INDUSTRIAL PROCESS FOR THE PREPARATION OF HEXANOIC ACID, 6-(NITROOXY)-, (1S,2E)-3-[(1R,2R,3S,5R)-2-[(2Z)-7-(ETHYLAMINO)-7-OXO-2-HEPTEN-1-YL]-3,5-DIHYDROXYCYCLOPENTYL]-1-(2-PHENYLETHYL)-2-PROPEN-1-YL ESTER AND HIGH PURE PRODUCT
The present invention relates to a process for preparing hexanoic acid, 6-(nitrooxy)-, (1S,2E)-3-[(1R,2R,3S,5R)-2-[(2Z)-7-(ethylamino)-7-oxo-2-hepten-1-yl]-3,5-dihydroxycyclopentyl]-1-(2-phenylethyl)-2-propen-1-yl ester
The present invention relates to a process for preparing hexanoic acid, 6-(nitrooxy)-, (1S,2E)-3-[(1R,2R,3S,5R)-2-[(2Z)-7-(ethylamino)-7-oxo-2-hepten-1-yl]-3,5-dihydroxycyclopentyl]-1-(2-phenylethyl)-2-propen-1-yl ester
The present invention relates to a process for preparing hexanoic acid, 6-(nitrooxy)-, (1S,2E)-3-[(1R,2R,3S,5R)-2-[(2Z)-7-(ethylamino)-7-oxo-2-hepten-1-yl]-3,5-dihydroxycyclopentyl]-1-(2-phenylethyl)-2-propen-1-yl ester
In accordance with the present invention, a pharmaceutical grade Compound (I) can be efficiently prepared by a one-pot reactions preparation step that includes the esterification of the 15-OH bimatoprost by coupling bimatoprost phenyl-boronate with 6-(nitrooxy) hexanoic acid and the removal of the boronate ester protecting group, followed by an efficient purification step.
The present invention relates to a process for preparing hexanoic acid, 6-(nitrooxy)-, (1S,2E)-3-[(1R,2R,3S,5R)-2-[(2Z)-7-(ethylamino)-7-oxo-2-hepten-1-yl]-3,5-dihydroxycyclopentyl]-1-(2-phenylethyl)-2-propen-1-yl ester
In accordance with the present invention, a pharmaceutical grade Compound (I) can be efficiently prepared by a one-pot reactions preparation step that includes the esterification of the 15-OH bimatoprost by coupling bimatoprost phenyl-boronate with 6-(nitrooxy) hexanoic acid and the removal of the boronate ester protecting group, followed by an efficient purification step.
The invention refers also to high purity Compound (I) substantially free of the impurity 15-(6-chlorohexanoyl) ester of bimatoprost and to ophthalmic pharmaceutical formulations containing the high purity compound.
C07C 405/00 - Compounds containing a five-membered ring having two side-chains in ortho position to each other, and having oxygen atoms directly attached to the ring in ortho position to one of the side-chains, one side-chain containing, not directly attached to the ring, a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, and the other side-chain having oxygen atoms attached in gamma-position to the ring, e.g. prostaglandins
A61K 31/5575 - Eicosanoids, e.g. leukotrienes having a cyclopentane ring, e.g. prostaglandin E2, prostaglandin F2-alpha
2.
METHOD FOR THE TREATMENT OF ANTERIOR ISCHEMIC OPTIC NEUROPATHY
The present invention concerns the use of [(2S)-1-(4-{[(3-chloro-4-methoxyphenyl)methyl]amino}-5-{[(pyrimidin-2-yl)methyl]carbamoyl}pyrimidin-2-yl) pyrrolidin-2-yl]methyl 6-(nitrooxy)hexanoate for the treatment of anterior ischemic optic neuropathy. The above compound ameliorates ocular blood flow in the patients and improves visual field and visual acuity.
The present invention concerns the use of [(2S)-1-(4-{[(3-chloro-4-methoxyphenyl)methyl]amino}-5-{[(pyrimidin-2-yl)methyl]carbamoyl}pyrimidin-2-yl) pyrrolidin-2-yl]methyl 6-(nitrooxy)hexanoate for the treatment of anterior ischemic optic neuropathy. The above compound ameliorates ocular blood flow in the patients and improves visual field and visual acuity.
[(2S)-1-(4-{[(3-Chloro-4-methoxyphenyl)methyl]amino}-5-{[(pyrimidin-2-yl) methyl]carbamoyl}pyrimidin-2-yl)pyrrolidin-2-yl]methyl 6-(nitrooxy)hexanoate is a nitric oxide releasing phosphodiesterase 5 inhibitor having the below reported formula (1)
The present invention concerns the use of [(2S)-1-(4-{[(3-chloro-4-methoxyphenyl)methyl]amino}-5-{[(pyrimidin-2-yl)methyl]carbamoyl}pyrimidin-2-yl) pyrrolidin-2-yl]methyl 6-(nitrooxy)hexanoate for the treatment of anterior ischemic optic neuropathy. The above compound ameliorates ocular blood flow in the patients and improves visual field and visual acuity.
[(2S)-1-(4-{[(3-Chloro-4-methoxyphenyl)methyl]amino}-5-{[(pyrimidin-2-yl) methyl]carbamoyl}pyrimidin-2-yl)pyrrolidin-2-yl]methyl 6-(nitrooxy)hexanoate is a nitric oxide releasing phosphodiesterase 5 inhibitor having the below reported formula (1)
Disclosed are aqueous ophthalmic compositions in the form of a solution comprising hexanoic acid, 6-(nitrooxy)-, (1S,2E)-3-[(1R,2R,3S,5R)-2-[(2Z)-7-(ethylamino)-7-oxo-2-hepten-1-yl]-3,5-dihydroxycyclopentyl]-1-(2-phenylethyl)-2-propen-1-yl ester and macrogol 15 hydroxystearate as the only solubilizing agent. Also disclosed are methods of treating ocular hypertension or glaucoma and methods of reducing intraocular pressure that include administering a therapeutically effective amount of the aqueous ophthalmic composition to a subject in need thereof.
A61K 31/222 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin with compounds having aromatic groups, e.g. dipivefrine, ibopamine
A61K 47/12 - Carboxylic acidsSalts or anhydrides thereof
A61K 47/18 - AminesAmidesUreasQuaternary ammonium compoundsAmino acidsOligopeptides having up to five amino acids
A61K 47/24 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
A61K 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharidesDerivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
4.
OPHTHALMIC PHARMACEUTICAL COMPOSITIONS CONTAINING A NITRIC OXIDE-RELEASING PHOSPHODIESTERASE 5 INHIBITOR AND METHOD FOR THE PREPARATION THEREOF
The present invention discloses aqueous ophthalmic formulations in the form of eye drops comprising [(2S)-1-(4-{[(3-chloro-4-methoxyphenyl)methyl]amino}-5-{[(pyrimidin-2-yl)methyl]carbamoyl}pyrimidin-2-yl)pyrrolidin-2-yl]methyl 6-(nitrooxy) hexanoate able to retain physical and chemical stability of the active ingredient over time.
The present invention relates the compound hexanoic acid, 6-(nitrooxy)-, (1S,2E)-3-[(1R,2R,3S,5R)-2-[(2Z)-7-(ethylamino)-7-oxo-2-hepten-1-yl]-3,5-dihydroxycyclopentyl]-1-(2-phenylethyl)-2-propen-1-yl ester (Compound (I)) effective for treating normal tension glaucoma, neovascular glaucoma and ocular diseases associated with retinopathy.
The present invention relates the compound hexanoic acid, 6-(nitrooxy)-, (1S,2E)-3-[(1R,2R,3S,5R)-2-[(2Z)-7-(ethylamino)-7-oxo-2-hepten-1-yl]-3,5-dihydroxycyclopentyl]-1-(2-phenylethyl)-2-propen-1-yl ester (Compound (I)) effective for treating normal tension glaucoma, neovascular glaucoma and ocular diseases associated with retinopathy.
Nitric oxide releasing phosphodiesterase type 5 (PDE5) inhibitors of formula (I) or (Ib) or (II) or a stereoisomer or a pharmaceutically acceptable salt thereof:
Nitric oxide releasing phosphodiesterase type 5 (PDE5) inhibitors of formula (I) or (Ib) or (II) or a stereoisomer or a pharmaceutically acceptable salt thereof:
useful for the treatment of ocular condition associated with elevated intraocular pressure such as ocular hypertension, glaucoma or retinopathies. Also disclosed are 3-[(2S)-2,3-bis(nitrooxy)propoxy]propanoic acid and 6-(nitrooxy)hexanoic acid for use in the treatment of ocular condition associated with elevated intraocular pressure such as ocular hypertension, glaucoma or retinopathies.
A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61K 31/197 - Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
C07D 403/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
The present invention relates to a process for preparing hexanoic acid, 6-(nitrooxy)-, (1S,2E)-3-[(1R,2R,3S,5R)-2-[(2Z)-7-(ethylamino)-7-oxo-2-hepten-1-yl]-3,5-dihydroxycyclopentyl]-1-(2-phenylethyl)-2-propen-1-yl ester of formula (I).
