2. Academic Validation
  3. 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

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

  • Surv Ophthalmol. 2002 Aug;47 Suppl 1:S13-33. doi: 10.1016/s0039-6257(02)00293-x.
Mark R Hellberg 1,  Marsha A McLaughlin,  Naj A Sharif,  Louis DeSantis,  Tom R Dean,  Evan P Kyba,  John E Bishop,  Peter G Klimko,  Paul W Zinke,  Robert D Selliah,  George Barnes,  Joseph DeFaller,  Angela Kothe,  Theresa Landry,  E Kenneth Sullivan,  Russell Andrew,  Alberta A Davis,  Lewis Silver,  Michael V W Bergamini,  Stella Robertson,  Alan L Weiner,  Verney L Sallee
Affiliations

Affiliation

  • 1 Department of Medicinal Chemistry, Alcon Research Ltd., 6201 South Freeway, Fort Worth, TX 76134, USA. Mark.Hellberg@AlconLabs.com
PMID: 12204698 DOI: 10.1016/s0039-6257(02)00293-x
Abstract

The structure-activity studies that led to the identification of travoprost, a highly selective and potent FP prostaglandin analog, and AL-6598, a DP prostaglandin analog, are detailed. In both series, the 1-alcohol analogs are very effective and are thought to be acting as prodrugs for the biologically active carboxylic acids. The efficacy of amide prodrugs depends on the degree of substitution and the size of the substituents. Selected compounds are profiled in vitro and in vivo preclinically. 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. In clinical studies, AL-6598 0.01% provided a sustained intraocular pressure reduction with q.d. application; b.i.d. provided greater intraocular pressure control. The acute and, apparently, conjunctival hyperemia associated with topical ocular AL-6598 can be attenuated while maintaining intraocular pressure-lowering efficacy by formulating with brimonidine.

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