- Compound serving as protein kinase inhibitor and application of compound
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The invention discloses a compound used as a protein kinase inhibitor and application of the compound, the compound has an obvious inhibition effect on protein kinase activity, can be used as a BTK inhibitor for preparing medicines for treating BTK-mediated diseases such as malignant tumors, autoimmune diseases and the like, and has wide application prospect.
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- IRAK DEGRADERS AND USES THEREOF
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The present invention provides compounds, compositions thereof, and methods of using the same.
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Paragraph 00962; 005054-005056
(2020/06/19)
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- Generation of highly potent DYRK1A-dependent inducers of human β-Cell replication via Multi-Dimensional compound optimization
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Small molecule stimulation of β-cell regeneration has emerged as a promising therapeutic strategy for diabetes. Although chemical inhibition of dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) is sufficient to enhance β-cell replicat
- Allegretti, Paul A.,Horton, Timothy M.,Abdolazimi, Yassan,Moeller, Hannah P.,Yeh, Benjamin,Caffet, Matthew,Michel, Guillermina,Smith, Mark,Annes, Justin P.
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supporting information
(2019/12/09)
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- Copper-Catalyzed and Indium-Mediated Methoxycarbonylation of Unactivated Alkyl Iodides with Balloon CO
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This work emphasizes the synthesis of alkyl esters via Cu-catalyzed and In-mediated alkoxycarbonylation of unactivated alkyl iodides in the presence of In or InI. The reactions were suitable for the preparation of primary, secondary, and even tertiary alkyl esters, representing an exceptionally rare example for the creation of quaternary carbon centers upon formation of esters. The preliminary mechanistic studies indicated that alkyl radicals were involved, and Cu/In/CO played a cooperative role in the carbonylation event.
- Chen, Yanchi,Su, Lei,Gong, Hegui
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supporting information
p. 4689 - 4693
(2019/06/27)
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- D2 Dopamine Receptor G Protein-Biased Partial Agonists Based on Cariprazine
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Functionally selective G protein-coupled receptor ligands are valuable tools for deciphering the roles of downstream signaling pathways that potentially contribute to therapeutic effects versus side effects. Recently, we discovered both Gi/o-bi
- Shen, Yudao,McCorvy, John D.,Martini, Michael L.,Rodriguiz, Ramona M.,Pogorelov, Vladimir M.,Ward, Karen M.,Wetsel, William C.,Liu, Jing,Roth, Bryan L.,Jin, Jian
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p. 4755 - 4771
(2019/05/08)
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- IRAK DEGRADERS AND USES THEREOF
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The present invention provides compounds, compositions thereof, and methods of using the same.
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Paragraph 1990; 1991
(2019/07/10)
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- NOVEL JAK1 SELECTIVE INHIBITORS AND USES THEREOF
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The new 1H-furo[3,2-b]imidazo[4,5-d]pyridine derivatives are selective Jak1 kinase inhibitors useful in treating disorders related to Jak1 activities such as autoimmune diseases or disorders, inflammatory diseases or disorders, and cancer or neoplastic di
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Page/Page column 44; 45
(2018/04/21)
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- 1,3 DI-SUBSTITUTED CYCLOBUTANE OR AZETIDINE DERIVATIVES AS HEMATOPOIETIC PROSTAGLANDIN D SYNTHASE INHIBITORS
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A compound of formula (I), wherein R, R1, R2, R3, Y, Y1, a, X, and Z are as defined herein. The compounds of the present invention are inhibitors of hematopoietic prostaglandin D synthase (H-PGDS) and can be useful in the treatment of Duchenne Muscular Dystrophy. 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 H-PGDS 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 121
(2018/04/27)
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- Prescreening of Nicotine Hapten Linkers in Vitro To Select Hapten-Conjugate Vaccine Candidates for Pharmacokinetic Evaluation in Vivo
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Since the demonstration of nicotine vaccines as a possible therapeutic intervention for the effects of tobacco smoke, extensive effort has been made to enhance nicotine specific immunity. Linker modifications of nicotine haptens have been a focal point for improving the immunogenicity of nicotine, in which the evaluation of these modifications usually relies on in vivo animal models, such as mice, rats or nonhuman primates. Here, we present two in vitro screening strategies to estimate and predict the immunogenic potential of our newly designed nicotine haptens. One utilizes a competition enzyme-linked immunoabsorbent assay (ELISA) to profile the interactions of nicotine haptens or hapten-protein conjugates with nicotine specific antibodies, both polyclonal and monoclonal. Another relies on computational modeling of the interactions between haptens and amino acid residues near the conjugation site of the carrier protein to infer linker-carrier protein conjugation effect on antinicotine antibody response. Using these two in vitro methods, we ranked the haptens with different linkers for their potential as viable vaccine candidates. The ELISA-based hapten ranking was in an agreement with the results obtained by in vivo nicotine pharmacokinetic analysis. A correlation was found between the average binding affinity (IC50) of the haptens to an anti-Nic monoclonal antibody and the average brain nicotine concentration in the immunized mice. The computational modeling of hapten and carrier protein interactions helps exclude conjugates with strong linker-carrier conjugation effects and low in vivo efficacy. The simplicity of these in vitro screening strategies should facilitate the selection and development of more effective nicotine conjugate vaccines. In addition, these data highlight a previously under-appreciated contribution of linkers and hapten-protein conjugations to conjugate vaccine immunogenicity by virtue of their inclusion in the epitope that binds and activates B cells.
