Abstract: This disclosure relates to novel compounds containing an H2S releasing moiety and a nitric oxide (NO) releasing moiety covalently linked with a core (e.g., a salicylic acid moiety) and the use of such compounds in treating inflammatory diseases, including cancers. Therapeutic potency of these compounds is significantly higher than NSAIDs containing a H2S-releasing moiety alone (HS-NSAIDs) and NSAID containing a NO-releasing moiety alone (NO-NSAIDs). The compounds, in addition, exhibit reduced side effect, e.g., reduced stomach ulcers, upon administration.

Abstract: The present invention relates to a method for reducing the production of methane emanating from the digestive activities of a ruminant and/or for improving ruminant animal performance by using, as active compound at least one organic molecule substituted at any position with at least one nitrooxy group, or a salt thereof, which is administrated to the animal together with the feed. The invention also relates to the use of these compounds in feed and feed additives such as premix, concentrates and total mixed ration (TMR) or in the form of a bolus.

Abstract: In one aspect, the invention relates to compounds having the formula: where R1, R2, R3, R7, R8, Z, X, b, and c are as defined in the specification, or a pharmaceutically acceptable salt thereof. These compounds are nitric oxide donors and have neprilysin inhibition activity. In another aspect, the invention relates to pharmaceutical compositions comprising such compounds; methods of using such compounds; and processes and intermediates for preparing such compounds.

Abstract: The invention relates to the use of di-aspirin (bis(2-carboxyphenyl)succinate) and its derivatives in the treatment of colon and colorectal cancer. It also relates to novel derivatives of di-aspirin and to a method of synthesis of the di-aspirin and its derivatives.

Abstract: A compound having the structure wherein R is, for example, Y is selected from the group consisting of 1) R5, 2) —C(R1R2) (C(R3R4))0-1Y1R5, and 3) —C(R1R2)—O—Y1R5; R1, R2, R3 and R4 are independently selected from the group consisting of hydrogen and C1-4 alkyl; R5 is; Y1 is selected from the group consisting of C(O)—O— and P(O)(OR6)—O—; and R6 is hydrogen or CH3, or a pharmaceutically acceptable salt thereof, and methods of using the compounds for treating hypertension.

Abstract: The present invention relates to a method for purifying naproxcinod comprising the steps of: a) dissolving or dispersing a mixture containing naproxcinod in an amount higher than 90% by weight in a solvent; b) cooling the solution or two phases dispersion under stirring to a temperature ranging from ?20° C. to 10° C. c) optionally seeding the solution with crystals of naproxcinod d) stirring, by maintaining the temperature in the range from ?40° C. to 10° C. e) collecting the formed solid by maintaining the temperature under 15° C. A further object of the invention is a crystalline form of naproxcinod.

Abstract: The present invention particularly relates to novel nitrate esters of paracetamol. The nitrate esters of paracetamol are prepared by reacting the paracetamol with dihaloalkyl compound and followed by reaction with silver nitrate to obtain the corresponding nitrate ester derivatives. The nitrate esters of paracetamol are useful as analgesic, anti-inflammatory agents.

Abstract: A compound having the structure R—Y wherein R is, for example, Y is selected from the group consisting of 1) R5, 2) —C(R1R2)(C(R3R4))0-1Y1R5, and 3) —C(R1R2)—O—Y1R5; R1, R2, R3 and R4 are independently selected from the group consisting of hydrogen and C1-4 alkyl; R5 is Y1 is selected from the group consisting of —C(O)—O— and —P(O)(OR6)—O—; and R6 is hydrogen or CH3, or a pharmaceutically acceptable salt thereof, and methods of using the compounds for treating hypertension.

Abstract: The present invention provides NO and, optionally, drug releasing macromers and oligomers wherein the drug molecule and NO releasing moiety are linked an absorbable macromer or oligomeric chain susceptible to hydrolytic degradation and wherein the macromer or oligomer comprises of repeat units derived from safe and biocompatible molecules such as glycolic acid, lactic acid, caprolactone and p-dioxanone. Furthermore, the present invention relates to controlled release of nitric oxide (NO) and/or drug molecule from a NO and drug releasing macromer or oligomer. Moreover, the present invention also relates to medical devices, medical device coatings and therapeutic formulations comprising of nitric oxide and drug releasing macromers and oligomers of the present invention.

