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1. WO2000025776 - COMPOSES ANTI-INFLAMMATOIRES NON STEROIDIENS NITROSES ET NITROSYLES, COMPOSITIONS ET PROCEDES D'UTILISATION

Note: Texte fondé sur des processus automatiques de reconnaissance optique de caractères. Seule la version PDF a une valeur juridique

[ EN ]

CLAIMS
What is claimed is:
1. A compound of formula (I), formula (II), formula (III) or formula (IV), wherein the compound of formula (I) is:



(I)

wherein
Rg is a hydrogen atom or a lower alkyl group;
Rh is:












or


n is an integer of 0 or 1;
X is:
(i) -T-B,-W-Bt-T-NOs;
(ii) -T-BrLy-Bx-T-NOs;
(iii) -T-B,-W-Bt-Wx-Bk-T-NOs;
(iv) -T-B,-(C(Rb)(RJ)p-Ex-T-NOs;
(v) -T-BrG-Bt-Wz-Bk-Gx-Br-T-NOs;
(viii) -T-B,-J-Ex-T-NOs; or
(ix) -T-B,-C(Re)=N-Ez-T-NOs;
wherein
s is an integer of 1 or 2;
T at each occurence is independently a covalent bond, a carbonyl, an oxygen,
-S(0)0- or -N(R Rr;
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 aryl carboxylic acid, an alkylcarboxylic ester, an arylcarboxylic ester, an alkylcarboxamido, an arylcarboxamido, an alkylaryl, an alkylsulfinyl, an alkylsulfonyl, an arylsulfinyl, an arylsulfonyl, a sulfonamido, a carboxamido, a carboxylic ester, an amino alkyl, an amino aryl, -CH2-C(T-Q)(Re)(Rf), or -(N202-)"»M+, wherein M+ is an organic or inorganic cation;
L at each occurrence is independently -C(O)-, -C(S)-, -T-, a heterocyclic ring, an aryl group, an alkenyl group, an alkynyl group, an arylheterocyclic ring, or -(CH2CH20)q;
q is an integer from 1 to 5;
B at each occurrence is independently an alkyl group, an aryl group, or -(C(Re)(Rf))p-, a heterocyclic ring, an aryl heterocyclic ring, or -(CH2CH20)q;
p is an integer from 1 to 10;
Re and Rf are each independently a hydrogen, an alkyl, a cycloalkoxy, a halogen, a hydroxy, an hydroxyalkyl, an alkoxyalkyl, an arylheterocyclic ring, an alkylaryl, 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, an alkylsulfonic acid, an arylsulfonic acid, an arylalkoxy, an alkylthio, an arylthio, a cyano, an aminoalkyl, an aminoaryl, an alkoxy, an aryl, an arylalkyl, an alkylaryl, a carboxamido, a alkyl carboxamido, an aryl carboxamido, an amidyl, a carboxyl, a carbamoyl, an alkylcarboxylic acid, an arylcarboxylic acid, an ester, a carboxylic ester, an alkylcarboxylic ester, an arylcarboxylic ester, a haloalkoxy, a sulfonamido, an alkylsulfonamido, an arylsulfonamido, a urea, a nitro, -T- NOs , or (C(Re)(Rf))k-T- NOs, or Re and Rf taken together are a heterocyclic ring, a cycloalkyl group or a bridged cycloalkyl group;

