The Experts below are selected from a list of 654 Experts worldwide ranked by ideXlab platform
Nicholas Bodor - One of the best experts on this subject based on the ideXlab platform.
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Ocular delivery of the β-adrenergic antagonist alprenolol by sequential bioactivation of its methoxime analogue
Journal of medicinal chemistry, 1995Co-Authors: Laszlo Prokai, Gábor Somogyi, Nicholas BodorAbstract:Ocular delivery of alprenolol, a beta-adrenergic antagonist, by site-specific bioactivation of its methoxime analogue results in significant and prolonged decrease of the intraocular pressure in rabbits after topical administration. Alprenolone methoxime is stable in isotonic phosphate vehicle but undergoes enzymatic hydrolysis to the corresponding ketone in the eye. The ketone is then converted to alprenolol by a carbonyl reductase present in the iris-ciliary body. The benefit of this chemical delivery system approach includes the facile release of a potential Antiglaucoma Agent only at the site of the action; thus, unwanted systemic effects of the drug can be avoided.
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Improved Delivery Through Biological Membranes. LVI. Pharmacological Evaluation of Alprenoxime—A New Potential Antiglaucoma Agent
Pharmaceutical Research, 1991Co-Authors: Nicholas Bodor, Alaaeldin ElkoussiAbstract:A new site-specific chemical delivery system (CDS) for alprenolol was designed and investigated as a potential novel Antiglaucoma Agent. The effect of this compound, alprenoxime (AO), on the intraocular pressure (IOP) of rabbits was evaluated after its uni- and bilateral administration. AO produced significant reduction of the IOP starting at 30 min and lasting for more than 6 hr after its topical administration. Both in rats and in rabbits the i.v. bolus injection of AO (6 mg/kg) led to insignificant transient bradycardia, while no activity was found after oral or topical administration. Alprenolol (ALP) in a similar dose produced a sustained and significant bradycardia for more than 30 min. When the beta-adrenergic blocking activity was assessed against isoprenaline-tachycardia, the same results were obtained, i.e., AO led to a transient brief activity, whereas ALP produced a significant long-lasting beta blockade. These results support the potent ocular hypotensive action and the weak systemic beta-adrenergic blocking and cardiovascular activity of AO: a significant improvement in the therapeutic index. This finding recommends alprenoxime as a potent site-specific Antiglaucoma Agent with minimal systemic side effects.
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improved delivery through biological membranes lvi pharmacological evaluation of alprenoxime a new potential Antiglaucoma Agent
Pharmaceutical Research, 1991Co-Authors: Nicholas Bodor, Alaaeldin ElkoussiAbstract:A new site-specific chemical delivery system (CDS) for alprenolol was designed and investigated as a potential novel Antiglaucoma Agent. The effect of this compound, alprenoxime (AO), on the intraocular pressure (IOP) of rabbits was evaluated after its uni- and bilateral administration. AO produced significant reduction of the IOP starting at 30 min and lasting for more than 6 hr after its topical administration. Both in rats and in rabbits the i.v. bolus injection of AO (6 mg/kg) led to insignificant transient bradycardia, while no activity was found after oral or topical administration. Alprenolol (ALP) in a similar dose produced a sustained and significant bradycardia for more than 30 min. When the beta-adrenergic blocking activity was assessed against isoprenaline-tachycardia, the same results were obtained, i.e., AO led to a transient brief activity, whereas ALP produced a significant long-lasting beta blockade. These results support the potent ocular hypotensive action and the weak systemic beta-adrenergic blocking and cardiovascular activity of AO: a significant improvement in the therapeutic index. This finding recommends alprenoxime as a potent site-specific Antiglaucoma Agent with minimal systemic side effects.
Alaaeldin Elkoussi - One of the best experts on this subject based on the ideXlab platform.
