- Pyrazolopyridine compound and preparation method thereof
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The embodiment of the invention discloses a pyrazolopyridine compound and a preparation method thereof. The preparation method includes the steps of: taking 2-chloro-4-amino-3-methylpyridine as the raw materials to prepare a compound shown as formula (III). The preparation method takes 2-chloro-4-amino-3-methylpyridine as the raw materials to prepare 4-chloro-1H-pyrazolo[4, 3-c]pyridine, has the advantages of cheap and easily available raw materials, high reaction activity, mild reaction conditions, simple separation and purification method, high product purity, etc., and can be well applied to industrial production.
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- KINASE INHIBITORS AND METHODS OF USE
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The present invention provides chemical entities or compounds and pharmaceutical compositions thereof that are capable of modulating lipid kinases such PB kinases, tryosine kinases and protein kinases such as mTOR. Also provided in the present invention are methods of using these compositions to modulate these kinases especially for therapeutic applications.
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Paragraph 0257; 0258
(2018/07/06)
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- Identification of an imidazopyridine scaffold to generate potent and selective TYK2 inhibitors that demonstrate activity in an in vivo psoriasis model
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Herein we report identification of an imidazopyridine class of potent and selective TYK2 inhibitors, exemplified by prototype 6, through constraint of the rotatable amide bond connecting the pyridine and aryl rings of compound 1. Further optimization led to generation of compound 30 that potently inhibits the TYK2 enzyme and the IL-23 pathway in cells, exhibits selectivity against cellular JAK2 activity, and has good pharmacokinetic properties. In mice, compound 30 demonstrated dose-dependent reduction of IL-17 production in a PK/PD model as well as in an imiquimod-induced psoriasis model. In this efficacy model, the IL-17 decrease was accompanied by a reduction of ear thickness indicating the potential of TYK2 inhibition as a therapeutic approach for psoriasis patients.
- Liang, Jun,Van Abbema, Anne,Balazs, Mercedesz,Barrett, Kathy,Berezhkovsky, Leo,Blair, Wade S.,Chang, Christine,Delarosa, Donnie,DeVoss, Jason,Driscoll, Jim,Eigenbrot, Charles,Goodacre, Simon,Ghilardi, Nico,MacLeod, Calum,Johnson, Adam,Bir Kohli, Pawan,Lai, Yingjie,Lin, Zhonghua,Mantik, Priscilla,Menghrajani, Kapil,Nguyen, Hieu,Peng, Ivan,Sambrone, Amy,Shia, Steven,Smith, Jan,Sohn, Sue,Tsui, Vickie,Ultsch, Mark,Williams, Karen,Wu, Lawren C.,Yang, Wenqian,Zhang, Birong,Magnuson, Steven
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p. 4370 - 4376
(2017/09/12)
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- NOVEL COMPOUNDS AS REARRANGED DURING TRANSFECTION (RET) INHIBITORS
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This invention relates to novel compounds which are inhibitors of the Rearranged during Transfection (RET) kinase, to pharmaceutical compositions containing them, to processes for their preparation, and to their use in therapy, alone or in combination, for the normalization of gastrointestinal sensitivity, motility and/or secretion and/or abdominal disorders or diseases and/or treatment related to diseases related to RET dysfunction or where modulation of RET activity may have therapeutic benefit including but not limited to all classifications of irritable bowel syndrome (IBS) including diarrhea-predominant, constipation-predominant or alternating stool pattern, functional bloating, functional constipation, functional diarrhea, unspecified functional bowel disorder, functional abdominal pain syndrome, chronic idiopathic constipation, functional esophageal disorders, functional gastroduodenal disorders, functional anorectal pain, inflammatory bowel disease, proliferative diseases such as non-small cell lung cancer, hepatocellular carcinoma, colorectal cancer, medullary thyroid cancer, follicular thyroid cancer, anaplastic thyroid cancer, papillary thyroid cancer, brain tumors, peritoneal cavity cancer, solid tumors, other lung cancer, head and neck cancer, gliomas, neuroblastomas, Von Hippel-Lindau Syndrome and kidney tumors, breast cancer, fallopian tube cancer, ovarian cancer, transitional cell cancer, prostate cancer, cancer of the esophagus and gastroesophageal junction, biliary cancer, adenocarcinoma, and any malignancy with increased RET kinase activity.
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Page/Page column 118
(2016/04/20)
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- HETEROCYCLIC COMPOUND
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The present invention provides a compound having a superior JAK inhibitory action, which is useful as an agent for the prophylaxis or treatment of autoimmune diseases (rheumatoid arthritis, psoriasis, inflammatory bowel disease, Sjogren's syndrome, Behcet's disease, multiple sclerosis, systemic lupus erythematosus, etc.), cancer (leukemia, uterine leiomyosarcoma, prostate cancer, multiple myeloma, cachexia, myelofibrosis, etc.) and the like, or a salt thereof. The present invention relates to a compound represented by the formula wherein each symbol is as defined in the specification, or a salt thereof.
