Novel use of guanylate cyclase activators for the treatment of respiratory insufficiency

• US 20050181066A1
• Filed: 04/24/2003
• Published: 08/18/2005
• Est. Priority Date: 04/26/2002
• Status: Abandoned Application

• Current Assignee: Altana Pharma AG (Takeda Pharmaceutical Company Limited)
• Original Assignee: Altana Pharma AG (Takeda Pharmaceutical Company Limited)
• Inventors: Schudt, Christian, Schermuly, Ralph, Grimminger, Friedrich Josef
• Application Number:
  US10/512,547
• Publication Number:
  US 20050181066A1
• Time in Patent Office: Days
• US Class Current: 424/608
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/21 Esters, e.g. nitroglycerine, selenocyanates
• CPC Class Codes: A61K 31/295 Iron group metal compounds
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/495 having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazinesA61K31/48 takes precedence ; with three nitrogen atoms A61K31/53
• CPC Class Codes: A61K 31/50 Pyridazines; Hydrogenated pyridazines
• CPC Class Codes: A61K 31/535 having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
• CPC Class Codes: A61K 38/10 Peptides having 12 to 20 amino acids A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61K 38/12 Cyclic peptides , e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61K 38/16 Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof enzyme inhibitors A61K38/005
• CPC Class Codes: A61K 38/2242 Atrial natriuretic factor complex: Atriopeptins, atrial natriuretic protein [ANP]; Cardionatrin, Cardiodilatin
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 11/08 Bronchodilators
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: A61P 9/12 Antihypertensives

Abstract

The invention relates to the novel use of guanylate cyclase activators for the treatment of partial and global respiratory failure.

Claims

1-19. -19. (canceled)

20. A pharmaceutical preparation comprising at least one guanylate cyclase activator and at least one nonselectively vasodilating antiobstructive agent.

21. A method of treating partial and global respiratory failure in a patient comprising administering to a patient in need thereof a therapeutically effective amount of a pharmaceutical preparation as claimed in claim 20.

22. A method of treating a disease or disorder in a patient comprising administering to a patient in need thereof a therapeutically effective amount of a pharmaceutical preparation as claimed in claim 20, wherein the disease or disorder is selected from the group consisting of COPD, bronchial asthma, latent pulmonary hypertension, emphysema, combined ventilation disturbances and chronic left heart failure with pulmonary congestion.

23. A pharmaceutical preparation according to claim 20, wherein the guanylate cyclase activator is an active ingredient selected from the group consisting of (9S,11S)-4-amino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-6,7,9,10-tetrahydro-5,9-methanopyrimido[4,5-d][1,3,6]oxadiazocin-11-ol, 5-cyclopropyl-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-pyrimidine-4-amine (BAY-41-2272), 2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-(4-morpholinyl)pyrimidine-4,6-diamine (BAY-41-8543), trans-4-acetamidocyclohexyl nitrate (BM-12.1307), 1-[2-(1,3-dimethyl-2-butenylidene)hydrazino]phthalazine (BUDRALAZINE), ethyl 3-{6-[N-(2-hydroxypropyl)-N-ethylamino]-3-pyridazinyl}carbazate (CADRALAZINE), trans-1,4-di(hydroxymethyl)cyclohexane dinitrate ester (CEDO-8956), 1-benzyl-3-[3-(dimethylamino)propoxy]-N-(4-methoxyphenyl)-1H-pyrazole-5-carboxamide (CFM-1571), 4-phenyl-3-(phenylsulfonyl)furazan 2-oxide (CHF-2206), 8-hydroxy-2-(nitratomethyl)-7-nitro-1,4-benzodioxane (E-4701), 1,2,3-propanetriyl trinitrate (GLYCEROL TRINITRATE), 1,4:

3,6-dianhydro-D-glucitol dinitrate (ISOSORBIDE DINITRATE), 1,4;