The present invention relates to a process for preparing hexanoic acid, 6-(nitrooxy)-, (1S,2E)-3-[(1R,2R,3S,5R)-2-[(2Z)-7-(ethylamino)-7-oxo-2-hepten-1-yl]-3,5-dihydroxycyclopentyl]-1-(2-phenylethyl)-2-propen-1-yl ester of formula (I).
The present invention relates to a process for preparing hexanoic acid, 6-(nitrooxy)-, (1S,2E)-3-[(1R,2R,3S,5R)-2-[(2Z)-7-(ethylamino)-7-oxo-2-hepten-1-yl]-3,5-dihydroxycyclopentyl]-1-(2-phenylethyl)-2-propen-1-yl ester of formula (I).
In accordance with the present invention, the compound (I) can be efficiently prepared with high purity by coupling bimatoprost in a boronate protected form with 6-(nitrooxy)hexanoyl chloride and removing the boronate protecting group.
The present invention relates to a process for preparing hexanoic acid, 6-(nitrooxy)-, (1S,2E)-3-[(1R,2R,3S,5R)-2-[(2Z)-7-(ethylamino)-7-oxo-2-hepten-1-yl]-3,5-dihydroxycyclopentyl]-1-(2-phenylethyl)-2-propen-1-yl ester of formula (I).
In accordance with the present invention, the compound (I) can be efficiently prepared with high purity by coupling bimatoprost in a boronate protected form with 6-(nitrooxy)hexanoyl chloride and removing the boronate protecting group.
The invention also relates to a process for the preparation of 6-(nitrooxy) hexanoic acid having a HPLC purity equal to or greater than 99% and containing an amount of 6-{[6-(nitrooxy)hexanoyl]oxy}hexanoic acid (compound (IXa) equal to or lower than 0.2%.
C07C 405/00 - Compounds containing a five-membered ring having two side-chains in ortho position to each other, and having oxygen atoms directly attached to the ring in ortho position to one of the side-chains, one side-chain containing, not directly attached to the ring, a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, and the other side-chain having oxygen atoms attached in gamma-position to the ring, e.g. prostaglandins
A61K 31/5575 - Eicosanoids, e.g. leukotrienes having a cyclopentane ring, e.g. prostaglandin E2, prostaglandin F2-alpha
C07C 201/02 - Preparation of esters of nitric acid
8.
INDUSTRIAL PROCESS FOR THE PREPARATION OF HEXANOIC ACID, 6-(NITROOXY)-, (1S,2E)-3-[(1R,2R,3S,5R)-2-[(2Z)-7-(ETHYLAMINO)-7-OXO-2-HEPTEN-1-YL]-3,5-DIHYDROXYCYCLOPENTYL]-1-(2-PHENYLETHYL)-2-PROPEN-1-YL ESTER AND HIGH PURE PRODUCT
The present invention relates to a process for preparing hexanoic acid, 6-(nitrooxy)-, (1S,2E)-3-[(1R,2R,3S,5R)-2-[(2Z)-7-(ethylamino)-7-oxo-2-hepten-1-yl]-3,5-dihydroxycyclopentyl]-1-(2-phenylethyl)-2-propen-1-yl ester
The present invention relates to a process for preparing hexanoic acid, 6-(nitrooxy)-, (1S,2E)-3-[(1R,2R,3S,5R)-2-[(2Z)-7-(ethylamino)-7-oxo-2-hepten-1-yl]-3,5-dihydroxycyclopentyl]-1-(2-phenylethyl)-2-propen-1-yl ester
The present invention relates to a process for preparing hexanoic acid, 6-(nitrooxy)-, (1S,2E)-3-[(1R,2R,3S,5R)-2-[(2Z)-7-(ethylamino)-7-oxo-2-hepten-1-yl]-3,5-dihydroxycyclopentyl]-1-(2-phenylethyl)-2-propen-1-yl ester
In accordance with the present invention, a pharmaceutical grade Compound (I) can be efficiently prepared by a one-pot reactions preparation step that includes the esterification of the 15-OH bimatoprost by coupling bimatoprost phenyl-boronate with 6-(nitrooxy)hexanoic acid and the removal of the boronate ester protecting group, followed by an efficient purification step.
The present invention relates to a process for preparing hexanoic acid, 6-(nitrooxy)-, (1S,2E)-3-[(1R,2R,3S,5R)-2-[(2Z)-7-(ethylamino)-7-oxo-2-hepten-1-yl]-3,5-dihydroxycyclopentyl]-1-(2-phenylethyl)-2-propen-1-yl ester
In accordance with the present invention, a pharmaceutical grade Compound (I) can be efficiently prepared by a one-pot reactions preparation step that includes the esterification of the 15-OH bimatoprost by coupling bimatoprost phenyl-boronate with 6-(nitrooxy)hexanoic acid and the removal of the boronate ester protecting group, followed by an efficient purification step.
The invention refers also to high purity Compound (I) substantially free of the impurity 15-(6-chlorohexanoyl) ester of bimatoprost and to ophthalmic pharmaceutical formulations containing the high purity compound.
C07C 235/34 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton containing six-membered aromatic rings having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
C07C 231/12 - Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
9.
INDUSTRIAL PROCESS FOR THE PREPARATION OF HEXANOIC ACID, 6-(NITROOXY)-, (1S,2E)-3-[(1R,2R,3S,5R)-2-[(2Z)-7-(ETHYLAMINO)-7-OXO-2-HEPTEN-1-YL]-3,5-DIHYDROXYCYCLOPENTYL]-1-(2-PHENYLETHYL)-2-PROPEN-1-YL ESTER AND HIGH PURE PRODUCT
The present invention relates to a process for preparing hexanoic acid, 6-(nitrooxy)-, (1S,2E)-3-[(1R,2R,3S,5R)-2-[(2Z)-7-(ethylamino)-7-oxo-2-hepten-1-yl]- 3,5-dihydroxycyclopentyl]-1-(2-phenylethyl)-2-propen-1-yl ester Compound (I). In accordance with the present invention, a pharmaceutical grade Compound (I) can be efficiently prepared by a one-pot reactions preparation step that includes the esterification of the 15-OH bimatoprost by coupling bimatoprost phenyl-boronate with 6- (nitrooxy)hexanoic acid and the removal of the boronate ester protecting group, followed by an efficient purification step. The invention refers also to high purity Compound (I) substantially free of the impurity 15-(6-chlorohexanoyl) ester of bimatoprost and to ophthalmic pharmaceutical formulations containing the high purity compound.
C07C 405/00 - Compounds containing a five-membered ring having two side-chains in ortho position to each other, and having oxygen atoms directly attached to the ring in ortho position to one of the side-chains, one side-chain containing, not directly attached to the ring, a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, and the other side-chain having oxygen atoms attached in gamma-position to the ring, e.g. prostaglandins
The invention relates to the use of nitric oxide releasing cyclic guanosine 3′,5′ monophosphate (cGMP) phosphodiesterase type 5 inhibitors (NO-PDES inhibitors) in a method for the treatment of dry age-related macular degeneration and geographic atrophy. This invention also relates to the use of such compounds to provide neuroprotection to the eye in a patient suffering from glaucoma or retinal neuropathies.
The present invention concerns the use of [(2S)-l-(4-{[(3-chloro-4- methoxyphenyl)methyl]amino}-5-{[(pyrimidin-2-yl)methyl]carbamoyl}pyrimidin-2-yl) pyrrolidin-2-yl]methyl 6-(nitrooxy)hexanoate for the treatment of anterior ischemic optic neuropathy. The above compound ameliorates ocular blood flow in the patients and improves visual field and visual acuity. [(2S)- 1 -(4- { [(3 -Chloro-4-methoxypheny l)methy 1] amino } -5- { [(pyrimidin-2-yl) methyl]carbamoyl}pyrimidin-2-yl)pyrrolidin-2-yl]methyl 6-(nitrooxy)hexanoate is a nitric oxide releasing phosphodiesterase 5 inhibitor having the below reported formula (1).
A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61K 31/573 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 9/00 - Medicinal preparations characterised by special physical form
The present invention relates to a treatment of vaso-occlusive crisis (VOC) associated with Sickle cell disease by administering a therapeutically effective amount of 4-(nitrooxy)butyl-(2S)-2-(6-methoxy-2-naphthyl) propanoate.
A61K 31/222 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin with compounds having aromatic groups, e.g. dipivefrine, ibopamine
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
13.
OPHTHALMIC PHARMACEUTICAL COMPOSITIONS CONTAINING A NITRIC OXIDE-RELEASING PHOSPHODIESTERASE 5 INHIBITOR AND METHOD FOR THE PREPARATION THEREOF
OPHTHALMIC PHARMACEUTICAL COMPOSITIONS CONTAINING A NITRIC OXIDE-RELEASING PHOSPHODIESTERASE 5 INHIBITOR AND METHOD FOR THE PREPARATION THEREOFThe present invention discloses aqueous ophthalmic formulations in the form of eye drops comprising [(2S)-1-(4-{[(3-chloro-4-methoxyphenyl)methyl]amino}-5-{[(pyrimidin-2-yl)methyl]carbamoyl}pyrimidin-2-yl)pyrrolidin-2-yl]methyl 6-(nitrooxy) hexanoate able to retain physical and chemical stability of the active ingredient over time.
