Claims
- 1. A compound of formula (I), formula (II), formula (II), formula (IV), formula (V), formula (VI), formula (VII), or formula (VIII):
wherein the compound of formula (I) is: 39wherein Ra is a hydrogen or an alkoxy; Rb is: 40a is an integer of 2 or 3; Rc is a heterocyclic group, a lower alkyl group, a hydroxyalkyl group, or an arylheterocyclic ring; D is:
(i) —NO; (ii) —NO2; (iii) —C(Rd)—O—C(O)—Y—Z—(C(Re)(Rf))p—T—Q; (iv) —C(O)—Y—Z—(G—(C(Re)(Rf))q′—T—Q)p; (v) —P—Z—(G—(C(Re)(Rf))q′—T—Q)p; (vi) —P—B1—V—Bt—Kr—Es—[C(Re)(Rf)]w—Ec—[C(Re)(Rf)]x—Kd—[C(Re)(Rf)]y—Ki—Ej—Kg—[C(Re)(Rf)]z—T—Q; or (vii) —P—F′n—Kr—Es—[C(Re)(Rf)]w—Ec—[C(Re)(Rf)]x—Kd—[C(Re)(Rf)]y—Ki—Ej—Kg—[C(Re)(Rf)]z—T—Q; wherein Rd is a hydrogen, a lower alkyl, a cycloalkyl, an aryl or an arylalkyl; Y is oxygen, S(O)o, lower alkyl or NRi, o is an integer from 0 to 2; 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, —CH2—C(T—Q)(Re)(Rf), or —(N2O2−).M+, wherein M+ in an organic or inorganic cation; 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—Q, or [C(Re)(Rf)]k—T—Q, or Re and Rf taken together are a carbonyl, a methanthial, a heterocyclic ring, a cycloalkyl group or a bridged cycloalkyl group; k is an integer from 1 to 3; p is an integer from 1 to 10; T is independently a covalent bond, oxygen, S(O)o or NRi; Z is a covalent bond, an alkyl, an aryl, an alkylaryl, an arylalkyl, a heteroalkyl, or (C(Re)(Rf))p; Q is —NO or —NO2; G is a covalent bond, —T—C(O)—, —C(O)—T— or T; q′ is an integer from 0 to 5; P is a carbonyl, a phosphoryl or a silyl; l and t are each independently an integer from 1 to 3; r, s, c, d, g, i and j are each independently an integer from 0 to 3; w, x, y and z are each independently an integer from 0 to 10; B at each occurrence is independently an alkyl, an aryl, or [C(Re)(Rf)]p; E at each occurrence is independently —T—, an alkyl, an aryl, or —(CH2CH2O)q; K at each occurrence is independently —C(O)—, —C(S)—, —T—, a heterocyclic ring, an aryl, an alkenyl, an alkynyl, an arylheterocyclic ring, or —(CH2CH2O)q; q is an integer of from 1 to 5; V is oxygen, S(O)o, or NRi; F′ at each occurrence is independently B or carbonyl; n is an integer from 2 to 5; with the proviso that when Ri is —CH2—C(T—Q)(Re)(Rf) or —(N2O2−).M+, or Re or Rf are T—Q, or [C(Re)(Rf)]k—T—Q then the “—T—Q” subgroup designated in D can be a hydrogen, an alkyl, an alkoxy, an alkoxyalkyl, an aminoalkyl, a hydroxy, or an aryl; wherein the compound of formula (II) is: 41wherein Rg is: 42wherein D1 is a hydrogen or D, where D is as defined herein, with the proviso that D1 must be D if there is no other D in the compound; wherein the compound of formula (III) is: 43wherein Rh is a hydrogen, —C(O)—ORk or —C(O)—X; Rk is hydrogen or lower alkyl; X is:
(1) —Y—(C(Re)(Rf))p—G1—(C(Re)(Rf))p—T—Q; or (2) 44wherein: G1 is a covalent bond, —T—C(O)—, —C(O)—T—, or —C(Y—C(O)—Rm)—; Rm is a heterocyclic ring; and W is a heterocyclic ring or NRqR′q wherein Rq and R′q are independently a lower alkyl, an aryl or an alkenyl, and Rj is hydrogen, —D or —(O)CRd; and wherein Y, Re, Rf, p, Q, D, T and Rd are as defined herein; wherein the compound of formula (IV) is: 45wherein A1 is oxygen or methylene, and X and are as defined herein; wherein the compound of formula (V) is: 46wherein R1 is: 47b is an integer of 0 or 1; Rn is: 48wherein A2 is oxygen or sulfur, R′k is independently selected from Rk and Rk, D and D1 are as defined herein; with the proviso that D1 must be D if there is no other D in the compound; wherein the compound of formula (VI) is: 49wherein Ro is: 50wherein Rk, D1 and D are as defined herein, with the proviso that D1 must be D if there is no other D in the compound; wherein the compound of formula (VII) is: 51wherein Rd, T and D are defined as herein; and wherein the compound of formula (VII) is: 52wherein Rt and Ru are each independently a hydrogen, a lower alkyl, a cycloalkyl, an aryl, or when taken together are a heterocyclic ring, and Rk, R′k, and D are as defined herein.
