Lifitegrast(SAR 1118)

Base Information

• Chemical Name: Lifitegrast(SAR 1118)
• CAS No.: 1025967-78-5
• Molecular Formula: C29H24Cl2N2O7S
• Molecular Weight: 615.491
• European Community (EC) Number: 813-044-8
• UNII: Q8VE5H5V6Z
• Mol file: 1025967-78-5.mol

Synonyms:Lifitegrast(SAR 1118);2271299-08-0;R-Lifitegrast;Lifitegrast, (R)-;Lifitegrast Impurity 8;Q8VE5H5V6Z;SCHEMBL22556043;(2S)-2-[[2-(1-benzofuran-6-carbonyl)-5,7-dichloro-3,4-dihydro-1H-isoquinoline-6-carbonyl]amino]-3-(3-methylsulfonylphenyl)propanoic acid;A936596;(R)-2-(2-(benzofuran-6-carbonyl)-5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carboxamido)-3-(3-(methylsulfonyl)phenyl)propanoic acid;D-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)-D-phenylalanine

Chemical Property of Lifitegrast(SAR 1118)

Chemical Property:

• Boiling Point: 811.9±65.0 °C(Predicted)
• PKA: 3.14±0.10(Predicted)
• PSA: 142.37000
• Density: 1.479±0.06 g/cm3(Predicted)
• LogP: 6.17690
• Storage Temp.: Hygroscopic, -20°C Freezer, Under inert atmosphere
• Solubility.: DMSO (Slightly, Heated, Sonicated), Methanol (Slightly, Sonicated)
• XLogP3: 4.7
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 7
• Exact Mass: 614.0681277
• Heavy Atom Count: 41
• Complexity: 1100

Purity/Quality:

99%min, ^*data from raw suppliers

Lifitegrast ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CS(=O)(=O)C1=CC=CC(=C1)CC(C(=O)O)NC(=O)C2=C(C=C3CN(CCC3=C2Cl)C(=O)C4=CC5=C(C=C4)C=CO5)Cl
• Isomeric SMILES: CS(=O)(=O)C1=CC=CC(=C1)C[C@H](C(=O)O)NC(=O)C2=C(C=C3CN(CCC3=C2Cl)C(=O)C4=CC5=C(C=C4)C=CO5)Cl
• 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 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.
• 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.

Technology Process of Lifitegrast(SAR 1118)

There total 62 articles about Lifitegrast(SAR 1118) which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 96.0%

lifitegrast dicyclohexylamine salt → (S)-2-(2-(benzofuran-6-carbonyl)-5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carboxamido)-3-(3-(methylsulfonyl)phenyl)propanoic acid (1025967-78-5)

Guidance literature:

With phosphoric acid; In dichloromethane; water; at 50 ℃; for 0.5h;

Reference yield: 92.0%

2-(benzofuran-6-carbonyl)-5,7-dichloro-1,2,3 ,4-tetrahydroisoquinoline-6-carboxylic acid + (S)-2-amino-3-(3-(methylsulfonyl)phenyl)propanoic acid → (S)-2-(2-(benzofuran-6-carbonyl)-5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carboxamido)-3-(3-(methylsulfonyl)phenyl)propanoic acid (1025967-78-5)

Guidance literature:

2-(benzofuran-6-carbonyl)-5,7-dichloro-1,2,3 ,4-tetrahydroisoquinoline-6-carboxylic acid; With [2-(1H-indol-3-yl)-ethyl]-methylamine; N-ethyl-N,N-diisopropylamine; HATU; In tetrahydrofuran; at 40 ℃; for 2h; Inert atmosphere;

(S)-2-amino-3-(3-(methylsulfonyl)phenyl)propanoic acid; In tetrahydrofuran; at 20 - 30 ℃;

Reference yield: 87.0%

(S)-2-amino-3-(3-(methylsulfonyl)phenyl)propanoic acid + 3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl 2-(benzofuran-6-carbonyl)-5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carboxylate → (S)-2-(2-(benzofuran-6-carbonyl)-5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carboxamido)-3-(3-(methylsulfonyl)phenyl)propanoic acid (1025967-78-5)

Guidance literature:

(S)-2-amino-3-(3-(methylsulfonyl)phenyl)propanoic acid; 3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl 2-(benzofuran-6-carbonyl)-5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carboxylate; With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 40 - 45 ℃;

With hydrogenchloride; In water; at 0 - 5 ℃; for 1h; pH=5;

upstream raw materials:

(2S)-3-(3-bromophenyl)-2-[(tert-butoxycarbonyl)amino]propanoic acid

(S)-2-((tert-butoxycarbonyl)amino)-3-((3-methylsulfonyl)phenyl)propanol

(S)-benzyl 2-((tert-butoxycarbonyl)amino)-3-((3-methylsulfonyl)phenyl)propionate

(2S)-2-amino-3-(3-(methanesulfonyl)phenyl)propionic acid benzyl ester hydrochloride

Refernces

• 1、 -. "A PROCESS FOR THE PREPARATION OF LIFITEGRAST". . . Retrieved 2019/10/23.
• 2、 -. "PROCESS FOR PREPARING LIFITEGRAST AND INTERMEDIATES THEREOF". . . Retrieved 2019/01/15.