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 47/14 - Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
A61K 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharidesDerivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
A61K 47/44 - Oils, fats or waxes according to two or more groups of Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
The present invention relates the compound hexanoic acid, 6-(nitrooxy)-, (1S,2E)- 3-[(1R,2R,3S,5R)-2-[(2Z)-7-(ethylamino)-7-oxo-2-hepten-1-yl]-3,5- dihydroxycyclopentyl]-1-(2-phenylethyl)-2-propen-1-yl ester (Compound (I)) effective for treating normal tension glaucoma, neovascular glaucoma and ocular diseases associated with retinopathy.
A61K 31/5575 - Eicosanoids, e.g. leukotrienes having a cyclopentane ring, e.g. prostaglandin E2, prostaglandin F2-alpha
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 31/573 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
The invention relates to ophthalmic compositions comprising a nitric oxide releasing phosphodiesterase type 5 inhibitor (NO-PDE5 inhibitor) and a prostaglandin analog, and to the use of these ophthalmic compositions for the treatment of all forms of glaucoma or ocular hypertension as well as eyes diseases or conditions associated with elevated intraocular pressure. The NO-PDE5 inhibitor is selected from the following compounds: [(2S)-1-(4-{[(3-chloro-4-methoxyphenyl)methyl]amino}-5-{[(pyrimidin-2-yl)methyl]carbamoyl}pyrimidin-2-yl)pyrrolidin-2-yl]methyl 6-(nitrooxy) hexanoate (Compound (1)), [(2S)-1-(4-{[(3-chloro-4-methoxyphenyl)methyl]amino}-5-{[(pyrimidin-2-yl)methyl]carbamoyl}pyrimidin-2-yl)pyrrolidin-2-yl]methyl 3-[(2S)-2,3-bis(nitrooxy)propoxy]propanoate (Compound (1A)) or 2-{4-[3-(5-Ethyl-4-oxo-7-propyl-4,5-dihydro-3H-pyrrolo[3,2-d]pyrimidin-2-yl)-4-propoxybenzene-1-sulfonyl]piperazin-1-yl}ethyl 3-[(2S)-2,3-bis(nitrooxy) propoxy]propanoate (Compound (2)). The prostaglandin analog is selected from latanoprost, bimatoprost, travoprost or tafluprost.
The present invention relates to a process for preparing the hexanoic acid, 6-(nitrooxy)-, (1S,2E)-3-[(1R,2R,3S,5R)-2-[(2Z)-7-(ethylamino)-7-oxo-2-hepten-1-yl]-3,5-dihydroxycyclopentyl]-1-(2-phenylethyl)-2-propen-1-yl ester of formula (I).
The present invention relates to a process for preparing the hexanoic acid, 6-(nitrooxy)-, (1S,2E)-3-[(1R,2R,3S,5R)-2-[(2Z)-7-(ethylamino)-7-oxo-2-hepten-1-yl]-3,5-dihydroxycyclopentyl]-1-(2-phenylethyl)-2-propen-1-yl ester of formula (I).
The present invention relates to a process for preparing the hexanoic acid, 6-(nitrooxy)-, (1S,2E)-3-[(1R,2R,3S,5R)-2-[(2Z)-7-(ethylamino)-7-oxo-2-hepten-1-yl]-3,5-dihydroxycyclopentyl]-1-(2-phenylethyl)-2-propen-1-yl ester of formula (I).
In accordance with the present invention, the compound (I) can be efficiently prepared with high purity by coupling bimatoprost in a boronate protected form with 6-(nitrooxy)hexanoyl chloride having an high chemical purity and removing the boronate protecting group.
The present invention relates to a process for preparing the hexanoic acid, 6-(nitrooxy)-, (1S,2E)-3-[(1R,2R,3S,5R)-2-[(2Z)-7-(ethylamino)-7-oxo-2-hepten-1-yl]-3,5-dihydroxycyclopentyl]-1-(2-phenylethyl)-2-propen-1-yl ester of formula (I).
In accordance with the present invention, the compound (I) can be efficiently prepared with high purity by coupling bimatoprost in a boronate protected form with 6-(nitrooxy)hexanoyl chloride having an high chemical purity and removing the boronate protecting group.
The high chemical pure 6-(nitrooxy)hexanoyl chloride is prepared from 6-(nitrooxy)hexanoic acid having a high chemical purity. The invention also relates to a process for the preparation and purification of 6-(nitrooxy) hexanoic acid.
C07C 405/00 - Compounds containing a five-membered ring having two side-chains in ortho position to each other, and having oxygen atoms directly attached to the ring in ortho position to one of the side-chains, one side-chain containing, not directly attached to the ring, a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, and the other side-chain having oxygen atoms attached in gamma-position to the ring, e.g. prostaglandins
17.
PROCESS FOR THE PREPARATION OF A NITRIC OXIDE DONATING PROSTAGLANDIN ANALOGUE
The present invention relates to a process for preparing hexanoic acid, 6-(nitrooxy)-, (1S,2E)-3-[(1R,2R,3S,5R)-2-[(2Z)-7-(ethylamino)-7-oxo-2-hepten-1-yl]-3,5-dihydroxycyclopentyl]-1-(2-phenylethyl)-2-propen-1-yl ester of formula (I). In accordance with the present invention, the compound (I) can be efficiently prepared with high purity by coupling bimatoprost in a boronate protected form with 6-(nitrooxy)hexanoyl chloride and removing the boronate protecting group. The invention also relates to a process for the preparation of 6-(nitrooxy) hexanoic acid having a HPLC purity equal to or greater than 99% and containing an amount of 6- {[6-(nitrooxy)hexanoyl]oxy}hexanoic acid (compound (IXa) equal to or lower than 0.2%.
C07C 405/00 - Compounds containing a five-membered ring having two side-chains in ortho position to each other, and having oxygen atoms directly attached to the ring in ortho position to one of the side-chains, one side-chain containing, not directly attached to the ring, a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, and the other side-chain having oxygen atoms attached in gamma-position to the ring, e.g. prostaglandins
C07C 201/02 - Preparation of esters of nitric acid
The invention relates to the use of nitric oxide releasing cyclic guanosine 3',5' monophosphate (cGMP) phosphodiesterase type 5 inhibitors (NO-PDE5 inhibitors) in a method for the treatment of dry age-related macular degeneration and geographic atrophy. This invention also relates to the use of such compounds to provide neuroprotection to the eye in a patient suffering from glaucoma or retinal neuropathies.
A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 47/18 - AminesAmidesUreasQuaternary ammonium compoundsAmino acidsOligopeptides having up to five amino acids
A61K 47/20 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
A61K 47/44 - Oils, fats or waxes according to two or more groups of Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
A61K 47/55 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
The invention relates to nitric oxide releasing phosphodiesterase type 5 (PDE5) inhibitors of formula or a stereoisomer or a pharmaceutically acceptable salt thereof:
useful for the treatment of ocular condition associated with elevated intraocular pressure such as ocular hypertension, glaucoma or retinopathies.
A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61K 31/197 - Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
C07D 403/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
The present invention relates to a treatment of vaso-occlusive crisis (VOC) associated with Sickle cell disease by administering a therapeutically effective amount of 4-(nitrooxy)butyl-(2S)-2-(6-methoxy-2-naphthyl) propanoate.
The invention relates to ophthalmic compositions comprising a nitric oxide releasing phosphodiesterase type 5 inhibitor (NO-PDE5 inhibitor) and a prostaglandin analog, and to the use of these ophthalmic compositions for the treatment of all forms of glaucoma or ocular hypertension as well as eyes diseases or conditions associated with elevated intraocular pressure. The NO-PDE5 inhibitor is selected from the following compounds: [(2S)-1-(4-{[(3-chloro-4-methoxyphenyl)methyl]amino}-5-{[(pyrimidin-2- yl)methyl]carbamoyl}pyrimidin-2-yl)pyrrolidin-2-yl]methyl 6-(nitrooxy) hexanoate (Compound (1)), [(2S)-1-(4-{[(3-chloro-4-methoxyphenyl)methyl]amino}-5- {[(pyrimidin-2-yl)methyl]carbamoyl}pyrimidin-2-yl)pyrrolidin-2-yl]methyl 3-[(2S)-2,3- bis(nitrooxy)propoxy]propanoate (Compound (1A)) or 2-{4-[3-(5-Ethyl-4-oxo-7-propyl- 4,5-dihydro-3H-pyrrolo[3,2-d]pyrimidin-2-yl)-4-propoxybenzene-1-sulfonyl]piperazin-1- yl}ethyl 3-[(2S)-2,3-bis(nitrooxy) propoxy]propanoate (Compound (2)). The prostaglandin analog is selected from latanoprost, bimatoprost, travoprost or tafluprost.
