Claims
- 1. A compound of Formula (I) or (II), or a pharmaceutically acceptable salt thereof; wherein the compound of Formula (I) is:
- 2. A composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier.
- 3. The compound of claim 1, wherein X is:
- 4. The compound of claim 1, wherein the compound of Formula (I) is a nitrosated acemetacin, a nitrosated aceclofenac, a nitrosated alminoprofen, a nitrosated amfenac, a nitrosated bendazac, a nitrosated benoxaprofen, a nitrosated bromfenac, a nitrosated bucloxic acid, a nitrosated butibufen, a nitrosated carprofen, a nitrosated cinmetacin, a nitrosated clopirac, a nitrosated diclofenac, a nitrosated etodolac, a nitrosated felbinac, a nitrosated fenclozic acid, a nitrosated fenbufen, a nitrosated fenoprofen, a nitrosated fentiazac, a nitrosated flunoxaprofen, a nitrosated flurbiprofen, a nitrosated ibufenac, a nitrosated ibuprofen, a nitrosated indomethacin, a nitrosated isofezolac, a nitrosated isoxepac, a nitrosated indoprofen, a nitrosated ketoprofen, a nitrosated lonazolac, a nitrosated loxoprofen, a nitrosated metiazinic acid, a nitrosated mofezolac, a nitrosated miroprofen, a nitrosated naproxen, a nitrosated oxaprozin, a nitrosated pirozolac, a nitrosated pirprofen, a nitrosated pranoprofen, a nitrosated protizinic acid, a nitrosated salicylamide, a nitrosated sulindac, a nitrosated suprofen, a nitrosated suxibuzone, a nitrosated tiaprofenic acid, a nitrosated tolmetin, a nitrosated xenbucin, a nitrosated ximoprofen, a nitrosated zaltoprofen a nitrosated zomepirac; the compound of Formula II is a nitrosated aspirin, a nitrosated acemetcin, a nitrosated bumadizon, a nitrosated carprofenac, a nitrosated clidanac, a nitrosated diflunisal, a nitrosated enfenamic acid, a nitrosated fendosal, a nitrosated flufenamic acid, a nitrosated flunixin, a nitrosated gentisic acid, a nitrosated ketorolac, a nitrosated meclofenamic acid, a nitrosated mefenamic acid, a nitrosated mesalamine, a nitrosated niflumic acid, a nitrosated salsalate, a nitrosated tolfenamic acid or a nitrosated tropensin.
- 5. A method for treating or reducing inflammation, pain or fever in a patient in need thereof comprising administering to the patient a therapeutically effective amount of the composition of claim 2.
- 6 A method for treating a gastrointestinal disorder in a patient in need thereof comprising administering to the patient a therapeutically effective amount of the composition of claim 2.
- 7. The method of claim 6, wherein the gastrointestinal disorder is an inflammatory bowel disease, Crohn's disease, gastritis, irritable bowel syndrome, constipation, ulcerative colitis, a peptic ulcer, a stress ulcer, a bleeding ulcer, gastric hyperacidity, dyspepsia, gastroparesis, Zollinger-Ellison syndrome, gastroesophageal reflux disease, a bacterial infection, short-bowel (anastomosis) syndrome, or a hypersecretory state associated with systemic mastocytosis or basophilic leukemia and hyperhistaminemia.
- 8. A method for facilitating wound healing in a patient in need thereof comprising administering to the patient a therapeutically effective amount of the composition of claim 2.
- 9. The method of claim 8, wherein the wound is an ulcer.
- 10. A method for treating or reversing gastrointestinal, renal and/or respiratory toxicity in a patient in need thereof comprising administering to the patient a therapeutically effective amount of the composition of claim 2.
- 11. A method for treating an inflammatory disease in patient in need thereof comprising administering to the patient a therapeutically effective amount of the composition of claim 2.
