(+)-Cloprostenol isopropyl ester

• CAS: 157283-66-4
• Catalog Number: ACM157283664
• Category: Main Products
• Molecular Weight: 467.0
• Molecular Formula: C25H35ClO6
• IUPAC Name: (+)-Cloprostenol isopropyl ester
• Assay: 0.99
• Exact Mass: 466.21200
• Grade: PHARM
• Packaging: 25 kg

Case Study

Synthesis of Triacylated Cloprostenol Isopropyl Ester Prodrugs

TANASE, CONSTANTIN I., et al. "Acylated Prodrugs of PGF."

Cloprostenol isopropyl ester is a PGF_2α analogue used as a veterinary luteolytic drug for controlling reproduction in farm animals and also has the effect of reducing intraocular pressure. In this work, several 9,11,15-triacylated derivatives of cloprostenol isopropyl ester were synthesized using cloprostenol isopropyl ester as the starting material.
The (±)- or (+)-cloprostenol isopropyl esters were acylated using acetic anhydride or acyl chlorides (pivaloyl chloride, stearoyl chloride, oleoyl chloride) alongside pyridine as an organic base, with or without an inert solvent such as toluene or dichloromethane. The resulting crude products were purified through pressure chromatography, yielding the pure 9,11,15-tri-acylated compounds 2a, 2b, and 2d as oils, while the stearoyl compound 2c was obtained in a crystalline form. The distinctive properties of compounds 2a-2d are listed in Table 1, and their molecular structures are confirmed by the 1H- and 13C-NMR spectra.

Ocular Hypotensive Efficacy of Cloprostenol Isopropyl Ester

Hellberg, Mark R., et al. Survey of ophthalmology, 2002, 47, S13-S33.

Cloprostenol isopropyl ester is a PGF_2α analog that is effective in reducing intraocular pressure (IOP). Studies have shown that cloprostenol isopropyl ester is an effective ocular hypotensive in laser-irradiated monkeys and an effective miotic in cats. In ocular hypertensive monkeys, travoprost, cloprostenol isopropyl ester, and PGF_2α isopropyl ester showed comparable ocular hypotensive efficacy.
In addition, structural modifications at the 1-position were explored to expand the prodrug beyond the isopropyl ester. The reduction of the 1-position (carboxylic acid) of cloprostenol yields the 1-alcohol derivative (4) or converts it into the primary amide (5). As anticipated, both the amide and alcohol prodrugs exhibit reduced binding affinity and decreased activity in functional assays. Both compounds cause miosis in cats. The 1-alcohol is a notably effective prodrug, with an ED5 of 0.025 g (compared to cloprostenol's ED5 of 0.01 g). The primary amide, while less potent (ED5 of 1 g) than the isopropyl ester or 1-alcohol in the feline pharmacodynamics model, remains active. Despite the biological activity of these prodrug modifications in inducing miosis through topical ocular application, none demonstrate an improved therapeutic index over cloprostenol isopropyl ester.