Abstract: 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.

Abstract: 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.

Abstract: 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)).

Abstract: 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.

Abstract: The invention relates to 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. 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.

Abstract: 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. The 6-(nitrooxy)hexanoyl chloride intermediate is prepared by ring-opening reaction of 2-caprolactone and subsequent nitration of the 6-hydroxyhexanoic acid potassium salt with a mixture of HNO3 and H2SO4 in dichloromethane.

Abstract: 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. The 6-(nitrooxy)hexanoyl chloride intermediate is prepared by ring-opening reaction of 2-caprolactone and subsequent nitration of the 6-hydroxyhexanoic acid potassium salt with a mixture of HNO3 and H2SO4 in dichloromethane.

Abstract: 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 F2? analog.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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 F2? analog.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.