- 12. The method of claim 11, wherein the inflammatory disease is a cardiovascular disorder, reperfusion injury to an ischemic organ, angiogenisis, arthritis, asthma, bronchitis, premature labor, tendinitis, bursitis, an autoimmune disease, an immunological disorder, a skin-related condition, neoplasia, an inflammatory process in a disease, pulmonary inflammation, a central nervous system disorder, allergic rhinitis, respiratory distress syndrome, endotoxin shock syndrome, a microbial infection, a bacterial-induced inflammation, a viral induced inflammation, a urinary disorder, a urological disorder, endothelial dysfunction, organ deterioration, tissue deterioration, a sexual dysfunction or activation, adhesion and infiltration of neutrophils at the site of inflammation.
- 13. The method of claim 12, wherein the neoplasia is a brain cancer, a bone cancer, an epithelial cell-derived neoplasia (epithelial carcinoma), a basal cell carcinoma, an adenocarcinoma, a gastrointestinal cancer, a lip cancer, a mouth cancer, an esophageal cancer, a small bowel cancer, a stomach cancer, a colon cancer, a liver cancer, a bladder cancer, a pancreas cancer, an ovary cancer, a cervical cancer, a lung cancer, a breast cancer, a skin cancer, a squamus cell cancer, a basal cell cancer, a prostate cancer, a renal cell carcinoma, a cancerous tumor, a growth, a polyp, an adenomatous polyp, a familial adenomatous polyposis or a fibrosis resulting from radiation therapy.
- 14. The method of claim 12, wherein the central nervous system disorder is cortical dementia, Alzheimer's disease, vascular dementia, multi-infarct dementia, pre-senile dementia, alcoholic dementia, senile dementia, memory loss or central nervous system damage resulting from stroke, ischemia or trauma.
- 15. A method for treating an ophthalmic disorder in a patient in need thereof comprising administering to the patient a therapeutically effective amount of the composition of claim 2.
- 16. The composition of claim 2, further comprising at least one therapeutic agent.
- 17. The composition of claim 16, wherein the therapeutic agent is a steroid, a nonsteroidal antiinflammatory compound, a cyclooxygenase inhibitor, a 5-lipoxygenase (5-LO) inhibitor, a leukotriene B4 receptor antagonist, a leukotriene A4 hydrolase inhibitor, a 5-HT agonist, a 3-hydroxy-3-methylglutaryl coenzyme A inhibitor, a H2 antagonist, an antineoplastic agent, an antiplatelet agent, a thrombin inhibitor, a thromboxane inhibitor, a decongestant, a diuretic, a sedating or non-sedating anti-histamine, an inducible nitric oxide synthase inhibitor, an opioid, an analgesic, a Helicobacter pylori inhibitor, a proton pump inhibitor, an isoprostane inhibitor, or a mixture of two or more thereof.
- 18. A method for treating or reducing inflammation, pain or fever in a patient in need thereof comprising administering to the patient a therapeutically effective amount of the composition of claim 16.
- 19. A method for treating a gastrointestinal disorder in a patient in need thereof comprising administering to the patient a therapeutically effective amount of the composition of claim 16.
- 20. The method of claim 19, wherein the gastrointestinal disorder is an inflammatory bowel disease, Crohn's disease, gastritis, irritable bowel syndrome, constipation, ulcerative colitis, a peptic ulcer, a stress ulcer, a bleeding ulcer, gastric hyperacidity, dyspepsia, gastroparesis, Zollinger-Ellison syndrome, gastroesophageal reflux disease, a bacterial infection, short-bowel (anastomosis) syndrome, or a hypersecretory state associated with systemic mastocytosis or basophilic leukemia and hyperhistaminemia.
- 21. A method for facilitating wound healing in a patient in need thereof comprising administering to the patient a therapeutically effective amount of the composition of claim 16.
- 22. The method of claim 21, wherein the wound is an ulcer.
- 23. A method for treating or reversing gastrointestinal, renal and/or respiratory toxicity in a patient in need thereof comprising administering to the patient a therapeutically effective amount of the composition of claim 16.
- 24. A method for for treating an inflammatory disease in patient in need thereof comprising administering to the patient a therapeutically effective amount of the composition of claim 16.
