1182917-01-6Relevant articles and documents
Discovery of a highly selective, brain-penetrant aminopyrazole LRRK2 inhibitor
Chan, Bryan K.,Estrada, Anthony A.,Chen, Huifen,Atherall, John,Baker-Glenn, Charles,Beresford, Alan,Burdick, Daniel J.,Chambers, Mark,Dominguez, Sara L.,Drummond, Jason,Gill, Andrew,Kleinheinz, Tracy,Le Pichon, Claire E.,Medhurst, Andrew D.,Liu, Xingrong,Moffat, John G.,Nash, Kevin,Scearce-Levie, Kimberly,Sheng, Zejuan,Shore, Daniel G.,Van De Po?l, Hervé,Zhang, Shuo,Zhu, Haitao,Sweeney, Zachary K.
, p. 85 - 90 (2013)
The modulation of LRRK2 kinase activity by a selective small molecule inhibitor has been proposed as a potentially viable treatment for Parkinson's disease. By using aminopyrazoles as aniline bioisosteres, we discovered a novel series of LRRK2 inhibitors. Herein, we describe our optimization effort that resulted in the identification of a highly potent, brain-penetrant aminopyrazole LRRK2 inhibitor (18) that addressed the liabilities (e.g., poor solubility and metabolic soft spots) of our previously disclosed anilino-aminopyrimidine inhibitors. In in vivo rodent PKPD studies, 18 demonstrated good brain exposure and engendered significant reduction in brain pLRRK2 levels post-ip administration. The strategies of bioisosteric substitution of aminopyrazoles for anilines and attenuation of CYP1A2 inhibition described herein have potential applications to other drug discovery programs.
TGF-betaR1 inhibitor and application thereof
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Paragraph 0193; 0195-0197, (2020/06/09)
The invention belongs to the field of medical chemistry, and particularly relates to a compound serving as a TGF-betaR1 inhibitor and application of the compound. Specifically, the invention providesa compound shown as a formula I or an isomer, a pharmaceutically acceptable salt, a solvate, a crystal or a prodrug thereof, a preparation method of the compounds, a pharmaceutical composition containing the compounds and application of the compounds or the composition to treatment and/or prevention of TGF-betaR1 related diseases, such as cancers, tissue hyperplasia diseases, fibrosis and inflammatory diseases. The compound provided by the invention shows significant inhibitory activity on TGF-betaR1 kinase, and is very expected to become a therapeutic agent for TGF-betaR1 related diseases.
9-SUBSTITUTED AMINO TRIAZOLO QUINAZOLINE DERIVATIVES AS ADENOSINE RECEPTOR ANTAGONISTS, PHARMACEUTICAL COMPOSITIONS AND THEIR USE
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Paragraph 54; 67-68, (2020/06/19)
In its many embodiments, the present invention provides certain 9-substituted amino triazolo quinazoline compounds of the structural Formula (I): (I), and pharmaceutically acceptable salts thereof, wherein, ring A, R1 and R2 are as defined herein, pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other therapeutically active agents), and methods for their preparation and use, alone and in combination with other therapeutic agents, as antagonists of A2a and/or A2b receptors, and in the treatment of a variety of diseases, conditions, or disorders that are mediated, at least in part, by the adenosine A2a receptor and/or the adenosine A2b receptor.
7-, 8-, and 10-SUBSTITUTED AMINO TRIAZOLO QUINAZOLINE DERIVATIVES AS ADENOSINE RECEPTOR ANTAGONISTS, PHARMACEUTICAL COMPOSITIONS AND THEIR USE
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Page/Page column 79; 95; 96, (2020/06/19)
In its many embodiments, the present invention provides certain 7-, 8-, and 10-substituted amino triazolo quinazoline derivatives of Formula (I): or a pharmaceutically acceptable salt thereof, wherein ring A, R1, R2, and R4 are as defined herein, pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other therapeutic agents), and methods for their preparation and use, alone and in combination with other therapeutic agents, as antagonists of A2a and/or A2b receptors, and their use in the treatment of a variety of diseases, conditions, or disorders that are mediated, at least in part, by the adenosine A2a receptor and/or the adenosine A2b receptor.
SUBSTITUTED HETEROARYL COMPOUNDS AND METHODS OF USE
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Paragraph 0395, (2017/03/28)
The present invention provides novel heteroaryl compounds, pharmaceutical acceptable salts and formulations thereof. They are useful in preventing, managing, treating or lessening the severity of a protein kinase-mediated disease. The invention also provides pharmaceutically acceptable compositions comprising such compounds and methods of using the compositions in the treatment of protein kinase-mediated disease.
Substituted heteroaryl compounds and composition thereof, and applicaitons of compounds and composition
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Paragraph 0612; 0613; 0614; 0615, (2017/07/31)
The invention provides substituted heteroaryl compounds and a composition thereof, and applicaitons of the compounds and the composition. The compounds are compounds represented by the formula (I) or the formula (II) or stereoisomers, tautomers, nitrogen oxides, solvates, metabolites, pharmaceutically acceptable salts or prodrugs of the compounds represented by the formula (I) or the formula (II). The invention also provides the pharmaceutical composition comprising the compounds; the compounds and the pharmaceutical composition can adjust the activity of protein kinase, and are used for prevention, processing, treatment and remission of diseases or disorders mediated by the protein kinase.
COMPOSITIONS USEFUL FOR TREATING DISORDERS RELATED TO KIT
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Paragraph 0223; 0224, (2015/04/28)
Compounds and compositions useful for treating disorders related to KIT and PDFGR are described herein.
SUBSTITUTED PYRIMIDINE COMPOUNDS, COMPOSITIONS AND MEDICINAL APPLICATIONS THEREOF
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Paragraph 00082, (2015/03/13)
The present disclosure relates to pyrimidine compounds of formula (I), their stereoisomers, tautomers, pharmaceutically acceptable salts, polymorphs, solvates, and hydrates thereof. The present disclosure also relates to process of preparation of these pyrimidine compounds, and to pharmaceutical compositions containing them. The compounds of the present disclosure are useful in the treatment, prevention or suppression of diseases and disorders mediated by epidermal growth factor receptor (EGFR) family kinases.
Five-And-Six-Membered Heterocyclic Compound, And Preparation Method, Pharmaceutical Composition And Use Thereof
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Paragraph 0484; 0485, (2015/12/07)
A five-and-six-membered heterocyclic compound as represented by general formula I, pharmaceutically acceptable salt, metabolite, metabolic precursors or drug precursors thereof, preparation method, pharmaceutical composition, and use thereof; the five-and-six-membered heterocyclic compound has activity as a Janus kinase (JAK) inhibitor, and can be used to prepare drugs for treating diseases caused by the abnormal activity of kinase, such as cell proliferation diseases like cancer.
SUBSTITUTED PYRROLOPYRIMIDINE COMPOUNDS, COMPOSITIONS THEREOF, AND METHODS OF TREATMENT THEREWITH
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Paragraph 0345, (2014/07/23)
Provided herein are Pyrrolopyrimidine Compounds having the following structure: wherein R1, R2, R3, and L are as defined herein, compositions comprising an effective amount of a Pyrrolopyrimidine Compound, and methods for treating or preventing breast cancer, more particularly triple negative breast cancer, comprising administering an effective amount of such Pyrrolopyrimidine Compounds to a subject in need thereof.