3,6-dianhydro-D-glucitol 5-mononitrate (ISOSORBIDE MONONITRATE), 6-methyl-3-[2-(nitrooxy)ethyl]-3,4-dihydro-2H-1,3-benzoxazin-4-one (ITF-1129), 7-[2-[4-(2-chlorophenyl)piperazin-1-yl]ethyl]-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione (KMUP-1), N-cyano-N′

-(2-nitrooxyethyl)-3-pyridinecarboxamidine (KRN-2391), 3-(2-nitrooxyethyl-3,4-dihydro-2H-1,3-benzoxazin-4-one (SINITRODIL), sodium pentacyanonitrosylferrate(II) (SODIUM NITROPRUSSIDE), N-(3-nitratopivaloyl)cysteine ethyl ester (SPM-3672), 3-[2-(acetamido)propionylthio]-2(R)-[2,2-dimethyl-3-(nitrooxy)propionamido]propionic acid ethyl ester (SPM-5185), 1,4;

3,6-dianhydro-2-deoxy-2-[[3-(1,2,3,6-tetrahydro-1,3-dimethyl-2,6-dioxopurin-7-yl)propyl]amino]-L-iditol 5-nitrate (TEOPRANITOL), glutaminyl-glutamyl-aspartyl-cysteinyl-glutamyl-leucyl-cysteinyl-isoleucyl-asparaginyl-valyl-alanyl-cysteinyl-threonyl-glycyl-cysteine (UROGUANYLINE), 1-benzyl-3-[5-(hydroxymethyl)furan-2-yl]-1H-indazole (YC-1), L-arginyl-L-seryl-L-seryl-L-cysteinyl-L-phenylalanylglycylglycyl-L-arginyl-L-methionyl-L-aspartyl-L-arginyl-L-isoleucyl-glycyl- L-alanyl-L-glutaminyl-L-serylglycyl-L-leucylglycyl-L-cysteinyl-L-asparaginyl-L-seryl-L-phenylalanyl-L-arginyl-L-tyrosine, cyclic (4→

20) disulfide (ANARITIDE), 1-de-L-leucine-2-de-L-alanine-3-deglycine-4-de-L-proline-5-de-L-arginine-17-L-methionine-atriopeptin-33 (rat) (CARPERITIDE), seryl-prolyl-lysyl-methionyl-valyl-glutaminyl-glycyl-seryl-glycyl-cysteinyl-phenylalanyl-glycyl-arginyl-lysyl-methionyl- aspartyl-arginyl-isoleucyl-seryl-seryl-seryl-seryl-glycyl-leucyl-glycyl-cysteinyl-lysyl-valyl-leucyl-arginyl-arginyl-histidine, cyclic (S-3.10-S-3.26)-disulfide (NESIRITIDE), 4-(N-(4-carboxybutyl)-N-[2-[2-[4-(2-phenylethyl)benzyloxy]phenyl]ethyl]aminomethyl]benzoic acid, 3-[2-(4-chlorophenylsulfanyl)-phenyl]-N-[4-(dimethylamino)butyl]-2-propanamide, 3-[2-(4-chlorophenylsulfanyl)phenyl]-N-[4-(dimethylamino)butyl]-2-propenamide and the pharmacologically acceptable salts of these compounds.

24. A pharmaceutical preparation according to claim 20, wherein the guanylate cyclase activator is an active ingredient selected from the group consisting of BM-12.1307, BUDRALAZINE, CADRALAZINE, GLYCEROL TRINITRATE, ISOSORBIDE DINITRATE, ISOSORBIDE MONONITRATE, KRN-2391, SINITRODIL, SODIUM NITROPRUSSIDE, TEOPRANITOL, ANARITIDE, CARPERITIDE, NESIRITIDE and the pharmacologically acceptable salts of these compounds.

25. A method of treating partial and global respiratory failure in a human in need thereof comprising the step of administering to said human a therapeutically effective amount of a guanylate cyclase activator.

26. A method according to claim 25 wherein the human in need is showing a mismatch of pulmonary ventilation and pulmonary perfusion.