- 25. The method of claim 24, wherein the inflammatory disease is a cardiovascular disorder, reperfusion injury to an ischemic organ, angiogenisis, arthritis, asthma, bronchitis, premature labor, tendinitis, bursitis, an autoimmune disease, an immunological disorder, a skin-related condition, neoplasia, an inflammatory process in a disease, pulmonary inflammation, a central nervous system disorder, allergic rhinitis, respiratory distress syndrome, endotoxin shock syndrome, a microbial infection, a bacterial-induced inflammation, a viral induced inflammation, a urinary disorder, a urological disorder, endothelial dysfunction, organ deterioration, tissue deterioration, a sexual dysfunction or activation, adhesion and infiltration of neutrophils at the site of inflammation.
- 26. The method of claim 25, wherein the neoplasia is a brain cancer, a bone cancer, an epithelial cell-derived neoplasia (epithelial carcinoma), a basal cell carcinoma, an adenocarcinoma, a gastrointestinal cancer, a lip cancer, a mouth cancer, an esophageal cancer, a small bowel cancer, a stomach cancer, a colon cancer, a liver cancer, a bladder cancer, a pancreas cancer, an ovary cancer, a cervical cancer, a lung cancer, a breast cancer, a skin cancer, a squamus cell cancer, a basal cell cancer, a prostate cancer, a renal cell carcinoma, a cancerous tumor, a growth, a polyp, an adenomatous polyp, a familial adenomatous polyposis or a fibrosis resulting from radiation therapy.
- 27. The method of claim 25, wherein the central nervous system disorder is cortical dementia, Alzheimer's disease, vascular dementia, multi-infarct dementia, pre-senile dementia, alcoholic dementia, senile dementia, memory loss or central nervous system damage resulting from stroke, ischemia or trauma.
- 28. A method for treating an ophthalmic disorder in a patient in need thereof comprising administering to the patient a therapeutically effective amount of the composition of claim 16.
- 29. A composition comprising at least one compound of claim 1 and at least one compound that donates, transfers or releases nitric oxide, or induces the production of endogenous nitric oxide or endothelium-derived relaxing factor, or is a substrate for nitric oxide synthase.
- 30. The composition of claim 29, further comprising a pharmaceutically acceptable carrier.
- 31. The composition of claim 29, wherein the compound that donates, transfers, or releases nitric oxide, or induces the production of endogenous nitric oxide or endothelium-derived relaxing factor or is a substrate for nitric oxide synthase is an S-nitrosothiol.
- 32. The composition of claim 31, wherein the S-nitrosothiol is S-nitroso-N-acetylcysteine, S-nitroso-captopril, S-nitroso-N-acetylpenicillamine, S-nitroso-homocysteine, S-nitroso-cysteine, S-nitroso-glutathione, or S-nitroso-cysteinyl-glycine.
- 33. The composition of claim 31, wherein the S-nitrosothiol is:
(i) HS(C(Re)(Rf))mSNO; (ii) ONS(C(Re)(Rf))mRe; or (iii) H2N—CH(CO2H)—(CH2)m—C(O)NH—CH(CH2SNO)—C(O)NH—CH2—CO2H; wherein m is an integer from 2 to 20; Re and Rf are each independently a hydrogen, an alkyl, a cycloalkoxy, a halogen, a hydroxy, an hydroxyalkyl, an alkoxyalkyl, an arylheterocyclic ring a cycloalkylalkyl, a heterocyclicalkyl, an alkoxy, a haloalkoxy, an amino, an alkylamino, a dialkylamino, an arylamino, a diarylamino, an alkylarylamino, an alkoxyhaloalkyl, a haloalkoxy, a sulfonic acid, a sulfonic ester, an alkylsulfonic acid, an arylsulfonic acid, an arylalkoxy, an alkylthio, an arylthio, a cyano, an aminoalkyl, an aminoaryl, an aryl, an arylalkyl, a carboxamido, a alkylcarboxamido, an arylcarboxamido, an amidyl, a carboxyl a carbamoyl, an alkylcarboxylic acid, an arylcarboxylic acid, an alkylcarbonyl, an arylcarbonyl, an ester, a carboxylic ester, an alkylcarboxylic ester, an arylcarboxylic ester, a haloalkoxy, a sulfonamido, an alkylsulfonamido, an