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Improved Delivery Through Biological Membranes. LVI. Pharmacological Evaluation of Alprenoxime—A New Potential Antiglaucoma Agent
Pharmaceutical Research, 1991Co-Authors: Nicholas Bodor, Alaaeldin ElkoussiAbstract:A new site-specific chemical delivery system (CDS) for alprenolol was designed and investigated as a potential novel Antiglaucoma Agent. The effect of this compound, alprenoxime (AO), on the intraocular pressure (IOP) of rabbits was evaluated after its uni- and bilateral administration. AO produced significant reduction of the IOP starting at 30 min and lasting for more than 6 hr after its topical administration. Both in rats and in rabbits the i.v. bolus injection of AO (6 mg/kg) led to insignificant transient bradycardia, while no activity was found after oral or topical administration. Alprenolol (ALP) in a similar dose produced a sustained and significant bradycardia for more than 30 min. When the beta-adrenergic blocking activity was assessed against isoprenaline-tachycardia, the same results were obtained, i.e., AO led to a transient brief activity, whereas ALP produced a significant long-lasting beta blockade. These results support the potent ocular hypotensive action and the weak systemic beta-adrenergic blocking and cardiovascular activity of AO: a significant improvement in the therapeutic index. This finding recommends alprenoxime as a potent site-specific Antiglaucoma Agent with minimal systemic side effects.
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improved delivery through biological membranes lvi pharmacological evaluation of alprenoxime a new potential Antiglaucoma Agent
Pharmaceutical Research, 1991Co-Authors: Nicholas Bodor, Alaaeldin ElkoussiAbstract:A new site-specific chemical delivery system (CDS) for alprenolol was designed and investigated as a potential novel Antiglaucoma Agent. The effect of this compound, alprenoxime (AO), on the intraocular pressure (IOP) of rabbits was evaluated after its uni- and bilateral administration. AO produced significant reduction of the IOP starting at 30 min and lasting for more than 6 hr after its topical administration. Both in rats and in rabbits the i.v. bolus injection of AO (6 mg/kg) led to insignificant transient bradycardia, while no activity was found after oral or topical administration. Alprenolol (ALP) in a similar dose produced a sustained and significant bradycardia for more than 30 min. When the beta-adrenergic blocking activity was assessed against isoprenaline-tachycardia, the same results were obtained, i.e., AO led to a transient brief activity, whereas ALP produced a significant long-lasting beta blockade. These results support the potent ocular hypotensive action and the weak systemic beta-adrenergic blocking and cardiovascular activity of AO: a significant improvement in the therapeutic index. This finding recommends alprenoxime as a potent site-specific Antiglaucoma Agent with minimal systemic side effects.
Shinsaku Yamane - One of the best experts on this subject based on the ideXlab platform.
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Discovery of Novel Seven-Membered Prostacyclin Analogues as Potent and Selective Prostaglandin FP and EP3 Dual Agonists.
ACS Medicinal Chemistry Letters, 2016Co-Authors: Isamu Sugimoto, Tohru Kambe, Tomotaka Okino, Tetsuo Obitsu, Nobukazu Ohta, Taihei Nishiyama, Akihiro Kinoshita, Taku Fujimoto, Hiromu Egashira, Shinsaku YamaneAbstract:A novel series of prostaglandin analogues with a seven-membered ring scaffold was designed, synthesized, and evaluated for the functional activation of prostaglandin receptors to identify potent and subtype-selective FP and EP3 dual agonists. Starting from the prostacyclin derivative 5b, a nonselective agonist for prostaglandin receptors, replacement of the core structure with an octahydro-2H-cyclopenta[b]oxepine scaffold led to the discovery of the potent and selective FP and EP3 dual agonist 11b as a lead compound for the development of an Antiglaucoma Agent.