Rb and Rc are each independently a haloalkyl, an alkenyl group, an akynyl group, a bridged cycloalkyl group, a heterocyclic ring, a cycloalkoxy, a halogen, a hydroxy, an hydroxyalkyl, an alkoxyalkyl, an arylheterocyclic ring, an alkylaryl, 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, an alkylsulfonic acid, an arylsulfonic acid, an arylalkoxy, an alkylthio, an arylthio, a cyano, an aminoalkyl, an aminoaryl, an alkoxy, an arylalkyl, an alkylaryl, a carboxamido, an alkyl carboxamido, an aryl carboxamido, an amidyl, a carboxyl, a carbamoyl, an alkylcarboxylic acid, an arylcarboxylic acid, an ester, a carboxylic ester, an alkylcarboxylic ester, an arylcarboxylic ester, a haloalkoxy, a sulfonamido, an alkylsulfonamido, an arylsulfonamido, a urea, a nitro, -T- NOs , or (C(Re)(Rf))k-T- NOs, or Rb and Rc taken together are a carbonyl, a methanthial, a heterocyclic ring, a cycloalkyl group or a bridged cycloalkyl group;
G is a covalent bond, -T-C(O)-, -C(0)-T- or T;
J is a carbonyl, a phosphoryl or a silyl;
k, 1, t and z are each independently an integer from 1 to 3;
y is an interger from 1 to 3;
x and r are each independently an interger from 0 to 3;
E at each occurrence is independently -C(O)-, -C(S)-, -T-, -(C(Re)(Rf))p-, an alkyl group, an aryl group, a heterocyclic ring, arylheterocyclic ring, or -(CH2CH20)q;
W is oxygen, -S(0)0-, -N(Ra)Rr, carbonyl, or methanthial;
with the proviso that when R, is -CH2-C(T-NOs)(Re)(Rf) or -(N202)"»M+, or Rb, Rc, Re or Rf are T- NOs or (C(Re)(R£))k-T- NOs, then the "-T- NOs " subgroup designated in X can be a hydrogen, an alkyl, an alkoxy, an alkoxyalkyl, an aminoalkyl, a hydroxy, a heterocyclic ring or an aryl group;
wherein the compound of formula (II) is:
0

RK — C- X
(II)

wherein
Rk is:





and X is as defined as herein;
wherein the compound of formula (III) is:


(HI)

wherein
X is as defined herein;
R, at each occurrence is independently R„ wherein R, is as defined herein;
Z is an aryl group; and
Au A2 and A3 comprise the other subunits of a 5- or 6-membered monocyclic aromatic ring and each of Al7 A2 and A3 is independently:
(1) C-RQ, wherein R0 at each occurrence is independently a
hydrogen, an alkyl, an alkoxyalkyl, a halogen or a nitro group;
(2) N-Rp, wherein Rp at each occurrence is independently a
covalent bond to an adjacent ring atom in order to render the ring
aromatic, a hydrogen, an alkyl, an arylalkyl, an aryl or a heteroaryl
group;
(3) a sulfur atom;
(4) an oxygen atom; or
(5) Ba=Bb, wherein Ba and Bb are each independently a nitrogen
atom or C-R0 wherein R0 is as defined herein;
wherein the compound of formula (IV) is:

(TV)
wherein
Rm is an alkyl group or an aryl group; and X, Z, Av A2 and A3 are as defined herein.
2. The compound of claim 1, wherein the compound is a nitrosated and/or nitrosylated aryl propionic acid compound, a nitrosated and/or
nitrosylated aryl acetic acid compound, a nitrosated and/or nitrosylated enolic anilide or a nitrosated and /or nitrosylated oxicam compound.
3. The compound of claim 2, wherein the nitrosated and/or nitrosylated aryl acetic acid or aryl propionic acid compound is aceclofenac, alcofenac, amfenac, brofenac, diclofenac, etodac, felbinac, flurbiprofen, fenoprofen, fenbufen, ibuprofen, indomethacin, indoprofen, ketoprofen, lonazolac, loxoprofen, mofezolac, miroprofen, naproxen, oxaprozin, pirprofen, sulindac, tiaprofen, or tolmetin; wherein the nitrosated and/or nitrosylated aryl acid compound is aspirin, acemetacin, carprofenac, diflunisal, etofenamate, flufenamic, flufenac, ketorolac, meclofenamic, mefenamic, or tolfenamic; wherein the nitrosated and/or nitrosylated enolic anilide is tenidap; wherein the nitrosated and/or nitrosylated oxicam compound is droxicam, piroxicam, isoxicam, lornoxicam, or ampiroxicam. 4. A composition comprising the compound of claim 1 and a
pharmaceutically acceptable carrier.
5. A method for treating, preventing or reducing inflammation, pain and fever in a patient in need thereof comprising administering to the patient a therapeutically effective amount of the pharmaceutical composition of claim 4.
6. A method for treating or reversing the gastrointestinal, renal or other toxicities resulting from the use of a nonsteroidal antiinflammatory compound by a patient comprising administering to the patient a therapeutically effective amount of the pharmaceutical composition of claim 4.
7. A method for treating or preventing a gastrointestinal disorder in a patient in need thereof comprising administering to the patient a therapeutically effective amount of the pharmaceutical composition of claim 4.
8. The method of claim 7, wherein the gastrointestinal disorder is a peptic ulcer, gastric hyperacidity, dyspepsia, gastroparesis, Zollinger-Ellison syndrome, gastroesophageal reflux disease, a stress ulcer, a bleeding peptic ulcer, short bowel syndrome, or a hypersecretory state associated with systemic mastocytosis or basophilic leukemia and hyperhistaminemia.
9. A method for treating an inflammatory disease or disorder in a patient in need thereof comprising administering to the patient a therapeutically effective amount of the pharmaceutical composition of claim 4.
