1,3-Oxazole-based selective picomolar inhibitors of cytosolic human carbonic anhydrase II alleviate ocular hypertension in rabbits: Potency is supported by X-ray crystallography of two leads
Copyright policy )1,3-Oxazole-based selective picomolar inhibitors of cytosolic human carbonic anhydrase II alleviate ocular hypertension in rabbits: Potency is supported by X-ray crystallography of two leads
Two lead 1,3-oxazole-based carbonic anhydrase inhibitors (CAIs) earlier identified as selective, picomolar inhibitors of hCA II (a cytosolic target for treatment of glaucoma) have been investigated further. Firstly, they were found to be conveniently synthesized on multigram scale, which enables further development. These compounds were found to be comparable in efficacy to dorzolamide eye drops when applied in the eye drop form as well. Finally, the reasons for unusually high potency of these compounds became understood from their high-resolution X-ray crystallography structures. These data significantly expand our understanding of heterocycle-based primary sulfonamides, many of which have recently emerged from our labs - particularly, from the corneal permeability standpoint.
- Pedagogical University Mozambique
- Yaroslavl State Pedagogical University Russian Federation
- New York University Italy
- St Petersburg University Russian Federation
- University of Florence Italy
Male, Binding Sites, Molecular Conformation, Molecular Dynamics Simulation, Crystallography, X-Ray, Carbonic Anhydrase II, Protein Structure, Tertiary, Carbonic anhydrase inhibitors; Isoform selectivity; Multigram synthesis; Ocular hypertension; Picomolar inhibition; Primary sulfonamide; X-ray crystallography; Animals; Binding Sites; Carbonic Anhydrase II; Carbonic Anhydrase Inhibitors; Crystallography, X-Ray; Humans; Intraocular Pressure; Male; Molecular Conformation; Molecular Dynamics Simulation; Ocular Hypertension; Oxazoles; Protein Structure, Tertiary; Rabbits; Biochemistry; Molecular Medicine; Molecular Biology; 3003; Drug Discovery3003 Pharmaceutical Science; Clinical Biochemistry; Organic Chemistry, Animals, Humans, Ocular Hypertension, Rabbits, Carbonic Anhydrase Inhibitors, Oxazoles, Intraocular Pressure
Male, Binding Sites, Molecular Conformation, Molecular Dynamics Simulation, Crystallography, X-Ray, Carbonic Anhydrase II, Protein Structure, Tertiary, Carbonic anhydrase inhibitors; Isoform selectivity; Multigram synthesis; Ocular hypertension; Picomolar inhibition; Primary sulfonamide; X-ray crystallography; Animals; Binding Sites; Carbonic Anhydrase II; Carbonic Anhydrase Inhibitors; Crystallography, X-Ray; Humans; Intraocular Pressure; Male; Molecular Conformation; Molecular Dynamics Simulation; Ocular Hypertension; Oxazoles; Protein Structure, Tertiary; Rabbits; Biochemistry; Molecular Medicine; Molecular Biology; 3003; Drug Discovery3003 Pharmaceutical Science; Clinical Biochemistry; Organic Chemistry, Animals, Humans, Ocular Hypertension, Rabbits, Carbonic Anhydrase Inhibitors, Oxazoles, Intraocular Pressure
selected citations These citations are derived from selected sources.This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).14 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Average impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!