- PROCESS FOR THE MANUFACTURE OF 1,4-DISUBSTITUTED PYRIDAZINE COMPOUNDS
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The invention relates to a novel process, novel process step(s) and novel intermediate(s) useful for the preparation of 1,4-disubstituted pyridazine compounds, such as 5-(1 H-Pyrazol-4-yl)-2-(6- ((2,2,6,6-tetramethylpiperidin-4-yl)oxy)pyridazin-3-yl)phenol.
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Page/Page column 62-63
(2022/01/05)
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- 1,5,7-TRISUBSTITUTED ISOQUINOLINE DERIVATIVES, PREPARATION THEREOF, AND USE THEREOF IN MEDICINES
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The present disclosure relates to 1,5,7-trisubstituted isoquinoline derivatives, their preparation and pharmaceutical use. In particular, the present disclosure discloses a compound of formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate or prodrug thereof, and a preparation method and use thereof. The definitions of the groups in the formula can be found in the specification and claims.
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Paragraph 0230; 0232; 0234
(2020/08/30)
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- Discovery and Optimization of Glucose Uptake Inhibitors
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Aerobic glycolysis, originally identified by Warburg as a hallmark of cancer, has recently been implicated in immune cell activation and growth. Glucose, the starting material for glycolysis, is transported through the cellular membrane by a family of glucose transporters (GLUTs). Therefore, targeting glucose transporters to regulate aerobic glycolysis is an attractive approach to identify potential therapeutic agents for cancers and autoimmune diseases. Herein, we describe the discovery and optimization of a class of potent, orally bioavailable inhibitors of glucose transporters, targeting both GLUT1 and GLUT3.
- Liu, Kevin G.,Kim, Ji-In,Olszewski, Kellen,Barsotti, Anthony M.,Morris, Koi,Lamarque, Christophe,Yu, Xuemei,Gaffney, Jack,Feng, Xiao-Jiang,Patel, Jeegar P.,Poyurovsky, Masha V.
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supporting information
p. 5201 - 5211
(2020/07/10)
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- TRICYCLIC DEGRADERS OF IKAROS AND AIOLOS
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Tricyclic cereblon binders for the degradation of Ikaros or Aiolos by the ubiquitin proteasome pathway for therapeutic applications are described.
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Page/Page column 449
(2020/10/21)
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- 3-(1H-PYRAZOL-4-YL)PYRIDINE ALLOSTERIC MODULATORS OF THE M4 MUSCARINIC ACETYLCHOLINE RECEPTOR
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The present invention is directed to pyrazol-4-yl-pyridine compounds which are allosteric modulators of the M4 muscarinic acetylcholine receptor. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which M4 muscarinic acetylcholine receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which M4 muscarinic acetylcholine receptors are involved.
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- TREATMENT OF INFLAMMATORY CONDITIONS AND AUTOIMMUNE DISEASES WITH GLUCOSE UPTAKE INHIBITORS
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This invention provides methods of treating inflammatory conditions and autoimmune diseases in a mammal, comprising administering to the mammalian subject in need thereof a therapeutically effective amount of a compound, or pro-drug thereof, or pharmaceutically acceptable salt or ester of said compound or pro-drug, wherein the compound is an inhibitor of glucose uptake. In particular aspects, the present invention provides a method of treating inflammatory conditions and autoimmune diseases in a mammal, and preferably a human, in which the glucose uptake inhibitor modulates the glucose transport of GLUTl and GLUT3.
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Paragraph 0125; 0126
(2018/11/22)
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- AZOLE-SUBSTITUTED PYRIDINE COMPOUND
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The present invention provides a compound represented by formula [I'| shown below or a pharmaceutically acceptable salt thereof that has an inhibitory effect on 20-HETE producing enzyme, wherein the structure represented by formula [III] shown below represents any of the structures represented by formula group [IV] shown below, wherein R1 represents a hydrogen atom, a fluorine atom, methyl, etc.; R2, R3, and R4 each independently represent a hydrogen atom, a fluorine atom, or methyl; W represents a single bond, C1-3alkanediyl, or the formula -O-CH2CH2-; and ring A represents (a) substituted C4-6cycloalkyl, (b) substituted 4- to 6-membered saturated nitrogen-containing heterocyclyl, (c) substituted phenyl, (d) substituted pyridyl, (e) substituted 2,3-dihydrobenzofuran, (f) 4- to 6-membered saturated oxygen-containing heterocyclyl, etc.