10. The method of claim 9, wherein the inflammatory disease or disorder is reperfusion injury to an ischemic organ, myocardial infarction, inflammatory bowel disease, rheumatoid arthritis, osteoarthritis, hypertension, psoriasis, organ transplant rejection, organ preservation, a female or male sexual dysfunction, radiation-induced injury, asthma, atherosclerosis, thrombosis, platelet aggregation, restenosis, metastasis, influenza, incontinence, stroke, burn, trauma, acute pancreatitis, pyelonephritis, hepatitis, an autoimmune disease, an immunological disorder, senile dementia, insulin-dependent diabetes mellitus, disseminated intravascular coagulation, fatty embolism, Alzheimer's disease, adult or infantile respiratory disease, carcinogenesis or a hemorrhage in a neonate.
11. A method for treating or preventing an ophthalmic disease or disorder in a patient in need thereof comprising administering to the patient a therapeutically effective amount of the pharmaceutical composition of claim 4.
12. The method of claim 11, wherein the ophthalmic disease or disorder is glaucoma, inflammation of the eye or elevation of intraocluar pressure.
13. 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.
14. The composition of claim 13, 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.
15. The composition of claim 14, wherein the S-nitrosothiol is S-nitroso- N-acetylcysteine, S-nitroso-captopril, S-nitroso-N-acetylpenicillamine, S-nitroso- homocysteine, S-nitroso-cysteine or S-nitroso-glutathione.
16. The composition of claim 14, wherein the S-nitrosothiol is:
(i) HS(C(Re)(Rf))mSNO;
(ii) ONS(C(Re)(Rf))mRe; and
(iii) H2N-CH(C02H)-(CH2)m-C(0)NH-CH(CH2SNO)-C(0)NH-CH2-C02H; 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, an alkylaryl, 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, an alkylsulfonic acid, an arylsulfonic acid, an arylalkoxy, an alkylthio, an arylthio, a cyano, an aminoalkyl, an aminoaryl, an alkoxy, an aryl, an arylalkyl, an alkylaryl, a carboxamido, a alkyl carboxamido, an aryl carboxamido, an amidyl, a carboxyl, a carbamoyl, an alkylcarboxylic acid, an arylcarboxylic acid, an ester, a carboxylic ester, an alkylcarboxylic ester, an arylcarboxylic ester, a haloalkoxy, a sulfonamido, an alkylsulfonamido, an arylsulfonamido, a urea, a nitro, or -T-Q; or Rc and Rf taken together are a carbonyl, a methanthial, a heterocyclic ring, a cycloalkyl group or a bridged cycloalkyl group; Q is -NO or -N02; and T is independently a covalent bond, a carbonyl, an oxygen, -S(0)0- or -N(Ra)Rr, wherein o is an integer from 0 to 2, Ra is a lone pair of electrons, a hydrogen or an alkyl group; R; is a hydrogen, an alkyl, an aryl, an alkylcarboxylic acid, an aryl carboxylic acid, an alkylcarboxylic ester, an arylcarboxylic ester, an alkylcarboxamido, an arylcarboxamido, an alkylaryl, an alkylsulfinyl, an alkylsulfonyl, an arylsulfinyl, an arylsulfonyl, a sulfonamido, a carboxamido, a carboxylic ester, an amino alkyl, an amino aryl, -CH2-C(T-Q)(Re)(Rf), or -(N202-)"»M+, wherein M+ is an organic or inorganic cation; with the proviso that when R, is -CH2-C(T-Q)(Re)(Rf) or -(N202-)»M+; then "-T-Q" can be a hydrogen, an alkyl group, an alkoxyalkyl group, an aminoalkyl group, a hydroxy group or an aryl group.