- 2. The compound of claim 1, wherein the compound is a haloalkylamine, an imidazoline, a quinazoline, an indole derivative, a phenoxypropanolamine, an alcohol, an alkaloid, an amine, a piperazine, a piperidine, moxisylyte, or niguldipine.
- 3. The compound of claim 2, wherein the haloalkylamine is phenoxybenzamine or dibenamine; wherein the imidazoline is phentolamine, tolazoline, idazoxan, deriglidole, RX 821002, BRL 44408 or BRL 4409; wherein the quinazoline is prazosine, terazosin, doxazosin, alfuzosin, bunazosin, ketanserin, trimazosin or abanoquil; wherein the indole derivative is carvedilol or BAM 1303; wherein the alcohol is labetalol or ifenprodil; wherein the alkaloid is ergotoxine, ergoconine, ergocristine, ergocryptine, rauwolscine, corynathine, raubascine, tetrahydroalstonine, apoyohimbine, akuammignie, β-yohimbine, yohimbol, pseudoyohimbine, epi-3α-yohimbine; 10-hydroxy-yohimbine or 11-hydroxy-yohimbine; wherein the amine is tamsulosin, benoxathian, atipamezole, tedisamil, mirtazipine, setiptiline, reboxitine, delequamine, chlorpromazine, phenothiazine, BE 2254, WB 4101 and HU 723, tedisamil, mirtazipine, setiptiline, reboxitine or delequamine; wherein the piperazine is naftopil, saterinone, urapidil, 5-methylurapidil, monatepil, SL 89.0591 or ARC 239; wherein the piperidine is haloperidol; and wherein the amide is indoramin or SB 216469.
- 4. A composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier.
- 5. A method for treating a sexual dysfunction in a patient in need thereof comprising administering to the patient a therapeutically effective amount of the composition of claim 4.
- 6. The method of claim 5, wherein the patient is female.
- 7. The method of claim 5, wherein the patient is male.
- 8. The method of claim 5, wherein the composition is administered orally, by intracavernosal injection, by transurethral application, or by transdermal application.
- 9. A method for treating benign prostatic hyperplasia, hypertension, congestive heart failure, variant (Printzmetal) angina, glaucoma, a neurodegenerative disorder, a vasospastic disease, a cognitive disorders, urge incontinence, or overactive bladder, or for reversing the state of anesthesia in a patient in need thereof comprising administering to the patient a therapeutically effective amount of the composition of claim 4.
- 10. The composition of claim 4, further comprising at least one vasoactive agent.
- 11. The composition of claim 10, wherein the vasoactive agent is a potassium channel activator, a calcium blocker, a β-blocker, a phosphodiesterase inhibitor, adenosine, an ergot alkaloid, a vasoactive intestinal peptide, a dopamine agonist, an opioid antagonist, a prostaglandin, an endothelin antagonist or a mixture thereof.
- 12. A method for treating a sexual dysfunction in a patient in need thereof comprising administering to the patient a therapeutically effective amount of the composition of claim 10.
- 13. The method of claim 12, wherein the patient is female.
- 14. The method of claim 12, wherein the patient is male.
- 15. The method of claim 12, wherein the composition is administered orally, by intracavernosal injection, by transurethral application or by transdermal application.
- 16. A method for treating benign prostatic hyperplasia, hypertension, congestive heart failure, variant (Printzmetal) angina, glaucoma, a neurodegenerative disorder, a vasospastic disease, a cognitive disorders, urge incontinence, or overactive bladder, or for reversing the state of anesthesia in a patient in need thereof comprising administering to the patient a therapeutically effective amount of the composition of claim 10.
- 17. 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.
- 18. The composition of claim 17, 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.
- 19. The composition of claim 18, 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.