The present invention relates to a treatment of vaso-occlusive crisis (VOC) associated with Sickle cell disease by administering a therapeutically effective amount of 4-(nitrooxy)butyl-(2S)-2-(6-methoxy-2-naphthyl) propanoate.
A61K 31/222 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin with compounds having aromatic groups, e.g. dipivefrine, ibopamine
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
23.
Ophthalmic compositions containing a nitric oxide releasing prostamide
The present invention provides aqueous ophthalmic compositions in the form of solution comprising hexanoic acid, 6-(nitrooxy)-, (1S,2E)-3-[(1R,2R,3S,5R)-2-[(2Z)-7-(ethylamino)-7-oxo-2-hepten-1-yl]-3,5-dihydroxycyclopentyl]-1-(2-phenylethyl)-2-propen-1-yl ester and macrogol 15 hydroxystearate as the only solubilizing agent, and a method for their preparation.
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 31/216 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
A61K 31/222 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin with compounds having aromatic groups, e.g. dipivefrine, ibopamine
A61K 47/12 - Carboxylic acidsSalts or anhydrides thereof
A61K 47/18 - AminesAmidesUreasQuaternary ammonium compoundsAmino acidsOligopeptides having up to five amino acids
A61K 47/24 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
A61K 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharidesDerivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
24.
Ophthalmic compositions containing a nitric oxide releasing prostamide
The present invention provides aqueous ophthalmic compositions in the form of solution comprising hexanoic acid, 6-(nitrooxy)-, (1S,2E)-3-[(1R,2R,3S,5R)-2-[(2Z)-7-(ethylamino)-7-oxo-2-hepten-1-yl]-3,5-dihydroxycyclopentyl]-1-(2-phenylethyl)-2-propen-1-yl ester and macrogol 15 hydroxystearate as the only solubilizing agent, and a method for their preparation.
A61K 31/216 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
A61K 31/222 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin with compounds having aromatic groups, e.g. dipivefrine, ibopamine
A61K 47/12 - Carboxylic acidsSalts or anhydrides thereof
A61K 47/18 - AminesAmidesUreasQuaternary ammonium compoundsAmino acidsOligopeptides having up to five amino acids
A61K 47/24 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
A61K 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharidesDerivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
25.
Process for the preparation of a nitric oxide donating prostaglandin analogue
The present invention relates to a process for preparing the hexanoic acid, 6-(nitrooxy)-, (1S,2E)-3-[(1R,2R,3S,5R)-2-[(2Z)-7-(ethylamino)-7-oxo-2-hepten-1-yl]-3,5-dihydroxycyclopentyl]-1-(2-phenylethyl)-2-propen-1-yl ester of formula (I).
In accordance with the present invention, the compound (I) can be efficiently prepared with high purity by coupling bimatoprost in a boronate protected form with 6-(nitrooxy)hexanoyl chloride and removing the boronate protecting group.
4 in dichloromethane.
C07C 231/12 - Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
C07C 405/00 - Compounds containing a five-membered ring having two side-chains in ortho position to each other, and having oxygen atoms directly attached to the ring in ortho position to one of the side-chains, one side-chain containing, not directly attached to the ring, a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, and the other side-chain having oxygen atoms attached in gamma-position to the ring, e.g. prostaglandins
C07C 291/02 - Compounds containing carbon and nitrogen and having functional groups not covered by groups containing nitrogen-oxide bonds
C07C 201/02 - Preparation of esters of nitric acid
26.
PROCESS FOR THE PREPARATION OF A NITRIC OXIDE DONATING PROSTAGLANDIN ANALOGUE
The present invention relates to a process for preparing the hexanoic acid, 6-(nitrooxy)-,(1S,2E)-3-[(1R,2R,3S,5R)-2-[(2Z)-7-(ethylamino)-7-oxo-2-hepten-1-yl]-3,5-dihydroxycyclopentyl]-1-(2-phenylethyl)-2-propen-1-yl ester of formula (I). In accordance with the present invention, the compound (I) can be efficiently prepared with high purity by coupling bimatoprost in a boronate protected form with 6-(nitrooxy)hexanoyl chloride having an high chemical purity and removing the boronate protecting group. The high chemical pure 6-(nitrooxy)hexanoyl chloride is prepared from 6-(nitrooxy)hexanoic acid having a high chemical purity. The invention also relates to a process for the preparation and purification of 6-(nitrooxy) hexanoic acid.
C07C 405/00 - Compounds containing a five-membered ring having two side-chains in ortho position to each other, and having oxygen atoms directly attached to the ring in ortho position to one of the side-chains, one side-chain containing, not directly attached to the ring, a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, and the other side-chain having oxygen atoms attached in gamma-position to the ring, e.g. prostaglandins
27.
Ophthalmic compositions containing a nitric oxide releasing prostamide
The present invention provides aqueous ophthalmic compositions in the form of solution comprising hexanoic acid, 6-(nitrooxy)-, (1S,2E)-3-[(1R,2R,3S,5R)-2-[(2Z)-7-(ethylamino)-7-oxo-2-hepten-1-yl]-3,5-dihydroxycyclopentyl]-1-(2-phenylethyl)-2-propen-1-yl ester and macrogol 15 hydroxystearate as the only solubilizing agent, and a method for their preparation.
This invention provides a method of lowering intraocular pressure in a patient having normal tension glaucoma, comprising contacting an eye of a subject having normal tension glaucoma with a pharmaceutical composition comprising an effective amount of Nitric Oxide releasing prostaglandin derivatives of formula (I).
The invention relates to nitric oxide releasing phosphodiesterase type 5 (PDE5) inhibitors of formula (I) or (lb) or (II) or a stereoisomer or a pharmaceutically acceptable salt thereof: useful for the treatment of ocular condition associated with elevated intraocular pressure such as ocular hypertension, glaucoma or retinopathies. The invention further relates to 3-[(2S)-2,3-bis(nitrooxy)propoxy]propanoic acid and 6-(nitrooxy)hexanoic acid for use in the treatment of ocular condition associated with elevated intraocular pressure such as ocular hypertension, glaucoma or retinopathies.
A61K 47/55 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
A61K 31/21 - Esters, e.g. nitroglycerine, selenocyanates
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 47/18 - AminesAmidesUreasQuaternary ammonium compoundsAmino acidsOligopeptides having up to five amino acids
A61K 47/20 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
A61K 47/44 - Oils, fats or waxes according to two or more groups of Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
C07D 403/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
The present invention provides aqueous ophthalmic compositions in the form of solution comprising hexanoic acid, 6-(nitrooxy)-, (1S,2E)-3-[(1R,2R,3S,5R)-2-[(2Z)-7-(ethylamino)-7-oxo-2-hepten-1-yl]-3,5-dihydroxycyclopentyl]-1-(2-phenylethyl)-2-propen-1-yl ester and macrogol 15 hydroxystearate as the only solubilizing agent, and a method for their preparation.
The present invention provides aqueous ophthalmic compositions in the form of solution comprising hexanoic acid, 6-(nitrooxy)-, (1S,2E)-3-[(1R,2R,3S,5R)-2-[(2Z)-7-(ethylamino)-7-oxo-2-hepten-1-yl]-3,5-dihydroxycyclopentyl]-1-(2-phenylethyl)-2-propen-1-yl ester and macrogol 15 hydroxystearate as the only solubilizing agent, and a method for their preparation.
C07C 405/00 - Compounds containing a five-membered ring having two side-chains in ortho position to each other, and having oxygen atoms directly attached to the ring in ortho position to one of the side-chains, one side-chain containing, not directly attached to the ring, a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, and the other side-chain having oxygen atoms attached in gamma-position to the ring, e.g. prostaglandins
C07C 291/02 - Compounds containing carbon and nitrogen and having functional groups not covered by groups containing nitrogen-oxide bonds
C07C 201/02 - Preparation of esters of nitric acid
The present invention provides nitric oxide releasing hyaluronic acid derivatives of formula (I) in which the carboxylic groups of the hyaluronic acid are partially esterified with a group capable to release nitric oxide: (I) The hyaluronic acid derivatives of the invention are able to release nitric oxide (NO) and they can be advantageously used in ophthalmology.
The present invention relates to nitric oxide donating isomannide derivatives, their use for treating glaucoma and ocular hypertension and formulations containing them. The present invention also relates to compositions comprising a nitric oxide donating isomannide derivative and one or more further active ingredients for the use in the treatment of glaucoma and ocular hypertension.
A61K 31/34 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
ocular pharmaceuticals; ophthalmic and ophthalmological preparations; pharmaceutical products for ophthalmological use; solutions for lubrication and rewetting the eyes; eye drops; solutions for ocular hydration; solutions for reducing ocular inflammation and pain associated with ocular pathologies; solutions for reducing symptoms associated with conjunctivitis; pharmaceutical preparations for the prevention and treatment of eye disorders, diseases and conditions; solutions and preparations for treating pathologies of the eyelids and eyelid margins; pharmaceutical preparations, namely, a topical preparation for the treatment of ocular disorders prescribed by ophthalmologists, eye surgeons, and optometrists
36.
