CAS 157283-68-6 Travoprost (HCID 5282226)

Overview

Travoprost is the isopropyl ester of prostaglandin F2alpha in which the pentyl group is replaced by a 3-(trifluoromethyl)phenoxymethyl group. A synthetic analogue of prostaglandin F2alpha, ophthalmic solutions of travoprost are used as a topical medication for controlling the progression of open-angle glaucoma and ocular hypertension, by reducing intraocular pressure. It is a pro-drug; the isopropyl ester group is hydrolysed by esterases in the cornea to the biologically active free acid, fluprostenol. It has a role as an antihypertensive agent, an antiglaucoma drug, a prodrug, a prostaglandin receptor agonist and an ophthalmology drug. It is an isopropyl ester, a prostaglandins Falpha and a member of (trifluoromethyl)benzenes. It is functionally related to a fluprostenol.

Names & identifiers

Preferred name: Travoprost
IUPAC: propan-2-yl (Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3R)-3-hydroxy-4-[3-(trifluoromethyl)phenoxy]but-1-enyl]cyclopentyl]hept-5-enoate
English name: Travoprost
Molecular formula: C26H35F3O6
Molecular weight: 500.55

Names & synonyms

Travoprost157283-68-6TravatanTravatan ZIzbaAL-6221AL6221Otx-tptravoprostumIDOSE TRWJ68R08KX9CHEBI:746859

Show more names

TrovoprostFLUPROSTENOL ISOPROPYL ESTER(5Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(E)-3-hydroxy-4-[3-(trifluoromethyl)phenoxy]buten-1-yl][cyclopentyl]hept-5-enoateTrivoFLU-IPRAL 6221ravoprosTrivoprostTravaprost

NSC-760366DTXSID80896948DTXCID401326382DUOTRAV COMPONENT TRAVOPROST(1R-(1alpha(Z),2beta(1E,3R*),3alpha,5alpha))-7-(3,5-Dihydroxy-2-(3-hydroxy-4-(3-(trifluoromethyl)phenoxy)-1-butenyl)cyclopentyl)-5-heptenoic acid, 1-methylethyl esterpropan-2-yl (5Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(1E,3R)-3-hydroxy-4-[3-(trifluoromethyl)phenoxy]but-1-en-1-yl]cyclopentyl]hept-5-enoate5-Heptenoic acid, 7-((1R,2R,3R,5S)-3,5-dihydroxy-2-((1E,3R)-3-hydroxy-4-(3-(trifluoromethyl)phenoxy)-1-butenyl)cyclopentyl)-, 1-methylethyl ester, (5Z)-isopropyl (Z)-7-((1R,2R,3R,5S)-3,5-dihydroxy-2-{(1E,3R)-3-hydroxy-4-[(alpha,alpha,alpha-trifluoro-m-tolyl)oxy]-1-butenyl}cyclopentyl)-5-heptenoate

Database identifiers

CAS: 157283-68-6
PubChem CID: 5282226
DTXSID: DTXSID80896948
ChEMBL: CHEMBL1200799
ChEBI: CHEBI:746859
UNII: WJ68R08KX9
EC Number: 682-028-9
Nikkaji: J1.152.432J

Properties

Computed structural properties

XLogP: 4.1
Topological polar surface area: 96.2 Å²
Hydrogen bond donors: 3
Hydrogen bond acceptors: 9
Rotatable bonds: 13
Heavy atoms: 35
Formal charge: 0
Complexity: 693