17. The composition of claim 13, 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, citrulline, ornithine or glutamine.
18. The composition of claim 13, 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-, ON-N- or ON-C- group;
(ii) a compound that comprises at least one 02N-0-, 02N-N-, 02N-S- or -02N-C- group;
(iii) a N-oxo-N-nitrosoamine having the formula: R:R2-N(0-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; or
3. a thionitrate having the formula: R1-(S)-N02, wherein R1 is 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.
19. The composition of claim 18, wherein the compound comprising at least one ON-O-, ON-N- or ON-C- group is an ON-O-polypeptide, an ON-N-polypepetide, an ON-C-polypeptide, an ON-O-amino acid, an ON-N-amino acid, an ON-C-amino acid, an ON-O-sugar, an ON-N-sugar, an ON-C-sugar, an ON-O-oligonucleotide, an ON-N-oligonucleotide, an ON-C-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, a straight or branched, saturated or unsaturated, substituted or unsubstituted, aliphatic or aromatic ON-C-hydrocarbon, an ON-O-heterocyclic compound, an ON-N- heterocyclic compound or a ON-C-heterocyclic compound.
20. The composition of claim 18, wherein compound comprising at least one 02N-0-, 02N-N-, 02N-S- or 02N-C- group is an 02N-0-polypeptide, an 02N-N- polypeptide, an 02N-S-polypeptide, an 02N-C-polypeptide, an 02N-0-amino acid, 02N-N-amino acid, 02N-S-amino acid, an 02N-C-amino acid, an 02N-0-sugar, an 02N-N-sugar, 02N-S-sugar, an 02N-C-sugar, an 02N-0-oligonucleotide, an 02N-N- oligonucleotide, an 02N-S-oligonucleotide, an 02N-C-oligonucleotide, a straight or branched, saturated or unsaturated, aliphatic or aromatic, substituted or
unsubstituted 02N-0-hydrocarbon, a straight or branched, saturated or
unsaturated, aliphatic or aromatic, substituted or unsubstituted 02N-N- hydrocarbon, a straight or branched, saturated or unsaturated, aliphatic or aromatic, substituted or unsubstituted 02N-S-hydrocarbon, a straight or branched, saturated or unsaturated, aliphatic or aromatic, substituted or unsubstituted 02N-C-hydrocarbon, an 02N-0-heterocyclic compound, an 02N-N-heterocyclic compound, an 02N-S-heterocyclic compound or an 02N-C-heterocyclic compound.

21. A method for treating, preventing or reducing inflammation, pain and fever in a patient in need thereof comprising administering to the patient a therapeutically effective amount of the pharmaceutical composition of claim 13.
22. A method for treating or reversing the gastrointestinal, renal or other toxicities of a nonsteroidal antiinflammatory compound administered to a patient comprising administering to the patient a therapeutically effective amount of the pharmaceutical composition of claim 13.
23. A method for treating or preventing a gastrointestinal disorder in a patient in need thereof comprising administering to the patient a therapeutically effective amount of the pharmaceutical composition of claim 13.
24. The method of claim 23, wherein the gastrointestinal disorder is a peptic ulcer, gastric hyperacidity, dyspepsia, gastroparesis, Zollinger-Ellison syndrome, gastroesophageal reflux disease, a stress ulcer, a bleeding peptic ulcer, short bowel syndrome, or a hypersecretory state associated with systemic
mastocytosis or basophilic leukemia and hyperhistaminemia.
25. A method for treating an inflammatory disease or disorder in a patient in need thereof comprising administering to the patient a therapeutically effective amount of the pharmaceutical composition of claim 13.