NITRIC OXIDE RELEASING PROSTAGLANDIN DERIVATIVES FOR TREATING NORMAL TENSION GLAUCOMA
This invention provides a method of lowering intraocular pressure in a patient having normal tension glaucoma, comprising contacting an eye of a subject having normal tension glaucoma with a pharmaceutical composition comprising an effective amount of Nitric Oxide releasing prostaglandin derivatives of formula (I).
The present invention relates to 15-nitrooxyderivatives of fluprostenol, their use for the treatment of glaucoma and ocular hypertension and formulation containing 15-nitrooxy derivatives of fluprostenol.
C07D 405/00 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
C07C 405/00 - Compounds containing a five-membered ring having two side-chains in ortho position to each other, and having oxygen atoms directly attached to the ring in ortho position to one of the side-chains, one side-chain containing, not directly attached to the ring, a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, and the other side-chain having oxygen atoms attached in gamma-position to the ring, e.g. prostaglandins
38.
Nitric oxide donating derivatives of latanoprost free acid
The present invention relates to 15-nitrooxyderivatives of latanoprost and 15-nitrooxyderivatives of latanoprost free acid, their use for the treatment of glaucoma and ocular hypertension and formulation containing 15-nitrooxyderivatives of latanoprost and 15-nitrooxyderivatives of latanoprost free acid.
C07C 405/00 - Compounds containing a five-membered ring having two side-chains in ortho position to each other, and having oxygen atoms directly attached to the ring in ortho position to one of the side-chains, one side-chain containing, not directly attached to the ring, a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, and the other side-chain having oxygen atoms attached in gamma-position to the ring, e.g. prostaglandins
03 - Cosmetics and toiletries; cleaning, bleaching, polishing and abrasive preparations
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
Eye lotions, eye gels, eye creams, non-medical. Collyriums; irrigation solutions for the eyes; injectable
pharmaceutical products and preparations for treatment of
eye diseases; pharmaceutical products for the eyes;
ophthalmologic products; pharmaceutical products for
ophthalmological use; eye lubricating and re-humidifying
solutions; eye-washes; food supplements for eye health;
eye moisturizing solutions; solutions for reduction of eye
pain and inflammation in connection with eye surgery and
other pathologies; pharmaceutical preparations for ocular
or intraocular surgery; solutions for reducing the symptoms
relating to conjunctivitis; pharmaceutical products for
prevention and treatment of eye diseases, disorders and
conditions; solutions and preparations for treating
pathologies of the eyelids and eyelid edge; pharmaceutical
products, namely topical products for treatment of ocular
disorders prescribed by ophthalmologists, eye surgeons and
optometrists.
03 - Cosmetics and toiletries; cleaning, bleaching, polishing and abrasive preparations
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
(1) Lotions pour les yeux, gels pour les yeux, crèmes ophtalmiques non médicales
(2) Collyres; solutions d'irrigation pour les yeux; préparations pharmaceutiques injectables destinées à traiter les pathologies de l'oeil; préparations pharmaceutiques pour le soin des yeux; préparations pharmaceutiques à usage ophtalmologique; solutions de lubrification et de réhumidification des yeux; préparations pour lavages oculaires; compléments alimentaires pour la santé de l'oeil; solutions pour hydratation oculaire; solutions pour réduire l'inflammation et la douleur oculaires liés à la chirurgie oculaire et à d'autres pathologies; préparations pharmaceutiques pour la chirurgie oculaire et intraoculaire nommément solutions ophtalmiques; solutions pour réduire les symptômes liés à la conjonctivite; préparations pharmaceutiques pour la prévention et le traitement des maladies, troubles et affections oculaires; solutions et préparations pour traiter des pathologies des paupières et du bord des paupières; préparations pharmaceutiques, à savoir produits topiques pour traitement de troubles oculaires prescrits par des ophtalmologistes, chirurgiens des yeux et optométristes
The present invention relates to nitric oxide donor carnosine derivatives having a great efficacy in reducing elevated intraocular pressure, to processes for their preparation and to their use in the treatment and/or prophylaxis of glaucoma and ocular hypertension.
The present invention relates to a pharmaceutical composition for use as a medicament in the prophylactic or therapeutic topical treatment of viral eye infections caused by adenovirus of subtype D or influenza A virus of subtype H7. The composition in its ready-for-use formulation comprises iota carrageenan as an active antiviral ingredient and is substantially free of a metal halide salt or contains no more than 0.5% w/v of a metal halide salt.
The present invention relates to 15-nitrooxyderivatives of latanoprost and 15-nitrooxyderivatives of latanoprost free acid, their use for the treatment of glaucoma and ocular hypertension and formulation containing 15-nitrooxyderivatives of latanoprost and 15-nitrooxyderivatives of latanoprost free acid.
A61K 31/5575 - Eicosanoids, e.g. leukotrienes having a cyclopentane ring, e.g. prostaglandin E2, prostaglandin F2-alpha
C07C 405/00 - Compounds containing a five-membered ring having two side-chains in ortho position to each other, and having oxygen atoms directly attached to the ring in ortho position to one of the side-chains, one side-chain containing, not directly attached to the ring, a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, and the other side-chain having oxygen atoms attached in gamma-position to the ring, e.g. prostaglandins
The present invention relates to 15-nitrooxyderivatives of fluprostenol, their use for the treatment of glaucoma and ocular hypertension and formulation containing 15-nitrooxyderivatives of fluprostenol.
C07C 405/00 - Compounds containing a five-membered ring having two side-chains in ortho position to each other, and having oxygen atoms directly attached to the ring in ortho position to one of the side-chains, one side-chain containing, not directly attached to the ring, a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, and the other side-chain having oxygen atoms attached in gamma-position to the ring, e.g. prostaglandins
45.
Ophthalmic compositions containing a nitric oxide donor
The present invention relates to compositions comprising a 4-nitrooxybutan-1-ol alkyl ester as nitric oxide donor. More specifically, the invention relates to compositions comprising 4-nitrooxybutan-1-ol alkyl ester as a nitric oxide donor and an ophthalmic drug, useful in controlling elevated intraocular pressure associated with glaucoma or ocular hypertension associated with other diseases or conditions. The invention is also directed to methods of controlling intraocular pressure utilizing said compositions.
The present invention relates to compositions for treating glaucoma and elevated ocular pressure. The compositions comprise a nitric oxide releasing isomannide derivative and a prostaglandin F2α analog.
A61K 31/164 - Amides, e.g. hydroxamic acids of a carboxylic acid with an aminoalcohol, e.g. ceramides
A61K 31/191 - Acyclic acids having two or more hydroxy groups, e.g. gluconic acid
A61K 31/343 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
The present invention relates to nitric oxide donor compounds having a quinone based structure, to processes for their preparation and to their use in the treatment and/or prophylaxis of glaucoma and ocular hypertension.
The present invention relates to novel nitric oxide donor compounds for the use in the treatment and/or prophylaxis of hypertensive glaucoma, normotensive glaucoma and ocular hypertension.
A61K 31/341 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
C07C 203/04 - Esters of nitric acid having nitrate groups bound to acyclic carbon atoms
A61K 31/21 - Esters, e.g. nitroglycerine, selenocyanates
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 31/122 - Ketones having the oxygen atom directly attached to a ring, e.g. quinones, vitamin K1, anthralin
A61K 47/44 - Oils, fats or waxes according to two or more groups of Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
49.
COMPOSITION EFFECTIVE AGAINST VIRAL CONJUNCTIVITIS
The present invention relates to a pharmaceutical composition for use as a medicament in the prophylactic or therapeutic topical treatment of viral eye infections caused by adenovirus of subtype D or influenza Avirus of subtype H7. The composition in its ready-for-use formulation comprises iota carrageenan as an active antiviral ingredient and is substantiallyfree of a metal halide salt or contains no more than 0.5% w/v of a metal halide salt.
The present invention relates to a pharmaceutical composition useful in the prophylactic or therapeutic topical treatment of viral eye infections caused by adenovirus of subtype D or influenza A virus of subtype H7. The composition in its ready-for-use formulation comprises iota carrageenan as an active antiviral ingredient and is essentially free of a metal halide salt or contains no more than 0.5% w/v of a metal halide salt.
03 - Cosmetics and toiletries; cleaning, bleaching, polishing and abrasive preparations
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
Eye lotions, eye gels, eye creams not for medical purposes. Eye washes; irrigating solutions for eye use; injectable pharmaceutical preparations for treating pathologies of the eye; ocular pharmaceuticals; ophthalmic and ophthalmological preparations; pharmaceutical products for ophthalmological use; solutions for lubrication and rewetting the eyes; eye drops; dietary supplements for eye health; solutions for ocular hydration; solutions for reducing ocular inflammation and pain associated with ocular surgery and other pathologies; pharmaceutical preparations for ocular or intraocular surgery; solutions for reducing symptoms associated with conjunctivitis; pharmaceutical preparations for the prevention and treatment of eye disorders, diseases and conditions; solutions and preparations for treating pathologies of the eyelids and eyelid margins; pharmaceutical preparations, namely, a topical preparation for the treatment of ocular disorders prescribed by ophthalmologists, eye surgeons, and optometrists.