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Discovery of Novel Seven-Membered Prostacyclin Analogues as Potent and Selective Prostaglandin FP and EP3 Dual Agonists
2016Co-Authors: Isamu Sugimoto, Tohru Kambe, Tomotaka Okino, Tetsuo Obitsu, Nobukazu Ohta, Taihei Nishiyama, Akihiro Kinoshita, Taku Fujimoto, Hiromu Egashira, Shinsaku YamaneAbstract:A novel series of prostaglandin analogues with a seven-membered ring scaffold was designed, synthesized, and evaluated for the functional activation of prostaglandin receptors to identify potent and subtype-selective FP and EP3 dual agonists. Starting from the prostacyclin derivative 5b, a nonselective agonist for prostaglandin receptors, replacement of the core structure with an octahydro-2H-cyclopenta[b]oxepine scaffold led to the discovery of the potent and selective FP and EP3 dual agonist 11b as a lead compound for the development of an Antiglaucoma Agent
Graham Ruecroft - One of the best experts on this subject based on the ideXlab platform.
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Synthesis of the Potent Antiglaucoma Agent, Travoprost
Organic Process Research & Development, 2002Co-Authors: Lee T. Boulton, Dean Brick, Martin E. Fox, Mark Jackson, Ian C. Lennon, Raymond Mccague, Nicholas Parkin, Darren Rhodes, Graham RuecroftAbstract:A commercial synthesis of the Antiglaucoma Agent, travoprost 2, is described. A total of 22 synthetic steps are required to provide the single enantiomer prostanoid, with the longest linear sequence being 16 steps from 3-hydroxybenzotrifluoride. The route is based upon a cuprate-mediated coupling of the single enantiomer vinyl iodide 13 and the tricyclic ketone 5, of high stereochemical purity, to yield the single isomer bicyclic ketone 15. A Baeyer−Villiger oxidation provides the lactone 16 as a crystalline solid, thus limiting the need for chromatographic purification. DIBAL-H reduction, Wittig reaction, esterification, and silyl group deprotection complete the synthesis of travoprost.
Isamu Sugimoto - One of the best experts on this subject based on the ideXlab platform.
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Discovery of Novel Seven-Membered Prostacyclin Analogues as Potent and Selective Prostaglandin FP and EP3 Dual Agonists.
ACS Medicinal Chemistry Letters, 2016Co-Authors: Isamu Sugimoto, Tohru Kambe, Tomotaka Okino, Tetsuo Obitsu, Nobukazu Ohta, Taihei Nishiyama, Akihiro Kinoshita, Taku Fujimoto, Hiromu Egashira, Shinsaku YamaneAbstract:A novel series of prostaglandin analogues with a seven-membered ring scaffold was designed, synthesized, and evaluated for the functional activation of prostaglandin receptors to identify potent and subtype-selective FP and EP3 dual agonists. Starting from the prostacyclin derivative 5b, a nonselective agonist for prostaglandin receptors, replacement of the core structure with an octahydro-2H-cyclopenta[b]oxepine scaffold led to the discovery of the potent and selective FP and EP3 dual agonist 11b as a lead compound for the development of an Antiglaucoma Agent.
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Discovery of Novel Seven-Membered Prostacyclin Analogues as Potent and Selective Prostaglandin FP and EP3 Dual Agonists
2016Co-Authors: Isamu Sugimoto, Tohru Kambe, Tomotaka Okino, Tetsuo Obitsu, Nobukazu Ohta, Taihei Nishiyama, Akihiro Kinoshita, Taku Fujimoto, Hiromu Egashira, Shinsaku YamaneAbstract:A novel series of prostaglandin analogues with a seven-membered ring scaffold was designed, synthesized, and evaluated for the functional activation of prostaglandin receptors to identify potent and subtype-selective FP and EP3 dual agonists. Starting from the prostacyclin derivative 5b, a nonselective agonist for prostaglandin receptors, replacement of the core structure with an octahydro-2H-cyclopenta[b]oxepine scaffold led to the discovery of the potent and selective FP and EP3 dual agonist 11b as a lead compound for the development of an Antiglaucoma Agent