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Paragraph 0733; 0734
(2019/01/08)
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- PYRROLOPYRIDINE RETINOIC ACID RECEPTOR-RELATED ORPHAN RECEPTOR MODULATORS AND USES THEREOF
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Provided herein are compounds of the formula (I): as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of Retinoic Acid Receptor-Related Orphan Receptor regulated diseases and disorders.
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Paragraph 0082; 0084
(2017/11/06)
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- 2,4-DISUBSTITUTED PHENYLENE-1,5-DIAMINE DERIVATIVES AND APPLICATIONS THEREOF, AND PHARMACEUTICAL COMPOSITIONS AND PHARMACEUTICALLY ACCEPTABLE COMPOSITIONS PREPARED THEREFROM
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The present invention provides a class of 2,4-substituted phenylene-1,5-diamine derivatives, having an inhibiting effect on EGFR tyrosine kinases, and pharmaceutically acceptable salt, stereoisomer, solvate or prodrug of said derivatives. See the description for the definition of each group in the formula. In addition, the present invention also discloses pharmaceutical compositions, pharmaceutically acceptable compositions and applications thereof.
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Paragraph 0328; 0329
(2017/01/31)
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- INDAZOLE RETINOIC ACID RECEPTOR-RELATED ORPHAN RECEPTOR MODULATORS AND USES THEREOF
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Provided herein are compounds of the formulas (I) and (II): as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of Retinoic Acid Receptor-Related Orphan Receptor regulated diseases and disorders.
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Paragraph 109
(2016/02/09)
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- AZAINDOLE RETINOIC ACID RECEPTOR-RELATED ORPHAN RECEPTOR MODULATORS AND USES THEREOF
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Provided herein are compounds of the formulas (I) and (II), as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of Retinoic Acid Receptor-Related Orphan Receptor regulated diseases and disorders.
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Paragraph 109
(2016/02/18)
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- BENZIMIDAZOLE RETINOIC ACID RECEPTOR-RELATED ORPHAN RECEPTOR MODULATORS AND USES THEREOF
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Provided herein are compounds of the formulas (I) and (II): as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of Retinoic Acid Receptor-Related Orphan Receptor regulated diseases and disorders.
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Paragraph 107
(2016/02/12)
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- SULFONAMIDE RETINOIC ACID RECEPTOR-RELATED ORPHAN RECEPTOR MODULATORS AND USES THEREOF
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Provided herein are compounds of the formula (I): as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of Retinoic Acid Receptor-Related Orphan Receptor regulated diseases and disorders.
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Paragraph 0201
(2016/02/16)
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- TREATMENT OF INFECTIOUS DISEASES WITH GLUCOSE UPTAKE INHIBITORS
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Provided are methods of treating infectious diseases in mammals comprising administering a compound that inhibits glucose uptake. Particular infectious diseases that may be treated include malaria, leishmaniasis, African trypanosomiasis, tuberculosis, HIV, HCMV or herpes virus. In a first aspect, the invention features a method of treating infectious diseases in a mammal, comprising administering to a mammalian subject in need thereof a therapeutically effective amount of a compound or prodrug thereof, or pharmaceutically acceptable salt or ester of said compound or prodrug, wherein the compound is an inhibitor of glucose uptake.
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Paragraph 0225; 0226
(2017/01/09)
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- GLUCOSE UPTAKE INHIBITORS
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Provided hererin are compounds that modulate glucose uptake activityand are useful for treating cancer, autoimmune diseases, inflammation, infectious diseases, and metabolic diseases. In certain embodiments, the compounds modulate glucose uptake activity by modulating cellular components, including, but not limited to those related to glycolysis and known transporters/co-transporters of glucose such as GLUT1 and other GLUT family members/alternative hexose transporters. In certain embodiments, the compounds have the structure of formula I: Formula (I) wherein the variables have the values disclosed herein.
