- NOVEL COMPOUNDS AND METHODS OF USE TREATING FRUCTOSE-RELATED DISORDERS OR DISEASES
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Disclosed herein are novel compounds that inhibit fructokinase (KHK or ketohexokinase) and the downstream metabolic effects mediated by fructose metabolism. Fructokinase inhibitors specifically block the metabolism of both dietary and endogenous fructose
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Page/Page column 61-62
(2020/10/27)
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- C3-CARBON LINKED GLUTARIMIDE DEGRONIMERS FOR TARGET PROTEIN DEGRADATION
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This invention provides Degronimers that have carbon-linked E3 Ubiquitin Ligase targeting moieties (Degrons), which can be linked to a targeting ligand for a protein that has been selected for in vivo degradation, and methods of use and compositions thereof as well as methods for their preparation.
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Page/Page column 335; 336
(2017/12/05)
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- 5-SULFAMOYL-2-HYDROXYBENZAMIDE DERIVATIVES
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The invention is directed to substituted salicylamide derivatives. Specifically, the invention is directed to compounds according to Formula (I): wherein R, R1 and R2 are as defined herein, or a pharmaceutically acceptable salt thereof. The compounds of the invention are inhibitors of CD73 and can be useful in the treatment of cancer, pre-cancerous syndromes and diseases associated with CD73 inhibition, such as AIDS, the treatment of HIV, autoimmune diseases, infections, atherosclerosis, and ischemia–reperfusion injury. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting CD73 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.
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Page/Page column 211
(2017/09/27)
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- 2,3-dimethyl-6-urea -2H-indazoles and its preparation method and application
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The invention discloses a 2, 3-dimethyl-6-urea-2H-indazole compound shown by the following general formula (I), medicinal salt or a solvent compound thereof, wherein Ar is substituted or unsubstituted phenyl or aromatic matrix. The invention also discloses a preparation method and application of the compound. The compound can regulate signal transduction of tyrosine kinase, inhibit bad cellular proliferation, and particularly has obvious curative effect for tumors.
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- N-indazole substituted thiourea derivatives and preparation method and application thereof
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The invention discloses N-indazole substituted thiourea derivatives and a preparation method and application thereof and belongs to the technical field of chemical medicine.The thiourea derivatives are a series of compounds simultaneously containing the 1H-indazole ring structure and the asymmetrical thiourea structure, and the compounds are not reported in the literature.The bioactivity test result analysis of the thiourea derivatives show that the compounds are good in antioxidant activity, the average scavenging rate is above 80%, the scavenging rate of the compound 12b, the compound 12c, and the compound 12d and the compound 12h is higher than 90%, the scavenging activity IC50 of the compound 12h on DPPH is 0.14mg/mL; part of the target compounds has certain inhibition activity on herpes viruses, vaccinia viruses, reoviruses, Coxsackie viruses, Feline coronary herpes viruses, HIV viruses and the like, and the compound 12c and the compound 12n are high in antivirus activity; the synthesized compounds hopefully have new bioactivity which is not expounded, and a certain material basis is provided for the development of new medicine.
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Paragraph 0119; 0120; 0121
(2016/10/09)
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- INDAZOLE AND AZAINDAZOLE SUBSTITUTED COMPOUNDS AS MGLUR4 ALLOSTERIC POTENTIATORS, COMPOSITIONS, AND METHODS OF TREATING NEUROLOGICAL DYSFUNCTION
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Compounds which are useful as allosteric potentiators/positive allosteric modulators of the metabotropic glutamate receptor subtype 4 (mGluR4); synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods o
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Paragraph 0214
(2016/08/23)
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- Effective Laboratory-Scale Preparation of Axitinib by Two CuI-Catalyzed Coupling Reactions
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The discovery and development of an efficient synthesis route to axinitib is reported. The first-generation route researched by Pfizer implemented two Pd-catalyzed coupling reactions as key steps. In this work, the development of Heck-type and C-S coupling reactions catalyzed by CuI is briefly described, using an economial and practical protocol. Aspects of this route, such as selecting optimal ligands, solvent, and other conditions, are discussed in detail. The scale-up experiment was carried out to provide more than 300 g of active pharmaceutical ingredients of axitinib in Form XLI with 99.9% purity in 39% yield. In short, we provide a new choice of synthesis route to axitinib, through two copper-catalyzed coupling reactions with good yield.
- Zhai, Li-Hai,Guo, Li-Hong,Luo, Yang-Hui,Ling, Yang,Sun, Bai-Wang
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p. 849 - 857
(2015/07/27)
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- Discovery of 2-(1H-indazol-1-yl)-thiazole derivatives as selective EP 1 receptor antagonists for treatment of overactive bladder by core structure replacement
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We have designed a series of potent EP1 receptor antagonists. These antagonists are a series of 2-(1H-indazol-1-yl)-thiazoles in which the core structure was replaced with pyrazole-phenyl groups. In preliminary conscious rat cystometry experiments, two representative candidates, 2 and 22, increased bladder capacity. In particular, the increase using 22 was approximately 2-fold that of the baseline. More detailed profiling of this compound and further optimization of this series promises to provide a novel class of drug for treating overactive bladder (OAB).
