Therapeutic uses of prostaglandin F(2α) analogues in ocular disease and novel synthetic strategies.
The pharmacological management of glaucoma and ocular hypertension has significantly changed over the last 18 years with the introduction of PGF2α analogues, more specifically latanoprost (6), travoprost (8), bimatoprost (10) and tafluprost (12). Prostanoids are currently the first-line medicines among ocular antihypertensive drugs in terms of efficacy, safety, patient compliance and medical economy. Their ability to effectively reduce intraocular pressure with once-per-day dosing, ocular tolerability comparable to timolol and general lack of systemic adverse effects have made them the mainstay of pharmacological therapy for glaucoma and ocular hypertension all over the world. The present review reports a novel, convergent and highly diastereoselective method for the synthesis of PGF2α analogues from the structurally advanced prostaglandin phenylsulfone (5Z)-(+)-15 and new ω-chain synthons. The biochemistry, clinical efficacy and side effects of four commercially available PGF2α analogues, currently used as first-line agents for reducing intraocular pressure in patients with glaucoma or ocular hypertension, are also discussed.
R&D Chemistry Department, Pharmaceutical Research Institute, Rydygiera 8, 01-793 Warsaw, Poland. i.dams@ifarm.eu
Iwona
I
Dams
Jaromir
J
Wasyluk
Marek
M
Prost
Andrzej
A
Kutner
D000577:Amides / Q000138:chemical synthesis / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D000069580:Bimatoprost; D003008:Cloprostenol / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology*; D005901:Glaucoma / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects; D000077338:Latanoprost; D009798:Ocular Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D011460:Prostaglandins F / Q000138:chemical synthesis / Q000494:pharmacology; D011461:Prostaglandins F, Synthetic / Q000138:chemical synthesis / Q000494:pharmacology; D016032:Randomized Controlled Trials as Topic; D000069557:Travoprost
D000577:Amides; D000959:Antihypertensive Agents; D011460:Prostaglandins F; D011461:Prostaglandins F, Synthetic; C485333:tafluprost; D003008:Cloprostenol; D000077338:Latanoprost; D015237:Dinoprost; D000069580:Bimatoprost; D000069557:Travoprost