- PROCESS FOR PREPARING AND PURIFYING THE LFA-1 ANTAGONIST LIFITEGRAST
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The invention relates to a process for the preparation of lifitegrast (I) comprising a) reacting benzofuran-6-carboxylic acid (II) with a non- chlorinated carboxyl activating agent; and b) reacting the activated compound obtained in step a) with compound (III) or a salt thereof to give lifitegrast. It also relates to a process for the purification of lifitegrast (I) by i) reacting lifitegrast with dicyclohexylamine to give the dicyclohexylamine salt of lifitegrast (la); ii) isolating the salt from the reaction medium; iii) converting the isolated salt into lifitegrast by treatment with an acid; and iv) isolating lifitegrast from the reaction medium. It also relates to the dicyclohexylamine salt of lifitegrast (la) and to a process for its preparation. (Formula I, III)
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Page/Page column 22; 23
(2019/02/13)
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- PROCESS FOR PREPARATION OF LIFITEGRAST
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The present invention relates to a process for the preparation of lifitegrast, a compound of formula I, the process comprising deprotecting a compound of formula III using a Lewis acid. The present invention also relates to lifitegrast organic amine salt, a compound of formula II, process for its preparation and conversion thereof to lifitegrast.
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Paragraph 0220
(2019/04/11)
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- A PROCESS TO OBTAIN A TETRAHYDROISOQUINOLINE DERIVATIVE
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The present invention relates to a process for preparing lifitegrast or a salt thereof, wherein the process comprises hydrogenation of compound II in a mixture comprising at least one solvent selected from the group consisting of acetonitrile, a ketone solvent, an ester solvent and a mixture thereof, preferably acetonitrile.
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Page/Page column 12; 13
(2019/06/09)
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- LFA-1 INHIBITOR AND POLYMORPH THEREOF
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Methods of preparation and purification of a compound, intermediates thereof, a polymorph thereof, and related compounds are disclosed. Formulations and uses thereof in the treatment of LFA -1 mediated diseases are also disclosed.
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Paragraph 00147; 00148; 00150; 00151
(2014/02/16)
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- Discovery and development of potent LFA-1/ICAM-1 antagonist SAR 1118 as an ophthalmic solution for treating dry eye
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LFA-1/ICAM-1 interaction is essential in support of inflammatory and specific T-cell regulated immune responses by mediating cell adhesion, leukocyte extravasation, migration, antigen presentation, formation of immunological synapse, and augmentation of T-cell receptor signaling. The increase of ICAM-1 expression levels in conjunctival epithelial cells and acinar cells was observed in animal models and patients diagnosed with dry eye. Therefore, it has been hypothesized that small molecule LFA-1/ICAM-1 antagonists could be an effective topical treatment for dry eye. In this letter, we describe the discovery of a potent tetrahydroisoquinoline (THIQ)-derived LFA-1/ICAM-1 antagonist (SAR 1118) and its development as an ophthalmic solution for treating dry eye.
- Zhong, Min,Gadek, Thomas R.,Bui, Minna,Shen, Wang,Burnier, John,Barr, Kenneth J.,Hanan, Emily J.,Oslob, Johan D.,Yu, Chul H.,Zhu, Jiang,Arkin, Michelle R.,Evanchik, Marc J.,Flanagan, W. Mike,Hoch, Ute,Hyde, Jennifer,Prabhu, Saileta,Silverman, Jeffrey A.,Wright, Jasmin
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p. 203 - 206
(2012/05/04)
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