The present invention relates to nitric oxide donor compounds having a quinone based structure, to processes for their preparation and to their use in the treatment of pathological conditions where a deficit of NO plays an important role in their pathogenesis.
C07C 203/04 - Esters of nitric acid having nitrate groups bound to acyclic carbon atoms
C07C 323/53 - Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being saturated and containing rings
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
C07C 323/22 - Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and doubly-bound oxygen atoms bound to the same carbon skeleton
The present invention relates to nitric oxide donor compounds having a quinone based structure, to processes for their preparation and to their use in the treatment of pathological conditions where a deficit of NO plays an important role in their pathogenesis.
C07C 203/04 - Esters of nitric acid having nitrate groups bound to acyclic carbon atoms
C07C 323/22 - Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and doubly-bound oxygen atoms bound to the same carbon skeleton
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 31/341 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
A61K 31/21 - Esters, e.g. nitroglycerine, selenocyanates
05 - Pharmaceutical, veterinary and sanitary products
42 - Scientific, technological and industrial services, research and design
44 - Medical, veterinary, hygienic and cosmetic services; agriculture, horticulture and forestry services
Goods & Services
Test strips for the diagnosis and/or detection of Adenovirus and allergies. Scientific and medical research for the diagnosis and/or detection of Adenovirus and allergies. Medical services, namely, the diagnosis and/or detection of Adenovirus and allergies; medical diagnostics namely the diagnosis and/or detection of Adenovirus and allergies; realization and evaluation of medical tests for the diagnosis and / or detection of Adenovirus and allergies.
05 - Pharmaceutical, veterinary and sanitary products
42 - Scientific, technological and industrial services, research and design
44 - Medical, veterinary, hygienic and cosmetic services; agriculture, horticulture and forestry services
Goods & Services
Test strips for the diagnosis and/or detection of Ocular Herpes. Scientific and medical research. Medical services, namely, the diagnosis and/or detection of Ocular Herpes; medical diagnostics; realization and evaluation of medical tests for the diagnosis and / or detection of Ocular Herpes.
03 - Cosmetics and toiletries; cleaning, bleaching, polishing and abrasive preparations
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
Eye lotions; Eye gels; Eye creams, not for medical purposes. Eye-washes; Injectable pharmaceutical preparations for treating pathologies of the eye; Ophthalmic and ophthalmological preparations; Solutions for lubrication and rewetting of the eyes; Dietary supplements for eye health; Solutions for ocular hydration.
03 - Cosmetics and toiletries; cleaning, bleaching, polishing and abrasive preparations
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
Eye lotions; Eye gels; Eye creams, not for medical purposes. Eye-washes; Injectable pharmaceutical preparations for treating pathologies of the eye; Ophthalmic and ophthalmological preparations; Solutions for lubrication and rewetting of the eyes; Dietary supplements for eye health; Solutions for ocular hydration.
03 - Cosmetics and toiletries; cleaning, bleaching, polishing and abrasive preparations
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
Eye lotions; Eye gels; Eye creams, not for medical purposes. Eye-washes; Injectable pharmaceutical preparations for treating pathologies of the eye; Ophthalmic and ophthalmological preparations; Solutions for lubrication and rewetting of the eyes; Dietary supplements for eye health; Solutions for ocular hydration.
03 - Cosmetics and toiletries; cleaning, bleaching, polishing and abrasive preparations
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
Eye lotions; Eye gels; Eye creams, not for medical purposes; Solutions for ocular hydration. Eye drops; Ophthalmic and ophthalmological preparations; Solutions for lubrication and rewetting of the eyes; Medicines for treating conditions of the eyes.
05 - Pharmaceutical, veterinary and sanitary products
10 - Medical apparatus and instruments
35 - Advertising and business services
42 - Scientific, technological and industrial services, research and design
44 - Medical, veterinary, hygienic and cosmetic services; agriculture, horticulture and forestry services
Goods & Services
Pharmaceutical preparations; dietary supplements; dietetic
substances adapted for medical use. Medical apparatus and instruments; diagnostic apparatus for
medical purposes. Retail and wholesale services of pharmaceutical products,
dietary supplements, dietetic substances adapted for medical
use, medical apparatus and instruments, diagnostic apparatus
for medical purposes; presentation of goods on communication
media for retail or wholesale purposes. Scientific and medical research; analysis and scientific
research services in the pharmaceutical field; research
services in the pharmaceutical field relative to
traceability and quality control of making pharmaceutical
products. Medical diagnostic services; medical evaluation services.
The present invention relates to nitric oxide donor compounds having a quinone based structure, to processes for their preparation and to their use in the treatment of pathological conditions where a deficit of NO plays an important role in their pathogenesis.
05 - Pharmaceutical, veterinary and sanitary products
10 - Medical apparatus and instruments
35 - Advertising and business services
42 - Scientific, technological and industrial services, research and design
44 - Medical, veterinary, hygienic and cosmetic services; agriculture, horticulture and forestry services
Goods & Services
[ Pharmaceutical preparations, namely, pharmaceutical preparations and substances for the treatment of ocular and ophthalmological diseases; respiratory system disease, gastrointestinal system disease, endocrine system disease, cardiovascular system disease, central nervous system disease, peripheral nervous system disease, musculoskeletal system disease, urinary system disease, integumentary system disease, reproductive system disease, skin and scalp disease, cancer, diabetes, thrombosis, arthritis, pain, inflammation, blood disease and disorders, cold, coughs, influenza, vertigo, nausea, vomiting, migraine, mouth and gum disease, burns; Dietetic foods adapted for medical use, namely, meal replacement bars, meal replacement drink mixes, minerals, vitamins ] [ Medical apparatus and instruments for use in the treatment of ocular and ophthalmological disease, respiratory system disease, gastrointestinal system disease, endocrine system disease, cardiovascular system disease, central nervous system disease, peripheral nervous systems disease, musculoskeletal systems disease, urinary system disease, integumentary system disease, reproductive system disease, skin and scalp disease, cancer, diabetes, thrombosis, arthritis, pain, inflammation, blood disease and disorders, cold, coughs, influenza, vertigo, nausea, vomiting, migraine, mouth and gum disease, burns; Diagnostic apparatus for medical purposes for detecting ocular and ophthalmological diseases, respiratory system disease, gastrointestinal system disease, endocrine system disease, cardiovascular system disease, central nervous system disease, peripheral nervous system disease, musculoskeletal system disease, urinary system disease, integumentary system disease, reproductive system disease, skin and scalp disease, cancer, diabetes, thrombosis, arthritis, pain, inflammation, blood disease and disorders, cold, coughs, influenza, vertigo, nausea, vomiting, migraine, mouth and gum disease, burns ] [ Online retail and wholesale store services featuring pharmaceutical products, dietary supplements, dietetic substances adapted for medical use, medical apparatus and instruments, and diagnostic apparatus for medical purposes ] Scientific and medical research; analysis and scientific research services in the pharmaceutical field; research services in the pharmaceutical field relative to traceability and quality control of making pharmaceutical products [ Medical evaluation services in the fields of ocular and ophthalmological diseases, respiratory system disease, gastrointestinal system disease, endocrine system disease, cardiovascular system disease, central nervous system disease, peripheral nervous system disease, musculoskeletal system disease, urinary system disease, integumentary system disease, reproductive system disease, skin and scalp disease, cancer, diabetes, thrombosis, arthritis, pain, inflammation, blood disease and disorders, cold, coughs, influenza, vertigo, nausea, vomiting, migraine, mouth and gum disease, and burns, for purposes of guiding treatment ]
05 - Pharmaceutical, veterinary and sanitary products
10 - Medical apparatus and instruments
35 - Advertising and business services
42 - Scientific, technological and industrial services, research and design
44 - Medical, veterinary, hygienic and cosmetic services; agriculture, horticulture and forestry services
Goods & Services
(1) Pharmaceutical preparations, namely pharmaceutical preparations and substances for the treatment of ocular and ophthalmological diseases , respiratory system diseases, gastrointestinal system diseases, endocrine system diseases, cardiovascular system diseases, central nervous system diseases, peripheral nervous system diseases, musculoskeletal system diseases, urinary system diseases, integumentary system diseases, reproductive system diseases, skin and scalp diseases, cancer, diabetes, thrombosis, arthritis, pain, inflammation, blood diseases and disorders, cold, coughs, influenza, vertigo, nausea, vomiting, migraine, mouth and gum diseases, burns; Dietary supplements for the treatment of ocular and ophthalmological diseases , respiratory system diseases, gastrointestinal system diseases, endocrine system diseases, cardiovascular system diseases, central nervous system diseases, peripheral nervous system diseases, musculoskeletal system diseases, urinary system diseases, integumentary system diseases, reproductive system diseases, skin and scalp diseases, cancer, diabetes, thrombosis, arthritis, pain, inflammation, blood diseases and disorders, cold, coughs, influenza, vertigo, nausea, vomiting, migraine, mouth and gum disease, burns; Dietetic substances adapted for medical use, namely meal replacement bars, meal replacement drink mixes, minerals, vitamins. Medical apparatus and instruments namely medical lamps, medical clamps, medical drainage tubes, medical electrodes, medical feeding tubes, medical respirators, medical scales, medical instruments for general examination, medical slings, medical spittoons, medical stretchers, medical thermometers; Diagnostic apparatus namely diagnostic devices, namely magnetic resonance imaging (MRI) diagnostic apparatus, ultrasonic medical diagnostic apparatus. (1) Retail and wholesale services of pharmaceutical products, dietary supplements, dietetic substances adapted for medical use, medical apparatus and instruments, namely diagnostic devices, namely magnetic resonance imaging (MRI) diagnostic apparatus, ultrasonic medical diagnostic apparatus, medical lamps, medical clamps, medical drainage tubes, medical electrodes, medical feeding tubes, medical respirators, medical scales, medical instruments for general examination, medical slings, medical spittoons, medical stretchers, medical thermometers; Presentation of goods on communication media for retail or wholesale purposes, namely on the Internet, on broadcast TV, in print publications, namely magazines, newspapers, on advertisement boards, on displays, and on point-of-sale displays. Scientific and medical research in the field of ophthalmology, cardiovascular diseases, treatment of bone diseases and treatment of muscular dystrophy; Analysis and scientific research services in the pharmaceutical field; research services in the pharmaceutical field relative to traceability and quality control of making pharmaceutical products; medical diagnostics; evaluation of medical diagnostics.
