in which 1-7H atoms may be replaced by F,is S-A, O-A, is phenyl or -alkylene-phenyl, each of which is unsubstituted or monosubstituted by R3, or is thienyl which is unsubstituted or monosubstituted by R3,
R2 is A, F, Cl, Br or O-A,
R3, R4
and R1 are each, independently of one another, A, O-A, S-A, O-alkylene-COOH, -alkylene-COOH or COOH,
R3 and R4 together are alternatively OCH2O, and
A is alkyl having 1-7 carbon atoms, and their salts;
l) the compounds of the formula I described in WO 9827077
114
in which
R
115
X is O or S,
R1 is H, Hal, OH, OA, A, alkylene-O-A, NO2, NH2, NH-acyl, SO2NH2, SO3-A, SO2NHA, CN or formyl,
R2, R3 and R4 are each, independently of one another, a phenyl group which is unsubstituted or monosubstituted or polysubstituted by R7, where R2 is additionally A or cycloalkyl, or are
116
with the proviso that at least one of the radicals R2, R3 or
R4 is an R8 radical which is unsubstituted or monosubstituted or polysubstituted by R7,
R5 is a phenyl group which is unsubstituted or monosubstituted or polysubstituted by Hal, OH, OA, A, S-A, NO2, NH2, NHA, NA2, NH-acyl, NHSO2A, NASO2A, NH(CO)NH2, NH(CO)NHA, formyl, NHCOOA, NA-acyl, NHCOO-alkylene-OA, NH(CO)NA2, N-piperidinyl-CONH, N-pyrrolidinyl-CONH, O(CH2),COOA, O(CH2)n,COOH, O(CHONOH, O(CH2),OA, CH2OH, CH2OA, COOH, COOA, CH2COOH or CH2COOA,
A is alkyl having 1-6 carbon atoms, in which one or two CH2 groups may be replaced by O or S atoms or by CR6CR6 groups andor 1-7H atoms may be replaced by F,
D is carbonyl or C(R6R6)m,
E is CH2,S or O,
Y is O or S,
R6 and R6 are each, independently of one another, H, F or A,
R7 is Hal, OH, OA, O-alkylene-R5, A, S-A, S-OA, SO2A, SOR5, SO2R5, NO2, NH2, NHA, NA2, NH-acyl, NHSO2A, NHSO2R5, NASO2A, NASO2R5, NH(CO)NH2, NH(CO)NHA, formyl, NH(CO)NHR5, NHCOOA, NA-acyl, NHCOOCH2R5, NHSO2CH2R5, NHCOO-alkylene-OA, NH(CO)NA2, 1-piperidinyl-CONH, 1-pyrrolidinyl-CONH, O(CH2),COOA, O(CH2)nCOOH, O(CH2),OH, O(CH2),OA, CH2OH, CH2OA, COOH, COOA, CH2COOH or CH2COOA,
R8 is a 5-7-membered heterocyclic radical having 1-4 N, O andor S atoms or is
117
G and Z are each, independently of one another, CH, N, O or S,
L is CH, CHCH or CH2CH2CH2,
Hal is fluorine, chlorine, bromine or iodine,
n is 0, 1 or 2, and
m is 1 or 2,
or a tautomeric cyclised form, and the (E)-isomers and the salts of all isomers;
m) the compounds of the formula I described in WO 9841515
118
in which
X is O or S,
R1 is H, Hal, OH, OA, A, NO2, NH2, NHA, NAA, NHCOR4, NHCOR6, NHSO2R6, NHSO2R6, S(O)mR8, SO3H, SO2NR4R4 or formyl,
R2 and R2 are each, independently of one another, A, (CH2)nAr, (CH2)nHet, CH2COAr, CH2COHet or OAr,
R2 is additionally also H,
R3 is COOR4, CN, 1H-tetrazol-5-yl or CONHSO2R5,
R4 and R4 are each, independently of one another, H or A,
R5 is A or Ar,
R6 is phenyl or naphthyl, each of which is unsubstituted or monosubstituted, disubstituted or trisubstituted by A, NH2, NHA, NA, NO2, CN or Hal,
R7 and R7 are each, independently of one another, H or alkyl having 1-6 carbon atoms,
A and A are each, independently of one another, alkyl having 1-6 carbon atoms, in which one or two CH2 groups may be replaced by O or S atoms or by CR7CR groups andor 1-7H atoms may be replaced by F, or benzyl,
Ar is phenyl or naphthyl, each of which is unsubstituted or monosubstituted, disubstituted or trisubstituted by A, OR4, NH2, NHA, NAA, NO2, CN, Hal, NHCOR4, NHCOR6, NHSO2R4, NHSO2R6, COOR4, OPh, CONH2, CONHA, CONAA, COR4, CONHSO2R4, CONHSO2R6, O(CH2)nCOOR4, O(CH2),OR4, SO3H, SO2NR4R4, S(O)mR8 or S(O)mR4,
Het is a monocyclic or bicyclic, saturated, unsaturated or aromatic heterocyclic radical having 1-4 N, O andor S atoms, bonded via N or C, which may be unsubstituted or monosubstituted, disubstituted or trisubstituted by
Hal, A, R3, NH2, NHA, NAA, NO2 andor O,
Hal is fluorine, chlorine, bromine or iodine,
m is 0, 1 or 2, and
n is 1 or 2,
where, if R2 is CH2COAr and R2 is H, R3 is not COOA, and salts thereof;
n) the compounds of the formula I described in WO 9841521
119
in which
Z is a single or double bond,
R1 is a
120
which is unsubstituted or monosubstituted in the phenyl part by R7, or is a
121
which is unsubstituted or monosubstituted in the cyclohexadienyl part by R7,
R2 is A, Ar-(CH2)m, cycloalkyl-(CH2)m, Het-(CH2)m or R1(CH2),
R3 and R3 are each, independently of one another, OR4, NHSO2R5, NH2, NHA or NAA,
R3 and R3 together are alternatively O, forming a cyclic anhydride,
R4 and R4 are each, independently of one another, H or A,
R5 is A or Ar,
R6 is phenyl or naphthyl, each of which is unsubstituted or monosubstituted, disubstituted or trisubstituted by A, NH2, NHA, NAA, NO2, CN or Hal,
R7 is A, COOR4, CN, 1H-tetrazol-5-yl, CONHSO2R6, Hal, OR4, NO2, NH2, NHA, NAA, NHCOR4, NHCOR4, NHSO2R4, NHSO2RG, S(O)kR4, S(O)kRe, SO2NR4R4 or formyl,
