latanoprost ethyl amide

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.

N-Desethyl Bimatoprost (17-phenyl trinor PGF2α amide) is an F-series PG analog in which the C-1 carboxyl group has been modified to an unsubstituted amide. PG esters have been shown to have ocular hypotensive activity. PG N-ethyl amides were recently introduced as alternative PG hypotensive prodrugs. Although it has been claimed that PG amides are not converted to the free acids in vivo, studies have shown that bovine and human corneal tissue converts the amides of various PGs to the free acids with a conversion efficiency of about 10-20% relative to the hydrolysis of isopropyl esters. 17-phenyl trinor PGF2α amide would be expected to show the typical intraocular effects of latanoprost, but with the much slower hydrolysis pharmacokinetics of the PG N-amides.

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.

Latanoprost dimethyl amide is a derivative of latanoprost and an isomer of latanoprost ethyl amide . N/A