Abstract: Nitroderivatives of prostaglandins having improved pharmacological activity and enhanced tolerability are described. They can be employed for the treatment of glaucoma and ocular hypertension.

Abstract: Disclosed herein are novel compositions and methods for treating or preventing a variety of disorders and conditions associated with lipid metabolism. The methods generally include administering to a patient in need thereof a therapeutically effective amount of a pharmaceutical composition comprising one or more fibric acid or statin derivative compositions alone or in combination with one or more lipid altering agents and/or PDE inhibitors.

Abstract: Nitroderivatives of prostaglandins having improved pharmacological activity and enhanced tolerability are described. They can be employed for the treatment of glaucoma and ocular hypertension.

Abstract: The present invention relates to new napthylene inhibitors of cyclooxygenase activity, pharmaceutical compositions thereof, and methods of use thereof

Abstract: The present invention relates to a new process for the preparation of the (S)-naproxen 4-nitrooxybutyl ester and to new intermediates obtained and used therein. The invention further relates to the use of the new intermediates for the manufacturing of pharmaceutically active compounds such as (S)-naproxen 4-nitrooxybutyl ester. The invention also relates to the use of (S)-naproxen 4-nitrooxybutyl ester prepared according to the process of the present invention for the manufacturing of a medicament for the treatment of pain.

Abstract: The invention describes novel nitrosated nonsteroidal antiinflammatory drugs (NSAIDs) and pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated NSAID, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or at least one therapeutic agent. The invention also provides novel compositions comprising at least one nitrosated NSAID, and at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one therapeutic agent. The invention also provides novel kits comprising at least one nitrosated NSAID, and, optionally, at least one nitric oxide donor and/or at least one therapeutic agent.

Abstract: The present invention relates to a method for purifying naproxcinod comprising the steps of: a) dissolving or dispersing a mixture containing naproxcinod in an amount higher than 90% by weight in a solvent; b) cooling the solution or two phases dispersion under stirring to a temperature ranging from ?20° C. to 10° C. c) optionally seeding the solution with crystals of naproxcinod d) stirring, by maintaining the temperature in the range from ?40° C. to 10° C. e) collecting the formed solid by maintaining the temperature under 15° C. A further object of the invention is a crystalline form of naproxcinod.

Abstract: Compounds or their salts of general formula (I): A-B—N(O)s wherein: s is an integer equal to 1 or 2; A=R-T1-, wherein R is the drug radical and T1=(CO)t or (X)t?, wherein X?O, S, NR1c, R1c is H or a linear or branched alkyl or a free valence, t and t? are integers and equal to zero or 1, with the proviso that t=1 when t?=0; t=0 when t?=1; B=-TB-X2—O— wherein TB=(CO) when t=0, TB=X when t?=0, X being as above defined; X2 is equal to R1B—X—R2B radical wherein X is as above defined, R1B and R2B, equal to or different from each other, are linear or branched C1-C6 alkylenes, or X2 is a radical wherein two alkylene chains C1-C4 are linked to nonadjacent positions of a central ring having 4 or 6 atoms, said ring being an unsaturated cycloaliphatic ring, or a saturated or aromatic heterocylic ring, containing one or two heteroatoms, equal or different, selected from O, S, N; wherein the unsaturated cycloaliphatic ring does not have aromatic character according to Huckel's rule.

Abstract: The present invention relates to nitrooxyderivative of antioxidant compounds of formula (I) and pharmaceutically acceptable salts or stereoisomers thereof for the treatment of chronic pain, in particular chronic neuropathic pain. The invention also describes composition comprising a nitrooxyderivative of a antioxidant compound of formula (I) and an analgesic drugs.