arylsulfonamido, an alkylsulfonyl, an alkylsulfonyloxy, an arylsulfonyl, an arylsulfonyloxy, a urea, a nitro, -T-Q-, or —(C(Rg)(Rh))k-T-Q or Re and Rf taken together are an oxo, a thial, a heterocyclic ring, a cycloalkyl group, an oxime, a hydrazone or a bridged cycloalkyl group; Q is —NO or —NO2; and T is independently a covalent bond, a carbonyl, an oxygen, —S(O)o— or —N(Ra)Ri—, wherein o is an integer from 0 to 2, Ra is a lone pair of electrons, a hydrogen or an alkyl group; Ri is a hydrogen, an alkyl, an aryl, an alkylcarboxylic acid, an arylcarboxylic acid, an alkylcarboxylic ester, an arylcarboxylic ester, an alkylcarboxamido, an arylcarboxamido, an alkylsulfinyl, an alkylsulfonyl, an alkylsulfonyloxy, an arylsulfinyl, an arylsulfonyloxy, an arylsulfonyl, a sulfonamido, a carboxamido, a carboxylic ester, an aminoalkyl, an aminoaryl, —CH2—C(T-Q)(Rg)(Rh), or —(N2O2—)−.M+, wherein M+ is an organic or inorganic cation; with the proviso that when Ri is —CH2—C(T-Q)(Rg)(Rh) or —(N2O2—).M+; then “-T-Q” can be a hydrogen, an alkyl group, an alkoxyalkyl group, an aminoalkyl group, a hydroxy group or an aryl group; and Rg and Rh at each occurrence are independently Re.
- 34. The composition of claim 29, wherein the compound that donates, transfers, or releases nitric oxide, or induces the production of endogenous nitric oxide or endothelium-derived relaxing factor, or is a substrate for nitric oxide synthase is L-arginine, L-homoarginine, N-hydroxy-L-arginine, nitrosated L-arginine, nitrosylated L-arginine, nitrosated N-hydroxy-L-arginine, nitrosylated N-hydroxy-L-arginine, nitrosated L-homoarginine, nitrosylated L-homoarginine), citrulline, ornithine, glutamine, lysine, an arginase inhibitor or a nitric oxide mediator.
- 35. The composition of claim 29, wherein the compound that donates, transfers, or releases nitric oxide, or induces the production of endogenous nitric oxide or endothelium-derived relaxing factor, or is a substrate for nitric oxide synthase is:
(i) a compound that comprises at least one ON—O— or ON—N— group; (ii) a compound that comprises at least one O2N—O—, O2N—N— or O2N—S— or group; (iii) a N-oxo-N-nitrosoamine having the formula: R1″R2″N—N(O-M+)—NO, wherein R1″ and R2″ are each independently a polypeptide, an amino acid, a sugar, an oligonucleotide, a straight or branched, saturated or unsaturated, aliphatic or aromatic, substituted or unsubstituted hydrocarbon, or a heterocyclic group, and M+ is an organic or inorganic cation.
- 36. The composition of claim 35, wherein the compound comprising at least one ON—O— or ON—N— group is an ON—O-polypeptide, an ON—N-polypeptide, an ON—O-amino acid, an ON—N-amino acid, an ON—O-sugar, an ON—N-sugar, an ON—O-oligonucleotide, an ON—N-oligonucleotide, a straight or branched, saturated or unsaturated, substituted or unsubstituted, aliphatic or aromatic ON—O-hydrocarbon, a straight or branched, saturated or unsaturated, substituted or unsubstituted, aliphatic or aromatic ON—N-hydrocarbon, an ON—O-heterocyclic compound or an ON—N-heterocyclic compound.
- 37. The composition of claim 35, wherein compound comprising at least one O2N—O—, O2N—N— or O2N—S— group is an O2N—O-polypeptide, an O2N—N-polypeptide, an O2N—S-polypeptide, an O2N—O-amino acid, O2N—N-amino acid, O2N—S-amino acid, an O2N—O-sugar, an O2N—N-sugar, O2N—S-sugar, an O2N—O-oligonucleotide, an O2N—N-oligonucleotide, an O2N—S-oligonucleotide, a straight or branched, saturated or unsaturated, aliphatic or aromatic, substituted or unsubstituted O2N—O-hydrocarbon, a straight or branched, saturated or unsaturated, aliphatic or aromatic, substituted or unsubstituted O2N—N-hydrocarbon, a straight or branched, saturated or unsaturated, aliphatic or aromatic, substituted or unsubstituted O2N—S-hydrocarbon, an O2N—O-heterocyclic compound, an O2N—N-heterocyclic compound or an O2N—S-heterocyclic compound.
