Document Detail

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.
MedLine Citation:
PMID:  12204698     Owner:  NLM     Status:  MEDLINE    
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.
Mark R Hellberg; 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
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Survey of ophthalmology     Volume:  47 Suppl 1     ISSN:  0039-6257     ISO Abbreviation:  Surv Ophthalmol     Publication Date:  2002 Aug 
Date Detail:
Created Date:  2002-09-02     Completed Date:  2002-12-20     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0404551     Medline TA:  Surv Ophthalmol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  S13-33     Citation Subset:  IM    
Department of Medicinal Chemistry, Alcon Research Ltd., 6201 South Freeway, Fort Worth, TX 76134, USA.
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MeSH Terms
Antihypertensive Agents / chemistry,  pharmacology,  therapeutic use*
Aqueous Humor / drug effects
Cloprostenol / analogs & derivatives*,  chemistry,  pharmacology,  therapeutic use*
Dinoprost / analogs & derivatives,  chemistry,  pharmacology,  therapeutic use*
Dose-Response Relationship, Drug
Glaucoma, Open-Angle / drug therapy*
Guinea Pigs
Intraocular Pressure / drug effects*
Macaca fascicularis
Ocular Hypertension / drug therapy
Randomized Controlled Trials as Topic
Receptors, Immunologic
Receptors, Prostaglandin / agonists*
Structure-Activity Relationship
Timolol / therapeutic use
Reg. No./Substance:
0/AL 6598; 0/Antihypertensive Agents; 0/Receptors, Immunologic; 0/Receptors, Prostaglandin; 0/prostaglandin D2 receptor; 0/prostaglandin F2alpha receptor; 157283-68-6/travoprost; 26839-75-8/Timolol; 40665-92-7/Cloprostenol; 551-11-1/Dinoprost

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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