Travoprost (HCID 5282226)

概要

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.

名称と識別子

優先名称: 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
現地名: トラボプロスト
英語名: Travoprost
分子式: C26H35F3O6
分子量: 500.55

名称と別名

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

名称をさらに表示

トラボプロストトラボプロスト (JAN)(5Z)-7-[(1R)-2β-[(1E,3R)-3-ヒドロキシ-4-[3-(トリフルオロメチル)フェノキシ]-1-ブテニル]-3α,5α-ジヒドロキシシクロペンタン-1α-イル]-5-ヘプテン酸イソプロピルプロパン-2-イル (5Z)-7-[(1R,2R,3R,5S)-3,5-ジヒドロキシ-2-[(1E,3R)-3-ヒドロキシ-4-[3-(トリフルオロメチル)フェノキシ]ブタ-1-エン-1-イル]シクロペンチル]ヘプタ-5-エノアートトラバタンズトロボプロスト(5Z)-7-[(1R,2R,3R,5S)-3,5-ジヒドロキシ-2-[(1E,3R)-3-ヒドロキシ-4-[3-(トリフルオロメチル)フェノキシ]-1-ブテニル]シクロペンチル]-5-ヘプテン酸イソプロピル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

データベース識別子

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

物性

構造計算による物性

XLogP: 4.1
極性表面積: 96.2 Å²
水素結合供与体数: 3
水素結合受容体数: 9
回転可能結合数: 13
重原子数: 35
形式電荷: 0
複雑度: 693

実験および物理化学的性質

Drugs · 2 件

Pharmaceuticals -> Listed in ZINC15

Pharmaceuticals -> Sensory organs -> Ophthalmologicals

LogP4.6

Solubility · 2 件

>16 mg/ml at 25.0°C

7.59e-03 g/L

Human Drugs · 5 件

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

物理化学的性質

比旋光度: 20 · D20 +14.6° (c = 1.0 in methylene chloride)
沸点: 584.8 · 584.8±50.0 °C(Predicted)
比重(密度): 1.245 · 1.245±0.06 g/cm3(Predicted)
闪点: 17 °C · 17 °C
貯蔵温度: -20 °C · Sealed in dry,Store in freezer, under -20°C
溶解性: ジクロロメタン（少量、超音波処理）、クロロホルム（少量）、メタノール（少量）
外見: エタノール溶液
酸解離定数(Pka): 13.43 · 13.43±0.20(Predicted)
色: 無色～ライトベージュ
BCS Class: 2 · 2
安定性: 光に敏感
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 データベース: 157283 · 157283-68-6(CAS DataBase Reference)

化学的性質

化学的特性Colorless Oil

安全と法規制

GHS分類

GHS Classification · 5 件

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.

危険有害性情報

Hazard Classes and CategoriesAcute Tox. 4 (18.8%)

毒性情報

Effects During Pregnancy and Lactation◉ Summary of Use during Lactation

安全データ

wgk: 1
ridadr: UN 1170 3/PG 2
hs_code: 2937500000
risk_code: 11-36/37/38
hazard_code: F,Xi
safety_code: 16-26-36-7
Hazard Classifications: Eye Irrit. 2Flam. Liq. 2
ストレージクラス: 3 - Flammable liquids

化学と産業

薬理情報

ATC Code · 3 件

S01EE04

S - Sensory organs

QS - Sensory organs

Protein BindingNo information is available.

Pharmacodynamics · 1 件

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 件

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 件

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.

応用分野 · 3 件

説明Travoprost 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.

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

一般的な説明Travoprost (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.

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補足説明 · 1 件

定義ChEBI: 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.