R5 and R5 are each, independently of one another, H or alkyl having 1-6 carbon atoms,
E is CH2 or O,
D is carbonyl or (CR4R4)n,
E and D together are alternatively CR4R4,
X is S or O,
A and A are each, independently of one another, alkyl having 1-6 carbon atoms, in which one or two CH2 groups may be replaced by O or S atoms or by CR8CR8groups andor 1-7H atoms may be replaced by F, or benzyl,
Ar is phenyl or naphthyl, each of which is unsubstituted or monosubstituted, disubstituted or trisubstituted by A, OR4, NH2, NHA, NAA, NO2 CN, Hal, NHCOR4, NHCORE, NHSO2R4, NHSO2R6, COOR4, OPh, CONH2, CONHA, CONAA, COR4, CONHSO2R4, CONHSO2R6, O(CH2),COOR4, O(CH2)nOR4, SO2NR4R4, S(O)kR6 or S(O)KR4,
Het is a monocyclic or bicyclic, saturated, unsaturated or aromatic heterocyclic radical having 1-4 N, O andor S atoms, bonded via N or C, which may be unsubstituted, monosubstituted or disubstituted or trisubstituted by Hal, A, COOR4, CN, 1H-tetrazol-5-yl, CONHSO2R5, NH2, NHA, NAA, NO2 andor O,
Hal is fluorine, chlorine, bromine or iodine,
k is 0, 1 or 2,
m is 0, 1 or 2, and
n is 1 or 2,
and the (Z)- and (E)-isomers and the salts of all isomers;
o) the compounds of the formula I described in WO 9842702
122
in which
R
123
X and Y are each, independently of one another, O or S,
R1 is H, OH, OA, A alkylene-O-A, NO2, NH2, NH-acyl, SO2NH2, SO2-A, SO2NHA, CN or formyl,
R2, R3
and R are each, independently of one another, 2 r Sr, which is unsubstituted or monosubstituted or polysubstituted by Hal, OH, OA, O-alkylene-R5, A, S-A, S-OA, SO2A, 5-OR5, SO2R5, NO2, NH2, NHA, NA2, NH-acyl, NHSO2A, NHSO2R5, NASO2A, NASO2R5, NH(CO)NH2, NH(CO)NHA, formyl, NH(CO)NHR5, NHCOOA, NA-acyl, NHCOOCH2R5, NHSO2CH2R5, NHCOO-alkylene-OA, NH(CO)NA2, 1-piperidinyl-CONH , 1-pyrrolidinyl-CONH, O(CH2)nCOOAf O(OH)COOH, O(CH2)nOH, O(CHOA, CH2OH, CH2OA, COOH, COOA, CH2COOH or CH2COOA,
124
R2 is additionally A or cycloalkyl,
R6 is a phenyl group which is unsubstituted or monosubstituted or polysubstituted by Hal, OH, OA, A, S-A, NO2, NH2, NHA, NA2, NH-acyl, NHSO2A, NASO2A, NH(CO)NH2, NH(CO)NHA, formyl, NHCOOA, NA-acyl, NHCOO-alkylene-OA, NH(CO)NA2, N-piperidinyl-CONH, N-pyrrolidinyl-CONH, O(CHO,COOA, O(CH2)nCOOH, O(CH2)nOH, O(CH2)nOA, CH2OH, CH2OA, COOH, COOA, CH2COOH or CH2COOA,
A is alkyl having 1-6 carbon atoms, in which one or two CH2 groups may be replaced by O or S atoms or by CR6CR6 groups andor 1-7H atoms may be replaced by F,
D is carbonyl or C(R6R6)m,
E is CH2, S or O,
R6 and R6 are each, independently of one another, H, F or A,
R7 is OC(Y)-NHR8,
R8 is alkyl having 1-10 carbon atoms which is unsubstituted or monosubstituted or disubstituted by R and in which 1-2 carbon atoms may be replaced by 0 andor S, andor may be substituted by O, or cycloalkyl, in which 1-2 carbon atoms may be replaced by N, O andor S,
R9 is phenyl which is unsubstituted or monosubstituted or disubstituted by Hal, or is naphthyl, A-OC(O) or Hal,
Hal is fluorine, chlorine, bromine or iodine,
n is 0, 1 or 2, and
m is 1 or 2,
and salts thereof;
p) the compounds of the formula I described in WO 9842709
125
in which
X is NR3, O or S,
R is 2,1,3-benzothiadiazol-4- or 5-yl or 2,1-benzoisothiazol-5- or 6-yl, each of which is unsubstituted or monosubstituted or disubstituted by R2 andor R2, or phenyl which is unsubstituted or monosubstituted, disubstituted or trisubstituted by R2 andor R2,
R1 is H or A,
R2 and R2 are each, independently of one another, H, A, OH, OA,
Hal, OCF3, OCHF2, OCO-A, O-alkylene-COOR1, O-alkylene-CH2OR1, or OCH2-phenyl or OCO-phenyl, each of which is unsubstituted or monosubstituted or disubstituted in the phenyl part by R4 andor R4,
R2 and R2 together are alternatively OCH2O, OCH2CH2O or OCH2CH2,
R3 is H, A, alkylene-O-A, CO-OA, or alkylene-phenyl which is unsubstituted or monosubstituted or disubstituted in the phenyl part by RW andor R4,
R4 and R4 are each, independently of one another, H, A, OH, OA,
Hal, COOR1 or CH2OR1,
A is alkyl having 1-6 carbon atoms,
Hal is fluorine, chlorine, bromine or iodine,
and their salts;
q) the compounds of the formula I described in WO 9905132
126
in which
R is
127
X is O or S,
R1 is H, Hal, OA or A,
R2, R3, R5,
and R6 are each, independently of one another, H, Hal, A, OA or R4,
R4 is O(CH2)nCY,
Cy is cycloalkyl having 3-8 carbon atoms,
A is alkyl having 1-6 carbon atoms, in which one or two CH2 groups may be replaced by O or S atoms or by CR5CR5 groups andor 1-7H atoms may be replaced by F,
R5 and R5 are each, independently of one another, H, F or A,
Hal is fluorine, chlorine, bromine or iodine,
n is 0, 1 or 2,
or a tautomeric cyclised form, and the (E)-isomers and the salts of all isomers.
27. Pharmaceutical formulation according to one of the preceding claims, comprising one or more excipients andor assistants.