Abstract: The present invention refers to a process for preparing a compound of general formula (A), as reported in the description, wherein R is a radical of a drug and R1-R12 are hydrogen or alkyl groups, m, n, o, q, r and s are each independently an integer from 0 to 6, and p is 0 or 1, and X is O, S, SO, SO2, NR13 or PR13 or an aryl, heteroaryl group, said process comprising reacting a compound of formula (B) R—COOZ (B) wherein R is as defined above and Z is hydrogen or a cation selected from: Li+, Na+, K+, Ca++, Mg++, tetralkylammonium, tetralkylphosphonium, with a compound of formula (C), as reported in the description, wherein R1-R12 and m, n, o, p, q, r, s are as defined above and Y is a suitable leaving group.

Abstract: Compounds are disclosed with activity towards killing dysproliferative cells in vitro and treating cancer in vivo. Cancers such as cancer of the colon, pancreas, prostate, lung, breast, urinary bladder, skin and liver are exemplary. Compounds, pharmaceutical compositions and methods of use are described.

Abstract: Chimeric nitrate esters and their use in the treatment of depression are disclosed. The chimeric nitrate esters also are useful in the treatment of depression and comorbidity associated with aging.

Abstract: The present invention relates to the use of the following compounds, their compositions, and their salts for the preparation of medicaments for the treatment of urinary incontinence and other diseases, the compounds having the general formula: A-X1—NO2 wherein: A=RCO(X)t, wherein t is the integer 0 or 1; X?O, NH, NR1C, wherein R1C is a linear or branched C1 to C10 alkyl group; when t=1, R= and X1=—YO—, wherein Y is a C1 to C20 alkylene, C5 to C7 cycloalkyl or oxyalkyl derivative.

Abstract: The present invention relates to a new process for the preparation of a compound of the following formula (I):

Abstract: The present invention is directed to compounds, combinations, compositions and methods for enhancing nitric oxide (NO) delivery to target sites, and in particular to muscle, both normal and dystrophic. Enhanced NO delivery according to the present invention may be achieved by using a combination of a muscle relaxant and an NO donor compound, or by using a compound of the invention: formula (I) wherein R1 is H, halo, C1-6 alkoxy or C1-6 alkyl; R2 is H, NO2 or C(O)NH2; R3 is H, NO2 or C(O)NH2; and at least one of R2 and R3 is NO2; or a pharmaceutically acceptable salt of the compound.

Abstract: Compounds or their salts of general formula (I): A-B-N(O)s wherein: s is an integer equal to 1 or 2; A=R-T1-, wherein R is the drug radical and T1=(CO)t or (X)t?, wherein X=O, S, NR1c, R1c is H or a linear or branched alkyl or a free valence, t and t? are integers and equal to zero or 1, with the proviso that t=1 when t?=0; t=0 when t?=1; B=-TB-X2—O— wherein TB=(CO) when t=0, TB=X when t?=0, X being as above defined; X2 is equal to R1B-X-R2B radical wherein X is as above defined, R1B and R2B, equal to or different from each other, are linear or branched C1-C6 alkylenes, or X2 is a radical wherein two alkylene chains C1-C4 are linked to nonadjacent positions of a central ring having 4 or 6 atoms, said ring being an unsaturated cycloaliphatic ring, or a saturated or aromatic heterocylic ring, containing one or two heteroatoms, equal or different, selected from O, S, N; wherein the unsaturated cycloaliphatic ring does not have aromatic character according to Huckel's rule.

Abstract: A process for obtaining nitroxyalklesters of the 2(S)(6-methoxy-2-naphthyl)-propanoic acid having an enantiomeric excess higher than or equal to 95%, preferably higher than or equal to 98%, characterized in that an halide of the 2-(S)-(6 methoxy-2-naphthyl)propanoic acid of formula A-Hal, wherein A is the acid acyl residue, is reacted in an inert organic solvent with an aliphatic nitroxyalkanol HO—Y—ONO2, wherein Y is a C2-C20 alkylene or a cycloalkylene from 3 to 8 carbon atoms, or an alkylene as defined containing a cycloalkylene as defined, in the presence of an inorganic base.