26. The method of claim 25, wherein the inflammatory disease or disorder is reperfusion injury to an ischemic organ, myocardial infarction, inflammatory bowel disease, rheumatoid arthritis, osteoarthritis, hypertension, psoriasis, organ transplant rejection, organ preservation, a female or male sexual dysfunction, radiation-induced injury, asthma, atherosclerosis, thrombosis, platelet aggregation, restenosis, metastasis, influenza, incontinence, stroke, burn, trauma, acute pancreatitis, pyelonephritis, hepatitis, an autoimmune disease, an
immunological disorder, senile dementia, insulin-dependent diabetes mellitus, disseminated intravascular coagulation, fatty embolism, Alzheimer's disease, adult or infantile respiratory disease, carcinogenesis or a hemorrhage in a neonate.
27. A method for treating or preventing an ophthalmic disease or disorder in a patient in need thereof comprising administering to the patient a therapeutically effective amount of the pharmaceutical composition of claim 13.
28. The method of claim 27, wherein the ophthalmic disease or disorder is glaucoma, inflammation of the eye or elevation of intraocluar pressure.
29. A kit comprising at least one compound of claim 1.
30. A kit 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.
31. The kit of claim 30, 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 kit 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 or S-nitroso-glutathione.
33. The kit of claim 31, wherein the S-nitrosothiol is:
(i) HS(C(Re)(Rf))mSNO;
(ii) ONS(C(Re)(Rf))mRe; and
(iii) H2N-CH(C02H)-(CH2)m-C(0)NH-CH(CH2SNO)-C(0)NH-CH2-C02H; 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, an alkylaryl, 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, an alkylsulfonic acid, an arylsulfonic acid, an arylalkoxy, an alkylthio, an arylthio, a cyano, an aminoalkyl, an aminoaryl, an alkoxy, an aryl, an arylalkyl, an alkylaryl, a carboxamido, a alkyl carboxamido, an aryl carboxamido, an amidyl, a carboxyl, a carbamoyl, an alkylcarboxylic acid, an arylcarboxylic acid, an ester, a carboxylic ester, an alkylcarboxylic ester, an arylcarboxylic ester, a haloalkoxy, a sulfonamido, an alkylsulfonamido, an arylsulfonamido, a urea, a nitro, or -T-Q; or Re and Rf taken together are a carbonyl, a methanthial, a heterocyclic ring, a cycloalkyl group or a bridged cycloalkyl group; Q is -NO or -N02; and T is independently a covalent bond, a carbonyl, an oxygen, -S(0)0- or -N(R R,-, wherein o is an integer from 0 to 2, Ra is a lone pair of electrons, a hydrogen or an alkyl group; Rs is a hydrogen, an alkyl, an aryl, an alkylcarboxylic acid, an aryl carboxylic acid, an alkylcarboxylic ester, an arylcarboxylic ester, an alkylcarboxamido, an arylcarboxamido, an alkylaryl, an alkylsulfinyl, an alkylsulfonyl, an arylsulfinyl, an arylsulfonyl, a sulfonamido, a carboxamido, a carboxylic ester, an amino alkyl, an amino aryl, -CH2-C(T-Q)(Re)(Rf), or -(N202-)"»M+, wherein M+ is an organic or inorganic cation; with the proviso that when R{ is -CH2-C(T-Q)(Re)(Rf) or -(N202-)»M+; then "-T-Q" can be a hydrogen, an alkyl group, an alkoxyalkyl group, an aminoalkyl group, a hydroxy group or an aryl group.
34. The kit of claim 30, 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, citrulline, ornithine or glutamine.
35. The kit of claim 30, 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-, ON-N- or ON-C-group;
(ii) a compound that comprises at least one 02N-0-, 02N-N-, 02N-S- or -02N-C- group;
(iii) a N-oxo-N-nitrosoamine having the formula: R1R2-N(0-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; or
(iv) a thionitrate having the formula: R1-(S)-N02, wherein R1 is 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.
36. The kit of claim 35, wherein the compound comprising at least one ON-O-, ON-N- or ON-C- group is an ON-O-polypeptide, an ON-N-polypepetide, an ON-C-polypeptide, an ON-O-amino acid, an ON-N-amino acid, an ON-C-amino acid, an ON-O-sugar, an ON-N-sugar, an ON-C-sugar, an ON-O-oligonucleotide, an ON-N-oligonucleotide, an ON-C-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, a straight or branched, saturated or unsaturated, substituted or unsubstituted, aliphatic or aromatic ON-C-hydrocarbon, an ON-O-heterocyclic compound, an ON-N-heterocyclic compound or a ON-C-heterocyclic compound.
37. The kit of claim 35, wherein compound comprising at least one 02N- O, O.N-N-, 02N-S- or 02N-C- group is an 02N-0-polypeptide, an 02N-N- polypeptide, an 02N-S-polypeptide, an 02N-C-polypeptide, an 02N-0-amino acid, 02N-N-amino acid, 02N-S-amino acid, an 02N-C-amino acid, an 02N-0-sugar, an 02N-N-sugar, 02N-S-sugar, an 02N-C-sugar, an 02N-0-oligonucleotide, an 02N-N-oligonucleotide, an 02N-S-oligonucleotide, an 02N-C-oligonucleotide, a straight or branched, saturated or unsaturated, aliphatic or aromatic, substituted or
unsubstituted 02N-0-hydrocarbon, a straight or branched, saturated or
unsaturated, aliphatic or aromatic, substituted or unsubstituted 02N-N-hydrocarbon, a straight or branched, saturated or unsaturated, aliphatic or aromatic, substituted or unsubstituted 02N-S-hydrocarbon, a straight or branched, saturated or unsaturated, aliphatic or aromatic, substituted or unsubstituted 02N- C-hydrocarbon, an 02N-0-heterocyclic compound, an 02N-N-heterocyclic compound, an 02N-S-heterocyclic compound or an 02N-C-heterocyclic compound.

