- Synthesis method of tirbanibulin intermediate
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The invention belongs to the technical field of synthesis of medical compounds, and particularly discloses a synthesis method of a tirbanibulin intermediate. According to the method, 4-[2-(4-bromophenoxy)ethyl]morpholine is adopted as a raw material, firstly reacts with an n-butyl magnesium lithium reagent and then reacts with isopropyl alcohol pinacol borate, and the tirbanibulin intermediate is synthesized through a one-pot method. The method is mild in reaction condition and simple to operate, the reaction product is single, the target product can be obtained at high yield through a simple post-treatment and recrystallization method, and the method is expected to be developed into an industrial production method.
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Paragraph 0028-0033; 0036-0042
(2022/01/10)
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- IN-FLOW PHOTOOXYGENATION OF AMINOTHIENOPYRIDINONES GENERATES NOVEL PTP4A3 PHOSPHATASE INHIBITORS
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The disclosure provides compounds that inhibit protein tyrosine phosphatase, such as protein tyrosine phosphatase 4A3 (PTP4A3). The disclosure also provides pharmaceutical compositions, uses, and methods of using the compounds, such as in the treatment of cancers. (I), wherein X is O or NH.
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Paragraph 00110
(2020/06/05)
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- NOVEL HETEROAROMATIC COMPOUNDS AS POTENT MODULATORS OF THE HIPPO-YAP SIGNALING PATHWAY LATS1/2 KINASES
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The present invention relates to novel heteroaromatic compounds of formulae (I) and (II) and pharmaceutically acceptable salts thereof. The compounds of the invention are useful as inhibitors of serine/threonine protein kinases LATS1 and LATS2. Also provided herein are processes for making compounds of formulae (I) and (II), and pharmaceutical compositions comprising the compounds of the invention. The present invention also provides methods of treating cancer with a compound of formula (I) or (II).
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Page/Page column 33
(2020/03/23)
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- BET INHIBITORS FOR MODULATING DUX4 EXPRESSION IN FSHD
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The present disclosure provides BET inhibitors of the formula: wherein the variables are defined herein, as well as pharmaceutical compositions thereof. The present disclosure also provides methods of treating a patient comprising administering a bromo- and extra-terminal (BET) domain inhibitor for the treatment of FSHD which modulates DUX4 expression. In some embodiments, the present methods comprise using one or more BET inhibitors as a therapeutic agent for the treatment of FSHD patients including patients who are being treated with one or more palliative treatments such as therapy and/or agents which lead to increased muscle mass.
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Page/Page column 94; 95
(2020/07/14)
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- In-flow photooxygenation of aminothienopyridinones generates iminopyridinedione PTP4A3 phosphatase inhibitors
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A continuous flow photooxygenation of 7-aminothieno[3,2-c]pyridin-4(5H)-ones to produce 7-iminothieno[3,2-c]pyridine-4,6(5H,7H)-diones has been developed, utilizing ambient air as the sole reactant. N-H Imines are formed as the major products, and excellent functional group tolerance and conversion on gram-scale without the need for chromatographic purification allow for facile late-stage diversification of the aminothienopyridinone scaffold. Several analogs exhibit potent in vitro inhibition of the cancer-associated protein tyrosine phosphatase PTP4A3, and the SAR supports an exploratory docking model.
- Tasker, Nikhil R.,Rastelli, Ettore J.,Blanco, Isabella K.,Burnett, James C.,Sharlow, Elizabeth R.,Lazo, John S.,Wipf, Peter
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supporting information
p. 2448 - 2466
(2019/03/06)
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- Discovery of Novel Dual Mechanism of Action Src Signaling and Tubulin Polymerization Inhibitors (KX2-391 and KX2-361)
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The discovery of potent, peptide site directed, tyrosine kinase inhibitors has remained an elusive goal. Herein we describe the discovery of two such clinical candidates that inhibit the tyrosine kinase Src. Compound 1 is a phase 3 clinical trial candidat
- Smolinski, Michael P.,Bu, Yahao,Clements, James,Gelman, Irwin H.,Hegab, Taher,Cutler, David L.,Fang, Jane W. S.,Fetterly, Gerald,Kwan, Rudolf,Barnett, Allen,Lau, Johnson Y. N.,Hangauer, David G.