- 38. The composition of claim 29, further comprising at least one therapeutic agent.
- 39. The composition of claim 38, wherein the therapeutic agent is a steroid, a nonsteroidal antiinflammatory compound, a cyclooxygenase-2 inhibitor, a 5-lipoxygenase (5-LO) inhibitor, a leukotriene B4 receptor antagonist, a leukotriene A4 hydrolase inhibitor, a 5-HT agonist, a HMG CoA inhibitor, a H2 antagonist, an antineoplastic agent, an antiplatelet agent, a thrombin inhibitor, a thromboxane inhibitor, a decongestant, a diuretic, a sedating or non-sedating anti-histamine, an inducible nitric oxide synthase inhibitor, an opioid, an analgesic, a Helicobacter pylori inhibitor, a proton pump inhibitor, an isoprostane inhibitor, or a mixture of two or more thereof.
- 40. A method for treating or reducing inflammation, pain or fever in a patient in need thereof comprising administering to the patient a therapeutically effective amount of the composition of claim 29 or 38.
- 41. A method for treating a gastrointestinal disorder in a patient in need thereof comprising administering to the patient a therapeutically effective amount of the composition of claim 29 or 38.
- 42. The method of claim 41, wherein the gastrointestinal disorder is an inflammatory bowel disease, Crohn's disease, gastritis, irritable bowel syndrome, constipation, ulcerative colitis, a peptic ulcer, a stress ulcer, a bleeding ulcer, gastric hyperacidity, dyspepsia, gastroparesis, Zollinger-Ellison syndrome, gastroesophageal reflux disease, a bacterial infection, short-bowel (anastomosis) syndrome, or a hypersecretory state associated with systemic mastocytosis or basophilic leukemia and hyperhistaminemia.
- 43. A method for facilitating wound healing in a patient in need thereof comprising administering to the patient a therapeutically effective amount of the composition of claim 29 or 38.
- 44. The method of claim 43, wherein the wound is an ulcer.
- 45. A method for treating or reversing gastrointestinal, renal and/or respiratory toxicity in a patient in need thereof comprising administering to the patient a therapeutically effective amount of the composition of claim 29 or 38.
- 46. A method for treating inflammatory disease in patient in need thereof comprising administering to the patient a therapeutically effective amount of the composition of claim 29 or 38.
- 47. The method of claim 46, wherein the inflammatory disease is a cardiovascular disorder, reperfusion injury to an ischemic organ, angiogenisis, arthritis, asthma, bronchitis, premature labor, tendinitis, bursitis, an autoimmune disease, an immunological disorder, a skin-related condition, neoplasia, an inflammatory process in a disease, pulmonary inflammation, a central nervous system disorder, allergic rhinitis, respiratory distress syndrome, endotoxin shock syndrome, a microbial infection, a bacterial-induced inflammation, a viral induced inflammation, a urinary disorder, a urological disorder, endothelial dysfunction, organ deterioration, tissue deterioration, a sexual dysfunction or activation, adhesion and infiltration of neutrophils at the site of inflammation.
- 48. The method of claim 47, wherein the neoplasia is a brain cancer, a bone cancer, an epithelial cell-derived neoplasia (epithelial carcinoma), a basal cell carcinoma, an adenocarcinoma, a gastrointestinal cancer, a lip cancer, a mouth cancer, an esophageal cancer, a small bowel cancer, a stomach cancer, a colon cancer, a liver cancer, a bladder cancer, a pancreas cancer, an ovary cancer, a cervical cancer, a lung cancer, a breast cancer, a skin cancer, a squamus cell cancer, a basal cell cancer, a prostate cancer, a renal cell carcinoma, a cancerous tumor, a growth, a polyp, an adenomatous polyp, a familial adenomatous polyposis or a fibrosis resulting from radiation therapy.