Abstract: The present invention refers to a process for preparing a compound of general formula (A), as reported in the description, wherein R is a radical of naproxen or bromonaproxen and R1–R12 are hydrogen or alkyl groups, m, n, o, q, r and s are each independently an integer from 0 to 6, and p is 0 or 1, and and X is O, S, SO, SO2, NR13 or PR13 or an aryl, heteroaryl group, said process comprising reacting a compound of formula (B) R—COOZ??(B) wherein R is as defined above and Z is hydrogen or a cation selected from: Li+, Na+, K+, Ca++, Mg++, tetralkylammonium, tetralkylphosphonium, with a compound of formula (C), as reported in the description, wherein R1–R12 and m, n, o, p, q, r, s are as defined above and Y is a suitable leaving group.

Abstract: The invention encompasses novel compounds of Formula I, which are nitric oxide-releasing prodrugs of diaryl-2-(5H) furanones useful in the treatment of cyclooxygenase-2 mediated diseases. The invention also encompasses certain pharmaceutical compositions and methods for treatment of cyclooxygenase-2 mediated diseases comprising the use of compounds of Formula I.

Abstract: Compounds or their salts of general formula (I): A—B—N(O)s wherein: s is an integer equal to 1 or 2; A=R—T1—, wherein R is the drug radical and T1=(CO)t or (X)t?, wherein X=O, S, NR1c, R1c is H or a linear or branched alkyl or a free valence, t and t? are integers and equal to zero or 1, with the proviso that t=1 when t?=0; t=0 when t?=1; B=—TB—X2—O— wherein TB=(CO) when t=0, TB=X when t?=0, X being as above defined; X2 is equal to R1B—X—R2B radical wherein X is as above defined, R1B and R2B, equal to or different from each other, are linear or branched C1–C6 alkylenes, or X2 is a radical wherein two alkylene chains C1–C4 are linked to nonadjacent positions of a central ring having 4 or 6 atoms, said ring being an unsaturated cycloaliphatic ring, or a saturated or aromatic heterocylic ring, containing one or two heteroatoms, equal or different, selected from O, S, N; wherein the unsaturated cycloaliphatic ring does not have aromatic character according to Huckel's rule.

Abstract: The invention encompasses novel compounds of Formula I, which are nitric oxide-releasing prodrugs of diaryl-2-(5H) furanones useful in the treatment of cyclooxygenase-2 mediated diseases. The invention also encompasses certain pharmaceutical compositions and methods for treating cyclooxygenase-2 mediated diseases comprising the use of compounds of Formula I. The above compounds may be used as a combination therapy with low-dose aspirin to treat chronic cyclooxygenase-2 mediated diseases or conditions while also reducing the risk of thrombotic cardiovascular events.

Abstract: The present invention describes novel nitrosated and/or nitrosylated cyclooxygenase 2 (COX-2) inhibitors and novel compositions comprising at least one nitrosated and/or nitrosylated cyclooxygenase 2 (COX-2) inhibitor, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or optionally, at least one therapeutic agent, such as, steroids, nonsteroidal antiinflammatory compounds (NSAID), 5-lipoxygenase (5-LO) inhibitors, leukotriene B4 (LTB4) receptor antagonists, leukotriene A4 (LTA4) hydrolase inhibitors, 5-HT agonists, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitors, H2antagonists, antineoplastic agents, antiplatelet agents, decongestants, diuretics, sedating or non-sedating anti-histamines, inducible nitric oxide synthase inhibitors, opioids, analgesics, Helicobacter pylori inhibitors, proton pump inhi

Abstract: The invention describes novel nitrosated nonsteroidal antiinflammatory drugs (NSAIDs) and pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated NSAID, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or at least one therapeutic agent. The invention also provides novel compositions comprising at least one nitrosated NSAID, and at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one therapeutic agent. The invention also provides novel kits comprising at least one nitrosated NSAID, and, optionally, at least one nitric oxide donor and/or at least one therapeutic agent.