- 20. The composition of claim 18, 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 of 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, am 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 —NO2; and T is independently a covalent bond, an oxygen, S(O)o or NRi, wherein o is an integer from 0 to 2, and 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, carboxamido, —CH2—C(T—Q)(Re)(Rf), or —(N2O2—)M+, wherein M+ in an organic or inorganic cation; with the proviso that when Ri is —CH2—C(T—Q)(Re)(Rf) 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.
- 21. The composition of claim 17, 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.
- 22. The composition of claim 17, 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 O2N—O—, O2N—N—, O2N—S— or —O2N—C— group; (iii) a N-oxo-N-nitrosoamine having the formula: R1R2—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; or (iv) a thionitrate having the formula: R1—(S)—NO2, 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.
- 23. The composition of claim 22, 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.
- 24. The composition of claim 22, wherein compound comprising at least one O2N—O—, O2N—N—, O2N—S— or O2N—C— group is an O2N—O-polypeptide, an O2N—N-polypeptide, an O2N—S-polypeptide, an O2N—C-polypeptide, an O2N—O-amino acid, O2N—N-amino acid, O2N—S-amino acid, an O2N—C-amino acid, an O2N—O-sugar, an O2N—N-sugar, O2N—S-sugar, an O2N—C-sugar, an O2N—O-oligonucleotide, an O2N—N-oligonucleotide, an O2N—S-oligonucleotide, an O2N—C-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, a straight or branched, saturated or unsaturated, aliphatic or aromatic, substituted or unsubstituted O2N—C-hydrocarbon, an O2N—O-heterocyclic compound, an O2N—N-heterocyclic compound, an O2N—S-heterocyclic compound or an O2N—C-heterocyclic compound.
- 25. A method for treating a sexual dysfunction in a patient in need thereof comprising administering to the patient a therapeutically effective amount of the composition of claim 17.
- 26. The method of claim 25, wherein the patient is female.
- 27. The method of claim 25, wherein the patient is male.
- 28. The method of claim 25, wherein the composition is administered by orally, intracavernosal injection, by transurethral application or by transdermal application.
- 29. A method for treating benign prostatic hyperplasia, hypertension, congestive heart failure, variant (Printzmetal) angina, glaucoma, a neurodegenerative disorder, a vasospastic disease, a cognitive disorders, urge incontinence, or overactive bladder, or for reversing the state of anesthesia in a patient in need thereof comprising administering to the patient a therapeutically effective amount of the composition of claim 17.
- 30. The composition of claim 17, further comprising at least one vasoactive agent.
- 31. The composition of claim 30, wherein the vasoactive agent is a potassium channel activator, a calcium blocker, a β-blocker, a phosphodiesterase inhibitor, adenosine, an ergot alkaloid, a vasoactive intestinal peptide, a dopamine agonist, an opioid antagonist, a prostaglandin, an endothelin antagonist or a mixture thereof.
- 32. A method for treating a sexual dysfunction in a patient in need thereof comprising administering to the patient a therapeutically effective amount of the composition of claim 30.
- 33. The method of claim 32, wherein the patient is female.
- 34. The method of claim 32, wherein the patient is male.
- 35. The method of claim 32, wherein the composition is administered orally, by intracavernosal injection, by transurethral application or by transdermal application.
- 36. A method for treating benign prostatic hyperplasia, hypertension, congestive heart failure, variant (Printzmetal) angina, glaucoma, a neurodegenerative disorder, a vasospastic disease, a cognitive disorders, urge incontinence, or overactive bladder, or for reversing the state of anesthesia in a patient in need thereof comprising administering to the patient a therapeutically effective amount of the composition of claim 30.
- 37. A composition comprising at least one α-adrenergic receptor antagonist 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.
- 38. The composition of claim 37, wherein the (α-adrenergic receptor antagonist is a haloalkylamine, an imidazoline, a quinazoline, an indole derivative, a phenoxypropanolamine, an alcohol, an alkaloid, an amine, a piperazine, a piperidine, an amide, moxisylyte, trazodone, dapiprozole, efaroxan, Recordati 15/2739, SNAP 1069, SNAP 5089, SNAP 5272, RS 17053, SL 89.0591, KMD 3213, spiperone, AH 11110A, chloroethylclonidine, BMY 7378 or niguldipine.