- 49. The method of claim 47, wherein the central nervous system disorder is cortical dementia, Alzheimer's disease, vascular dementia, multi-infarct dementia, pre-senile dementia, alcoholic dementia, senile dementia, memory loss or central nervous system damage resulting from stroke, ischemia or trauma.
- 50. A method for treating an ophthalmic disorder in a patient in need thereof comprising administering to the patient a therapeutically effective amount of the composition of claim 29 or 38.
- 51. A kit comprising at least one compound of claim 1.
- 52. The kit of claim 51, further comprising (i) at least one compound that donates, transfers or releases nitric oxide, induces the production of endogenous nitric oxide or endothelium-derived relaxing factor, or is a substrate for nitric oxide synthase; (ii) at least one therapeutic agent; or (iii) at least one compound that donates, transfers or releases nitric oxide, induces the production of endogenous nitric oxide or endothelium-derived relaxing factor, or is a substrate for nitric oxide synthase and at least one therapeutic agent.
- 53. The kit of claim 52, wherein the at least one compound that donates, transfers or releases nitric oxide, induces the production of endogenous nitric oxide or endothelium-derived relaxing factor, or is a substrate for nitric oxide synthase; the at least one therapeutic agent; or the at least one compound that donates, transfers or releases nitric oxide, induces the production of endogenous nitric oxide or endothelium-derived relaxing factor, or is a substrate for nitric oxide synthase and at least one therapeutic agent; are in the form of separate components in the kit
- 54. A kit comprising the composition of claim 16, 29 or 38.
- 55. A compound selected from the group consisting of
2-(2-(nitrooxy)ethylthio)ethyl (2S)-2-(6-methoxy(2-naphthyl))propanoate; 2-((2-(nitrooxy)ethyl)sulfonyl)ethyl (2S)-2-(6-methoxy(2-naphthyl))propanoate; 2-((2-(nitrooxy)ethyl)sulfinyl)ethyl (2S)-2-(6-methoxy(2-naphthyl))propanoate; 2-((2-(nitrooxy)ethyl)4-nitrophenyl)amino)ethyl 2-(6-methoxy-2-naphthyl)propanoate; 2R)-2,3-bis(nitrooxy)propyl(2S)-2(6-methoxy(2-naphthyl)propanoate; (2R)-7-(nitrooxy)-4,8-dioxabicyclo(3.3.0)oct-2-yl(2S)-2-(6-methoxy (2-naphthyl)) propanoate; phosphonomethyl (2S)-2-(6-methoxy(2-naphthyl))propanoate 3-(nitrooxy) propylamine nitric acid salt; phosphonomethyl (2S)-2-(6-methoxy(2-naphthyl))propanoate 4-nitro-1-(nitrooxy)-2-((nitrooxy)methyl)but-2-ylamine salt; (5-((nitrooxy)methyl-1,3-dioxan-5-yl)methyl (2S)-2-(6-methoxy(2-naphthyl))-propanoate; 2,2-bis(nitrooxy)propyl (2S)-2-(6-methoxy(2-naphthyl))propanoate; 3-(4-((nitrooxy)methyl)phenylcarbonyloxy)-2-oxopropyl (2S)-2-(6-methoxy(2-naphthyl))propanoate; 2-methyl-2-nitro-3-(nitrooxy)propyl(2S)-2-(6-methoxy(2-naphthyl))propanoate; 2-nitro-3-(nitrooxy)-2-((nitrooxy)methyl)propyl (2S)-2-(6-methoxy(2-naphthyl))propanoate; 2-(N-(2-(nitrooxy)ethyl)carbamoyloxy)ethyl (2S)-2-(6-methoxy(2-naphthyl))propanoate; 3-(2-(nitrooxy)ethoxy)phenyl (2S)-2-(6-methoxy(2-naphthyl)propanoate; 4-(2-(nitrooxy)ethoxy)phenyl (2S)-2-(6-methoxy(2-naphthyl))propanoate; (N-methyl-N-(2-(nitrooxy)ethyl)carbamoyl)methyl (2S)-2-(6-methoxy(2-naphthyl))propanoate; (N-ethyl-N-(2-(nitrooxy)ethyl)carbamoyl)methyl (2S)-2-(6-methoxy(2-naphthyl))propanoate; 2-(4-((nitrooxy)methyl)piperidyl)-2-oxoethyl (2S)-2-(6-methoxy(2-naphthyl))propanoate; (N-methyl-N-(((2-(nitrooxy)ethyl)oxycarbonyl)methyl)carbamoyl)methyl (2S)-2-(6-methoxy(2-naphthyl))propanoate; (N-methyl-N-(((3-(nitrooxy)propyl)oxycarbonyl)methyl)carbamoyl)methyl (2S)-2-(6-methoxy(2-naphthyl))propanoate; (N-methyl-N-((N-(2-(nitrooxy)ethyl)carbamoyl)methyl)carbamoyl)methyl (2S)-2-(6-methoxy(2-naphthyl))propanoate; ((2-(nitrooxy)ethyl)oxycarbonyl)methyl 2-(6-methoxy-2-naphthyl)propanoate; (N-(3-(nitrooxy)propyl)carbamoyl)methyl 2-(6-methoxy-2-naphthyl)propanoate; ((2-((2-(nitrooxy)ethyl)sulfonyl)ethyl)oxycarbonyl)methyl 2-(6-methoxy-2-naphthyl)propanoate; 1S, 5S, 2R, 6R)-6-(nitrooxy)-4,8-dioxabicyclo(3.3.0)oct-2-yl)oxycarbonyl) methyl (2S)-2-(6-methoxy (2-naphthyl))propanoate; (2S)-2,3-bis(nitrooxy)propyl(2S)-2-(6-methoxy-5-nitro(2naphthyl)) propanoate; 2S)-2-hydroxy-3-(nitrooxy)propyl (2S)-2-(6-methoxy(2-naphthyl))propanoate; (2R)-2-hydroxy-3-(nitrooxy)propyl (2S)-2-(6-methoxy(2-naphthyl)) propanoate; (2S)-2 (6-methoxy(2-naphthyl))-N-((N-(2 (nitrooxy)ethyl)carbamoyl) methoxy)propanamide; 3-(2-(4-((nitrooxy)methyl)phenyl)acetyloxy)-2-oxopropyl (2S)-2-(6-methoxy(2-naphthyl))propanoate; 2-(4-(2-(nitrooxy)ethyl)piperidyl)-2-oxoethyl (2S)-2-(6-methoxy(2-naphthyl))propanoate; 4-((2-(nitrooxy)ethyl)oxycarbonyl)phenyl (2S)-2-(6-methoxy(2-naphthyl))propanoate; 2-((2-(nitrooxy)ethyl)oxycarbonyl)phenyl (2S)-2-(6-methoxy(2-naphthyl)propanoate; (N-methyl-N-(3-(nitrooxy)propyl)carbamoyl)methyl (2S)-2-(6-methoxy(2-naphthyl))propanoate; (2S)-2-(6-methoxy(2-naphthyl))N-(2-(4-((nitrooxy)methyl)piperidyl)-2-oxoethoxy)propanamide; 3-((2-(nitrooxy)ethyl)oxycarbonyl)phenyl (2S)-2-(6-methoxy(2-naphthyl)propanoate; 2-(4-(2-(nitrooxy)ethyl)piperazinyl)-2-oxoethyl (2S)-2-(6-methoxy(2-naphthyl))propanoate hydrogen chloride; 3-((2S)-2-(6-methoxy(2-naphthyl)propanoyloxy)-2-methyl-2-((nitrooxy)methyl)propyl (2S)-2-(6-methoxy(2-naphthyl)propanoate; 2-(4-(2-(nitrooxy)ethoxy)phenoxy)ethyl (2S)-2-(6-methoxy(2-naphthyl))propanoate; 2-((2S)-2-(6-methoxy(2-naphthyl))propanoyloxy)ethyl 3-(nitrooxy)-propyl ethane-1,2-dioate; N-((2S)-2-(6-methoxy(2-naphthyl))propanoylamino)-4 (nitrooxy)butanamide; 4-((2S)-2-(6-methoxy(2-naphthyl))propanoyloxy)(2S,3S)-2,3-bis(nitrooxy)butyl (2S)-2-(6-methoxy(2-naphthyl))propanoate (2S,3S)-2,3-bis(nitrooxy)-4-hydroxybutyl (2S)-2-(6-methyoxy(2-naphthyl))propanoate; 