Abstract: The invention encompasses novel compounds of Formula I, which are nitric oxide-releasing prodrugs of diaryl-2-(5H) furanones useful in the treatment of cyclooxygenase-2 mediated diseases.

Abstract: Nitro-oxyderivative compounds or salts thereof having the following general formula (I): A-(B)b0-(C)c0-NO2 wherein: c0 is an integer and is 0 or 1, b0 is an integer and is 0 or 1, A=R-T1-, wherein R is the radical of an analgesic drug for the chronic pain, in particular for the neuropathic pain; B is such that its precursor is selected from anminoacids, hydroxyacids, polyalcohols, compounds containing at least one acid function; C is a bivalent radical containing an aliphatic, heterocyclic or aromatic radical.

Abstract: The invention describes novel nitrosated and/or nitrosylated cyclooxygenase 2 (COX-2) selective inhibitors and novel compositions comprising at least one nitrosated and/or nitrosylated cyclooxygenase 2 (COX-2) selective inhibitor, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or, optionally, at least one therapeutic agent.

Abstract: A process for obtaining nitroxyalkylesters of the 2-(S)-(6-methoxy-2-naphthyl)-propanoic acid having an enantiomeric excess higher than or equal to 95%, preferably higher than or equal to 98%, characterized in that an halide of the 2-(S)-(6-methoxy-2-naphthyl)-propanoic acid of formula A-Hal, wherein A is the acid acyl residue, is reacted in an inert organic solvent with an aliphatic nitroxyalkanol HO—Y—ONO2, wherein Y is a C2-C20 alkylene or a cycloalkylene from 3 to 8 carbon atoms, or an alkylene as defined containing a cycloalkylene as defined, in the presence of an inorganic base.

Abstract: A process for obtaining (nitroxymethyl)phenyl esters of salicylic acid derivatives of formula (I) wherein R1 is the OCOR3 group characterized in that it comprises the following steps: a) reaction of a halide of a salicylic acid derivative with hydroxybenzylacohol in the presence of a base: b) nutration of the obtained product in anhydrous conditions by a mixture of nitric acid with a different inorganic acid, or an organic acid, or an anhydride of one or two organic acids: c) recovery of the final product.

Abstract: In accordance with the present invention, there are provided modified forms of nonsteroidal anti-inflamamatory drugs (NSAIDs). Modified NSAIDs according to the invention provide a new class of anti-inflammatory agent which provide the therapeutic benefits of NSAIDs while causing a much lower incidence of side-effects then typically observed with such agents.

Abstract: Disclosed are (i) compounds of a steroid, a &bgr;-agonist, an anticholinergic, a mast cell stabilizer and a phosphodiesterase (PDE) inhibitor directly or indirectly linked to a NO or NO2 group or a group which stimulates endogenous production of NO or EDRF in vivo; (ii) compositions of steroids, &bgr;-agonists, anticholinergics, mast cell stabilizers and PDE inhibitors, which can optionally be substituted with at least one NO or NO2 moiety or a group which stimulates endogenous production of NO or EDRF in vivo, and a compound that donates, transfers or releases nitric oxide as a charged species, i.e., nitrosonium (NO+) or nitroxyl (NO−), or as the neutral species, nitric oxide (NO•) or that stimulates endogenous production of NO or EDRF in vivo; and (iii) uses for them in preventing and/or treating respiratory disorders.

Abstract: Disclosed are compounds of formula X, 1

Abstract: Nitric oxide donor compounds of the formula: are provided. In the formula, R is (CH2)n, wherein n ranges from 1 to 8 and wherein each hydrogen atom on the alkylene group and on the phenyl groups can optionally be replaced by a substituent selected from the group consisting of alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, halo, and hydroxy groups. A particularly preferred compound is 1,3-(nitrooxymethyl)phenyl 2-hydroxybenzoate. The compounds are useful for treating and preventing various conditions, including coronary artery disease.

