- Synthesis, structural characterization and antimycobacterial evaluation of several halogenated non-nitro benzothiazinones
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8-Nitro-1,3-benzothiazin-4-ones (BTZs), with BTZ043 and PBTZ169 as the most advanced compounds, represent a new class of potent antitubercular agents, which irreversibly inhibit decaprenylphosphoryl-β-d-ribose-2′-epimerase (DprE1), an enzyme crucial for c
- Madikizela, Balungile,Eckhardt, Tamira,Goddard, Richard,Richter, Adrian,Lins, Anika,Lehmann, Christoph,Imming, Peter,Seidel, Rüdiger W.
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p. 1523 - 1533
(2021/06/14)
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- Hit-to-Lead Optimization of Benzoxazepinoindazoles As Human African Trypanosomiasis Therapeutics
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Human African trypanosomiasis (HAT) is a neglected tropical disease caused by infection with either of two subspecies of the parasite Trypanosoma brucei. Due to a lack of economic incentive to develop new drugs, current treatments have severe limitations in terms of safety, efficacy, and ease of administration. In an effort to develop new HAT therapeutics, we report the structure-activity relationships around T. brucei for a series of benzoxazepinoindazoles previously identified through a high-throughput screen of human kinase inhibitors, and the subsequent in vivo experiments for HAT. We identified compound 18, which showed an improved kinase selectivity profile and acceptable pharmacokinetic parameters, as a promising lead. Although treatment with 18 cured 60% of mice in a systemic model of HAT, the compound was unable to clear parasitemia in a CNS model of the disease. We also report the results of cross-screening these compounds against T. cruzi, L. donovani, and S. mansoni.
- Klug, Dana M.,Tschiegg, Laura,Diaz, Rosario,Rojas-Barros, Domingo,Perez-Moreno, Guiomar,Ceballos, Gloria,García-Hernández, Raquel,Martinez-Martinez, Maria Santos,Manzano, Pilar,Ruiz, Luis Miguel,Caffrey, Conor R.,Gamarro, Francisco,Pacanowska, Dolores Gonzalez,Ferrins, Lori,Navarro, Miguel,Pollastri, Michael P.
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p. 2527 - 2546
(2019/11/28)
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- NOVEL COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF DISEASES
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The present invention discloses compounds according to Formula I: wherein R1, R2a, X, Y, and Z are as defined herein. The present invention relates to compounds, methods for their production, pharmaceutical compositions comprising th
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Paragraph 0397; 0398
(2020/01/08)
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- NOVEL COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF DISEASES
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The present invention discloses compounds according to Formula (I): wherein R1, R2, R3a, R3b, X, Y1, Y2, Y3, and Z are as defined herein. The present invention relates to compounds, methods for their production, pharmaceutical compositions comprising the same, and methods of treatment using the same, for the prophylaxis and/or treatment of inflammatory diseases, autoinflammatory diseases, autoimmune diseases, proliferative diseases, fibrotic diseases, transplantation rejection, diseases involving impairment of cartilage turnover, congenital cartilage malformation, diseases involving impairment of bone turnover, diseases associated with hypersecretion of TNFα, interferons, IL-6, IL-12 and/or IL-23, respiratory diseases, endocrine and/or metabolic diseases, cardiovascular diseases, dermatological diseases, and/or abnormal angiogenesis associated diseases by administering the compound of the invention.
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Paragraph 0485; 0507; 0532; 0533
(2019/06/17)
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- COMPOUNDS USEFUL AS KINASE INHIBITORS
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This invention relates to novel compounds. The compounds of the invention are tyrosine kinase inhibitors. Specifically, the compounds of the invention are useful as inhibitors of Bruton's tyrosine kinase (BTK).The invention also contemplates the use of the compounds for treating conditions treatable by the inhibition of Bruton's tyrosine kinase, for example cancer, lymphoma, leukemia and immunological diseases.
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Paragraph 00252
(2017/07/14)
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- A 2,6-difluoro-4-bromophenylacetic formyl chloride method for the preparation of (by machine translation)
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The invention discloses a 2, the 6 [...] difluoro -4 the method for preparing [...] bromophenylacetic formyl chloride, relates to the technical field of organic synthesis, to 3, the 5 two fluoro bromobenzene [...], diisopropylamine, composite material, ca
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Paragraph 0022
(2016/11/17)
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- FUNGICIDAL PYRAZOLES
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Disclosed are compounds of Formula 1, including all geometric and stereoisomers, N-oxides, and salts thereof, wherein Q1, Q2, X, R1, R1a and R2 are as defined in the disclosure. Also disclosed are com
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Page/Page column 45
(2015/03/13)
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- CHEMICAL COMPOUNDS
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The invention is directed to to substituted indazole derivatives. Specifically, the invention is directed to compounds according to Formula I: wherein R1 - R6 and X are defined herein. The compounds of the invention are inhibitors of PDK1 and can be useful in the treatment of disorders characterized by constitutively activated ACG kinases such as cancer and more specifically leukemia and cancers of the breast, colon, and lung. 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 PDK1 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 47
(2010/11/04)
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- TRIAZOLOPYRAZINE COMPOUNDS USEFUL FOR THE TREATMENT OF DEGENERATIVE & INFLAMMATORY DISEASES
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Novel [1.2.4]triazolo[1,5-a]pyrazine compounds are disclosed that have a formula represented by the following (formula I). The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, arthritis, inflammation, and others.
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Page/Page column 101
(2008/06/13)
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