27. The method according to claim 25, wherein the human in need has an exercise-dependent mismatch.

28. The method according to claim 25, wherein the human in need has an age-related mismatch.

29. The method according to claim 25, wherein the human in need has a pathologically caused mismatch.

30. The method according to claim 25, wherein the human in need has a mismatch of V/Q<

0.1.

31. The method according to claim 25, wherein the human in need is a COPD patient.

32. The method according to claim 31, wherein the human in need is a COPD patient with a predominant bronchitis component.

33. The method according to claim 31, wherein the human in need is a COPD patient with a V/Q<

0.1.

34. The method according to claim 31, wherein the human in need is a COPD patient with an emphysematous component.

35. The method according to claim 31, wherein the human in need is a COPD patient with a V/Q>

10.

36. A method according to claim 25, wherein the human in need has orthopnoea.

37. A method according to claim 25, wherein the human in need has sleep apnoea.

38. The method according to claim 25, wherein the human in need has a therapy-induced mismatch.

39. The method according to claim 38, wherein the human in need has a mismatch caused by administration of nonselectively vasodilating medicaments.

40. The method according to claim 39, wherein the nonselectively vasodilating medicament is a non-selectively vasodilating antiobstructive agent.

41. The method according to claim 40, wherein the nonselectively vasodilating antiobstructive agent is selected from the group consisting of endothelin antagonist, Ca channel blocker, ACE inhibitor, ATII antagonist and β

blocker.

43. The method according to claim 25, wherein the guanylate cyclase activator is an active ingredient selected from the group consisting of (9S,11S)-4-amino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-6,7,9,10-tetrahydro-5,9-methanopyrimido[4,5-d][1,3,6]oxadiazocin-11-ol, 5-cyclopropyl-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidine-4-amine (BAY-41-2272), 2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-(4-morpholinyl)pyrimidine-4,6-diamine (BAY-41-8543), trans-4-acetamidocyclohexyl nitrate (BM-12.1307), 1-[2-(1,3-dimethyl-2-butenylidene)hydrazino]-phthalazine (BUDRALAZINE), ethyl 3-{6-[N-(2-hydroxypropyl)-N-ethylamino]-3-pyridazinyl}-carbazate (CADRALAZINE), trans-1,4-di(hydroxymethyl)cyclohexane dinitrate ester (CEDO-8956), 1-benzyl-3-[3(dimethylamino)propoxy]-N-(4-methoxyphenyl)-1H-pyrazole-5-carboxamide (CFM-1571), 4-phenyl-3-(phenylsulfonyl)furazan 2-oxide (CHF-2206), 8-hydroxy-2-(nitratomethyl)-7-nitro-1,4-benzodioxane (E-4701), 1,2,3-propanetriyl trinitrate (GLYCEROL TRINITRATE), 1,4:

3,6-dianhydro-D-glucitol dinitrate (ISOSORBIDE DINITRATE), 1,4;

3,6-dianhydro-D-glucitol 5-mononitrate (ISOSORBIDE MONONITRATE), 6-methyl-3-[2-(nitrooxy)ethyl]-3,4-dihydro-2H-1,3-benzoxazin-4-one (ITF-1129), 7-[2-[4-(2-chlorophenyl)piperazin-1-yl]ethyl]-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione (KMUP-1), N-cyano-N′

-(2-nitrooxyethyl)-3-pyridinecarboxamidine (KRN-2391), 3-(2-nitrooxyethyl)-3,4-dihydro-2H-1,3-benzoxazin-4-one (SINITRODIL), sodium pentacyanonitrosyl-ferrate(II) (SODIUM NITROPRUSSIDE), N-(3-nitratopivaloyl)cysteine ethyl ester (SPM-3672), 3-[2-(acetamido)propionylthio]-2(R)-[2,2-dimethyl-3-(nitrooxy)-propionamido]propionic acid ethyl ester (SPM-5185), 1,4;

