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lifitegrast

CAS No.
1025967-78-5
Chemical Name:
lifitegrast
Synonyms
Lifitegrast-d4;liftegrast;Lifitegrast Impurity;CS-2633;(S)-2-(2-(benzofuran-6-carbonyl)-5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carboxamido)-3-(3-(methylsulfonyl)phenyl)propanoic acid;Amipak;SHP-606;SAR 1118;Lifitegras;ifitegrast
CBNumber:
CB92738258
Molecular Formula:
C29H24Cl2N2O7S
Molecular Weight:
615.48
MDL Number:
MFCD28502439
MOL File:
1025967-78-5.mol
Last updated:2023-08-22 17:11:26

lifitegrast Properties

Melting point >163°C (dec.)
Boiling point 811.9±65.0 °C(Predicted)
Density 1.479±0.06 g/cm3(Predicted)
storage temp. Hygroscopic, -20°C Freezer, Under inert atmosphere
solubility DMSO (Slightly, Heated, Sonicated), Methanol (Slightly, Sonicated)
form Solid
pka 3.14±0.10(Predicted)
color White to Off-White
Stability Hygroscopic
FDA UNII 038E5L962W
ATC code S01XA25

SAFETY

Risk and Safety Statements

Symbol(GHS)  GHS hazard pictograms
GHS07
Signal word  Warning
Hazard statements  H302-H315-H319-H335
Precautionary statements  P261-P305+P351+P338

lifitegrast price More Price(27)

Manufacturer Product number Product description CAS number Packaging Price Updated Buy
Cayman Chemical 22588 Lifitegrast ≥98% 1025967-78-5 5mg $32 2024-03-01 Buy
Cayman Chemical 22588 Lifitegrast ≥98% 1025967-78-5 10mg $61 2024-03-01 Buy
Cayman Chemical 22588 Lifitegrast ≥98% 1025967-78-5 25mg $139 2024-03-01 Buy
Cayman Chemical 22588 Lifitegrast ≥98% 1025967-78-5 50mg $243 2024-03-01 Buy
TRC L465955 Lifitegrast 1025967-78-5 100mg $275 2021-12-16 Buy
Product number Packaging Price Buy
22588 5mg $32 Buy
22588 10mg $61 Buy
22588 25mg $139 Buy
22588 50mg $243 Buy
L465955 100mg $275 Buy

lifitegrast Chemical Properties,Uses,Production

Application

Lifitegrast is used for the treatment of signs and symptons of dry eye diseases. It also Inhibites corneal inflammation that is capable of causing pains, blurred vision and ocular discomfort in sufferer.

Description

Lifitegrast (Xiidra; lifitegrast sodium; SAR1118; SHP606; SPD606) is a lymphocyte functionassociated antigen-1 (LFA-1) antagonist. It inhibits T-cell inflammation by blocking the binding of two key surface proteins (LFA-1 and ICAM-1) that mediate the chronic inflammatory cascade associated with dry eye disease. In a phase III clinical trial, lifitegrast 5% ophthalmic solution (50 mg/mL) is administered as a single 0.2mL eye drop twice a day into each eye for an 84 day treatment period.
Lifitegrast
Lifitegrast does not currently have Marketing Authorisation in the EU for any indication. Lifitegrast is licensed for use in the USA for treatment of the signs and symptoms of dry eye disease. The most common adverse reactions (incidence 5-25%) reported following the use of lifitegrast are instillation site irritation, dysgeusia, and decreased visual acuity.

Chemical Properties

Lifitegrast is a white to off-white powder which is soluble in water.

Uses

Lifitegrast is used for the treatment of signs and symptons of dry eye diseases. It also Inhibites corneal inflammation that is capable of causing pains, blurred vision and ocular discomfort in sufferer.

Indications

Topical lifitegrast was approved by the FDA for the treatment of dry eye. Lifitegrast decreases inflammation by blocking the interaction between intercellular adhesion molcule 1 and lymphocyte function- -associated antigen 1. In four, large, multicellular, randomized clinical trials, lifitegrast was shown to be effective in improving the signs and symptoms of dry eye. The side effects of lifitegrast include transient ocular irritation and dysgeusia. Further studies are needed to explore the effectiveness of combination therapy such as the concomitant use of topical cyclosporine and topical liftegrast.

Definition

ChEBI: An N-acyl-L-alpha-amino acid obtained by formal condensation of the carboxy group of N-[2-(1-benzofuran-6-carbonyl)]-5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carboxylic acid with he amino group of 3-(methanesulfonyl)-L-phenylalanine. Used for treatment of keratoconjunctivitis sicca (dry eye syndrome).

Mechanism of action

Lifitegrast binds to the integrin lymphocyte function-associated antigen-1 (LFA-1), a cell surface protein found on leukocytes and blocks the interaction of LFA-1 with its cognate ligand intercellular adhesion molecule-1 (ICAM-1). ICAM-1 may be overexpressed in corneal and conjunctival tissues in dry eye disease. LFA-1/ICAM-1 interaction can contribute to the formation of an immunological synapse resulting in T-cell activation and migration to target tissues. In vitro studies demonstrated that lifitegrast may inhibit T-cell adhesion to ICAM-1 in a human T-cell line and may inhibit secretion of inflammatory cytokines in human peripheral blood mononuclear cells. The exact mechanism of action of lifitegrast in dry eye disease is not known.