2-((3-((nitrooxy)methyl)phenyl)carbonylamino)ethyl (2S)-2-(6-methoxy(2-napthyl propanoate; (2R)-2-(nitrooxy)-3-(phenylmethoxy)propyl (2S)-2-(6-methoxy(2-naphthyl))propanoate; 2-(N-methyl(4-((nitrooxy)methyl)phenyl)carbonylamino)ethyl (2S)-2-(6-methoxy(2-naphthyl))propanoate; (1S,2S,5S,6R)-6-(nitrooxy)-4,8-dioxabicyclo(3.3.0)oct-2-yl 2-(1-((4-chlorophenyl)carbonyl)-5-methoxy-2-methylindol-3-yl)acetate; (1S,2S,5S,6R)-6-(nitrooxy)-4,8-dioxabicyclo(3.3.0)oct-2-yl 2-(2-((2,6-dichlorophenyl)amino)phenyl)acetate; 2-(((4-methylphenyl)sulfonyl)(2-(nitrooxy)ethyl)amino)ethyl (2S)-2-(6-methoxy(2-naphthyl))propanoate; 2-(N-methyl-2-(4-((nitrooxy)methyl)phenyl)acetylamino)ethyl (2S)-2-(6-methoxy(2-naphthyl))propanoate; (2R)-2,3-bis(nitrooxy)propyl 2-(1-((4-chlorophenyl)carbonyl)-5-methoxy-2-methylindol-3-yl)acetate; (2S)-2,3-bis(nitrooxy)propyl 2-(1-((4-chlorophenyl)carbonyl)-5-methoxy-2-methylindol-3-yl)acetate; (2S)-2,3-bis(nitrooxy)propyl 2-(2-((2,6-dichlorophenyl)amino)phenyl)acetate; (2R)-2,3-bis(nitrooxy)propyl 2-(2-((2,6-dichlorophenyl)amino)phenyl)acetate; (2S)-2-(6-methoxy(2-naphthyl))-1-(4-(nitrooxy)butylthio)propan-1-one; (N-methyl-N-(2-(nitrooxy)ethyl)carbamoyl)methyl 2-(1-((4-chlorophenyl)carbonyl)-5-methoxy-2-methylindol-3-yl)acetate; (N-(2-(nitrooxy)ethyl)carbamoyl)methyl 2-(1-((4-chlorophenyl)carbonyl)-5-methoxy-2-methylindol-3-yl)acetate; (N-(2-(nitrooxy)ethyl)carbamoyl)methyl 2-(2-((2,6-dichlorophenyl) amino)phenyl)acetate; or a pharmaceutically acceptable salt thereof.
- 56. A composition comprising at least one compound of claim 55 and a pharmaceutically acceptable carrier.
- 57. The composition of claim 56, further comprising (i) at least one compound that donates, transfers or releases nitric oxide, induces the production of endogenous nitric oxide or endothelium-derived relaxing factor, or is a substrate for nitric oxide synthase; (ii) at least one therapeutic agent; or (iii) at least one compound that donates, transfers or releases nitric oxide, induces the production of endogenous nitric oxide or endothelium-derived relaxing factor, or is a substrate for nitric oxide synthase and at least one therapeutic agent.
- 58. A kit comprising at least one compound of claim 55.
RELATED APPLICATIONS
[0001] This application claims priority to U.S. Application No. 60/393,111 filed Jul. 3, 2002; U.S. Application No. 60/397,979 filed Jul. 24, 2002; U.S. Application No. 60/418,353 filed Oct. 16, 2002; U.S. Application No. 60/449,798 filed Feb. 26, 2003; and to U.S. Application No. 60/456,182 filed Mar. 21, 2003.
Provisional Applications (5)
|
Number |
Date |
Country |
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60393111 |
Jul 2002 |
US |
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60397979 |
Jul 2002 |
US |
|
60418353 |
Oct 2002 |
US |
|
60449798 |
Feb 2003 |
US |
|
60456182 |
Mar 2003 |
US |
Patent Application
20040024057