3,6-dianhydro-2-deoxy-2-[[3-(1,2,3,6-tetrahydro-1,3-dimethyl-2,6-dioxopurin-7-yl)propyl]amino]-L-iditol 5-nitrate (TEOPRANITOL), glutaminyl-glutamyl-aspartylcysteinyl-glutamyl-leucyl-cysteinyl-isoleucyl-asparaginyl-valyl-alanyl-cysteinyl-threonyl-glycyl-cysteine (UROGUANYLINE), 1-benzyl-3-[5-(hydroxymethyl)furan-2-yl]-1H-indazole (YC-1), L-arginyl-L-seryl-L-seryl-L-cysteinyl-L-phenylalanylglycylglycyl-L-arginyl-L-methionyl-L-aspartyl-L-arginyl-L-isoleucyl-glycyl- L-alanyl-L-glutaminyl-L-serylglycyl-L-leucylglycyl-L-cysteinyl-Lasparaginyl-L-seryl-L-phenylalanyl-L-arginyl-L-tyrosine, cyclic (4→

20) disulfide (ANARITIDE), 1-de-L-leucine-2-de-L-alanine-3-deglycine-4-de-L-proline-5-de-L-arginine-17-L-methionine-atriopeptin-33 (rat) (CARPERITIDE), seryl-prolyl-lysyl-methionyl-valyl-glutaminyl-glycyl-seryl-glycyl-cysteinyl-phenylalanyl-glycyl-arginyl-lysyl-methionyl- aspartyl-arginyl-isoleucyl-seryl-seryl-seryl-seryl-glycyl-leucyl-glycyl-cysteinyl-lysyl-valyl-leucyl-arginyl-arginyl-histidine, cyclic (S-3.10-S-3.26)-disulfide (NESIRITIDE), 4-[N-(4-carboxybutyl)-N-[2-[2-[4-(2-phenylethyl)benzyloxy]phenyl]ethyl]aminomethyl]benzoic acid, 3-[2-(4-chlorophenylsulfanyl)-phenyl]-N-[4-(dimethylamino)butyl]-2-propanamide, 3-[2-(4-chlorophenylsulfanyl)phenyl]-N-[4-(dimethylamino)butyl]-2-propenamide and the pharmacologically acceptable salts of these compounds.

44. The method according to claim 25, wherein the guanylate cyclase activator is an active ingredient selected from the group consisting of BM-12.1307, BUDRALAZINE, CADRALAZINE, GLYCEROL TRINITRATE, ISOSORBIDE DINITRATE, ISOSORBIDE MONONITRATE, KRN-2391, SINITRODIL, SODIUM NITROPRUSSIDE, TEOPRANITOL, ANARITIDE, CARPERITIDE, NESIRITIDE and the pharmacologically acceptable salts of these compounds.

42. A method of treating muscular dysfunction in a human showing a perfusion/demand mismatch comprising the step of administering to said human a therapeutically effective amount of a guanylate cyclase activator.

45. The method according to claim 42, wherein the guanylate cyclase activator is an active ingredient selected from the group consisting of (9S,11S)-4-amino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-6,7,9,10-tetrahydro-5,9-methanopyrimido[4,5-d][1,3,6]oxadiazocin-11-ol, 5-cyclopropyl-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidine-4-amine (BAY-41-2272), 2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-(4-morpholinyl)pyrimidine-4,6-diamine (BAY-41-8543), trans-4-acetamidocyclohexyl nitrate (BM-12.1307), 1-[2-(1,3-dimethyl-2-butenylidene)hydrazino]-phthalazine (BUDRALAZINE), ethyl 3-{6-[N-(2-hydroxypropyl)-N-ethylamino]-3-pyridazinyl}-carbazate (CADRALAZINE), trans-1,4-di(hydroxymethyl)cyclohexane dinitrate ester (CEDO-8956), 1-benzyl-3-[3-(dimethylamino)propoxy]-N-(4-methoxyphenyl)-1H-pyrazole-5-carboxamide (CFM-1571), 4-phenyl-3-(phenylsulfonyl)furazan 2-oxide (CHF-2206), 8-hydroxy-2-(nitratomethyl)-7-nitro-1,4-benzodioxane (E-4701), 1,2,3-propanetriyl trinitrate (GLYCEROL TRINITRATE), 1,4:

