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AL-8810: A Novel Prostaglandin F2α Analog with Selective Antagonist Effects at the Prostaglandin F2α (FP) Receptor
A novel analog of prostaglandin F 2α [AL-8810; (5 Z , 13E)-(9 S ,11 S ,15 R )-9,15-dihydroxy-11-fluoro-15-(2-indanyl)-16,17,18,19,20-pentanor-5,13-prostadienoic acid] has been discovered withExpand
AL-8810: a novel prostaglandin F2 alpha analog with selective antagonist effects at the prostaglandin F2 alpha (FP) receptor.
The results suggest that AL-8810 is a unique, selective antagonist at the FP receptor, a heretofore unavailable pharmacological tool that should be valuable for studying FP receptor-mediated functional responses in complex biological systems. Expand
Identification and characterization of the ocular hypotensive efficacy of travoprost, a potent and selective FP prostaglandin receptor agonist, and AL-6598, a DP prostaglandin receptor agonist.
Clinical studies show that travoprost 0.004% (isopropyl ester) provided intraocular pressure control superior to timolol 0.5% when used as monotherapy in patients with open-angle glaucoma or ocular hypertension, and AL-6598 0.01% provided a sustained intraocular Pressure reduction with q.i.d. application. Expand
The hydrolysis of the prostaglandin analog prodrug bimatoprost to 17-phenyl-trinor PGF2alpha by human and rabbit ocular tissue.
Separate in vitro studies clearly show that both bimatoprost and 17-phenyl-trinor PGF(2alpha) have affinity for and are agonists at the human FP receptor, and strongly suggests that the ocular hypotensive effect of bim atoprost can be attributed to its activity as a prostaglandin receptor agonist either directly or through its role as a prodrug. Expand
Novel benzodifuran analogs as potent 5-HT2A receptor agonists with ocular hypotensive activity.
A series of 8-substituted benzodifuran analogs was prepared and evaluated for 5-HT(2A) receptor binding and activation. Several compounds containing ether and ester functionality were found to beExpand
Discovery, characterization and clinical utility of prostaglandin agonists for the treatment of glaucoma
A hypothesis was advanced that the IOP‐lowering effect of PGF2α isopropyl ester was due to activation of its cognate PG‐FP receptor, while side effects were largely due to promiscuous interaction with other PG receptors and provided the first marketed FP‐class PG agonist analogue (FP‐PGA) ocular hypotensive agent, latanoprost. Expand
3-Oxa-15-cyclohexyl prostaglandin DP receptor agonists as topical antiglaucoma agents.
A series of prostaglandin DP agonists containing a 3-oxa-15-cyclohexyl motif was synthesized and evaluated in several in vitro and in vivo biological assays, finding that selected amide prodrugs of the carboxylic acid enhance in vivo potency, presumably by increasing bioavailability. Expand
Update and commentary on the pro-drug bimatoprost and a putative ‘prostamide receptor’
An update on the discovery of potent and efficacious intraocular pressure (IOP)-lowering FP-class prostaglandin (PG) analogs is provided and published data is discussed that addresses the debate in this arena. Expand
Prostaglandin FP receptor antagonists: discovery, pharmacological characterization and therapeutic utility
It appears that AL‐8810 has become the FP receptor antagonist of choice, having a sub‐micromolar in vitro potency and ≥2 log unit selectivity against most other PG receptors when tested in several cell‐ and tissue‐based functional assays. Expand
15-Fluoro prostaglandin FP agonists: a new class of topical ocular hypotensives.
Evaluation of selected ester prodrugs of these 15-fluoro prostaglandins in vivo highlighted their generally low propensity to elicit hyperemia or ocular irritation in rabbits and efficacious intraocular pressure-lowering property in monkeys. Expand