latanoprost acid

Latanoprost acid is a selective agonist of prostanoid receptors and inhibits RANKL-induced osteoclastogenesis and function through the inhibition of c-fos NFATc1 pathway. Latanoprost acid can be used in studies about lowering pressure inside the eyes.

Latanoprost is an F-series prostaglandin (PG) analog which has been approved for use as an ocular hypotensive drug. Latanoprost is an isopropyl ester, a prodrug form which is converted to latanoprost (free acid) by endogenous esterase enzymes. The free acid form is 200 times more potent than latanoprost as a ligand for the human recombinant FP receptor. 5-trans Latanoprost (free acid) is an isomer of latanoprost (free acid) wherein the double bond between carbons 5 and 6 has been changed from cis (Z) to trans (E). The trans isomer of latanoprost occurs as an impurity in commercial preparations of the bulk drug product. The present compound was prepared primarily as an analytical standard for detection and quantitation of this impurity. From what can be inferred from the study of other trans isomers of F-type prostaglandins, the biological activity of this isomer is likely to be similar to that of the cis isomer. However, there are no specific published reports on the biological activity, and on reducing intraocular pressure in particular, of 5-trans latanoprost.

15-keto Latanoprost is a potential metabolite of latanoprost when administered to animals and is a common minor impurity in commercial preparations of the bulk drug compound. Although much less potent than latanoprost, 15-keto Latanoprost can still produce a small but measurable decrease (1 mm Hg) in intraocular pressure in normal cynomolgus monkeys at a dose of 1 μg eye. It also acts as a miotic in normal cats, causing an 8 mm Hg reduction in pupillary diameter at 5 μg eye, though it is not as potent as many other F-type prostaglandins, such as prostaglandin F2α, which achieves the same effect at less than 1 μg eye.

Latanoprost ethyl amide (Lat-NEt) is a latanoprost analog in which the C-1 carboxyl group has been modified to an N-ethyl amide. Prostaglandin esters exhibit ocular hypotensive activity, and prostaglandin N-ethyl amides have recently been introduced as alternative ocular hypotensive prodrugs. Although it has been claimed that prostaglandin ethyl amides are not converted to free acids in vivo, studies in our laboratories show that bovine and human corneal tissue can convert the N-ethyl amides of various prostaglandins to free acids at a rate of about 2.5 μg g corneal tissue hr. Lat-NEt is expected to exhibit the typical intraocular effects of latanoprost free acid, but with much slower hydrolysis pharmacokinetics characteristic of prostaglandin N-amides.

Prostaglandin F2α (PGF2α), acting through the FP receptor, causes smooth muscle contraction and exhibits potent luteolytic activity. 17-trifluoromethylphenyl trinor Prostaglandin F2α (17-trifluoromethylphenyl trinor PGF2α) is an analog of PGF2α that shares the meta-trifluoromethyl group of travoprost with the 17-phenyl trinor modification of latanoprost. It is anticipated to be a potent and selective agonist of the FP receptor, with potential applications in glaucoma and luteolysis. 17-trifluoromethylphenyl trinor PGF2α ethyl amide is a lipophilic analog of 17-trifluoromethylphenyl trinor PGF2α. Ethyl amides of PGs can serve as prodrugs, as they are hydrolyzed in certain tissues to generate the bioactive free acid.

15(S)-Latanoprost is an analog of latanoprost in which the hydroxyl at carbon 15 is inverted relative to latanoprost. The IC50 values for the free acid forms of latanoprost and 15(S)-latanoprost were determined to be 3.6 nM and 24 nM, respectively, in a FP receptor binding assay using the cat iris sphincter muscle. A 3 μg dose of 15(S)-latanoprost caused a 1 mmHg reduction of IOP in normotensive cynomolgus monkeys. 15(S)-Latanoprost is a potential impurity in most commercial preparations of the latanoprost bulk drug product.

17-phenyl trinor PGF2α N-ethyl amide is an F-series prostaglandin analog approved as an ocular hypotensive drug, sold under the Allergan trade name Bimatoprost. The N-ethyl amide prostaglandin prodrugs are converted into the active free acid more slowly than analogous prostaglandin ester prodrugs like latanoprost. This product is the isopropyl ester of the free acid prostaglandin corresponding to Bimatoprost. The free acid, 17-phenyl trinor PGF2α, is a potent FP receptor agonist, and in human and animal glaucoma models, FP receptor agonist activity closely correlates with intraocular hypotensive activity. The 17-phenyl trinor PGF2α isopropyl ester derivative was examined for IOP-lowering activity during latanoprost's development and, at a dose of 3 μg eye in monkeys, was the most potent analog, reducing IOP by 1.3 mm Hg more than latanoprost, though it was also significantly more irritating to the eye.

Prostaglandin F2α (PGF2α), acting through the FP receptor, causes smooth muscle contraction and exhibits potent luteolytic activity. 17-trifluoromethylphenyl trinor PGF2α is an analog of PGF2α that shares the meta-trifluoromethyl group of travoprost with the 17-phenyl trinor modification of latanoprost. It is anticipated to be a potent and selective agonist of the FP receptor, with potential applications in glaucoma and luteolysis. 17-trifluoromethylphenyl trinor PGF2α methyl ester is a lipophilic analog of 17-trifluoromethylphenyl trinor PGF2α. Methyl esters of PGs serve as prodrugs, as they are efficiently hydrolyzed in certain tissues to generate the bioactive free acid.

A number of 17-phenyl trinor prostaglandin F2α(17-phenyl trinor PGF2α) derivatives have been approved for the treatment of glaucoma.1,2,3Of these, the ones wherein the 13,14-double bond has been hydrogenated retain relatively good potency, but show a significantly reduced incidence of local irritant side effects.417-trifluoromethylphenyl-13,14-dihydro trinor PGF2αbears an aromatic ring which is reminiscent of the trifluoromethyl-phenoxy ring of travoprost ((+)-fluprostenol isopropyl ester). As an ocular hypotensive agent, it would be expected that 17-trifluoromethylphenyl-13,14-dihydro trinor PGF2αwould act very much like the free acid of latanoprost.

Latanoprost, the isopropyl ester of 17-phenyl-13,14-dihydro prostaglandin F2α, serves as a prodrug for the free acid form, a potent FP receptor agonist in the eye. Isopropyl 5-(diphenylphosphoryl)pentanoate may exist as a potential trace impurity in commercial latanoprost preparations.