- 39. The composition of claim 38, wherein the haloalkylamine is phenoxybenzamine or dibenamine; wherein the imidazoline is phentolamine, tolazoline, idazoxan, deriglidole, RX 821002, BRL 44408 or BRL 4409; wherein the quinazoline is prazosine, terazosin, doxazosin, alfuzosin, bunazosin, ketanserin, trimazosin or abanoquil; wherein the indole derivative is carvedilol or BAM 1303; wherein the alcohol is labetalol or ifenprodil; wherein the alkaloid is ergotoxine, ergoconine, ergocristine, ergocryptine, rauwolscine, corynathine, raubascine, tetrahydroalstonine, apoyohimbine, akuammignie, β-yohimbine, yohimbol, pseudoyohimbine, epi-3α-yohimbine; 10-hydroxy-yohimbine or 11-hydroxy-yohimbine; wherein the amine is tamsulosin, benoxathian, atipamezole, tedisamil, mirtazipine, setiptiline, reboxitine, delequamine, chlorpromazine, phenothiazine, BE 2254, WB 4101 and HU 723, tedisamil, mirtazipine, setiptiline, reboxitine or delequamine; wherein the piperazine is naftopil, saterinone, urapidil, 5-methylurapidil, monatepil, SL 89.0591 or ARC 239; wherein the piperidine is haloperidol; and wherein the amide is indoramin or SB 216469.
- 40. The composition of claim 37, 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.
- 41. The composition of claim 40, 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.
- 42. The composition of claim 40, 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 of 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, am 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 —NO2; and T is independently a covalent bond, an oxygen, S(O)o or NRi, wherein o is an integer from 0 to 2, and Re 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, carboxamido, —CH2—C(T—Q)(Re)(Rf), or —(N2O2—)M+, wherein M+ in an organic or inorganic cation; with the proviso that when Ri is —CH2—C(T—Q)(Re)(Rf) 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.
- 43. The composition of claim 37, 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.
- 44. The composition of claim 37, 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 O2N—O—, O2N—N—, O2N—S— or —O2N—C— group; (iii) a N-oxo-N-nitrosoamine having the formula: R1R2—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; or (v) a thionitrate having the formula: R1—(S)—NO2, wherein R1 is a polypeptide, an amino acid, a sugar, an oligonucleotide, a straight or branched, saturated or go unsaturated, aliphatic or aromatic, substituted or unsubstituted hydrocarbon, or a heterocyclic group.
- 45. The composition of claim 44, 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.
- 46. The composition of claim 44, wherein compound comprising at least one O2N—O—, O2N—N—, O2N—S— or O2N—C— group is an O2N—O-polypeptide, an O2N—N-polypeptide, an O2N—S-polypeptide, an O2N—C-polypeptide, an O2N—O-amino acid, O2N—N-amino acid, O2N—S-amino acid, an O2N—C-amino acid, an O2N—O-sugar, an O2N—N-sugar, O2N—S-sugar, an O2N—C-sugar, an O2N—O-oligonucleotide, an O2N—N-oligonucleotide, an O2N—S-oligonucleotide, an O2N—C-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, a straight or branched, saturated or unsaturated, aliphatic or aromatic, substituted or unsubstituted O2N—C-hydrocarbon, an O2N—O-heterocyclic compound, an O2N—N-heterocyclic compound, an O2N—S-heterocyclic compound or an O2N—C-heterocyclic compound.
- 47. A method for treating a sexual dysfunction in a patient in need thereof comprising administering to the patient a therapeutically effective amount of the composition of claim 37.
- 48. The method of claim 47, wherein the patient is female.
- 49. The method of claim 47, wherein the patient is male.
- 50. The method of claim 47, wherein the composition is administered by orally, intracavernosal injection, by transurethral application or by transdermal application.
- 51. A method for treating benign prostatic hyperplasia, hypertension, congestive heart failure, variant (Printzmetal) angina, glaucoma, a neurodegenerative disorder, a vasospastic disease, a cognitive disorders, urge incontinence, or overactive bladder, or for reversing the state of anesthesia in a patient in need thereof comprising administering to the patient a therapeutically effective amount of the composition of claim 37.
- 52. The composition of claim 37, further comprising at least one vasoactive agent.
- 53. The composition of claim 52, wherein the vasoactive agent is a potassium channel activator, a calcium blocker, a β-blocker, a phosphodiesterase inhibitor, adenosine, an ergot alkaloid, a vasoactive intestinal peptide, a dopamine agonist, an opioid antagonist, a prostaglandin, an endothelin antagonist or a mixture thereof.
- 54. A method for treating a sexual dysfunction in a patient in need thereof comprising administering to the patient a therapeutically effective amount of the composition of claim 52.
- 55. The method of claim 54, wherein the patient is female.
- 56. The method of claim 54, wherein the patient is male.