Abstract: The present invention provides a compound containing at least one sulfhydryl group and at least one NO donor group, wherein said compound contains one or more protected sulfhydryl groups linked to at least one aromatic ring or a heteroaromatic ring with a nitrogen in the ring structure, which ring is substituted by one or more substitutes bearing at least one terminal —ONO2 group. The present invention further provides pharmaceutical compositions comprising one or more of said compounds as an active ingredient.

Abstract: A nitrate salt of a compound selected from the group consisting of: salbutamol having the formula (I)

Abstract: Nitric oxide donor compounds of the formula: 1

Abstract: Compounds of the general formula A—X1—NO2, or their pharmaceutical compositions, wherein A contains a prostaglandin residue, X1 is a bivalent connecting bridge.

Abstract: 1,2 and 1,3-dinitrate esters are prepared from polyols containing 1,2- or 1,3-diol fragments using an alkyl or aryl boronic acid to form a cyclic boronate ester derivative which is then reacted with dinitrogen pentoxide to directly generate the dinitrate ester. In the cyclic ester from the 1,2- or 1,3-hydroxyl groups are protected and other reactions may then be carried out on other parts of the molecule of which the fragment form a part, leaving the dinitrate ester to be produced subsequently in the final step. High yields are obtained at both stages.

Abstract: Compounds and their compositions, of general formula: A--X.sub.1 --NO.sub.2 are used as medicaments wherein: A=R(COX).sub.t t=0 or 1; X=O and the remaining substituents are defined in the specification.

Abstract: Compounds of formula (I): in which:R.sub.a and R.sub.b, identical or different, represent hydrogen or alkyl or together form a bond,R.sub.C represents hydroxyl optionally substituted alkoxy, or optionally substituted amino,R.sub.1 represents hydrogen or --O--NO.sub.2, --O--NO, or --S--NO,R.sub.2 and R.sub.3, identical or different, represent hydrogen, alkyl, or optionally substituted phenyl,X represents oxygen or --NH--CO--,m represents 0 or 1,n represents an integer such that 0.ltoreq.n.ltoreq.6,p represents 0 or 1,R.sub.4 represents hydrogen, optionally substituted alkyl, optionally substituted phenyl, or a group as defined in the description,R.sub.5 represents hydrogen or alkyl,R.sub.6 represents hydrogen or alkyl,or R.sub.5 and R.sub.6 together form a chain --(CH.sub.2).sub.t -- in which t represents 1 or 2,q represents 0, 1, or 2,r represents an integer such that 0.ltoreq.r.ltoreq.6,R.sub.d and R.sub.

Abstract: New compounds and their compositions having anti-inflammatory, analgesic and anti-thrombotic activities, of the general formula: A--X.sub.1 --NO.sub.2 or their salts, wherein: A is R(COX.sub.u).sub.t, wherein t is zero or 1 and u is zero or 1; and X is O, NH or NR.sub.1C wherein R.sub.1C is C.sub.1 -C.sub.10 alkyl; and R is(Ia) wherein R.sub.1 is acetoxoy, preferably n ortho-position with respect to --CO-- and R.sub.2 is hydrogen; or derivatives of acetylsalylsalicyclic acid; and X.sub.1 is --YO-- wherein Y is C.sub.1 -C.sub.20 alkylene, C.sub.5 -C.sub.7 cycloalkylene, oxy-alkyl derivatives and oxy-methyl benzyl derivatives.

Abstract: Nitric esters from derivatives of 2-(2,6-dihalophenylamino) phenylacetoxyacetic acid with the formula (I), where: ?A.ident.F, Cl or Br; X.ident.O, NH or NR (R.ident.C.sub.1 -C.sub.8 alkyl); R.sub.1 and R.sub.2 independently.ident.C.sub.1 -C.sub.8 alkyl and n is a whole number from 1 to 10. The procedure includes the condensation of 2-(2,6-diahlophenylamino) phenylacetoxyacetic acid with a compound with the formula: ##STR1## where Y.ident.OH, NH.sub.2 or NHR and Z is Cl, Br or ONO.sub.2.