Pharmacokinetics

In a subset of dry eye disease patients (n=47) enrolled in a Phase 3 trial, the pre-dose (trough) plasma concentrations of lifitegrast were measured after 180 and 360 days of topical ocular dosing (1 drop twice daily) with Xiidra (lifitegrast ophthalmic solution) 5%. A total of nine (9) of the 47 patients (19%) had plasma lifitegrast trough concentrations above 0.5 ng/mL (the lower limit of assay quantitation). Trough plasma concentrations that could be quantitated ranged from 0.55 ng/mL to 3.74 ng/mL.

Side effects

A multicenter, randomized, double-masked, placebo-controlled phase 3 study (n = 331) evaluating the safety of lifitegrast ophthalmic solution for the treatment of dry eye disease reported the most common non-ocular effect was dysgeusia (change in taste) occurring in 16.4% of patients in the lifitegrast group and 1.8% of the placebo group.

Synthesis

After Boc protection, reaction with sodium methanesulfinate in the presence of copper iodide, K2CO3, and L-proline gave rise to sulfonate 176. Esterification of 176 with benzyl alcohol followed by removal of the Boc group within 177 yielded the corresponding HCl salt of the aminoester 178. Amide bond coupling with acid 179 furnished amide 180, which was then subjected to 4 N HCl in dioxane resulting in trityl removal and arrival at HCl salt 181 in 88% yield over two steps. Tetrahydroisoquinoline 181 was then coupled with commercial benzofuranyl acid 182 to give rise to lifitegrast benzyl ester in 90% yield. Finally, saponification delivered lifitegrast (XIX) in 88% yield.
Tetrahydroisoquinoline-6-carboxylic acid 179 was prepared starting from commercial 3,5-dichlorobenzaldehyde 183. Reductive amination with 1-chloro-2-aminoethane 184 gave chloroethyl amine 185, which underwent an efficient intramolecular Friedel-Crafts reaction using AlCl3 to generate the corresponding tetrahydroisoquinoline 186 in 91% yield. N-Tritylation of 186 proceeded in 89% yield, and this was followed by a directed o-metalation reaction and carbon dioxide quench to furnish the requisite acid 179 in 75% yield.

Synthesis_1025967-78-5

1194550-67-8
1025967-78-5
Synthesis of lifitegrast from benzyl (S)-2-(2-(benzofuran-6-carbonyl)-5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carboxamido)-3-(3-(methylsulfonyl)phenyl)propanoate
Global( 235)Suppliers
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PharmOrgSyn Laboratories Co., Ltd.
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Hangzhou Cyanochem Co., Ltd.
+86 17788583750 sales@cyanochem.com CHINA 283 58
Chengdu Pukang Biotechnology Co., Ltd
028-82550498 export@pu-kang.com CHINA 210 58

View Lastest Price from lifitegrast manufacturers

Image Update time Product Price Min. Order Purity Supply Ability Manufacturer
Lifitegrast pictures 2024-03-12 Lifitegrast
1025967-78-5
US $0.00 / g 1g 98% HPLC 100KG shandong perfect biotechnology co.ltd
lifitegrast pictures 2023-11-27 lifitegrast
1025967-78-5
US $0.00 / KG 1KG 99% 20 TONS Wuhan Senwayer Century Chemical Co.,Ltd
Lifitegrast pictures 2023-08-22 Lifitegrast
1025967-78-5
US $50.00 / kg 1kg 99.9% 10000tons Anhui Ruihan Technology Co., Ltd
  • Lifitegrast pictures
  • Lifitegrast
    1025967-78-5
  • US $0.00 / g
  • 98% HPLC
  • shandong perfect biotechnology co.ltd
  • lifitegrast pictures
  • lifitegrast
    1025967-78-5
  • US $0.00 / KG
  • 99%
  • Wuhan Senwayer Century Chemical Co.,Ltd
  • Lifitegrast pictures
  • Lifitegrast
    1025967-78-5
  • US $50.00 / kg
  • 99.9%
  • Anhui Ruihan Technology Co., Ltd
lifitegrast Lifitegrast, SAR 1118 L-Phenylalanine,N-[[2-(6-benzofuranylcarbonyl)-5,7-dichloro-1,2,3,4-tetrahydro-6-isoquinolinyl]carbonyl]-3-(methylsulfonyl)- N-[[2-(6-Benzofuranylcarbonyl)-5,7-dichloro-1,2,3,4-tetrahydro-6-isoquinolinyl]carbonyl]-3-(methylsulfonyl)-L-phenylalanine SAR 1118 (S)-2-(2-(benzofuran-6-carbonyl)-5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carboxamido)-3-(3-(methylsulfonyl)phenyl)propanoic Lifitegrast(API) SAR-1118;SAR1118 Lifitegrast (This product is only available in Japan.) Lifitegrast (Xiidra) SHP-606 Lifitegras Lifitegrast Lifitegrast API Lifitegrast-d6 Amipak ifitegrast (S)-2-(2-(benzofuran-6-carbonyl)-5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carboxamido)-3-(3-(methylsulfonyl)phenyl)propanoic acid liftegrast Lifitegrast-d4 Lifitegrast Impurity CS-2633 Litahistite 1025967-78-5 1025967-90-4 C29H24Cl2N2O7S API