bay-58-2667 and Glaucoma

bay-58-2667 has been researched along with Glaucoma* in 1 studies

Other Studies

1 other study(ies) available for bay-58-2667 and Glaucoma

Article	Year
The Discovery of ( S)-1-(6-(3-((4-(1-(Cyclopropanecarbonyl)piperidin-4-yl)-2-methylphenyl)amino)-2,3-dihydro-1 H-inden-4-yl)pyridin-2-yl)-5-methyl-1 H-pyrazole-4-carboxylic Acid, a Soluble Guanylate Cyclase Activator Specifically Designed for Topical Ocul Journal of medicinal chemistry, 2018, 03-22, Volume: 61, Issue:6 Soluble guanylate cyclase (sGC), the endogenous receptor for nitric oxide (NO), has been implicated in several diseases associated with oxidative stress. In a pathological oxidative environment, the heme group of sGC can be oxidized becoming unresponsive to NO leading to a loss in the ability to catalyze the production of cGMP. Recently a dysfunctional sGC/NO/cGMP pathway has been implicated in contributing to elevated intraocular pressure associated with glaucoma. Herein we describe the discovery of molecules specifically designed for topical ocular administration, which can activate oxidized sGC restoring the ability to catalyze the production of cGMP. These efforts culminated in the identification of compound (+)-23, which robustly lowers intraocular pressure in a cynomolgus model of elevated intraocular pressure over 24 h after a single topical ocular drop and has been selected for clinical evaluation. Topics: Administration, Ophthalmic; Administration, Topical; Animals; CHO Cells; Cricetinae; Cricetulus; Cyclic GMP; Drug Discovery; Enzyme Activators; Glaucoma; Humans; Intraocular Pressure; Macaca fascicularis; Ophthalmic Solutions; Oxidation-Reduction; Rabbits; Soluble Guanylyl Cyclase	2018

Article

Year

The Discovery of ( S)-1-(6-(3-((4-(1-(Cyclopropanecarbonyl)piperidin-4-yl)-2-methylphenyl)amino)-2,3-dihydro-1 H-inden-4-yl)pyridin-2-yl)-5-methyl-1 H-pyrazole-4-carboxylic Acid, a Soluble Guanylate Cyclase Activator Specifically Designed for Topical Ocul

Journal of medicinal chemistry, 2018, 03-22, Volume: 61, Issue:6

Soluble guanylate cyclase (sGC), the endogenous receptor for nitric oxide (NO), has been implicated in several diseases associated with oxidative stress. In a pathological oxidative environment, the heme group of sGC can be oxidized becoming unresponsive to NO leading to a loss in the ability to catalyze the production of cGMP. Recently a dysfunctional sGC/NO/cGMP pathway has been implicated in contributing to elevated intraocular pressure associated with glaucoma. Herein we describe the discovery of molecules specifically designed for topical ocular administration, which can activate oxidized sGC restoring the ability to catalyze the production of cGMP. These efforts culminated in the identification of compound (+)-23, which robustly lowers intraocular pressure in a cynomolgus model of elevated intraocular pressure over 24 h after a single topical ocular drop and has been selected for clinical evaluation.

Topics: Administration, Ophthalmic; Administration, Topical; Animals; CHO Cells; Cricetinae; Cricetulus; Cyclic GMP; Drug Discovery; Enzyme Activators; Glaucoma; Humans; Intraocular Pressure; Macaca fascicularis; Ophthalmic Solutions; Oxidation-Reduction; Rabbits; Soluble Guanylyl Cyclase

2018