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supporting information
p. 4704 - 4719
(2018/06/20)
-
- Discovery of 1-(4-(4-Amino-3-(4-(2-morpholinoethoxy)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)phenyl)-3-(5-(tert-butyl)isoxazol-3-yl)urea (CHMFL-FLT3-213) as a Highly Potent Type II FLT3 Kinase Inhibitor Capable of Overcoming a Variety of FLT3 Kinase Mutan
-
FLT3-ITD mutant has been observed in about 30% of AML patients and extensively studied as a drug discovery target. On the basis of our previous study that ibrutinib (9) exhibited selective and moderate inhibitory activity against FLT3-ITD positive AML cel
- Wang, Aoli,Li, Xixiang,Chen, Cheng,Wu, Hong,Qi, Ziping,Hu, Chen,Yu, Kailin,Wu, Jiaxin,Liu, Juan,Liu, Xiaochuan,Hu, Zhenquan,Wang, Wei,Wang, Wenliang,Wang, Wenchao,Wang, Li,Wang, Beilei,Liu, Qingwang,Li, Lili,Ge, Jian,Ren, Tao,Zhang, Shanchun,Xia, Ruixiang,Liu, Jing,Liu, Qingsong
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p. 8407 - 8424
(2017/11/03)
-
- FLT3 kinase novel inhibitors and use thereof (by machine translation)
-
The present invention provides FLT3 kinase novel inhibitors, of formula (I) compound or its pharmaceutically acceptable salt, solvate, isomer, ester, acid, metabolite, or prodrug. The invention also provides formula (I) compound of the pharmaceutical comp
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Paragraph 0153; 0156; 0157
(2018/01/05)
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- ANTIVIRAL COMPOUNDS
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The present invention discloses compounds of Formula I: wherein the variables in Formula I are defined as described herein. Also disclosed are pharmaceutical compositions containing such compounds and methods for using the compounds of Formula I in the prevention or treatment of HCV infection.
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Page/Page column 440
(2014/09/29)
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- NOVEL HYDROXAMIC ACID DERIVATIVE
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Provided is a novel compound which is useful as a pharmaceutical composition by inhibiting an LpxC activity, thereby exhibiting potent antimicrobial activity against gram-negative bacteria including Pseudomonas aeruginosa and its drug resistant bacteria. Provided is a hydroxamic acid derivative represented by the following general formula [1] or a pharmaceutically acceptable salt thereof:
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Paragraph 0358
(2013/03/26)
-
- AZACARBOLINE DERIVATIVES, PREPARATION METHOD THEREOF AND THERAPEUTIC USE OF SAME
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The invention relates to novel azacarbonlines having formula (I), wherein: R3, R4 represent independently H; hal; CF3; substituted oxy, optionally substituted alkoxy; optionally substituted amino; substituted carbonyl; optionally substituted carboxyl; optionally substituted amide; sulphur, such as optionally substituted sulphones, sulphoxides or sulphides; linear, branched or cyclic C1-C10 alkyl optionally comprising an optionally substituted heteroatom; optionally substituted linear, branched or cyclic C2-C7 alkenyl; optionally substituted linear or branched C2-C6 alkynyl; optionally substituted aryl or heteroaryl; of which may be optionally substituted; in the form of a base or an acid addition salt. The invention also relates to the use of same in therapeutics for the treatment of cancer and to synthesis methods.