Experimental & physicochemical properties

Drugs · 2 items

Pharmaceuticals -> Listed in ZINC15

Pharmaceuticals -> Sensory organs -> Ophthalmologicals

LogP4.6

Solubility · 2 items

>16 mg/ml at 25.0°C

7.59e-03 g/L

Human Drugs · 5 items

Breast Feeding; Lactation; Milk, Human; Antiglaucoma Agents; Prostaglandins

FDA approved drugs -> Active ingredient

EMA approved medicines: Human medicine

FDA approved drugs -> Active ingredient

Physical DescriptionLiquid

Physicochemical properties

alpha: 20 · D20 +14.6° (c = 1.0 in methylene chloride)
Boiling point: 584.8 · 584.8±50.0 °C(Predicted)
Density: 1.245 · 1.245±0.06 g/cm3(Predicted)
Flash point: 17 °C · 17 °C
storage temp.: -20 °C · Sealed in dry,Store in freezer, under -20°C
solubility: Dichloromethane (Sparingly, Sonicated), Chloroform (Sparingy), Methanol (Sparing
form: ethanol solution
pka: 13.43 · 13.43±0.20(Predicted)
color: Colourless to Light Beige
BCS Class: 2 · 2
Stability: Light Sensitive
InChIKey: MKPLKVHSHYCHOC-AHTXBMBWSA-N
SMILES: C(OC(C)C)(=O)CCC/C=C\C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1/C=C/[C@@H](O)COC1=CC=CC(C(F)(F)F)=C1
CAS DataBase Reference: 157283 · 157283-68-6(CAS DataBase Reference)
FDA UNII: 68 R08KX9 · WJ68R08KX9
ATC code: 1 EE04 · S01EE04
UNSPSC Code: 41116107 · 41116107
NACRES: 77 · NA.77
Symbol(GHS): 2 · GHS02,GHS07
Signal word: Danger
Hazard statements: 225 · H225-H319
Precautionary statements: 210 · P210-P233-P240-P241-P242-P305+P351+P338
Hazard Codes: F,Xi
Risk Statements: 11 · 11-36/37/38
Safety Statements: 16 · 16-26-36-7
RIDADR: 1170 · UN 1170 3/PG 2
WGK Germany: 1 · 1
HS Code: 2937500000 · 2937500000
Storage Class: 3 · 3 - Flammable liquids
Hazard Classifications: 2 Flam · Eye Irrit. 2Flam. Liq. 2

Safety & regulation

GHS classification

GHS Classification · 5 items

This chemical does not meet GHS hazard criteria for 6.2% (1 of 16) of reports.

Warning

H302 (18.8%): Harmful if swallowed [Warning Acute toxicity, oral]

P203, P260, P261, P263, P264, P264+P265, P270, P271, P273, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P318, P319, P321, P330, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 16 reports by companies from 7 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Hazard information

Hazard Classes and CategoriesAcute Tox. 4 (18.8%)

Toxicology

Effects During Pregnancy and Lactation◉ Summary of Use during Lactation

Safety data

wgk: 1
ridadr: UN 1170 3/PG 2
hs_code: 2937500000
risk_code: 11-36/37/38
Signal word: Danger
Symbol(GHS): GHS02,GHS07
hazard_code: F,Xi
safety_code: 16-26-36-7
Storage Class: 3 - Flammable liquids
Hazard statements: H225-H319
Hazard Classifications: Eye Irrit. 2Flam. Liq. 2
Precautionary statements: P210-P233-P240-P241-P242-P305+P351+P338

Chemistry & industry

Pharmacology

ATC Code · 3 items

S01EE04

S - Sensory organs

QS - Sensory organs

Protein BindingNo information is available.

Pharmacodynamics · 1 item

Travoprost demonstrates preferential affinity and full agonist activity for the prostaglandin FP receptor in the nanomolar range. Travoprost shows no significant affinity for other prostanoid or non-prostanoid receptors. Travoprost-induced reduction of intraocular pressure is observed about two hours after administration, and the maximum effect is reached after 12 hours. Significant lowering of intraocular pressure can be maintained for periods exceeding 24 hours with a single dose.

