528882-16-8Relevant academic research and scientific papers
FUSED PYRIMIDINE COMPOUNDS, COMPOSITIONS AND MEDICINAL APPLICATIONS THEREOF
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, (2021/04/02)
The present disclosure relates to a class of fused pyrimidine compounds of Formula I, their stereoisomers, tautomers, pharmaceutically acceptable salts, polymorphs, solvates, and hydrates thereof. The present disclosure also relates to a process of preparation of these fused pyrimidine compounds, and to pharmaceutical compositions containing them.
N-alkyl-hydroxybenzoyl anilide hydroxamates as dual inhibitors of HDAC and HSP90, downregulating IFN-γ induced PD-L1 expression
Mehndiratta, Samir,Lin, Mei-Hsiang,Wu, Yi-Wen,Chen, Chun-Han,Wu, Tung-Yun,Chuang, Kuo-Hsiang,Chao, Min-Wu,Chen, Yi-Ying,Pan, Shiow-Lin,Chen, Mei-Chuan,Liou, Jing-Ping
, (2019/10/28)
Novel dual inhibitors of histone deacetylase (HDAC) and heat-shock protein 90 (HSP90) are synthesized and evaluated. These compounds are endowed with potent HDAC and HSP90 inhibitory activities with IC50 values in nanomolar range with Compound 20 (HDAC IC50 = 194 nM; HSP90α IC50 = 153 nM) and compound 26 (HDAC IC50 = 360 nM; HSP90α IC50 = 77 nM) displaying most potent HDAC and HSP90α inhibitory activities. Both of these compounds induce HSP70 expression and down regulate HSP90 client proteins which play important roles in the regulation of survival and invasiveness in cancer cells. In addition, compounds 20 and 26 induce acetylation of α-tubulin and histone H3. Significantly, compounds 20 and 26 could effectively reduce programmed death-ligand 1 (PD-L1) expression in IFN-γ treated lung H1975 cells in a dose dependent manner. These findings suggest that dual inhibition of HDAC and HSP90 that can modulate immunosuppressive ability of tumor area may provide a better therapeutic strategy for cancer treatment in the future.
COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF INTERLEUKIN-1 RECEPTOR-ASSOCIATED KINASE 4 POLYPEPTIDES
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, (2019/06/07)
The present disclosure relates to bifunctional compounds, which find utility as modulators of Interleukin-1 Receptor-Associated Kinase 4 (IRAK-4); the target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hppel-Lindau, cereblon, ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.
BENZODIAZEPINE DERIVATIVES AS CCK2/GASTRIN RECEPTOR ANTAGONISTS
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, (2016/03/26)
The invention relates to benzodiazepine derivatives of formula (A) useful as CCK2/gastrin receptor antagonists, their preparation and their use in the treatment or prevention of disorders associated with CCK2/gastrin receptors, disorders caused by or associated with hypergastrinaemia, and gastric acid-related disorders.
HETEROARYL COMPOUNDS AND USES THEREOF
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, (2015/07/02)
The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.
HETEROARYL COMPOUNDS AND USES THEREOF
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, (2014/07/08)
The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.
PURINONE COMPOUNDS AS KINASE INHIBITORS
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, (2013/08/14)
Disclosed herein are compounds that form covalent bonds with Bruton's tyrosine kinase (Btk). Also described are irreversible inhibitors of Btk. In addition, reversible inhibitors of Btk are also described. Also disclosed are pharmaceutical compositions th
HETEROCYCLIC COMPOUND AND USE THEREOF
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, (2011/10/12)
A compound represented by formula (I) or a salt thereof, which has a potent Raf inhibitory activity. In formula (I), R1 represents an optionally substituted C1-6 alkyl, etc.; X represents —O— or —NR2— (wherein R2 represents a hydrogen atom or a C1-6 alkyl); Y represents a group represented by formula 2 (2ii or 2ii) (wherein ring A represents an optionally substituted benzene ring; Z represents a group represented by (1) —NR3CO—W1—, (2) —NR3CO—W1—O—, (3) —NR3CO—W1—O—W2—, (4) —NR3CO—W1—S—, (5) —NR3CO—W1—NR4—, (6) —NR3COO—, (7) —NR3COO—W1—, (8) —NR3CO—CO—, or (9) —NR3CONR4— (wherein R3 and R4 each represents a hydrogen atom, etc., and W1 and W2 each represents an optionally substituted C1-6 alkylene, etc.); and R5 represents an optionally substituted five- or six-membered ring group.
Novel, achiral 1,3,4-benzotriazepine analogues of 1,4-benzodiazepine-based CCK2 antagonists that display high selectivity over CCK1 receptors
McDonald, Iain M.,Austin, Carol,Buck, Ildiko M.,Dunstone, David J.,Griffin, Eric,Harper, Elaine A.,Hull, Robert A. D.,Kalindjian, S. Barret,Linney, Ian D.,Low, Caroline M. R.,Pether, Michael J.,Spencer, John,Wright, Paul T.,Adatia, Trushar,Bashall, Alan
, p. 2253 - 2261 (2007/10/03)
A series of 1,3,4-benzotriazepine-based CCK2 antagonists have been devised by consideration of the structural features that govern CCK receptor affinity and the receptor subtype selectivity of 1,4-benzodiazepine- based CCK2 antagonists. In contrast to the latter compounds, these novel 1,3,4-benzotriazepines are achiral, yet they display similar affinity for CCK2 receptors to the earlier molecules and are highly selective over CCK1 receptors.
1, 3, 4-BENZOTRIAZEPIN-2-ONE SALTS AND THEIR USE AS CCK RECEPTOR LIGANDS
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Page 26, (2008/06/13)
This invention relates to pharmaceutically acceptable salts of compounds of formula (I) wherein: W is N or N+-O-; R2 is an optionally substituted C1 to C18 hydrocarbyl group wherein up to three C atoms may optionally be replaced by N, O and/or S atoms. R3 is -(CR11R12)m-X-(CR13R14)p-R9; m is 0, 1, 2, 3 or 4; p is 0, 1 or 2; X is a bond, -CR15=CR16-, -C≡C-, C(O)NH, NHC(O), C(O)NMe, NMeC(O), C(O)O, NHC(O)NH, NHC(O)O, OC(O)NH, NH, O, CO, SO2, SO2NH, C(O)NHNH, R9 is H ; C1 to C6 alkyl ; or phenyl, naphthyl, pyridyl, benzimidazolyl, indazolyl, quinolinyl, isoquinolinyl, tetrahydroisoquinolinyl, indolinyl, isoindolinyl, indolyl, isoindolyl or 2-pyridonyl substituted with -L-Q. R4 is an optionally substituted C1 to C18 hydrocarbyl group wherein up to three C atoms may optionally be replaced by N, O and/or S atoms ; and Such salts are useful, for example, for the treatment of gastrin related disorders.
