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A practical synthesis of LFA-1 inhibitors utilizing CuCl-promoted intramolecular cyclization of thiohydantoins |
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| Authors: | Xiao-jun Wang Li Zhang Yibo Xu Dhileepkumar Krishnamurthy Richard Varsolona Laurence Nummy Sherry Shen Rogelio P Frutos Denis Byrne JC Chung Vittorio Farina Chris H Senanayake |
| Institution: | Chemical Development Department, Boehringer Ingelheim Pharmaceuticals Inc., 900 Ridgebury Road, PO Box 368, Ridgefield, CT 06877-0368, USA |
| Abstract: | An efficient and chromatography-free approach for synthesis of a new class of LFA-1 inhibitors was developed. A copper(I) chloride-promoted intramolecular cyclization of thiohydantoins 7a-b serves as a key step to highly functionalized bicyclic guanidines 5a-b, that were subsequently converted to 1H-imidazo1,2-a]imidazol-2-one LFA-1 inhibitors. This process has been successfully implemented in the pilot plant to produce multikilogram quantities of LFA-1 inhibitors such as 1a-b. |
| Keywords: | LFA-1 inhibitor Bicyclic guanidine Thiohydantoin Imidazolidinone |
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