Mechanism of Action · 1 item

Travoprost is a prodrug. Upon administration, travoprost is absorbed through the cornea and hydrolyzed to its active metabolite, travoprost free acid. The ester moiety of the free acid allows for enhanced penetration into the aqueous humour. While the exact mechanism of travoprost is largely unknown, it is believed to be related to its full agonist activity for the prostaglandin FP receptor. By binding to the FP receptor, travoprost free acid increases the outflow of aqueous humour via the trabecular meshwork and uveoscleral pathways, thereby reducing the intraocular pressure.

Biological Half-LifeThe terminal elimination half-life of travoprost free acid was estimated from fourteen subjects and ranged from 17 minutes to 86 minutes with the mean half-life of 45 minutes.

Metabolism/Metabolites · 1 item

Travoprost, an isopropyl ester prodrug, is hydrolyzed by esterases in the cornea to its biologically active free acid. Systemically, travoprost free acid is metabolized to inactive metabolites via beta-oxidation of the α (carboxylic acid) chain to give the 1,2-dinor and 1,2,3,4-tetranor analogs, via oxidation of the 15-hydroxyl moiety, as well as via reduction of the 13, 14 double bond.

Applications · 5 items

DescriptionTravoprost was launched in the US as Travatan, an ophthalmic solution (0.004%) administered topically for the treatment of elevated intraocular hypertension (lOP) through open-angle glaucoma, a common optic neuropathy and a leading cause of blindness. Travoprost is the isopropyl ester of (+)-fluprostenol, a new prostaglandin derivative belonging to the PGF2α, analog class. This compound can be prepared in 8 steps from a bicyclic lactone aldehyde by a Wittig alkylidenation followed, after 2 ketonic reductions, by a lactol opening to prostenoic acid while protecting and deprotecting appropriately. Travoprost is a full agonist of FP receptors with a greater affinity than PGF2α, (K1 = 52 nM). Pharmacologic studies in rabbits treated daily for a week demonstrated a significant increase of the microvascular optic nerve head blood flow without significant alterations in the systemic flow. In several placebo-controlled clinical studies with hundreds of patients suffering from open-angle glaucoma or ocular hypertension, travoprost (1 to 4 pm daily) dose-dependently reduced lOP (by about 30% at 4 pm); it was shown equal or superior to latanoprost, another prostaglandin analog (5 pm daily) or the adrenergic ~-blocker timolol (500 pm bid). In addition, travoprost was safe and well tolerated with a low incidence of conjunctival hyperaemia.

UsesTravoprost is a selective FP prostaglandin receptor agonist used to treat glaucoma (1,2).

UsesSelective FP prostaglandin receptor agonist. Isopropyl ester of (+)-fluprostenol. Antiglaucoma

Usestreatment conditions arising from excess uric acid, eg chronic gout

General DescriptionTravoprost (Travatan and Travatan-Z) is supplied asa 2.5- or 5.0-mL sterile 0.004% ophthalmic solution in a4.0- or 7.5-mL size container. Travoprost is claimed to bethe most potent and FP-specific analog in this product category. Cautions and side effects are similar to those givenpreviously.

Suppliers100 total

北京华美互利生物化工010-56205725 · [email protected]

Shanghai Biolang Biotechnology Co., Ltd.+86-15970428662 +86-13397199602 · [email protected]

江苏恒盛药业有限公司0512-58726293

合肥翰刚医药科技有限公司+8618062405514 · [email protected]

Baoji Guokang Healthchem co.,ltd+8615604608665 15604608665 · [email protected]

Additional notes · 1 item

DefinitionChEBI: The isopropyl ester of prostaglandin F2alpha in which the pentyl group is replaced by a 3-(trifluoromethyl)phenoxymethyl group. A synthetic analogue of prostaglandin F2alpha, ophth lmic solutions of travoprost are used as a topical medication for controlling the progression of open-angle glaucoma and ocular hypertension, by reducing intraocular pressure. It is a pro-drug; the isopropyl ester group is hydrolysed by esterases in the co nea to the biologically active free acid, fluprostenol.