- UREA INHIBITORS OF MICRO-RNA
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The present disclosure relates to compounds and methods which may be useful as inhibitors of the expression of miRNA, for use in the treatment or prevention of cancer.
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- N - (4 - (3 - amino - 1 H - indazole - 4 - yl) phenyl) - N' - (2 - fluoro - 5 - methylphenyl) urea intermediate preparation method
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The invention provides a preparation method of N-(4-(3-amino-1H-indazol-4-yl) phenyl)-N'-(2-fluoro-5-methylphenyl) urea and an intermediate thereof. Specifically, the invention provides a preparation method of a borate ester compound as shown in a formula I, and the preparation method comprises the following steps: enabling a compound as shown in a formula III to react with a compound as shown in a formula IV to generate a compound as shown in a formula V, and enabling the compound as shown in the formula V to react with a boron reagent to generate the compound as shown in the formula I. The method has the characteristics of convenience in reaction, easiness in obtainment of the intermediate, high yield, high product purity of above 98.5%, low cost of raw materials and the like, and is suitable for industrial application.
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Paragraph 0137; 0142; 0143
(2018/03/02)
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- Novel Hydroximic Acid Derivative and Medical Application Thereof
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The present invention relates to a kind of new hydroximic acid derivatives, in particular, hydroximic acid derivatives of pyrazolopyrimidine and their medical applications, which have inhibition to histone deacetylase 1 and two kinds of tyrosine kinases (vascular endothelial cell growth factor receptors as well as platelet-derived growth factor receptors) simultaneously, and thus can be used for treatment of diseases related to those three kinds of enzymes. This kind of compounds both exerts a synergistic effect sufficiently to increase biological activity, and avoids problems caused by different properties and metabolisms, therefore is more practical and has good prospects.
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Paragraph 0071
(2016/07/27)
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- Linifanib-a multi-targeted receptor tyrosine kinase inhibitor and a low molecular weight gelator
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In this study we demonstrate that linifanib, a multi-targeted receptor tyrosine kinase inhibitor, with a key urea containing pharmacophore, self-assembles into a hydrogel in the presence of low amounts of solvent. We demonstrate the role of the urea functional group and that of fluorine substitution on the adjacent aromatic ring in promoting self-assembly. We have also shown that linifanib has superior mechanical strength to two structurally related analogues and hence increased potential for localisation at an injection site for drug delivery applications. This journal is
- Marlow, Maria,Al-Ameedee, Mohammed,Smith, Thomas,Wheeler, Simon,Stocks, Michael J.
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p. 6384 - 6387
(2015/04/14)
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- UREA DERIVATIVES AND USES THEREOF
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The present invention provides novel compounds of any one of Formulae (I)-(III), and pharmaceutical compositions thereof. Also provided are particles (e.g., nanoparticles) comprising compounds of Formula (I)-(III) and pharmaceutical compositions thereof that are mucus penetrating. The invention also provides methods and kits for using the inventive compounds, and pharmaceutical compositions thereof, for treating and/or preventing diseases associated with abnormal or pathological angiogenesis and/or aberrant signaling of a growth factor (e.g., vascular endothelial growth factor (VEGF)), such as proliferative diseases (e.g., cancers, benign neoplasms, inflammatory diseases, autoimmune diseases) and ocular diseases (e.g., macular degeneration, glaucoma, diabetic retinopathy, retinoblastoma, edema, uveitis, dry eye, blepharitis, and post-surgical inflammation) in a subject in need thereof.
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- The discovery and development of a safe, practical synthesis of ABT-869
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The discovery, development and implementation of two chemical routes to ABT-869 is reported. Optimization of the first-generation heterocycle formation and Suzuki coupling is briefly described. Key features of the second-generation synthesis include the development of a safe hydrazine condensation by utilizing an inorganic base to increase the onset temperature of exothermic decomposition. The second-generation Suzuki reaction is discussed in detail, culminating in the use of an oxygen monitor as a PAT to maximize reproducibility on scale.