38. A compound selected from the group consisting of 2-[4-methyl-4- (nitrosothio)piperidyl]ethyl 2-{2-[(2,6-dichlorophenyl)amino]phenyl}acetate hydrochloride; 2-(methyl{[(nitrosothio)cyclohexyl]methyl}amino)ethyl 2-{2-[(2,6- dichlorophenyl)amino]phenyl}acetate hydrochloride; 2-(methyl{ [(nitroso thio) cyclohexyl]methyl}amino)ethyl (2S)-2-(6-methoxy(2-naphthyl))propanoate hydrochloride; 3-{methyl{[(nitrosothio)cyclohexyl]methyl}amino)propyl
2-{2-[(2,6-dichlorophenyl)amino]phenyl}acetate; 4-({methyl[2-methyl-2- (nitrosothio)propyl]amino}methyl)phenyl (2S)-2-(6-methoxy(2-naphthyl)) propanoate hydrochloride; 2-[4-(nitrosothio)-4-piperdyl]ethyl 2-{2-[(2,6- dichlorophenyl)amino]phenyl}acetate hydrochloride; 2-[2-(2-|2-[(2,6- dichlorophenyl)amino]phenyl}acetoxy)ethoxy]ethyl 3-(N-{[(nitrosothio)cyclohexyl] methyl}-N-benzylcarbamoyl)propanoate; 2-(4-[2-methyl-2-(nitrosothio)propyl] piperazinyljethyl 2-{2-[(2,6-dichlorophenyl)amino]phenyl}acetate citrate; 2-[2-(tert-butyl)-5-(nitrosothio)-l,3-dioxan-5-yl]ethyl (2S)-2-(6-methoxy(2-naphthyl)) propanoate; 5-(bis{[(nitrosothio)cyclohexyl]methyl)amino)pentyl (2S)-2-(6-methoxy(2-naphthyl))propanoate; 2-({3-[(2S)-2-(6-methyl(2-naphthyl))propanoyloxy] propyl} {[(nitrosothio)cyclohexyl]methyl}amino)acetic acid; 3-(methyl{[l-methyl-4-(nitrosothio)(4-piperidyl)]methyl}amino)propyl 2-{2-[(2,6-dichlorophenyl)amino] phenyl} acetate; 2-[l-methyl-4-(nitrosothio)-4-piperidyl]ethyl 2-{2-[(2,6-dichlorophenyl)amino]phenyl}acetate citrate; 2-[l-methyl-4-(nitrosothio)-4-piperidyl]ethyl 2-[4-(2-methylpropyl)phenyl]propanoate citrate; 2-[1-methyl -4-(nitrosothio)-4-piperidyl]ethyl (2S) 2-(6-methoxy(2-naphthyl)) propanoate citrate;
2-[l-methyl-4-(nitrosothio)-4-piperidyl]ethyl 2-[3-(phenylcarbonyl) phenyl] propanoate citrate; 2-[l-methyl-4-(nitrosothio)-4-piperidyl]ethyl 2{l-[(4-chlorophenyl) carbonyl]-5-methoxy-2-methylindol-3-yl}acetate citrate; 2-(methyl[2-methyl {[(nitrosothiol)cyclohexyl]methyl}amino)ethyl 2-{2-[(2,6-dichlorophenyl)amino] phenyl}acetate bis nitric acid salt; 2-{methyl[2-methyl{[(nitrosothiol)cyclohexyl] methyl}amino)ethyl 2-{l-[(4-chlorophenyl)carbonyl]-5-methoxy-2-methylindol-3-yl}acetate; 2-([(rrdmethylamino)ethyl]{[(nitrosothio)cyclohexyl]methyl}amino) ethyl 2-{2-[(2,6- dichorophenyl)amino]phenyl} acetate; 2-[4-methyl-4 (nitrosothio)piperidyl] ethyl (2S)-2-(6-methoxy(2-naphthyl))propanoate; 2-(methyl{[l-methyl-4-(nitrosothio) (4- piperidyl)]methyl}amino)ethyl (2S)-2-(6-methoxy(2-naphthyl))propanoate hydrochloride; 3-[4-methyl-4-(nitrosothio)piperidyl]propyl 2-{2-[(2,6- dichlorophenyl) amino]phenyl)acetate; 3-[4-methyl-4-(nitrosothio)piperidyl]propyl (2S)-2-(6-methoxy (2-naphthyl))propanoate; 2-[2-({N-[2-methyl-2- (nitrosothio)propyljcarbamoyl} methoxy) acetylamino]ethyl 2-{2-[(2,6- dichlorophenyl)amino]phenyl}acetate;
