- INHIBITOR OF BTK AND MUTANTS THEREOF
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The disclosure includes compounds of Formula (I) (1) wherein Q0, Q1, Q2, Q3, Q4, Z, W, i, j, m, n, Warhead, R0, R1, R3, R4, R5, R6, and R7, are defined herein. Also disclosed is a method for treating a neoplastic disease, autoimmune disease, and inflammatory disorder with these compounds.
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- DIAMINOPYRIMIDINE DERIVATIVES AND PROCESSES FOR THE PREPARATION THEREOF
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The present invention provides a diaminopyrimidine derivative or its pharmaceutically acceptable salt, a process for the preparation thereof, a pharmaceutical composition comprising the same, and a use thereof. The diaminopyrimidine derivative or its pharmaceutically acceptable salt functions as a 5-HT4 receptor agonist, and therefore can be usefully applied for preventing or treating dysfunction in gastrointestinal motility, one of the gastrointestinal diseases, such as gastroesophageal reflux disease (GERD), constipation, irritable bowel syndrome (IBS), dyspepsia, post-operative ileus, delayed gastric emptying, gastroparesis, intestinal pseudo-obstruction, drug-induced delayed transit, or diabetic gastric atony.
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- Applications of parallel synthesis to lead optimization
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Parallel synthesis of focused compound libraries for hit confirmation and lead optimization are certainly important drivers for shortening the lead discovery phase in the pharmaceutical and crop protection industries. In this article we show with permission of Roche and Syngenta three real case studies where Polyphor synthesized focused libraries for lead validation and optimization using high-throughput parallel synthesis and purification techniques. The three examples differ significantly in the synthetic strategies which were employed as well as in the chemical complexity of the final products. A multigeneration approach towards insecticidal triazines, the application of a sequential three-component reaction towards insecticidal and fungicidal thiazoles and finally a multistep synthesis approach of advanced building blocks followed by a two-step final derivatization towards novel antiviral N-hydroxy-indolin-2-ones are presented. In all cases 100-200 analogues were synthesized using parallel synthesis in solution followed by purification of the final products by parallel flash or high-throughput (unattended) HPLC (coupled to MS) within four months. Promising biological results were obtained in all three cases.
- Altorfer, Michael,Ermert, Philipp,Faessler, Juerg,Farooq, Saleem,Hillesheim, Elke,Jeanguenat, Andre,Klumpp, Klaus,Maienfisch, Peter,Martin, Joseph A.,Merrett, John H.,Parkes, Kevin E.B.,Obrecht, Jean-Pierre,Pitterna, Thomas,Obrecht, Daniel
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p. 262 - 269
(2007/10/03)
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