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Page/Page column 72
(2011/08/04)
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- Discovery of a novel class of triazolones as Checkpoint Kinase inhibitors - Hit to lead exploration
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Checkpoint Kinase-1 (Chk1, CHK1, CHEK1) is a Ser/Thr protein kinase that mediates cellular responses to DNA-damage. A novel class of Chk1 inhibitors, triazoloquinolones/triazolones (TZ's) was identified by high throughput screening. The optimization of th
- Oza, Vibha,Ashwell, Susan,Brassil, Patrick,Breed, Jason,Deng, Chun,Ezhuthachan, Jay,Haye, Heather,Horn, Candice,Janetka, James,Lyne, Paul,Newcombe, Nicholas,Otterbien, Ludo,Pass, Martin,Read, Jon,Roswell, Sian,Su, Mei,Toader, Dorin,Yu, Dingwei,Yu, Yan,Valentine, Anna,Webborn, Peter,White, Ann,Zabludoff, Sonya,Zheng, Xiaolan
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scheme or table
p. 5133 - 5138
(2010/10/19)
-
- PHARMACEUTICAL COMPOSITIONS FOR MODULATING A KINASE CASCADE AND METHODS OF USE THEREOF
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The invention relates to a pharmaceutical composition comprising 2-(5-(4-(2- mopholinoethoxy)phenyl)pyridin-2-yl)-N-benzylacetamide or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.
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Page/Page column 52
(2009/05/28)
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- COMPOSITION AND METHODS FOR MODULATING A KINASE CASCADE
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The invention relates to compositions of N-benzyl-2-(5-(4-(2- morpholinoethoxy)phenyl)pyridin-2-yl)acetamide (KX2-391) and methods for modulating one or more components of a kinase cascade.
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Page/Page column 62
(2008/12/07)
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- 1,4-DISUBSTITUTED 3-CYANO-PYRIDONE DERIVATIVES AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF MGLUR2-RECEPTORS
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The present invention relates to novel compounds, in particular novel pyridinone de- rivat ives according to Formula (I) wherein all radicals are defined in the application and claims. The compounds accord- ing to the invention are positive allosteric mod
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Page/Page column 44-45
(2010/11/28)
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- Compositions and methods of treating cell proliferation disorders
-
The invention relates to compounds and methods for treating cell proliferation disorders.
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Page/Page column 83-84
(2008/06/13)
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- Use of 8-amino-aryl-substituted imidazopyrazines as kinase inhibitors
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The present invention relates to 8-amino-aryl-substituted imidazopyrazines which modulate the activity of protein kinases (“PKs”). The compounds of this invention are therefore useful in treating disorders related to abnormal PK activity. Pharmaceutical compositions comprising these compounds, methods of treating diseases utilizing pharmaceutical compositions comprising these compounds and methods of preparing them are also disclosed.
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- NOVEL FUSED TRIAZOLONES AND THE USES THEREOF
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This invention relates to novel compounds having the structural diagram (I) and to their pharmaceutical compositions and to their methods of use. These novel compounds provide a treatment or prophylaxis of cancer.
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Page 101-102
(2010/02/08)
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- AMINOHETEROARYL COMPOUNDS AS PROTEIN KINASE INHIBITORS
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Aminopyridine and aminopyrazine compounds of formula (1), compositions including these compounds, and methods of their use are provided. Preferred compounds of formula 1 have activity as protein kinase inhibitors, including as inhibitors of c-MET.
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-
- Use of 8-amino-aryl-substituted imidazopyrazines as kinase inhbitors
-
The present invention relates to 8-amino-aryl-substituted imidazopyrazines which modulate the activity of protein kinases (“PKs”). The compounds of this invention are therefore useful in treating disorders related to abnormal PK activity. Pharmaceutical compositions comprising these compounds, methods of treating diseases utilizing pharmaceutical compositions comprising these compounds and methods of preparing them are also disclosed.
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-
- Antiinflammation agents
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Compounds, compositions and methods that are useful in the treatment of inflammatory, immunoregulatory, metabolic, infectious and cell proliferative diseases or conditions are provided herein. In particular, the invention provides compounds which modulate the expression and/or function of proteins involved in inflammation, metabolism, infection and cell proliferation. The subject compounds contain a fused heterobicyclic ring.
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Page/Page column 47-48
(2010/02/06)
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