28. Use of a pharmaceutical preparation according to one of claims 16 to 27 for the preparation of a medicament for the treatment of angina, high blood pressure, high pulmonary pressure, congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), cor pulmonale, dextrocardiac insufficiency, atherosclerosis, conditions of reduced patency of the heart vessels, peripheral vascular diseases, strokes, bronchitis, allergic asthma, chronic asthma, allergic rhinitis, glaucoma, irritable bowel syndrome, tumours, renal insufficiency, liver cirrhosis, erectile dysfunction and for the treatment of female sexual disorders.
29. Use according to claim 28 for the preparation of a medicament for the treatment of high pulmonary pressure, congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), cor pulmonale andor dextrocardiac insufficiency.
30. Set (kit) consisting of separate packs of
(a) an effective amount of 4-4-(3-chloro-4-methoxybenzylamino)benzothieno2,3-dpyrimidin-2-ylcyclohexanecarboxylic acid andor physiologically acceptable salts andor solvates thereof and
(b) an effective amount of an endothelin receptor antagonist.
31. Pharmaceutical formulation comprising at least one compound of the formula I-II
128
in which
R1 and R2 are each, independently of one another, H, A or Hal, where one of the radicals R1-or R2 is alwaysH,
R1 and R2 together are alternatively alkylene having 3-5 carbon atoms,
R3 and R4 are each, independently of one another, H, A, OH, OA or Hal,
R3 and R4 together are alternatively alkylene having 3-5 carbon atoms, OCH2CH2, OCH2O or OCH2CH2O,
X is R1 or R6, each of which is monosubstituted by R7,
R5 is linear or branched alkylene having 1-10 carbon atoms, in which one or two CH2 groups may be replaced by CHCH groups, or C2H4(CHO2)m,
R6 is cycloalkylalkylene having 6-12 carbon atoms,
R7 is COOH, COOA, CONH2, CONHA, CON(A)2 or CN,
A is alkyl having from 1 to 6 carbon atoms,
Hal is F, Cl, Br or I,
m is 1 or 2, and
n is 0, 1, 2 or 3,
andor physiologically acceptable salts andor solvates thereof and at least one endothelin receptor antagonist.
32. Pharmaceutical formulation according to claim 31, comprising at least one compound of the formula I-II according to claim 31 in which
X is R5 or R5, each of which is substituted by COOH or COOA.
33. Pharmaceutical formulation according to claim 31, comprising at least one compound of the formula I-II according to claim 31 in which
R1 and R2 are each, independently of one another, H, A or Hal, where at least one of the radicals R1 and R2 is alwaysH.
R3 and R4 together are alkylene having 3-5 carbon atoms, OCH2CH2, OCH2O or OCH2CH2O,
X is R1 or R6, each of which is substituted by COOH or COOA.
34. Pharmaceutical formulation according to claim 31, comprising at least one compound of the formula I-II according to claim 31 in which
R1 and R2 are each, independently of one another, H, A or Hal, where at least one of the radicals R1 and R2 is always
R3 and R4 are each, independently of one another, H, A, OA or Hal,
R3 and R4 together are alkylene having 3-5 carbon atoms, OCH2CH2, OCH2O or OCH2CH2O,
X is R1 or RW, each of which is substituted by COOH or COOA,
n is 1 or 2.
35. Pharmaceutical formulation according to claim 31, comprising at least one compound of the formula I-II according to claim 31 in which
R1 and R2 are each, independently of one another, H, A or Hal, where one of the radicals R1 and R2 is alwaysH,
R1 and R2 together are alternatively alkylene having 3-5 carbon atoms,
R3 and R4 are each, independently of one another, H, A, OA or Hal,
R3 and R4 together are alternatively CCH2C,
X is R5 which is monosubstituted by R7,
R5 is linear or branched alkylene having 1-10 carbon atoms, or C6H4CH2,
R7 is COOH or COOA,
A is alkyl having from 1 to 6 carbon atoms,
Hal is F, Cl, Br or 1,
m is 1, and
n is 1 or 2.
36. Pharmaceutical formulation according to claim 31, comprising at least one compound of the formula I-II according to claim 31 in which
R1 and R2 are each, independently of one another, H, A or Hal, where one of the radicals R1 and R2 is alwaysH,
R1 and R2 together are alternatively alkylene having 3-5 carbon atoms,
R3 and R4 are each, independently of one another, H, A, OH, OA or Hal,
R3 and R4 together are alternatively OCH2O,
X is R5 which is monosubstituted by R7,
R5 is linear or branched alkylene having 1-10 carbon atoms, or C6H4CH2,
R7 is COOH or COOA,
A is alkyl having from 1 to 6 carbon atoms,
Hal is F, Cl, Br or 1,
m is 1, and
n is 1 or 2.
37. Pharmaceutical formulation according to claim 31, comprising at least one compound of the formula I-II according to claim 31, selected from the group consisting of
(a) 3-4-(3-chloro-4-methoxybenzylamino)-5,6,7,8-tetrahydro-1-benzothieno2,3-dpyrimidin-2-ylpropionic acid;
(b) 4-4-(3,4-methylenedioxybenzylamino)-5,6,7,8-tetrahydro-1-benzothieno2,3-dpyrimidin-2-ylbutyric acid;
(c) 7-4-(3,4-methylenedioxybenzylamino)-5,6,7,8-tetrahydro-1-benzothieno2,3-d3pyrimidin-2-ylheptanoic acid;
(d) 7-4-(3-chloro-4-methoxybenzylamino)-5,6,7,8-tetrahydro-1-benzothieno2,3-dpyrimidin-2-ylheptanoic acid;
(e) 5-4-(3-chloro-4-methoxybenzylamino)-5,6,7,8-tetrahydro-1-benzothieno2,3pyrimidin-2-ylvaleric acid;
(e) 5-4-(3-chloro-4-methoxybenzylamino)-6-methylthieno2,3d-pyrimidin-2-ylvaleric acid;
(g) 4-4-(3-chloro-4-methoxybenzylamino)-6-methylthieno2,3-d-pyrimidin-2-ylbutyric acid;
(h) 4-4-(3,4-methylenedioxybenzylamino)-6-methylthieno2,3-d-pyrimidin-2-ylbutyric acid;
(i) 2-4-4-(3-chloro-4-methoxybenzylamino)-5,6,7,8-tetrahydro-1-benzothieno2,3-dpyrimidin-2-ylcyclohexyl-1-ylacetic acid;
(k) 5-4-(3,4-methylenedioxybenzylamino)-6-methylthieno2,3-d-pyrimidin-2-ylvaleric acid.
38. Pharmaceutical formulation according to claim 31, comprising 5-4-(3-chloro-4-methoxybenzylamino)-5,6,7,8-tetrahydro-1-benzothieno-2,3-dpyrimidin-2-ylvaleric acid, ethanolamine salt.