- Kruger, Albert W.,Rozema, Michael J.,Chu-Kung, Alexander,Gandarilla, Jorge,Haight, Anthony R.,Kotecki, Brian J.,Richter, Steven M.,Schwartz, Albert M.,Wang, Zhe
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experimental part
p. 1419 - 1425
(2010/04/22)
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- 3-Amino-benzo[d]isoxazoles as novel multitargeted inhibitors of receptor tyrosine kinases
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A series of benzoisoxazoles and benzoisothiazoles have been synthesized and evaluated as inhibitors of receptor tyrosine kinases (RTKs). Structure-activity relationship studies led to the identification of 3-amino benzo[d]isoxazoles, incorporating a N,N′-
- Ji, Zhiqin,Ahmed, Asma A.,Albert, Daniel H.,Bouska, Jennifer J.,Bousquet, Peter F.,Cunha, George A.,Diaz, Gilbert,Glaser, Keith B.,Guo, Jun,Harris, Christopher M.,Li, Junling,Marcotte, Patrick A.,Moskey, Maria D.,Oie, Tetsuro,Pease, Lori,Soni, Nirupama B.,Stewart, Kent D.,Davidsen, Steven K.,Michaelides, Michael R.
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p. 1231 - 1241
(2008/12/20)
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- SUBSTITUTED PYRAZOLOPYRIDINES, COMPOSITIONS CONTAINING THEM, METHOD FOR THE PRODUCTION THEREOF, AND THEIR USE
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The disclosure relates to substituted pyrazolo-pyridines, compositions containing them, methods for the production thereof, and to their use as medicaments, in particular, as anticancer agents.
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Page/Page column 21
(2010/11/30)
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- SUBSTITUTED 4-AMINO-PYRROLOTRIAZINE DERIVATIVES USEFUL FOR TREATING HYPER-PROLIFERATIVE DISORDERS AND DISEASES ASSOCIATED WITH ANGIOGENESIS
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This invention relates to novel pyrrozolotriazine compounds, pharmaceutical compositions containing such compounds and and the use of those compounds or compositions for treating hyper-proliferative and/or angiogenesis disorders, as a sole agent or in combination with other active ingredients.
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Page/Page column 199; 205
(2010/11/27)
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- Discovery of N-(4-(3-amino-1H-indazol-4-yl)phenyl)-N′-(2-fluoro-5- methylphenyl)urea (ABT-869), a 3-aminoindazole-based orally active multitargeted receptor tyrosine kinase inhibitor
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In our continued efforts to search for potent and novel receptor tyrosine kinase (RTK) inhibitors as potential anticancer agents, we discovered, through a structure-based design, that 3-aminoindazole could serve as an efficient hinge-binding template for kinase inhibitors. By incorporating an N,N′-diaryl urea moiety at the C4-position of 3-aminodazole, a series of RTK inhibitors were generated, which potently inhibited the tyrosine kinase activity of the vascular endothelial growth factor receptor and the platelet-derived growth factor receptor families. A number of compounds with potent oral activity were identified by utilizing an estradiol-induced mouse uterine edema model and an HT1080 human fibrosarcoma xenograft tumor model. In particular, compound 17p (ABT-869) was found to possess favorable pharmacokinetic profiles across different species and display significant tumor growth inhibition in multiple preclinical animal models.
- Dai, Yujia,Hartandi, Kresna,Ji, Zhiqin,Ahmed, Asma A.,Albert, Daniel H.,Bauch, Joy L.,Bouska, Jennifer J.,Bousquet, Peter F.,Cunha, George A.,Glaser, Keith B.,Harris, Christopher M.,Hickman, Dean,Guo, Jun,Li, Junling,Marcotte, Patrick A.,Marsh, Kennan C.,Moskey, Maria D.,Martin, Ruth L.,Olson, Amanda M.,Osterling, Donald J.,Pease, Lori J.,Soni, Niru B.,Stewart, Kent D.,Stoll, Vincent S.,Tapang, Paul,Reuter, David R.,Davidsen, Steven K.,Michaelides, Michael R.
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p. 1584 - 1597
(2008/02/01)
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- Indazole and benzisoxazole kinase inhibitors
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Compounds having the formula are useful for inhibiting protein tyrosine kinases. The present invention also discloses methods of making the compounds, compositions containing the compounds, and methods of treatment using the compounds.
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