Bimatoprost is the Allergan trade name for 17-phenyl trinor prostaglandinF2α ethyl amide (17-phenyl trinor PGF2α ethyl amide), an F-series PG analog which has been approved for use as an ocular hypotensive drug. Oxidation of the C-15 hydroxyl group produces 15-keto-17-phenyl trinor PGF2α ethyl amide. 15-keto-17-phenyl trinor PGF2α ethyl amide is a potential metabolite of 17-phenyl trinor PGF2α ethyl amide when 17-phenyl trinor PGF2α ethyl amide is administered to intact animals. No pharmacological studies on 15-keto-17-phenyl trinor PGF2α ethyl amide have been reported.
Isoprostanes are produced by the non-enzymatic, free radical peroxidation of phospholipid-esterified arachidonic acid. They have been used as biomarkers of oxidative stress, but they also have been found to have potent biological activity. ent-8-iso-15(S)-ProstaglandinF2α (ent-8-iso-15(S)-PGF2α) is a potent vasoconstrictor of porcine retinal and brain microvessels with EC50 values of 15 and 24 nM, respectively. This isoprostane is about ten-fold more potent than 8-iso-PGF2α in a whole blood platelet aggregation inhibition assay.
13,14-dihydro ProstaglandinF2α (13,14-dihydro PGF2α) is the analog of PGF2α which has no unsaturation in the lower side chain. It causes luteolysis in hamsters with a potency five times higher than PGF2α. The ED50 value for 13,14-dihydro PGF2α as a luteolytic agent in hamsters is 1.5 µg 100 g.[1]
15(S)-15-methyl ProstaglandinF2α (15(S)-15-methyl PGF2α) has been shown to have potent uterine stimulant and abortifacient properties when administered intramuscularly to induce labor. 15(S)-15-methyl PGF2α isopropyl ester is a lipophilic analog of 15(S)-15-methyl PGF2α methyl ester, which may be hydrolyzed in vivo to the fully active free acid.
8-iso-13,14-dihydro-15-keto ProstaglandinF2α (8-iso-13,14-dihydro-15-keto PGF2α) is a metabolite of the isoprostane, 8-isoprostane (8-iso PGF2α), in rabbits, monkeys and humans. 8-iso PGF2α is a PG-like product of non-specific lipid peroxidation. In both humans and monkeys, exogenously infused 8-isoprostane is converted primarily to metabolites having 2 or 4 carbon atoms removed from the top side chain by β-oxidation. A similar pattern is observed when tritiated 8-isoprostane is infused into rabbits. Early in the infusion (within 10 minutes) 8-iso-13,14-dihydro-15-keto PGF2α was a significant component of the metabolite profile, which was comprised mostly of dinor 8-isoprostane metabolites. 8-iso-13,14-dihydro-15-keto PGF2α weakly inhibits the U-46619 or collagen-induced aggregation of human platelets, although a number of the E-series isoprostanes are much more potent in this assay.
8-iso-15-keto ProstaglandinF2α (8-iso-15-keto PGF2α) is a metabolite of the isoprostane 8-iso PGF2α in rabbits, monkeys, and humans. 8-isoprostane (8-iso PGF2α) is a prostaglandin-like product of non-specific lipid peroxidation. In both humans and monkeys, exogenously infused 8-iso PGF2α is converted primarily to metabolites having 2 or 4 carbon atoms removed from the top side chain by β-oxidation. A similar pattern is observed when tritiated 8-iso PGF2α is infused into rabbits. Early in the infusion (within 1-2 minutes) 8-iso -15-keto PGF2α was a major component of the metabolite profile, which was comprised mostly of unmetabolized 8-iso PGF2α. 8-iso -15-keto PGF2α is a vasoconstrictor when tested on the rat isolated thoracic aorta, acting via the TP (thromboxane) receptor.
