- Design, synthesis, and structure-activity-relationship of a novel series of CXCR4 antagonists
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The important roles of the CXCL12/CXCR4 axis in numerous pathogenic pathways involving HIV infection and cancer metastasis make the CXCR4 receptor an attractive target for the development of therapeutic agents. Through scaffold hybridization of a few known CXCR4 antagonists, a series of novel aminopyrimidine derivatives was developed. Compound 3 from this new scaffold demonstrates excellent binding affinity with CXCR4 receptor (IC50 = 54 nM) and inhibits CXCL12 induced cytosolic calcium increase (IC50 = 2.3 nM). Furthermore, compound 3 possesses good physicochemical properties (MW 353, clogP 2.0, PSA 48, pKa 6.7) and exhibits minimal hERG and CYP isozyme (e.g. 3A4, 2D6) inhibition. Collectively, these results strongly support further optimization of this novel scaffold to develop better CXCR4 antagonists.
- Li, Zhanhui,Wang, Yujie,Fu, Chunyan,Wang, Xu,Wang, Jun Jun,Zhang, Yi,Zhou, Dongping,Zhao, Yuan,Luo, Lusong,Ma, Haikuo,Lu, Wenfeng,Zheng, Jiyue,Zhang, Xiaohu
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- CRYSTALLINE SALTS OF (S)-6-((1-ACETYLPIPERIDIN-4-YL)AMINO)-N-(3-(3,4-DIHYDROISOQUINOLIN-2(1H)-YL)-2-HYDROXYPROPYL)PYRIMIDINE-4-CARBOXAMIDE
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Disclosed are novel crystalline salts of (S)-6-((1-acetylpiperidin-4-yl)amino)-N-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)pyrimidine-4-carboxamide and pharmaceutical compositions containing the same. Also disclosed are processes for the prepar
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Page/Page column 22
(2016/01/25)
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- NOVEL COMPOUNDS
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The present invention relates to new CGRP-antagonists of general formula I wherein U, V, X, Y, R1, R2, R3 and R4 are defined as in the description, the tautomers, the isomers, the diastereomers, the enantiomers, the hydrates, the mixtures thereof and the salts thereof and the hydrates of the salts, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases, medicaments containing these compounds, their use and processes for preparing them.
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Page/Page column 39
(2011/02/18)
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- CGRP ANTAGONISTS
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The present invention relates to new CGRP-antagonists of general formula I wherein U, V, X, Y, R1, R2 and R3 are defined as stated hereinafter, the tautomers, the isomers, the diastereomers, the enantiomers, the hydrates, the mixtures thereof and the salts thereof and the hydrates of the salts, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases, pharmaceutical compositions containing these compounds, their use and processes for preparing them.
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Page/Page column 71
(2011/04/18)
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- CGRP ANTAGONISTS
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The present invention relates to novel CGRP antagonists of the general formula (I) in which U, V, X, Y, R1, R2, R3 are defined as described below, the tautomers, isomers, diastereomers, enantiomers, hydrates, mixtures and salts thereof, and the hydrates of the salts, particularly the physiologically compatible salts thereof having inorganic or organic acids or bases, pharmaceuticals comprising said compounds, the use thereof, and the method for the production thereof.
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Page/Page column 28
(2011/08/02)
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- NOVEL COMPOUNDS
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The present invention relates to new CGRP-antagonists of general formula I wherein U, V, X, Y, R1, R2, R3 and R4 are defined as mentioned in the description, the tautomers thereof, the isomers thereof, the diastereomers thereof, the enantiomers thereof, the hydrates thereof, the mixtures thereof and the salts thereof as well as the hydrates of the salts, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases, medicaments containing these compounds, the use thereof and processes for the preparation thereof.
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Page/Page column 79
(2011/08/22)
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- COMPOUNDS FOR TREATMENT OF DUCHENNE MUSCULAR DYSTROPHY
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Compounds of formula (I): wherein R1, L2, R2, L3, R3, L4 and R4 are as defined herein, upregulate endogenous utrophin in predictive screens, and thus, are useful for the treatment or prophylaxis of conditions such as Duchenne muscular dystrophy, Becker muscular dystrophy, and cachexia.
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Page/Page column 91
(2010/04/03)
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- SOLUBILIZED THIAZOLOPYRIDINES
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Provided herein are novel sirtuin-modulating compounds Structural Formula (I): and methods of use thereof. The sirtuin-modulating compounds may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders including, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benfit from increased mitochondrial activity. Also provided are compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent.
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Page/Page column 115
(2009/06/27)
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- MGluR5 modulators V
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The present invention is directed to novel compounds, to a process for their preparation, their use in therapy and pharmaceutical compositions comprising the novel compounds.
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Page/Page column 32
(2008/06/13)
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- BENZIMIDAZOLE CARBOXAMIDES AS RAF KINASE INHIBITORS
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The present invention relates to benzimidazole carboxamides of formula (I), the use of the compounds of formula (I) as inhibitors of as inhibitors of one or more kinases, the use of the compounds of formula (I) for the manufacture of a pharmaceutical composition and a method of treatment, comprising administering said pharmaceutical composition to a patient. Accordingly, the compound of Formula (I) or a pharmaceutically acceptable salt thereof is administered for the treatment of diseases mediated by one or more kinase phathways, preferably by the raf kinase pathway, especially cancers.
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Page/Page column 132
(2008/06/13)
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