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1 General aspects (0)   1.1 Epidemiology (16)   1.2 Population genetics (1)   1.3 Pathogenesis (1)   1.4 Quality of life (10)   1.5 Glaucomas as cause of blindness (4)   1.6 Prevention and screening (7) 2 Anatomical structures in glaucoma (0)   2.1 Conjunctiva (7)   2.2 Cornea (18)   2.3 Sclera (7)   2.4 Anterior chamber angle (1)   2.5 Meshwork (0)     2.5.1 Trabecular meshwork (4)     2.5.2 Schlemms canal (1)     2.5.3 Scleral outlet channels (1)   2.6 Aqueous humor dynamics (0)     2.6.1 Production (2)     2.6.2 Outflow (2)       2.6.2.1 Trabecular meshwork (7)       2.6.2.2 Uveoscleral (0)     2.6.3 Compostion (2)   2.7 Episcleral veins and venous pressure (1)   2.8 Iris (5)   2.9 Ciliary body (1)   2.10 Lens (1)   2.11 Vitreous body (0)   2.12 Choroid, peripapillary choroid, peripapillary atrophy (1)   2.13 Retina and retinal nerve fibre layer (20)   2.14 Optic disc (13)   2.15 Optic nerve (3)   2.16 Chiasma and retrochiasmal central nervous system (5)   2.17 Stem cells (1)   2.20 Other (0) 3 Laboratory methods (0)   3.1 Microscopy (2)   3.2 Electron microscopy (2)   3.3 Immunohistochemistry (3)   3.4 Molecular genetics (0)     3.4.1 Linkage studies (0)     3.4.2 Gene studies (13)   3.5 Molecular biology incl. SiRNA (19)   3.6 Cellular biology (28)   3.7 Biochemistry (5)   3.8 Pharmacology (16)   3.9 Pathophysiology (2)   3.10 Immunobiology (7)   3.11 Pharmacogenetics (0)   3.12 Proteomics (0)   3.13 In vivo imaging (0)     3.13.1 Laser Scanning (0)       3.13.1.1 Confocal Scanning Laser Ophthalmoscopy (0)       3.13.1.2 Confocal Scanning Laser Polarimetry (0)     3.13.2 Optical Coherence Tomography (0)       3.13.2.1 Anterior Segment (0)       3.13.2.2 Posterior Segment (0)     3.13.3 RGC Imaging (0)     3.13.4 Other (1)   3.20 Other (0) 4 Tissue culture of ocular cells (0) 5 Experimental glaucoma; animal models (1)   5.1 Rodent (30)   5.2 Primates (6)   5.3 Other (15) 6 Clinical examination methods (0)   6.1 Intraocular pressure measurement; factors affecting IOP (0)     6.1.1 Devices, techniques (19)     6.1.2 Fluctuation, circadian rhythms (5)     6.1.3 Factors affecting IOP (7)   6.2 Tonography, aqueous flow measurement (see also 2.6) (1)   6.3 Biomicroscopy (slitlamp) (0)     6.3.1 Anterior segment (1)     6.3.2 Posterior segment (3)   6.4 Gonioscopy (1)   6.5 Ophthalmoscopy (0)   6.6 Visual field examination and other visual function tests (0)     6.6.1 Conventional manual (0)     6.6.2 Automated (19)     6.6.3 Special methods (e.g. color, contrast, SWAP etc.) (11)   6.7 Electro-ophthalmodiagnosis (3)   6.8 Photography (0)     6.8.1 Anterior segment (1)     6.8.2 Posterior segment (5)   6.9 Computerized image analysis (0)     6.9.1 Laser scanning (0)       6.9.1.1 Confocal Scanning Laser Ophthalmoscopy (13)       6.9.1.2 Confocal Scanning Laser Polarimetry (8)     6.9.2 Optical coherence tomography (0)       6.9.2.1 Anterior (8)       6.9.2.2 Posterior (28)     6.9.5 Other (3)   6.10 Fluorescein (ICG) angiography (0)     6.10.1 Anterior segment (0)     6.10.2 Posterior segment (1)   6.11 Bloodflow measurements (24)   6.12 Ultrasonography and ultrasound biomicroscopy (7)   6.13 Provocative tests (2)   6.19 Telemedicine (2)   6.20 Progression (9)   6.30 Other (1) 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(0)     9.4.1 Steroid-induced glaucoma (9)     9.4.2 Glaucomas associated with disorders of the cornea, conjunctiva, sclera (0)       9.4.2.1 Iridocorneal endothelial syndrome (ICE, incl. irisatrophy) (3)       9.4.2.2 Posterior polymorphous dystrophy (0)       9.4.2.3 Fuchs' endothelial dystrophy (0)       9.4.2.5 Other (0)     9.4.3 Glaucomas associated with disorders of the iris and ciliary body (0)       9.4.3.1 Pigmentary glaucoma (3)       9.4.3.5 Other (0)     9.4.4 Glaucomas associated with disorders of the lens (0)       9.4.4.1 Exfoliation syndrome (15)       9.4.4.2 Glaucomas associated with cataracts (0)       9.4.4.3 Glaucomas associated with lens dislocation (1)       9.4.4.5 Other (1)     9.4.5 Glaucomas associated with disorders of the retina, choroid and vitreous (2)       9.4.5.1 Neovascular glaucoma (6)       9.4.5.5 Other (2)     9.4.6 Glaucomas associated