2,3-dinor-11β-ProstaglandinF2α (2,3-dinor-11β-PGF2α) was recovered from the urine of both normal monkeys and humans when infused with radiolabeled PGD2, where it represented approximately 1% and 4% of the infused radiolabeled dose, respectively. 2,3-dinor-11β-PGF2α has also been recovered from the urine of mastocytosis patients, where it is excreted in large amounts. In human asthmatic patients, 2,3-dinor-11β-PGF2α represents about 40% (as determined by GC/MS) of the immunoreactive 11β-PGF2α when measured using 's 11β-PGF2α EIA Kit . The excretion rate for 2,3-dinor-11β-PGF2α is approximately 200-250 ng/24 hours in a normal adult.
PGF2α 1,15-lactone is a lipid-soluble internal ester of PGF2α. Hydrolysis of the lactone readily produces free PGF2α in plasma. In rhesus monkeys, a total dose of 15 mg of PGF2α 1,15-lactone terminates early pregnancy, whereas PGF2α is ineffective.
ProstaglandinF2α (PGF2α), acting through the FP receptor, causes smooth muscle contraction and exhibits potent luteolytic activity. 17-trifluoromethylphenyl trinor ProstaglandinF2α (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.
20-hydroxy ProstaglandinF2α (20-hydroxy PGF2α) is the ω-oxidation product of PGF2α. Cultured type II alveolar cells from pregnant rabbits metabolize exogenous PGF2α via microsomal cytochrome P450 ω-oxidation, producing 20-hydroxy PGF2α and its 15-hydroxy PGDH metabolites. Cells from male rabbits exhibit only the 15-hydroxy PGDH pathway.
17-phenyl trinor ProstaglandinF2α N-ethyl amide (17-phenyl trinor PGF2α) is an F-series prostaglandin analog which has been approved for use as an ocular hypotensive drug, sold under the Allergan trade name 17-phenyl trinor PGF2α ethyl amide. Investigations in our lab have shown that 17-phenyl trinor PGF2α ethyl amide is converted by an amidase enzymatic activity in the human cornea to yield the corresponding free acid, with a conversion rate of about 25 μg cornea 24 hours. The free acid, 17-phenyl trinor PGF2α, is a potent FP receptor agonist. 15(R)-17-phenyl trinor PGF2α is the 15-epi, or unnatural isomer of this active free acid metabolite. It has much diminished FP receptor-mediated activity
Bimatoprost is an F-series prostaglandin (PG) analog which has been approved for use as an ocular hypotensive drug. Oxidation of the C-15 hydroxyl group and amide hydrolysis of Bimatoprost produces 15-keto-17-phenyl trinor PGF2α. 15-keto-17-phenyl trinor PGF2α is a potential metabolite of bimatoprost when administered to animals. 15-keto PG analogs are potential minor impurities in commercial preparations of their corresponding bulk drug compounds. Although much less potent that the parent compound, 15-keto PGs still retain the ability to produce a small but measurable decrease (1 mm Hg) in the intraocular pressure of normal cynomolgus monkeys when administered at a dose of 1 μg eye. 15-keto Latanoprost (15-keto-17-phenyl-13,14-dihydro trinor PGF2α isopropyl ester) is a miotic in the normal cat eye, causing an 8 mm reduction in pupillary diameter at 5 μg eye. Again, this is not as potent as many other F-type PGs; for example, PGF2α will produce this degree of miosis at a dose of less than 1 μg eye.
The actions of many clinical F-series prostaglandins (PGs), including those used for estrous synchronization and for reduction of intraocular pressure (IOP), are mediated through the PGF2α (FP) receptor. 16-phenoxy tetranor ProstaglandinF2α cyclopropyl methyl amide (16-phenoxy tetranor PGF2α cyclopropyl methyl amide) is an analog of PGF2α containing a 16-phenoxy group on the lower (ω) side chain and a cyclopropyl methyl amide at the C-1 position. There are no published reports on the biological activity of 16-phenoxy tetranor PGF2α cyclopropyl methyl amide.