- 57. The method of claim 54, wherein the composition is administered by orally, intracavernosal injection, by transurethral application or by transdermal application.
- 58. A method for treating benign prostatic hyperplasia, hypertension, congestive heart failure, variant (Printzmetal) angina, glaucoma, a neurodegenerative disorder, a vasospastic disease, a cognitive disorders, urge incontinence, or overactive bladder, or for reversing the state of anesthesia in a patient in need thereof comprising administering to the patient a therapeutically effective amount of the composition of claim 52.
- 67. A composition comprising at least one (α-adrenergic receptor antagonist and at least one vasoactive agent.
- 60. The composition of claim 59, wherein the vasoactive agent is a potassium channel activator, a calcium blocker, a β-blocker, a phosphodiesterase inhibitor adenosine, an ergot alkaloid, a vasoactive intestinal peptide, a dopamine agonist, an opioid antagonist, a prostaglandin, an endothelin antagonist or a mixture thereof.
- 61. The composition of claim 59, wherein the α-adrenergic receptor antagonist is a haloalkylamine, an imidazoline, a quinazoline, an indole derivative, a phenoxypropanolamine, an alcohol, an alkaloid, an amine, a piperazine, a piperidine, an amide, moxisylyte, trazodone, dapiprozole, efaroxan, Recordati 15/2739, SNAP 1069, SNAP 5089, SNAP 5272, RS 17053, SL 89.0591, KMD 3213, spiperone, AH 11110A, chloroethylclonidine, BMY 7378 and niguldipine.
- 62. The compound of claim 61, wherein the haloalkylamine is phenoxybenzamine or dibenamine; wherein the imidazoline is phentolamine, tolazoline, idazoxan, deriglidole, RX 821002, BRL 44408 or BRL 4409; wherein the quinazoline is prazosine, terazosin, doxazosin, alfuzosin, bunazosin, ketanserin, trimazosin or abanoquil; wherein the indole derivative is carvedilol or BAM 1303; wherein the alcohol is labetalol or ifenprodil; wherein the alkaloid is ergotoxine, ergoconine, ergocristine, ergocryptine, rauwolscine, corynathine, raubascine, tetrahydroalstonine, apoyohimbine, akuammignie, β-yohimbine, yohimbol, pseudoyohimbine, epi-3α-yohimbine; 10-hydroxy-yohimbine or 11-hydroxy-yohimbine; wherein the amine is tamsulosin, benoxathian, atipamezole, tedisamil, mirtazipine, setiptiline, reboxitine, delequamine, chlorpromazine, phenothiazine, BE 2254, WB 4101 and HU 723, tedisamil, mirtazipine, setiptiline, reboxitine or delequamine; wherein the piperazine is naftopil, saterinone, urapidil, 5-methylurapidil, monatepil, SL 89.0591 or ARC 239; wherein the piperidine is haloperidol; and wherein the amide is indoramin or SB 216469.
- 63. A method for treating a sexual dysfunction in a patient in need thereof comprising administering to the patient a therapeutically effective amount of the composition of claim 59.
- 64. The method of claim 63, wherein the patient is female.
- 65. The method of claim 63, wherein the patient is male.
- 66. The method of claim 63, wherein the composition is administeredorally, by intracavernosal injection, by transurethral application or by transdermal application.
- 67. A method for treating benign prostatic hyperplasia, hypertension, congestive heart failure, variant (Printzmetal) angina, glaucoma, a neurodegenerative disorder, a vasospastic disease, a cognitive disorders, urge incontinence, or overactive bladder, or for reversing the state of anesthesia in a patient in need thereof comprising administering to the patient a therapeutically of the composition of claim 59.
RELATED APPLICATIONS
[0001] This application is a continuation-in-part of U.S. application Ser. No. 09/145,143, filed Sep. 1, 1998, which is a continuation-in-part of U.S. application Ser. No. 08/714,313, filed Sep. 18, 1996, allowed, which is a continuation-in-part of U.S. application Ser. No. 08/595,732, filed Feb. 2, 1996, issued as U.S. Pat. No. 5,932,538.
Continuation in Parts (3)
|
Number |
Date |
Country |
| Parent |
09145143 |
Sep 1998 |
US |
| Child |
10146671 |
May 2002 |
US |
| Parent |
08714313 |
Sep 1996 |
US |
| Child |
09145143 |
Sep 1998 |
US |
| Parent |
08595732 |
Feb 1996 |
US |
| Child |
08714313 |
Sep 1996 |
US |
Patent Application
20020143007