64.
PROCESS FOR THE PREPARATION OF NITRATE ACID ESTER OF ORGANIC COMPOUNDS
The present invention relates to a one-step process for the synthesis of nitric acid esters or 15N isotopically labeled nitrate esters of organic compounds starting from the correspondent alcohols. Formula (I).
05 - Pharmaceutical, veterinary and sanitary products
10 - Medical apparatus and instruments
35 - Advertising and business services
42 - Scientific, technological and industrial services, research and design
Goods & Services
Pharmaceutical preparations; dietary supplements; dietetic substances adapted for medical use. Medical apparatus and instruments; Diagnostic apparatus for medical purposes. Retail and wholesale services of pharmaceutical products, dietary supplements, dietetic substances adapted for medical use, medical apparatus and instruments, diagnostic apparatus for medical purposes; presentation of goods on communication media for retail or wholesale purposes. Scientific and medical researches; analysis and scientific research services in the pharmaceutical field; research services in the pharmaceutical field relative to traceability and quality control of making pharmaceutical products; medical diagnostics; evaluation of medical diagnostics.
66.
Nitric oxide enhancing prostaglandin compounds, compositions and methods of use
The invention provides methods for treating ophthalmic disorders comprising at least one nitric oxide enhancing prostaglandin compound or a pharmaceutically acceptable salt thereof, and, optionally, at least one nitric oxide enhancing compound and/or at least one therapeutic agent. The nitric oxide enhancing prostaglandin compounds comprise at least one heterocyclic nitric oxide donor group and/or at least one nitroxide group.
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
A61K 31/4523 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
A61K 31/41 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which is nitrogen, e.g. tetrazole
A61K 31/535 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and at least one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
C07D 233/02 - Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
C07D 263/06 - Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by oxygen atoms, attached to ring carbon atoms
C07D 265/06 - 1,3-OxazinesHydrogenated 1,3-oxazines not condensed with other rings
C07D 211/94 - Oxygen atom, e.g. piperidine N-oxide
C07D 209/46 - Iso-indolesHydrogenated iso-indoles with an oxygen atom in position 1
C07D 207/46 - Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with hetero atoms directly attached to the ring nitrogen atom
67.
STATIN DERIVATES AND INTERMEDIATES FOR THEIR PRODUCTION
Dinitrate statins having improved pharmacological activity are described. They can be employed for treating and/or preventing several diseases, in particular acute coronary syndromes, neurodegenerative disorders as well as for reducing cholesterol levels.
C07D 207/34 - Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
A61K 31/40 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
The invention relates to nitrooxyderivatives of Gamma- aminobutyric acid analogs (GABA analogs) for treating neuropathic pain and in particular diabetic neuropathy. The invention also relates to pharmaceutical formulation comprising such derivatives, to a process for their preparation.
C07C 203/04 - Esters of nitric acid having nitrate groups bound to acyclic carbon atoms
C07C 271/16 - Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by singly-bound oxygen atoms
The present invention relates to nitric oxide releasing derivatives of serotonin norepinephrine reuptake inhibitors and their use for the treatment of pain, having the following general formula (I) or pharmaceutically acceptable salts thereof: wherein : A is selected from the formulas (1a) and (1b). The present invention also relates to pharmaceutical formulation comprising such derivatives, to a process for their preparation and to intermediates useful for their preparation.
C07D 333/20 - Radicals substituted by singly bound hetero atoms other than halogen by nitrogen atoms
C07C 271/22 - Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
A61K 31/381 - Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
A61K 31/325 - Carbamic acidsThiocarbamic acidsAnhydrides or salts thereof
A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID]
70.
PROCESS FOR PREPARING (11BETA, 16ALPHA)-9-FLUORO-11-HYDROXY-16,17-[1-METHYL-ETHYLIDENEBIS(OXY)]-21-[1-OXO-[4-(NITROOXYMETHYL)BENZOXY]]PREGNA-1,4-DIEN-3,20-DIONE
This invention relates to a new process for preparing (11 β, 16α)-9-fluoro-11 - hydroxy-16,17-[1 -methyl -ethyl idenebis(oxy)]-21 -[1 -oxo-[4- (nitrooxymethyl)benzoxy]]pregna-1,4-dien-3,20-dione, comprising the steps of (i) reaction of triamcinolone acetonide with 4-(nitrooxymethyl)benzoic, 4- dimethylaminopyridine and N-N'-diisopropylcarbodiimide, (ii) crystallisation, and (iii) controlled precipitation.
This invention relates to a new process for preparing 4-nitro-oxy-methyl- benzoic acid, comprising the following steps: a) reaction of 4-chloromethyl-benzoic acid with silver nitrate and in the presence of an acid as a catalyst in acetonitrile at reflux temperature, followed by cooling and adding of a polar aprotic solvent; b) separation of the silver salts by filtration, followed by washout with a polar aprotic solvent; c) precipitation of the 4-nitro-oxy-methyl-benzoic acid with water from the filtrate obtained in step b); and d) drying of the 4-nitro-oxy-methyl-benzoic acid.
Nitroderivatives of prostaglandins having improved pharmacological activity and enhanced tolerability are described. They can be employed for the treatment of glaucoma and ocular hypertension.
The invention relates to a nitric oxide releasing naproxen derivative of formula (I) and its use for the treatment of diseases associated with pain and inflammation. This NO releasing naproxen derivative shows a surprisingly improved gastrointestinal safety and possesses cardio-protective benefits.
The present invention refers to nitric oxide donor aspirin derivatives, a process for their preparation and pharmaceutical compositions containing -them. Formula (I) wherein R is selected from the group consisting of A) (R0) t -CH (ONO2) -R2 B) (R0) t - CH (ONO2 ) - (CR3R4 ) P-CH (ONO2 ) -R2 C) (R0) t -O- (CR3R4 ) n -CH (ONO2) -R2 D) (R0) t -O- (CR3R4 ) n -CH (ONO2 ) - (CR3R4 ) P-CH (ONO2 ) -R2.
C07C 291/02 - Compounds containing carbon and nitrogen and having functional groups not covered by groups containing nitrogen-oxide bonds
C07D 295/14 - Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
The invention relates to nitric oxide donors of the formula (I) and pharmaceutically acceptable salts or stereoisomers thereof:
2— or
2 groups.
The invention also provides novel compositions comprising at least one compound of the invention and at least one therapeutic agent.
The present invention relates to the use of nitric oxide releasing derivatives of paracetamol for retarding or reversing muscular dystrophies such as Duchenne and Becker dystrophies.
A61K 31/167 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen atom of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
A61P 21/00 - Drugs for disorders of the muscular or neuromuscular system
77.
Nitric oxide enhancing prostaglandin compounds, compositions and methods of use
The invention provides compositions and kits comprising at least one nitric oxide enhancing prostaglandin compound or a pharmaceutically acceptable salt thereof, and, optionally, at least one nitric oxide enhancing compound and/or at least one therapeutic agent. The invention also provides methods for (a) treating ophthalmic disorders; (b) treating cerebrovascular disorders; (c) treating cardiovascular disorders; (d) treating benign prostatic hyperplasia (BPH); (e) treating peptic ulcers; (e) treating sexual dysfunctions and (f) inducing abortions. The nitric oxide enhancing prostaglandin compounds comprise at least one heterocyclic nitric oxide donor group and/or at least one nitroxide group.