39. Pharmaceutical formulation according to claims 31 to 38, in which the endothelin receptor antagonist is selected from the group consisting of bosentan, tezosentan and sitaxentan.
40. Pharmaceutical formulation according to claims 31 to 38, in which the endothelin receptor antagonist is selected from the group consisting of
a) BMS-193884 (EP 558258),
b) BMS-207940 (Pharmaprojects (13.06.97)),
c) BQ-123 (Exp.Opin.Invest.Drugs, 1997, 6, No.5, 475487),
d) SB-209670 (Exp.Opin.Invest.Drugs, 1997, 6, No.5, 475487),
e) SB-217242 (Exp.Opin.Invest.Drugs, 1997, 6, No.5, 475487),
f) SB-209598 (Trends in Pharmacol. Sci., 17, 177-81,1996),
g) TAK-044 (Exp.Opin.Invest.Drugs, 1997, 6, No.5, 475-487),
h) Bosentan (Trends in Pharmacol. Sci., 18, 408-12, 1997),
i) PD-156707 (J.Med.Chem., 40, No.7, 1063-74, 1997),
j) L-749329 (Bioorg.Med.Chem.Lett., 7, No.3, 275-280,1997),
k) L-754142 (Exp.Opin.Invest.Drugs, 1997, 6, No.5, 475487),
l) ABT-627 (J.Med.Chem., 40, No.20, 3217-27,1997),
m) A-127772 (J.Med.Chem., 39, No.5, 1039-1048, 1996),
n) A-206377 (2131 American Chemical Society National Meeting, San Francisco, Calif., USA, 13-17 April 1997, Poster, MEDI 193),
o) A-182086 (J. Med.Chem., 40, No.20, 3217-27, 1997),
p) EMD-93246 (211th American Chemical Society National Meeting, New Orleans, USA, 1996, Poster, MEDI 143),
q) EMD-122801 (Bioorg.Med.Chem.Lett., 8, No.1, 17-22, 1998),
r) ZD-1611 (Trends in Pharmacol. Sci., 18, 408-12, 1997),
s) AC-610612 (R&D Focus Drug News (18.05.98)),
t) T-0201 (7CP Annual Meeting of the Japanese Pharmacological Society, Chiba, Japan, 22-15 March 1997, Lecture, 0-133),
u) J-104132 (R&D Focus Drug News (15.12.97)),
129
41. Pharmaceutical formulation according to claims 31 to 38, In which the endothelin receptor antagonist is selected from
a) the compounds of the formula I described in EP 0733626
130
in which
-AB-CD- is a CHCHCHCH group in which 1 or 2 CH has (have) been replaced by N,
Ar is Ph or naphthyl, each of which is unsubstituted or monosubstituted, disubstituted or trisubstituted by H,
Hal, A, alkenyl having up to 6 carbon atoms, Ph, OPh, NO2, NR4R5, NHCOR4, CF3, OCF3, CN, OR4, COOR4, (CH2),COOR4, (CH2),NR4R5, NCO or NHCONR4R5,
R1, R2
and R3 breach, independently of one another, absent, H, Hal, A, CF3, NO2, NR4R5, CN, COOR4, NHCOR4,
R4 and R5 are each, independently of one another, H or A, or together are alternatively CH2(CH2)nCH2,
A is alkyl having from 1 to 6 carbon atoms,
Ph is phenyl,
X is O or S,
Hal is F, Cl, Br or I,
n is 1, 2 or 3,
and their salts, with the exception of
4-methyl-N-(2,1,3-benzothiadiazol-4-yl)benzenesulfonamide, 4-methyl-N-(2,1,3-benzothiadiazol-5-yl)benzenesulfonamide, 4-nitro-N-(2,1,3-benzothiadiazol-4-yl)benzenesulfonamide, 4-nitro-N-(2, 1,3-benzothiadiazol-5-yl)benzenesulfonamide, 4-amino-N-(2,1,3-benzo-thiadiazol-4-yl)benzenesulfonamide and 4-amino-N-(2,1,3-benzothiadiazol-5-yl)benzenesulfonamide;
b) the compounds of the formula I described in EP 0733626
131
in which
X is a saturated, partially unsaturated or completely unsaturated 3- to 4-membered alkylene chain, in which from 1 to 3 carbon atoms may be replaced by N andor from 1 to 2 carbon atoms may be replaced by 1-2 O atoms andor 1-2 S atoms, but where at most up to 3 carbon atoms may be replaced and where, in addition, a single, double or triple substitution of the alkylene chain andor of a nitrogen located therein by A, R8 andor NR4R4 may occur, and where furthermore one CH2 group in the alkylene chain may also be replaced by a CO group,
A is alkyl having 1-6 carbon atoms, in which one or two CH2 groups may be replaced by O or S atoms or by CR4CR4 groups and in addition 1-7H atoms may be replaced by F,
R1 is H or A,
R2 is COOR4, CN, 1H-tetrazol-5-yl or CONHSO2R8,
R3 is Ar,
R4 and R4 are each, independently of one another, H, alkyl having from 1 to 6 carbon atoms or benzyl,
Ar is phenyl or naphthyl, each of which is unsubstituted or monosubstituted, disubstituted or trisubstituted by R5, R6 or R7, or is a
132
which is unsubstituted or monosubstituted or disubstituted in the phenyl part by R5 or R6,
R5, R6
and R7 are each, independently of one another, R4, OR4, Hal, CF3, OCF3, OCHF2, OCH2F, NO2, NR4R, NHCOR4, CN2NHSO2R4, COOR4, COR4, CONHSO2R8, O(CH2)nR2, OPh, O(CH2)nOR4 or S(O)mR4,
R8 is phenyl or naphthyl, each of which is unsubstituted or monosubstituted, disubstituted or trisubstituted by A, OR1, NR4R4 or Hal,
E is CH2 or O,
D is carbonyl or (C(R4R4)n,
Hal is F, Cl, Br or I,
m is 0, 1 or 2,
n is 1 or 2,
and their salts;
c) the compounds of the formula I described in EP 0755934
133
in which
Y-Z- is NR7CO-_-NC(OR7) or NCR8,
R1 is Ar,
R2 is COOR6, CN2H-tetrazol-5-yl or CONHSO2Ar,
R3, R4 and R5 are each, independently of one another, R6, OR6, S(O)mR6, Hal, NO2, NR6R8, NHCOR6, NHSO2R6, OCOR6, COOR1 or CN,
R6 and R6 are each, independently of one another, H, alkyl having from 1 to 6 carbon atoms, benzyl or phenyl,