- Arutla, Viswanath,Leal, Joseph,Liu, Xiaowei,Sokalingam, Sriram,Raleigh, Michael,Adaralegbe, Adejimi,Liu, Li,Pentel, Paul R.,Hecht, Sidney M.,Chang, Yung
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supporting information
p. 286 - 298
(2017/05/15)
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- ATX MODULATING AGENTS
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Compounds of formula (I) can modulate the activity of autotaxin (ATX).
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Page/Page column 139
(2015/12/24)
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- CYCLOHEXYL AMIDE DERIVATIVES AS CRF RECEPTOR ANTAGONISTS
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There are described cydohexyl amide derivatives useful as corticotropin releasing factor (CRF) receptor antagonists
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Page/Page column 99
(2016/02/02)
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- AMINE-DERIVATIVES HAVING NPY Y5 RECEPTOR ANTAGONISTIC ACTIVITY AND THE USES THEREOF
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This invention provides an anorectic or anti-obesity composition comprising a compound of the formula (I): formula (I): a pharmaceutically acceptable salt or solvate thereof, wherein R1 is optionally substituted lower alkyl,Y is —S(O)n- wherein n is 1 or 2, or —CO—,R2 is hydrogen or lower alkyl, R7 is hydrogen or lower alkyl,X is lower alkylene, lower alkenylene, arylene, cycloalkylene or the like, andZ is lower alkyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl or the like.
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Page/Page column 21
(2010/12/26)
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- AMINE DERIVATIVE HAVING NPY Y5 RECEPTOR ANTAGONIST ACTIVITY
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This invention provides a compound of the formula (I): a pharmaceutically acceptable salt or solvate thereof, wherein R1 is optionally substituted lower alkyl, Y is -S(O)n- wherein n is 1 or 2, or -CO-, R2 is hydrogen or lower alkyl,
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Page/Page column 30
(2009/02/10)
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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 56
(2010/11/26)
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- FUSED FURAN COMPOUND
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The present invention provides a condensed furan compound of the formula (I): wherein Ring X is benzene, pyridine, or the like; Y is an optionally substituted amino, an optionally substituted cycloalkyl, an optionally substituted aryl, an optionally substituted saturated heterocyclic group, an optionally substituted unsaturated heterocyclic group; A is a single bond, lower alkylene, lower alkenylidene, lower alkenylene or an oxygen atom; R3 is hydrogen or the like; and , R4 is hydrogen, or the like, or pharmaceutically acceptable salts thereof, which is useful as a medicament, particularly, as an activated blood coagulation factor X inhibitor.
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Page/Page column 116-117
(2008/06/13)
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- Oxidosqualene cyclase (OSC) inhibitors for the treatment of dyslipidemia
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Novel inhibitors of oxidosqualene cyclase (OSC) for the treatment of dyslipidemia are reported. Starting point for the chemistry program was a set of compounds derived from a fungicide project which, in addition to high affinity for OSC from Candida albicans, also showed high affinity for the human enzyme (hOSC). Here the evaluation process of different scaffolds is outlined for two representative series, the phenyl substituted benzo[d]isothiazoles and the aminocyclohexanes. The most promising compounds derived from the latter series were further profiled in vivo and showed promising properties with respect to modulation of lipid parameters. Schweizerische Chemische Gesellschaft.
- Dehmlow, Henrietta,Ackermann, Jean,Aebi, Johannes,Blum-Kaelin, Denise,Chucholowski, Alexander,Coassolo, Philippe,Hartman, Peter,Kansy, Manfred,Maerki, Hans Peter,Morand, Olivier,Von Der Mark, Elisabeth,Panday, Narendra,Ruf, Armin,Thoma, Ralf,Schulz-Gasch, Tanja
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