A61K 31/5355 - Non-condensed oxazines containing further heterocyclic rings
A61K 31/4523 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
A61K 31/41 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which is nitrogen, e.g. tetrazole
A61K 31/4025 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil not condensed and containing further heterocyclic rings, e.g. cromakalim
C07D 413/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 209/46 - Iso-indolesHydrogenated iso-indoles with an oxygen atom in position 1
C07D 207/46 - Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with hetero atoms directly attached to the ring nitrogen atom
78.
NEW NO-RELEASING STEROIDS FOR THE TREATMENT OF RETINA AND MACULA LUTEA DISEASES
The invention relates to compounds of general formula (I) and pharmaceutically acceptable salts or stereoisomers thereof (formula1) The compounds are useful for treating diabetic macular edema, diabetic retinopathy, macular degeneration, age- related macular degeneration and other diseases of retina and macula lutea.
A61K 31/573 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
The invention relates to compounds of general formula (I) and pharmaceutically acceptable salts or stereoisomers thereof. The compounds are useful in the treatment of illnesses wherein the known steroid, parent or precursor steroid, is generally applied, with increased benefit in terms of pharmacological profile and fewer or milder side effects than those of the known steroids.
C07J 41/00 - Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
A61K 31/57 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
A61P 5/44 - GlucocorticosteroidsDrugs increasing or potentiating the activity of glucocorticosteroids
A compound having the structure (formula 1) wherein R is a "sartan family" moiety Z is a nitroxy carrying moiety, or a pharmaceutically acceptable salt thereof. The compounds are active against hypertension.
A61K 31/4178 - 1,3-Diazoles not condensed and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
A61K 31/4184 - 1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
C07D 405/12 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
A61P 9/00 - Drugs for disorders of the cardiovascular system
81.
NITRO DERIVATIVES OF FURASEMIDE AND THEIR USE AS DIURETICS
A compound having the structure wherein X is selected from the group consisting of: a bond, -NHCH2(CH2)nCH2OC(O), -CH2NHC(O)CH2NHC(O)-, -CH2OC(O), -OCH(CH3)OC(O)-, -OCH2OC(O)-, -O-, -NR1-, -CR1R3-, -(CH2)P-, -(CH2)qNR1C(O)-, -CHR5NR2C(O)-, -(CH2)qC(O)-, -(CH2)qC(O)NR1-, or a pharmaceutically acceptable salt thereof, and methods of using the compounds for treating hypertension.
A61K 31/4355 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having oxygen as a ring hetero atom
A61P 9/00 - Drugs for disorders of the cardiovascular system
C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
82.
GLUCOCORTICOIDS ATTACHED TO NITRATE ESTERS VIA AN AROMATIC LINKER IN POSITION 21 AND THEIR USE IN OPHTHALMOLOGY
The invention relates to nitrooxy derivatives of fluocinolone acetonide, triamcinolone acetonide, betamethasone and beclomethasone, methods for their preparation, pharmaceutical compositions containing these compounds, and methods of using these compounds and compositions for treating diabetic macular edema, diabetic retinopathy, macular degeneration, age-related macular degeneration and other diseases of retina and macula lutea.
C07J 41/00 - Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
C07J 71/00 - Steroids in which the cyclopenta[a]hydrophenanthrene skeleton is condensed with a heterocyclic ring
A61K 31/573 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
A61P 5/44 - GlucocorticosteroidsDrugs increasing or potentiating the activity of glucocorticosteroids
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.
A compound having the structure (I) wherein R is an angiotensin II receptor antagonist selected from the group consisting of (IIa)- (IIh); A is (Formula) wherein Rl and R2 are independently selected from the group consisting of hydrogen and C1-4 alkyl. Y is X0-Z wherein X0 is selected from the group consisting of: -O-, -O-CO-, -OCOO-, -OCONH- and -OSO2-; Z is a nitric oxide releasing moiety, or a pharmaceutically acceptable salt thereof.
C07D 403/10 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a carbon chain containing aromatic rings
A61K 31/34 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
A61K 31/41 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which is nitrogen, e.g. tetrazole
The present invention relates to compositions comprising atorvastatin 4- (nitrooxy) butyl ester and a hypolipidemic, in particular ezetimibe and fenofibrate. The invention discloses also their use as cholesterol-reducing drugs, as drugs having immunosuppressive properties, antioxidant, antithrombotic and anti-inflammatory activity, effects on endothelial function, and for treating and/or preventing acute coronary syndromes, stroke, atherosclerosis, neurodegenerative disorders, such as Alzheimer's and Parkinson's disease as well as autoimmune diseases, such as multiple sclerosis.
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.
A01N 43/40 - Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
Nitroderivatives of prostaglandins having improved pharmacological activity and enhanced tolerability are described. They can be employed for the treatment of glaucoma and ocular hypertension.
C07C 291/00 - Compounds containing carbon and nitrogen and having functional groups not covered by groups
C07C 405/00 - Compounds containing a five-membered ring having two side-chains in ortho position to each other, and having oxygen atoms directly attached to the ring in ortho position to one of the side-chains, one side-chain containing, not directly attached to the ring, a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, and the other side-chain having oxygen atoms attached in gamma-position to the ring, e.g. prostaglandins
C07D 403/10 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a carbon chain containing aromatic rings
C07D 409/06 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
New angiotensin II receptor blocker nitroderivatives of general formula (I) and pharmaceutically acceptable salts or stereoisomers thereof: and their use for treating cardiovascular, renal and chronic liver diseases, inflammatory processes and metabolic syndromes.
C07D 403/10 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a carbon chain containing aromatic rings
C07D 403/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
A61P 9/00 - Drugs for disorders of the cardiovascular system
90.
Pharmaceutical formulation of nitrooxyderivatives of NSAIDs
A01N 37/00 - Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
A61K 31/21 - Esters, e.g. nitroglycerine, selenocyanates
C07C 229/00 - Compounds containing amino and carboxyl groups bound to the same carbon skeleton
C07C 239/00 - Compounds containing nitrogen-to-halogen bondsHydroxylamino compounds or ethers or esters thereof
C07C 259/00 - Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups
The invention relates to nitric oxide donors of the formula (I) and pharmaceutically acceptable salts or stereoisomers thereof : wherein A and A' are independently selected from the group consisting of H and -(X)s-Y with the proviso that at least one of A or A' is not H; wherein s is 0 or 1; X is selected from the group consisting of : -CO-, -COO-, -CONH- and -SO2- or (A); Y is straight or branched C1-C20 alkyl chain, preferably C1- C10 alkyl chain, substituted with one or two -ONO2; or C1-C6 alkylenoxy- C1-C5 alkyl wherein the alkyl group is substituted by one or two -ONO2 groups. The invention also provides novel compositions comprising at least one compound of the invention and at least one therapeutic agent.
A61P 9/00 - Drugs for disorders of the cardiovascular system
A61K 31/34 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
The present invention relates to compositions comprising a nitric oxide releasing paracetamol and an anticonvulsant drug. The compositions of the invention can be used use in the treatment of neuropathic pain in particular diabetic neuropathic pain, painful post-infarct syndrome, pain caused by chemotherapeutic treatment or pain arising from infections by viral agents.
A compound having the structure (A) wherein R is an angiotensin receptor antagonist active group, and Y is 1) -(CH2)3R5, 2) -C(O)(CH2)2R5, 3) -C(R1R2)OC(O)O(CH2)nR5, wherein n is 1 or 2, 4) -C(R1R2)OC(O)CH2CH2R5, 5) -C(R1R2)OC(O)OCH2CH2C(R3R4)R5, Formula (B), and Formula (C) provided that when Y is -C(O)(CH2)2R5, then R is Formula (D) R1, R2, R3 and R4 are independently selected from the group consisting of hydrogen and C1-4 alkyl; R5 is CH(ONO2)CH(ONO2)R6; R6 is selected from CH3, CH2CH3 and CH(CH3)2; or a pharmaceutically acceptable salt or hydrate thereof, which is useful for treating hypertension.
C07D 403/10 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a carbon chain containing aromatic rings
A61K 31/41 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which is nitrogen, e.g. tetrazole
The invention relates to the technical field of anti-inflammatory compounds, specifically those of a steroid nature, in particular to a new amorphous form of a nitrooxy derivative of a corticosteroid, its pharmaceutical formulations and its use in the treatment or prevention of diseases or symptoms of the skin or mucous membranes.
C07J 41/00 - Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
A61K 31/57 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
C07C 203/04 - Esters of nitric acid having nitrate groups bound to acyclic carbon atoms
C07C 317/44 - SulfonesSulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton
C07C 323/62 - Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton
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.
A61K 31/22 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
A61K 31/40 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
A61K 31/405 - Indole-alkanecarboxylic acidsDerivatives thereof, e.g. tryptophan, indomethacin
The present invention relates to a process for the preparation of 1,4-butanediol mononitrate as intermediate for large scale preparation of high purity nitrooxybutyl ester of pharmaceutically active compounds.