R7 is (CH2),Ar,
R8 is Ar or OAr,
Ar is phenyl which is unsubstituted or monosubstituted, disubstituted or trisubstituted by R9, R10 or R11, or is unsubstituted naphthyl or a
134
which is unsubstituted or monosubstituted or disubstituted in the phenyl part by R9 or R10, or is a
135
which is unsubstituted or monosubstituted or disubstituted in the cyclohexadienyl part by R9 or R10,
R9, R10
and R11 are each, independently of one another, R6, OR6, Hal, CF3, OCF3, OCHF2, OCH2F, NO2, N6R6R6, NHCOR8, CN, NHSO2R8, COOR8, COR6, CONHSO2Ar, O(CH2)nR2, O(CH2)nOR6 or S(O)mR6,
E is CH2, S or O,
D is carbonyl or C(R6R6)n,
Hal is F, Cl, Br or 1,
X is O or S,
m is 0, 1 or 2,
n is 1 or 2,
and their salts;
d) the compounds of the formula I described in EP 0757039
136
in which Y-Z- is NR7CO, NC(OR7) or NCR1,
R1 is Ar,
R2 is COORB, (CH2),COOR , CN, 1H-tetrazol-5-yl or CONHSO2Ar,
R3, R4
and R5 are each, independently of one another, R6, OR6, S(O)mR6, Hal, NO2, NR6R6, NHCOR6, NHSO2R6, OCOR6, COR6, COOR6 or CN, where R3 and R4 together may alternatively be an O(CH2),O group,
R6 and R6 are each, independently of one another, H, alkyl having from 1 to 6 carbon atoms, benzyl or phenyl,
R7 is (CH2)nAr,
R8 is Ar or OAr,
Ar is phenyl which is unsubstituted or monosubstituted, disubstituted or trisubstituted by R9, R10 or R11, or is unsubstituted naphthyl or a
137
which is unsubstituted or monosubstituted or disubstituted in the phenyl part by R9 or R10, or is a
138
which is unsubstituted or monosubstituted or disubstituted in the cyclohexadienyl part by R9 or R10,
R9, R10
and R11 are each, independently of one another, R, OR6, Hal, CF3, OCF3, OCHF2, OCH2F, NO2, NR6R6, NHCOR6, CN, NHSO2R6, COOR6, COR6, CONHSO2Ar, O(CH2)nR2, O(CH2)nOR6 or S(O)mR6,
E is CH2, S or O,
D is carbonyl or C(R6R6)n,
X is O or S,
Hal is F, Cl, Br or I,
m is 0, 1 or 2,
n is 1 or 2,
and their salts;
e) the compounds of the formula I described in EP 0796250
139
in which
Y is C(R4R4)C(R4R4), CR4CR4 or C(R4R4)S,
R1 is Het, Ar, R3 or R4,
R2 is Ar or a
140
which is unsubstituted or monosubstituted or disubstituted in the phenyl part by A, R3, OR4, NH2, NHA, NA2, NO2, CN, Hal, NHCOR4, NHSO2R4, COOR4, COR4, CONHSO2R6, O(CH2),R3, OPh, O(CH2)nOR4 or S(O)nR4, or a
141
which is unsubstituted or monosubstituted or disubstituted in the cyclohexadienyl part by A, R3, OR4, NH2, NHA, NA2, NO2, CN, Hal, NHCOR4, NHSO2R4, COOR4, COR4, CONHSO2R6, O(CH2)nR3, OPh, O(CH2),OR4 or S(O),R,
R3 is CN, COOH, COOA, CONHSO2R1 or 1H-tetrazol-5-yl,
R4 and R4 are each, independently of one another, H, A, or phenyl or benzyl, each of which is unsubstituted or monosubstituted by alkoxy,
R5 is A or Ar,
R6 is phenyl or naphthyl, each of which is unsubstituted or monosubstituted, disubstituted or trisubstituted by A, OR5, NH2, NHA, NA2, NO2, CN or Hal,
A is alkyl having 1-6 carbon atoms, in which one or two CH2 groups may be replaced by O or S atoms or by CR4CR4 groups and in addition 1-7H atoms may be replaced by F, or benzyl,
Ar is phenyl or naphthyl, each of which is unsubstituted or monosubstituted, disubstituted or trisubstituted by A, OR4, NH2, NHA, NA2, NO2, CN, Hal, NHCOR4, NHSO2RC, COOR4 COR4, CONHSO2R6, O(CH2)nR3, OPh, O(CH2)nOR4 or S(O)mR4,
Het is a monocyclic or bicyclic, saturated, unsaturated or aromatic heterocyclic radical having from 1 to 4 N, O andor S atoms, bonded via N or C, which may be unsubstituted or monosubstituted, disubstituted or trisubstituted by Hal, A, R3, NH2, NHA, NA2, CN, NO2 andor carbonyl oxygen,
D is carbonyl or C(R4R4),
E is CH2, S or O,
Hal is F, Cl, Br or I,
X is O or S,
m is 0, 1 or 2,
n is 1 or 2,
and their salts;
f) the compounds of the formula I described in WO 9719077
142
in which
R
143
X is O or S,
R1 is H, Hal, OH, OA, A, alkylene-O-A, NO2, NH2, NH-acyl, SO2NH2, SO3-A, SO2NHA, CN or formyl,
R2 is H or A,
R5, R6, R6
R7 and R8 are each, independently of one another, H, Hal, OH, OA, O-alkylene-R4, A, S-A, NO2, NH2, NHA, NA2, NH-acyl, NHSO2A, NHSO2R4, NASO2A, NASO2R4, NH(CO)NH2, NH(CO)NHA, formyl, NH(CO)NH-phenyl, NHCOOA, NA-acyl, NHR4, NHCOOR4, NHCOO-benzyl, NHSO2-benzyl, NHCOO-alkylene-OA, NH(CO)NA2, N-piperidinyl-CONH, N-pyrrolidinyl-CONH, O(CH2)nCOOR2, O(CHONOR2, CH2OH or CH2OA,
R3 and R1 together are alternatively OCH2O, OCH2CH2O, OCH2CH2, OCF2O or OCF2CF2O,
R4 is phenyl which is unsubstituted or monosubstituted or polysubstituted by R3 andor R6,
A is alkyl having 1-6 carbon atoms,
Hal is fluorine, chlorine, bromine or iodine,
n is 1 or 2,
and their salts;
g) the compounds of the formula I described in WO 9730982
144
in which
R
145
X is O or S,
R1 is H, Hal, OH, OA, A, alkylene-O-A, NO2, NH2, NH-acyl, SO2NH2, SO3-A, SO2NHA, CN or formyl,
R2, R3