3,6-dianhydro-D-glucitol dinitrate (ISOSORBIDE DINITRATE), 1,4;

3,6-dianhydro-D-glucitol 5-mononitrate (ISOSORBIDE MONONITRATE), 6-methyl-3-[2-(nitrooxy)ethyl)-3,4-dihydro-2H-1,3-benzoxazin-4-one (ITF-1129), 7-[2-[4-(2-chlorophenyl)piperazin-1-yl]ethyl]-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione (KMUP-1), N-cyano-N′

-(2-nitrooxyethyl)-3-pyridinecarbox-amidine (KRN-2391), 3-(2-nitrooxyethyl)-3,4-dihydro-2H-1,3-benzoxazin-4-one (SINITRODIL), sodium pentacyanonitrosyl-ferrate(II) (SODIUM NITROPRUSSIDE), N-(3-nitratopivaloyl)cysteine ethyl ester (SPM-3672), 3-[2-(acetamido)propionylthio]-2(R)-[2,2-dimethyl-3-(nitrooxy)-propionamido]propionic acid ethyl ester (SPM-5185), 1,4;

3,6-dianhydro-2-deoxy-2-[[3-(1,2,3,6-tetrahydro-1,3-dimethyl-2,6-dioxopurin-7-yl)propyl]amino]-L-iditol 5-nitrate (TEOPRANITOL), glutaminyl-glutamyl-aspartylcysteinyl-glutamyl-leucyl-cysteinyl-isoleucyl-asparaginyl-valyl-alanyl-cysteinyl-threonyl-glycyl-cysteine (UROGUANYLINE), 1-benzyl-3-[5-(hydroxymethyl)furan-2-yl]-1H-indazole (YC-1), L-arginyl-L-seryl-L-seryl-L-cysteinyl-L-phenylalanylglycylglycyl-L-arginyl-L-methionyl-L-aspartyl-L-arginyl-L-isoleucyl-glycyl-L- alanyl-L-glutaminyl-L-serylglycyl-L-leucylglycyl-L-cysteinyl-Lasparaginyl-L-seryl-L-phenylalanyl-L-arginyl-L-tyrosine, cyclic (4→

20) disulfide (ANARITIDE), 1-de-L-leucine-2-de-L-alanine-3-deglycine-4-de-L-proline-5-de-L-arginine-17-L-methionine-atriopeptin-33 (rat) (CARPERITIDE), seryl-prolyl-lysyl-methionyl-valyl-glutaminyl-glycyl-seryl-glycyl-cysteinyl-phenylalanyl-glycyl-arginyl-lysyl-methionyl- aspartyl-arginyl-isoleucyl-seryl-seryl-seryl-seryl-glycyl-leucyl-glycyl-cysteinyl-lysyl-valyl-leucyl-arginyl-arginyl-histidine, cyclic (S-3.10-S-3.26)-disulfide (NESIRITIDE), 4-[N-(4-carboxybutyl)-N-[2-[2-[4-(2-phenylethyl)benzyloxy]phenyl]ethyl]aminomethyl]benzoic acid, 3-[2-(4-chlorophenylsulfanyl)-phenyl]-N-[4-(dimethylamino)butyl]-2-propanamide, 3-[2-(4-chlorophenylsulfanyl)phenyl]-N-[4-(dimethylamino)butyl]-2-propenamide and the pharmacologically acceptable salts of these compounds.

46. The method according to claim 42, wherein the guanylate cyclase activator is an active ingredient selected from the group consisting of BM-12.1307, BUDRALAZINE, CADRALAZINE, GLYCEROL TRINITRATE, ISOSORBIDE DINITRATE, ISOSORBIDE MONONITRATE, KRN-2391, SINITRODIL, SODIUM NITROPRUSSIDE, TEOPRANITOL, ANARITIDE, CARPERITIDE, NESIRITIDE and the pharmacologically acceptable salts of these compounds.