- Atobe, Masakazu,Naganuma, Kenji,Kawanishi, Masashi,Morimoto, Akifumi,Kasahara, Ken-Ichi,Ohashi, Shigeki,Suzuki, Hiroko,Hayashi, Takahiko,Miyoshi, Shiro
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p. 1327 - 1333
(2014/03/21)
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- Identification of 3-sulfonylindazole derivatives as potent and selective 5-HT6 antagonists
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As part of our efforts to develop agents for cognitive enhancement, we have been focused on the 5-HT6 receptor in order to identify potent and selective ligands for this purpose. Herein we report the identification of a novel series of 3-sulfonylindazole derivatives with acyclic amino side chains as potent and selective 5-HT6 antagonists. The synthesis and detailed SAR of this class of compounds are reported.
- Liu, Kevin G.,Robichaud, Albert J.,Greenfield, Alexander A.,Lo, Jennifer R.,Grosanu, Cristina,Mattes, James F.,Cai, Yanxuan,Zhang, Guo Ming,Zhang, Jean Y.,Kowal, Dianne M.,Smith, Deborah L.,Di, Li,Kerns, Edward H.,Schechter, Lee E.,Comery, Thomas A.
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scheme or table
p. 650 - 662
(2011/02/28)
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- Optimisation of ITK inhibitors through successive iterative design cycles
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Based on a hit cluster of compounds inhibiting interleukin-2 inducible T-cell kinase (ITK) in the submicromolar range a series of ITK inhibitor libraries were synthesized. Through iterative design cycles including kinase crystal structure information, indolylindazole libraries were identified which showed low nanomolar activity in enzymatic and cellular assays. The potential of these novel lead series was confirmed through in vivo tests in an anti-CD3-IL2 mouse model. The intravenous administration of highly potent ITK inhibitor 11o resulted in dose-dependent, efficient suppression of IL-2.
- Herdemann, Matthias,Weber, Alexander,Jonveaux, Jér?me,Schwoebel, Frank,Stoeck, Michael,Heit, Isabelle
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scheme or table
p. 1852 - 1856
(2011/05/05)
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- BICYCLIC NITROGEN-CONTAINING HETEROCYCLIC COMPOUNDS
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A nitrogen-containing bicyclic heterocyclic compound represented by the following formula (1) is provided. When the compound or a salt thereof is administered to a human being or an animal, the compound has a strong antagonistic action against EP1 recepto
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Page/Page column 40
(2010/03/02)
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- VEGFR INHIBITORS CONTAINING A ZINC BINDING MOIETY
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The present invention relates to VEGFR inhibitors and their use in the treatment of cell proliferative diseases such as cancer. The said derivatives may further act as HDAC inhibitors.
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Page/Page column 51
(2009/04/25)
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- p38 MAP kinase inhibitors and methods for using the same
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Compounds of formula Ia or Ib: wherein X and Y are nitrogen or CRe, and R1, R2, R3, R4 and R5 are as defined herein. Also disclosed are methods of making the subject compounds and methods o
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Page/Page column 24
(2008/06/13)
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- METHODS FOR PREPARING INDAZOLE COMPOUNDS
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The invention relates to methods for preparing indalzole compounds having formula (I) or pharmaceutically acceptable salts or solvates thereof. Compounds of the formula (I) are useful as anti-angiogenesis agents and as agents for modulating and/or inhibiting the activity of protein kinases, thus providing treatments for cancer or other diseases associated with cellular proliferation mediated by protein kinases.
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Page/Page column 21
(2008/06/13)
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- METHODS FOR PREPARING INDAZOLE COMPOUNDS
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The invention relates to methods for preparing compounds of formula (I): or pharmaceutically acceptable salts or solvates thereof. Compounds of the formula (I) are useful as anti-angiogenesis agents and as agents for modulating and/or inhibiting the activity of protein kinases, thus providing treatments for cancer or other diseases associated with cellular proliferation mediated by protein kinases.
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Page/Page column 30
(2010/11/30)
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- Design and synthesis of 6-anilinoindazoles as selective inhibitors of c-Jun N-terminal kinase-3
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The structure-based design and synthesis of a new series of c-Jun N-terminal kinase-3 inhibitors with selectivity against JNK1 and p38α is reported. The novel series of substituted 6-anilinoindazoles were designed based on a combination of hits from high
- Swahn, Britt-Marie,Huerta, Fernando,Kallin, Elisabet,Malmstroem, Jonas,Weigelt, Tatjana,Viklund, Jenny,Womack, Patrick,Xue, Yafeng,Oehberg, Liselotte
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p. 5095 - 5099
(2007/10/03)
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- P38 inhibitors and methods of use thereof
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This invention relates to inhibitors of p38, and methods for producing these inhibitors. The invention also provides pharmaceutical compositions comprising the inhibitors of the invention and methods of utilizing the inhibitors and pharmaceutical compositions in the treatment and prevention of various disorders mediated by p38.
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Page/Page column 20
(2008/06/13)
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- Indazole compounds and pharmaceutical compositions for inhibiting protein kinases, and methods for their use
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Indazole compounds that modulate and/or inhibit the activity of certain protein kinases are described. These compounds and pharmaceutical compositions containing them are capable of mediating tyrosine kinase signal transduction and thereby modulate and/or inhibit unwanted cell proliferation. The invention is also directed to the therapeutic or prophylactic use of pharmaceutical compositions containing such compounds, and to methods of treating cancer and other disease states associated with unwanted angiogenesis and/or cellular proliferation, such as diabetic retinopathy, neovascular glaucoma, rheumatoid arthritis, and psoriasis, by administering effective amounts of such compounds.
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