and R4 are each, independently of one another, a phenyl group which is unsubstituted or monosubstituted or polysubstituted by Hal, OH, OA, O-alkylene R5, A, S-A, SOA, SO2A, SOR5, SO2R5, NO2, NH2, NHA, NA2, NH-acyl, NHSO2A, NHSO2R5, NASO2A, NASO2R5, NH(CO)NH2, NH(CO)NHA, formyl, NH(CO)NHR6, NHCOOA, NA-acyl, NHCOOCH2R5, NHSO2CH2R5, NHCOO-alkylene-OA, NH(CO)NA2, 1-piperidinyl-CONH, 1-pyrrolidinyl-CONH, O(CH2),COOA, O(CH2),COOH, O(CH2),OH, O(CH2)nOA, CH2OH, CH2OA, COOH, COOA, CH2COOH or CH2COOA,
146
R2 is additionally A or cycloalkyl,
R5 is a phenyl group which is unsubstituted or monosubstituted or polysubstituted by Hal, OH, OA, A, S-A, NO2, NH2, NHA, NA2, NH-acyl, NHSO2A, NASO2A, NH(CO)NH2, NH(CO)NHA, formyl, NHCOOA, NA-acyl, NHCOO-alkylene-OA, NH(CO)NA2, N-piperidinyl-CONH, N-pyrrolidinyl-CONH, O(CH2)nCOOA, O(CH2),COOH, O(CH2)nOH, O(CH2)nOA, CH2OH, CH2OA, COH1, COOA, CH2COOH or CH2COOA,
A is alkyl having 1-6 carbon atoms, in which one or two CH2 groups may be replaced by O or S atoms or by CR6CR6 groups andor 1-7H atoms may be replaced by F,
D is carbonyl or C(R6R6)m,
E is CH2, S or O,
Y is O or S,
R6 and R6 are each, independently of one another, H, F or A,
Hal is fluorine, chlorine, bromine or iodine,
n is 1 or 2, and
m is 1 or 2,
or a tautomeric cyclised form, and the (E)-isomers and the salts of all isomers;
h) the compounds of the formula I described in WO 9730996
147
in which
-AB-CD- is a CHCHCHCH group, in which, in addition, 1 or 2 CH may be replaced by N,
Het is a monocyclic or bicyclic, saturated, unsaturated or aromatic heterocyclic radical having from 1 to 4 N, O andor S atoms which is unsubstituted or substituted by -Z-R6,
R1,R2
and R3 are each, independently of one another, absent, H, Hal, A, CF3, NO2, NR4R5, CN, COOR4 or NHCOR4,
R4 and R5 are each, independently of one another, H or A, or together are alternatively CH2(CH2)nCH2,
R6 is a phenyl radical, benzothiadiazol-5-yl or benzoxadiazol-5-yl radical, each of which is unsubstituted or monosubstituted, disubstituted or trisubstituted by R7, Re andor R1,
R7, R8
and R9 are each, independently of one another, A, O-A, CN, COOH, COOA, Hal, formyl, CO-A, and R7 and R8 are alternatively O(CH2)mO,
A is alkyl having from 1 to 6 carbon atoms,
X is O or S,
Z is CO, CONH, CO(CH2)n, CHCH, (CH2)n, CONHCO, NHCONH, NHCOO, OCONH, COO or OCO,
Hal is F, Cl, Br or I,
m is 1 or 2, and
n is 1, 2 or 3,
and their salts;
i) the compounds of the formula I described in DE 19609597
148
in which
Ar is naphthyl which is monosubstituted by NH2, NHA or NA2, and
A is alkyl having from 1 to 6 carbon atoms,
and their physiologically acceptable salts;
j) the compounds of the formula I described in DE 19612101
149
in which
Y-Z- is NR4CO or NCR5,
R1 is Ar,
R2 is H, alkyl having 1-6 carbon atoms which is unsubstituted or monosubstituted, disubstituted or trisubstituted by OR3 or Hal, or (CH2)mPh or (CH2)m-cycloalkyl, each of which is unsubstituted or monosubstituted, disubstituted or trisubstituted by R3, OR3 or Hal,
R3 and R3 are each, independently of one another, H, alkyl having 1-6 carbon atoms or benzyl,
R4 is CH2Ar,
R5 is OCH2Ar,
Ar is phenyl which is unsubstituted or monosubstituted, disubstituted or trisubstituted by R6, R7 or R3, or a
150
which is unsubstituted or monosubstituted in the phenyl part by R6, or a
151
which is unsubstituted or monosubstituted in the cyclohexadienyl part by R6;
E is CH2 or O,
D is carbonyl or (CH2)n,
E and D together are alternatively CHCR9,
R6, R6 are each, independently of one another, R3, OR3 or Hal,
R7 is R3, OR3, Hal, NO2, NH2, NHR3, NR3R3, NHCOR3, COOR3, O(CH2)nRn or O(CH2)nOR3,
R8 is Ph which is unsubstituted or monosubstituted, disubstituted or trisubstituted by R3, OR3, Hal, NO2, NH2, NHR6, NR6R6, NHCOR3 or COOR3,
R9 is H, OH, CH2OH or COOR3,
Hal is F, Cl, Br or I, Ph is phenyl,
m is 0 or 1,
n is 1 or 2,
and their salts;
k) the compounds of the formula I described in WO 9827091
152
in which
R is phenyl which is unsubstituted or monosubstituted, disubstituted or trisubstituted by R3, R4 or R6, or 2,1,3-benzothiadiazolyl which is unsubstituted or monosubstituted by R2,
R1 is A, in which 1-7H atoms may be replaced by F,is S-A, O-A, is phenyl or -alkylene-phenyl, each of which is unsubstituted or monosubstituted by R1, or is thienyl which is unsubstituted or monosubstituted by R3,
R2 is A, F, Cl, Br or O-A,
R3, R4
and R1 are each, independently of one another, A, O-A, S-A, O-alkylene-COOH, -alkylene-COOH or COOH,
R3 and R4 together are alternatively OCH2O, and
A is alkyl having 1-7 carbon atoms, and their salts;
l) the compounds of the formula I described in WO 9827077
153
in which
R
154
X is O or S,
R1 is H, Hal, OH, OA, A, alkylene-O-A, NO2, NH2, NH-acyl, SO2NH2, SO3-A, SO2NHA, CN or formyl,
R2, R3
and R4 are each, independently of one another, a phenyl group which is unsubstituted or monosubstituted or polysubstituted by R7, where R2 is additionally A or cycloalkyl, or are
155
with the proviso that at least one of the radicals R2, R3 or
R4 is an R8 radical which is unsubstituted or monosubstituted or polysubstituted by R7,