with inflammation, uveitis (4)     9.4.7 Glaucomas associated with ocular trauma (3)     9.4.8 Glaucomas associated with intraocular tumors (2)     9.4.9 Glaucomas associated with elevated episcleral venous pressure (0)       9.4.10 Glaucomas associated with hemorrhage (0)     9.4.11 Glaucomas following intraocular surgery (0)       9.4.11.1 Ciliary block (malignant) glaucoma (0)       9.4.11.2 Glaucomas in aphakia and pseudophakia (3)       9.4.11.3 Epithelial, fibrous, and endothelial proliferation (0)       9.4.11.4 Glaucomas associated with corneal surgery (2)       9.4.11.5 Glaucomas associated with vitreoretinal surgery (2)     9.4.15 Glaucoma in relation to systemic disease (18)     9.4.20 Other (0) 10 Differential diagnosis e.g. anterior and posterior ischemic optic neuropathy (7) 11 Medical treatment (0)   11.1 General management, indication (3)   11.2 Cholinergic drugs (0)   11.3 Adrenergic drugs (0)     11.3.1 Epinephrine (0)     11.3.2 Thymoxamine, dapiprazole (0)     11.3.3 Apraclonidine, brimonidine (2)     11.3.4 Betablocker (8)     11.3.5 Other (0)   11.4 Prostaglandins (22)   11.5 Carbonic anhydrase inhibitors (1)     11.5.1 Systemic (0)     11.5.2 Topical (5)   11.6 Osmotic treatment (0)   11.7 Treatment of bloodflow (0)   11.8 Neuroprotection (31)   11.9 Gene therapy (2)   11.13 Combination therapy (0)     11.13.1 Betablocker and pilocarpine (0)     11.13.2 Betablocker and carbon anhydrase inhibitor (3)     11.13.3 Betablocker and brimonidine (0)     11.13.4 Betablocker and prostaglandin (6)     11.13.5 Other (0)   11.14 Investigational drugs; pharmacological experiments (17)   11.15 Other drugs in relation to glaucoma (10)   11.16 Vehicles, delivery systems, pharmacokinetics, formulation (11)   11.17 Cooperation with medical therapy e.g. persistency, compliance, adherence (4)   11.20 Other (0) 12 Surgical treatment (0)   12.1 General management, indication (0)   12.2 Laser iridotomy (6)   12.3 Laser iridoplasty (1)   12.4 Laser trabeculoplasty and other laser treatment of the angle (9)   12.7 Surgical iridectomy (2)   12.8 Filtering surgery (1)     12.8.1 Without tube implant (9)     12.8.2 With tube implant or other drainage devices (14)     12.8.3 Non-perforating (10)     12.8.4 Using laser (0)     12.8.5 Other (0)     12.8.10 Woundhealing antifibrosis (12)     12.8.11 Complications, endophthalmitis (6)   12.9 Trabeculotomy, goniotomy (3)   12.10 Cyclodestruction (2)   12.11 Cyclodialysis (0)   12.12 Cataract extraction (0)     12.12.1 Intracapsular (0)     12.12.2 Extracapsular (0)     12.12.3 Phacoemulsification (2)   12.14 Combined cataract extraction and glaucoma surgery (0)     12.14.1 Intracapsular (0)     12.14.2 Extracapsular (2)     12.14.3 Phacoemulsification (14)   12.15 Capsulotomy (0)   12.16 Vitrectomy (0)   12.17 Anesthesia (2)   12.20 Other (3) 13 Therapeutic prognosis and outcome (0)   13.1 Prognostic factors (0)   13.2 Outcome (0)     13.2.1 IOP (1)     13.2.2 Visual field (0)       13.2.2.1 Progression (1)       13.2.2.2 Improvement (0)     13.2.3 Other (0) 14 Costing studies; pharmacoeconomics (5) 15 Miscellaneous (25)

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Abstract #22896 Published in IGR 11-1

Chroman-3-amides as potent Rho kinase inhibitors

Chen YT; Bannister TD; Weiser A; Griffin E; Lin L; Ruiz C; Cameron MD; Schurer S; Duckett D; Schroter T
Bioorganic and Medicinal Chemistry Letters 2008; 18: 6406-6409

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Inhibition of Rho kinase (ROCK) is an attractive strategy for the treatment of diseases such as hypertension, glaucoma, and cancer. Here we report chroman-3-amides as highly potent ROCK inhibitors with sufficient kinase selectivity, excellent cell activity, good microsomal stability, and desirable pharmacokinetic properties for study as potential therapeutic agents.

Dr. Y. Feng, Department of Molecular Therapeutics, Translational Research Institute, The Scripps Research Institute, Florida, 130 Scripps Way, Jupiter, FL 33458, USA. yfeng@scripps.edu

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Classification:

11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)

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