[2-({N-[2-methyl-2-(nitrosothio)propyl]carbamoyl}methoxy)acetyloxy]methyl 2-{2- [(2,6-dichlorophenyl)amino]phenyl}acetate; 2-[4-(nitrosothio)-4-piperidyl]ethyl (2S)-2-(6-methoxy(2-naphthyl)) propanoate hydrochloride; {[3- (methyl{[(nitrosothio) cyclohexyl]methyl}amino)propyl]oxycarbonyl}methyl 2-{2- [(2,6 dichlorophenyl) amino]phenyl}acetate; 2-{4-[3-methyl-3- (nitrosothio)butanoyl]piperazinyl } ethyl 2- { 2-[(2,6-dichlorophenyl)methyl]phenyl}acetate; {4-[dicyclopropyl(nitrosothio)methyl]-l-methyl-4-piperidyl}methyl (2S)-2-(6-methoxy(2-naphthyl))propanoate;
2-(2-[(2,6-dichlorophenyl)amino]phenyl}-l-(2-{methyl[2-methyl-2-(nitrosothio) propyl]amino}ethylthio)ethan-l-one hydrochloride; 2-{2-[(2,6-dichlorophenyl) amino]phenyl}-l-[2-(methyl{[(nitrosothio)cyclohexyl]methyl}amino)ethylthio]ethan-l-one;_4-({dethyl[2-methyl-2-(nitrosothio)propyl]amino}methyl)phenyl 2-{2-[(2,6-dichlorophenyl)amino]phenyl}acetate;.(2R,3R)-2,3-dihydroxy-3-{N-[2-methyl-2 (nitrosothio)propyl]carbamoyl) propyl 2-{2-[(2,6-dichlorophenyl)amino]phenyl) acetate; 2-{l-[2-methyl-2-(nitrosothio)propyl]-4-piperidyl}ethyl 2-|2-[(2,6-dichlorophenyl)amino]phenyl}acetate;_{(2S)-l-[2-methyl-2-(nitrosothio)propyl] pyrrolidin-2yl} methyl 2-{2-[(2,6-dichlorophenyl)amino]phenyl}acetate;
2-({4-[2-methyl-2-(nitrosothio)propyl]piperazinyl)ethoxy)ethyl 2-{l-[(4-chlorophenyl) carbonyl]-5-methoxy-2-methylindol-3-yl}acetate; 2-(2-{4-[2-methyl-2-(nitrosothio) propyl]piperazinyl}ethoxy)ethyl (2S)-2-(6-methoxy(2-naphthyl))propanoate;
4-({4-[2-methyl-2-(nitrosothio)propyl]piperazinyl}methyl)phenyl 2-{l-[(4-chlorophenyl)carbonyl]-5-methoxy-2-methylindol-3-yl}acetate; 5-({4-[2-methyl-2-(nitrosothio)propyl]piperazinyl}carbonyl)-2 pyridyl 2-(l-[(4- chlorophenyl)carbonyl]-5-methoxy-2-methylindol-3-yl}acetate; 5-({4-[2-methyl-2- (nitrosothio)propyl] piperazinyl) carbonyl)-2 pyridyl 2-{l-[(4-chlorophenyl)carbonyl]-5-methoxy-2-methylindol-3-yl}acetate; 2-{[2-(2-{l-[(4-chlorophenyl)carbonyl]-5-methoxy-2-methylindol-3-yl}
acetyloxy)ethyl]{[(nitrosothio)cyclohexyl]methyl}amino}acetic acid;
2-(methyl{l-[2-methyl-2-(nitrosothio)propyl](4-piperidyl)}amino)ethyl (2S)-2-(6-methoxy(2-naphthyl))propanoate; 3-{(4S)-4-[l-methyl-l-(nitrosothio)ethyl]-2-oxo-l,3-oxazolidin-3-yl}propyl (2S)-2-(6-methoxy(2-naphthyl))propanoate; |ethoxy[3-methyl-3-(nitrosothio)butoxy]phosphonyl} methyl (2S)-2-(6-methoxy (2-naphthyl)) propanoate; 6-(4-{[2-methyl-2-(nitrosothio)propyl]amino}pyrimidin-2-ylthio)hexyl (2S)-2-(6-methoxy(2-naphthyl))propanoate; {(2S,5S)-5-[l-methyl-l-(nitrosothio)ethyl]-3,6-dioxopiperazin-2-yl}methyl (2S)-2-(6-methoxy(2-naphthyl))propanoate; 2-(N-methyl {l-[2-methyl-2-(nitrosothio)propyl](4 piperidyl)} carbonylamino)ethyl (2S)-2-(6-methoxy(2-naphthyl))propanoate; 4-({4-[2-methyl-2-(nitrosothio)propyl] piperazinyl} carbonyl)phenyl 2-{2-[(2,6-dichlorophenyl)amino]phenyl}acetate; and
3-[(2S)-2-(6-methoxy (2-naphthyl)propanoyloxy]-2-oxopropyl-3-methyl-3-(nitrosothio) butanoate.
39. A composition comprising at least one compound of claim 38 and a pharmaceutically acceptable carrier.