R5 is a phenyl group which is unsubstituted or monosubstituted or polysubstituted by Hal, OH, OA, A, S-A, NO2, NH2, NHA, NA2, NH-acyl, NHSO2A, NASO2A, NH(CO)NH2, NH(CO)NHA, formyl, NHCOOA, NA-acyl, NHCOO-alkylene-OA, NH(CO)NA2, N-piperidinyl-CONH, N-pyrrolidinyl-CONH, O(CH2)nCOOA, O(CH2)nCOOH, O(CH2)nOH, O(CH2),OA, CH2OH, CH2OA, COOH, COOA, CH2COOH or CH2COOA,
A is alkyl having 1-6 carbon atoms, in which one or two CH2 groups may be replaced by O or S atoms or by CR6 CR6 groups andor 1-7H atoms may be replaced by F,
D is carbonyl or C(R6R6)m,
E is CH2, S or O,
Y is O or S,
R6 and R6 are each, independently of one another, H, F or A,
R7 is Hal, OH, OA, O-alkylene-R6, A, S-A, S-OA, SO2A, SOR, SO2R2, NO2, NH2, NHA, NA2, NH-acyl, NHSO2A, NHSO2R5, NASO2A, NASO2R5, NH(CO)NH2, NH(CO)NHA, formyl, NH(CO)NHR6, NHCOOA, NA-acyl, NHCOOCH2R5, NHSO2CH2R5, NHCOO-alkylene-OA, NH(CO)NA2, 1-piperidinyl-CONH, 1-pyrrolidinyl-CONH, O(CH2)nCOOA, O(CH2),COOH, O(CH2),OH, O(CH2),OA, CH2OH, CH2OA, COOH, COOA, CH2COOH or CH2COOA,
R8 is a 5-7-membered heterocyclic radical having 14 N, O andor S atoms or is
156
G and Z are each, independently of one another, CH, N, O or S,
L is CH, CHCH or CH2CH2CH2,
Hal is fluorine, chlorine, bromine or iodine,
n is 0, 1 or 2, and
m is 1 or 2,
or a tautomeric cyclised form, and the (E)-isomers and the salts of all isomers;
m) the compounds of the formula i described in WO 9841515
157
in which
X is O or S,
R1 is H, Hal, OH, OA, A, NO2, NH2, NHA, NAA, NHCOR4, NHCOR6, NHSO2R4, NHSO2R6, S(O)mR6, SO3H, SO2NR4R4 or formyl,
R2 and R3 are each, independently of one another, A, (CH2),Ar, (CH2),Het, CH2COAr, CH2COHet or OAr,
R2 is additionally also H,
R3 is COOR4, CN, 1H-tetrazol-5-yl or CONHSO2R6,
R4 and R4 are each, independently of one another, H or A,
R5 is A or Ar,
R6 is phenyl or naphthyl, each of which is unsubstituted or monosubstituted, disubstituted or trisubstituted by A, NH2, NHA, NAA, NO2, CN or Hal,
R7 and R1 are each, independently of one another, H or alkyl having 1-6 carbon atoms,
A and A are each, independently of one another, alkyl having 1-6 carbon atoms, in which one or two CH2 groups may be replaced by O or S atoms or by CR7CR groups andor 1-7H atoms may be replaced by F, or benzyl,
Ar is phenyl or naphthyl, each of which is unsubstituted or monosubstituted, disubstituted or trisubstituted by A, OR4, NH2, NHA, NAA, NO2, CN, Hal, NHCOR4, NHCORB, NHSO2R4, NHSO2R4, COOR4, OPh, CONH2, CONHA, CONAA, COR4, CONHSO2R4, CONHSO2R6, O(CH2)nCOOR4, O(CH2)nOR4, SO3H, SO2NR4R4, S(O)mR6 or S(O)mR4,
Het is a monocyclic or bicyclic, saturated, unsaturated or aromatic heterocyclic radical having 1-4 N, O andor S atoms, bonded via N or C, which may be unsubstituted or monosubstituted, disubstituted or trisubstituted by
Hal, A, R3, NH2, NHA, NAA, NO2 andor O,
Hal is fluorine, chlorine, bromine or iodine,
m is 0, 1 or 2, and
n is 1 or 2,
where, if R2 is CH2COAr and RZ is H, R3 is not COOA,
and salts thereof;
n) the compounds of the formula I described in WO 9841521
158
in which
Z is a single or double bond,
R1 is a
159
which is unsubstituted or monosubstituted in the phenyl part by R7, or is a
160
which is unsubstituted or monosubstituted in the cyclohexadienyl part by R1,
R2 is A, Ar-(CH2)m, cycloalkyl-(CH2)m, Het-(CH2)m or R1(CH2)m,
R3 and R3 are each, independently of one another, OR4, NHSO2R5, NH2, NHA or NAA,
R1 and R1 together are alternatively O, forming a cyclic anhydride,
R4 and R4 are each, independently of one another, H or A,
R5 is A or Ar,
R6 is phenyl or naphthyl, each of which is unsubstituted or monosubstituted, disubstituted or trisubstituted by A, NH2, NHA, NAA, NO2, CN or Hal,
R7 is A, COOR4, CN, 1H-tetrazol-5-yl, CONHSO2R5, Hal, OR4, NO2, NH2, NHA, NAA, NHCOR4, NHCOR6, NHSO2R4, NHSO2R6, S(O)kR4, S(O)kR4, SO2NR4R4 or formyl,
R8 and R8 are each, independently of one another, H or alkyl having 1-6 carbon atoms,
E is CH, or O,
D is carbonyl or (CR4R4)n,
E and D together are alternatively CR4R4,
X is S or O,
A and A are each, independently of one another, alkyl having 1-6 carbon atoms, in which one or two CH2 groups may be replaced by O or S atoms or by CR8CR8 groups andor 1-7H atoms may be replaced by F, or benzyl,
Ar is phenyl or naphthyl, each of which is unsubstituted or monosubstituted, disubstituted or trisubstituted by A, OR4, NH2, NHA, NAA, NO2, CN, Hal, NHCOR4, NHCOR8, NHSO2R4, NHSO2R6, COOR4, OPh, CONH2, CONHA, CONAA, COR4, CONHSO2R4, CONHSO2R6, O(CH2)nCOOR4, O(CH2)nOR4, SO2NR4R4, S(O)kR6 or S(O)kR4,
Het is a monocyclic or bicyclic, saturated, unsaturated or aromatic heterocyclic radical having 1-4 N, O andor S atoms, bonded via N or C, which may be unsubstituted, monosubstituted or disubstituted or trisubstituted by Hal, A, COOR4, CN, 1H-tetrazol-5-yl, CONHSO2R5, NH2, NHA, NAA, NO2 andor O,
Hal is fluorine, chlorine, bromine or iodine,
k is 0, 1 or 2,