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- HETEROCYCLIC COMPOUNDS AND METHODS OF USE
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The present application discloses compounds that are inhibitors of Btk, compounds that are inhibitors of ΡΒΚδ, and compounds that are dual inhibitors of both Btk and PI3Kδ. Also described are methods for synthesizing such inhibitors and methods for using such inhibitors for the treatment of diseases wherein inhibition of Btk and PI3Kδ provides a therapeutic benefit to a patient having the disease.
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- PYRAZOLOPYRIDINES AND PYRAZOLOPYRIDINES AND THEIR USE AS TYK2 INHIBITORS
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The invention provides compounds of Formula (I), stereoisomers or pharmaceutically acceptable salts thereof, wherein A, X, R1, R2, R4 and R5 are defined herein, a pharmaceutical composition that includes a compound of Formula (I) and a pharmaceutically acceptable carrier, adjuvant or vehicle, and methods of using the compound or composition in therapy, as TYK2 Kinase inhibitors.
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Page/Page column 77
(2012/06/01)
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- PYRAZOLOPYRIDINES AS INHIBITORS OF THE KINASE LRRK2
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The present invention relates to compounds of formula I, or pharmaceutically acceptable salts or esters thereof, (Formula I) wherein R1 is selected from: aryl; heteroaryl; -NHR3; fused aryl-C4-7 -heterocycloalkyl; -CONR4R5; - NHCOR6; -C3-7-cycloalkyl,-NR3R6; -OR3; OH; NR4R5; and alkyl optionally substituted with a substituent selected from R11 and a group A; wherein said aryl, heteroaryl, fused aryl-C4-7 -heterocycloalkyl and C4-7-heterocycloalkyi are each optionally substituted with one or more substituents selected from C1-6-alkyl, C3-7-cycloalkyl, heteroaryl, C4-7-heterocycloalkyl, aryl and a group A, and said C1-6- alkyl, C3-7-cycloalkyl, heteroaryl, C4-7-heterocycloalkyl, and aryl substituents are in turn each optionally substituted with one or more groups selected from R11 and a group A; R2 is selected from hydrogen, aryl, C1-6-alkyl, C2-6-alkenyl, C3-7-cycloalkyl, heteroaryl, heterocycloalkyi, fused aryl-C4-7-rheterocycloalkyl and halogen, wherein said C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, fused aryl-C4-7 -heterocycloalkyl and C4-7 -heterocycloalkyl are each optionally substituted with one or more substituents selected from R11 and A. Further aspects relate to pharmaceutical compositions and therapeutic uses of said compounds
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- COMPOUNDS
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A compound of formula (I), or a pharmaceutically acceptable salt or ester thereof, wherein R1 is selected from: aryl; heteroaryl; -NHR3; fused aryl-C4-7-heterocycloalkyI; -CONR4R5; -NHCOR6; -C3-7-cycloalkyl; -O-C3-7-cycloalkyl; -NR3R6; and optionally substituted -C1-6 alkyl; wherein said aryl, heteroaryl, fused aryl-C4-7-heterocycloalkyl and C4-7-heterocycloalkyl are each optionally substituted; R2 is selected from hydrogen, aryl, C1-6-alkyl, C2-6-alkenyl, C3-7-cycloalkyl, heteroaryl, C4-7 heterocycloalkyl and halogen, wherein said C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl and C4-7-heterocycloalkyl are each optionally substituted. Further aspects relate to pharmaceutical compositions, therapeutic uses and process for preparing compounds of formula (I).
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- NITROGENOUS FUSED BICYCLIC COMPOUND
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A novel nitrogenous fused bicyclic compound represented by the following general formula [1] or a pharmacologically acceptable salt of the compound. They have excellent SK channel blocking activity and are useful as a medicine. [I] (In the formula, R 0 represents hydrogen, halogeno, etc.; R 1 represents a group represented by the formula (a) or (b); A represents a group represented by the formula (X) or (Y); D 1 , D 2 and D 3 each represents N or CH; R 2 represents halogeno or optionally halogenated lower alkyl, etc.; R 3 represents hydrogen or lower alkyl; and Q represents lower alkylene.)
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Page/Page column 63
(2010/11/26)
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- PIPERAZINE AND PIPERIDINE DERIVATIVES AS ANTI-HIV-AGENTS
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This invention relates to a compound of formula (I) or pharmaceutically acceptable salts, solvates or derivatives thereof, wherein R1 to R5 are defined in the description, and to processes for the preparation thereof, intermediates used in their preparation, compositions containing them and the uses of such derivatives. The compounds of the present invention inhibit the interaction of gp120 with CD4 and are 10 therefore of use in the treatment of HIV, a retroviral infection genetically related to HIV, or AIDS.
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Page/Page column 52
(2008/06/13)
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