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Paragraph 0405-0406
(2017/01/09)
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- Cell Penetrant Inhibitors of the KDM4 and KDM5 Families of Histone Lysine Demethylases. 2. Pyrido[3,4-d]pyrimidin-4(3H)-one Derivatives
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Following the discovery of cell penetrant pyridine-4-carboxylate inhibitors of the KDM4 (JMJD2) and KDM5 (JARID1) families of histone lysine demethylases (e.g., 1), further optimization led to the identification of non-carboxylate inhibitors derived from pyrido[3,4-d]pyrimidin-4(3H)-one. A number of exemplars such as compound 41 possess interesting activity profiles in KDM4C and KDM5C biochemical and target-specific, cellular mechanistic assays.
- Westaway, Susan M.,Preston, Alex G. S.,Barker, Michael D.,Brown, Fiona,Brown, Jack A.,Campbell, Matthew,Chung, Chun-Wa,Drewes, Gerard,Eagle, Robert,Garton, Neil,Gordon, Laurie,Haslam, Carl,Hayhow, Thomas G.,Humphreys, Philip G.,Joberty, Gerard,Katso, Roy,Kruidenier, Laurens,Leveridge, Melanie,Pemberton, Michelle,Rioja, Inma,Seal, Gail A.,Shipley, Tracy,Singh, Onkar,Suckling, Colin J.,Taylor, Joanna,Thomas, Pamela,Wilson, David M.,Lee, Kevin,Prinjha, Rab K.
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p. 1370 - 1387
(2016/03/05)
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- RETINOIC ACID RECEPTOR-RELATED ORPHAN RECEPTOR MODULATORS AND USES THEREOF
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Provided herein are compounds of the formula (I): as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of Retinoic Acid Receptor-Related Orphan Receptor regulated diseases and disorders.
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Paragraph 0165; 0167
(2015/09/28)
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- RETINOIC ACID RECEPTOR-RELATED ORPHAN RECEPTOR MODULATORS AND USES THEREOF
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Provided herein are compounds of the formula (I): as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of Retinoic Acid Receptor-Related Orphan Receptor regulated diseases and disorders.
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Paragraph 0207; 0209
(2015/09/28)
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- SUBSTITUTED PYRIDOPYRAZINES AS SYK INHIBITORS
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The present invention relates to pyridopyrazine compounds of formula (I), pharmaceutical compositions thereof and methods of use therefore, wherein R1, R2, R3, L, m, p and W are as defined in the specification.
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Page/Page column 43
(2014/06/24)
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- NOVEL 4-(SUBSTITUTED-AMINO)-7H-PYRROLO[2,3-d]PYRIMIDINES AS LRRK2 INHIBITORS
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The present invention provides novel 4,5-disubstituted-7H-pyrrolo[2,3- c/]pyrimidine derivatives of Formula I, and the pharmaceutically acceptable salts thereof wherein R1, R2, R3, R4 and R5 are as defined in the specification. The invention is also directed to pharmaceutical compositions comprising the compounds of formula I and to use of the compounds in the treatment of diseases associated with LRRK2, such as neurodegenerative diseases including Parkinson's disease or Alzheimer's disease, cancer, Crohn's disease or leprosy.
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Page/Page column 60; 61; 62
(2014/01/17)
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- HETEROCYCLIC AMIDES AS ITK INHIBITORS
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The present invention is directed to heterocyclic amide compounds of formula (I) as Tec kinase inhibitors, in particular ITK (interleukin-2 inducible tyrosine kinase) inhibitors. Also provided herein are processes for preparing compounds described herein,
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Page/Page column 72
(2014/03/21)
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- 1,2-DISUBSTITUTED-4-BENZYLAMINO-PYRROLIDINE DERIVATIVES AS CETP INHIBITORS USEFUL FOR THE TREATMENT OF DISEASES SUCH AS HYPERLI PIDEMIA OR ARTERIOSCLEROSIS
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The present invention provides a compound of formula (I): wherein the variants R1, R2, R3, R4, R6, R7 are as defined herein, and wherein said compound is an inhibitor of CETP, and thus can be employed for the treatment of a disorder or disease mediated by CETP or responsive to the inhibition of CETP.
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Page/Page column 80-81
(2009/07/17)
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