m is 0, 1 or 2, and
n is 1 or 2,
and the (Z)- and (E)-isomers and the salts of all isomers;
o) the compounds of the formula I described in WO 9842702
161
in which
R
162
X and Y are each, independently of one another, O or S,
R1 is H, Hal, OH, OA, A, alkylene-O-A, NO2, NH., NH-acyl, SO2NH2, SO2-A, SO2NHA, CN or formyl,
R2, R3 and R4 are each, independently of one another, a phenyl group which is unsubstituted or monosubstituted or polysubstituted by Hal, OH, OA, O-alkylene-R5, A, S-A, S-OA, SO2A, SOR5, SO2R5, NO2, NH2, NHA, NA2, NH-acyl, NHSO2A NHSO2R5, NASOA, NASO2R5, NH(CO)NH2, NH(CO)NHA, formyl, NH(CO)NHR5, NHCOOA, NA-acyl, NHCOOCH2R5, NHSO2CH2R5, NHCOO-alkylene-OA, NH(CO)NA2, 1-piperidinyl-CONH, 1-pyrrolidinyl-CONH, O(CH2),COOA, O(CH2),COOH, O(CH2)nOH, O(CH2)nOA, CH2OH, CH2OA, COOH, COOA, CH2COOH or CH2COOA,
163
R2 is additionally A or cycloalkyl,
R5 is a phenyl group which is unsubstituted or monosubstituted or polysubstituted by Hal, OH, OA, A, 8-A, NO2, NH2, NHA, NA2, NH-acyl, NHSO2A, NASO2A, NH(CO)NH2, NH(CO)NHA, formyl, NHCOOA, NA-acyl, NHCOO-alkylene-OA, NH(CO)NA2, N-piperidinyl-CONH, N-pyrrolidinyl-CONH, O(CH2)nCOOA, O(CH2)nCOOH, O(CH2)nOH, O(CH2)nOA, CH2OH, CH2OA, COOH, COOA, CH2COOH or CH2COOA,
A is alkyl having 1-6 carbon atoms, in which one or two CH2 groups may be replaced by O or S atoms or by CR6CR6 groups andor 1-7H atoms may be replaced by F,
D is carbonyl or IC(R6R6))m,
E is CH2, S or O,
R6 and R6 are each, independently of one another, H, F or A,
R7 is OC(Y)-NHR1,
R8 is alkyl having 1-10 carbon atoms which is unsubstituted or monosubstituted or disubstituted by R1 and in which 1-2 carbon atoms may be replaced by 0 andor S, andor may be substituted by O, or cycloalkyl, in which 1-2 carbon atoms may be replaced by N, O andor S,
R9 is phenyl which is unsubstituted or monosubstituted or disubstituted by Hal, or is naphthyl, A-OC(O) or Hal,
Hal is fluorine, chlorine, bromine or iodine,
n is 0, 1 or 2, and
m is 1 or 2,
and salts thereof;
p) the compounds of the formula I described in WO 9842709
164
in which
X is NR3, O or S,
R is 2,1,3-benzothiadiazol-4- or 5-yl or 2,1-benzoisothiazol-5- or 6-yl, each of which is unsubstituted or monosubstituted or disubstituted by R2 andor R2, or phenyl which is unsubstituted or monosubstituted, disubstituted or trisubstituted by R2 andor R2,
R1 is H or A,
R2 and R2 are each, independently of one another, H, A, OH, OA,
Hal, OCF3, OCHF2, OCO-A, O-alkylene-COOR1, O-alkylene-CH2OR1, or OCH2-phenyl or OCO-phenyl, each of which is unsubstituted or monosubstituted or disubstituted in the phenyl part by R4 andor R4,
R2 and R2 together are alternatively OCH2O, OCH2CH2O or OCH2CH2,
R3 is H, A, alkylene-O-A, CO-OA, or alkylene-phenyl which is unsubstituted or monosubstituted or disubstituted in the phenyl part by R4 andor R4,
R4 and R4 are each, independently of one another, H, A, OH, OA,
Hal, COOR1 or CH2OR1,
A is alkyl having 1-6 carbon atoms,
Hal is fluorine, chlorine, bromine or iodine,
and their salts;
q) the compounds of the formula I described in WO 9905132
165
in which
R
166
X is O or S,
R1 is H, Hal, OA or A,
R2, R3, R5, and R6 are each, independently of one another, H, Hal, A, OA or R4,
R4 is O(CH2)n-Cy,
Cy is cycloalkyl having 3-8 carbon atoms,
A is alkyl having 1-6 carbon atoms, in which one or two CH2 groups may be replaced by O or S atoms or by CR5CR5 groups andor 1-7H atoms may be replaced by F.
R5 and R5 are each, independently of one another, H, F or A,
Hal is fluorine, chlorine, bromine or iodine,
n is 0, 1 or 2 ,
or a tautomeric cyclised form, and the (E)-isomers and the salts of all isomers.
42. Pharmaceutical formulation according to one of the preceding claims, comprising one or more excipients andor assistants.
43. Use of a pharmaceutical preparation according to one of claims 31 to 42 for the preparation of a medicament for the treatment of angina, high blood pressure, high pulmonary pressure, congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), cor pulmonale, dextrocardiac insufficiency, atherosclerosis, conditions of reduced patency of the heart vessels, peripheral vascular diseases, strokes, bronchitis, allergic asthma, chronic asthma, allergic rhinitis, glaucoma, irritable bowel syndrome, tumours, renal insufficiency, liver cirrhosis, erectile dysfunction and for the treatment of female sexual disorders.
44. Use according to claim 43 for the preparation of a medicament for the treatment of high pulmonary pressure, congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), cor pulmonale andor dextrocardiac insufficiency.
45. Set (kit) consisting of separate packs of
(a) an effective amount of 5-4-(3-chloro-4-methoxybenzylamino)-5,6,7,8-tetrahydro-1-benzothieno2,3-dpyrimidin-2-ylvaleric acid andor physiologically acceptable salts andor solvates thereof and
(b) an effective amount of an endothelin receptor antagonist.