- Synthesis and Biopharmaceutical Evaluation of Imatinib Analogues Featuring Unusual Structural Motifs
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A convenient synthesis of imatinib, a potent inhibitor of ABL1 kinase and widely prescribed drug for the treatment of a variety of leukemias, was devised and applied to the construction of a series of novel imatinib analogues featuring a number of non-aromatic structural motifs in place of the parent molecule's phenyl moiety. These analogues were subsequently evaluated for their biopharmaceutical properties (e.g., ABL1 kinase inhibitory activity, cytotoxicity). The bicyclo[1.1.1]pentane- and cubane-containing analogues were found to possess higher themodynamic solubility, whereas cubane- and cyclohexyl-containing analogues exhibited the highest inhibitory activity against ABL1 kinase and the most potent cytotoxicity values against cancer cell lines K562 and SUP-B15. Molecular modeling was employed to rationalize the weak activity of the compounds against ABL1 kinase, and it is likely that the observed cytotoxicity of these agents arises through off-target effects.
- Nicolaou, Kyriacos C.,Vourloumis, Dionisios,Totokotsopoulos, Sotirios,Papakyriakou, Athanasios,Karsunky, Holger,Fernando, Hanan,Gavrilyuk, Julia,Webb, Damien,Stepan, Antonia F.
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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 00803; 0028-0030
(2021/06/26)
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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 00512; 00535-00537
(2021/06/26)
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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 00146; 00147-00148
(2021/08/13)
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- CHEMICAL COMPOUNDS
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The present invention describes novel compounds, or their pharmaceutically acceptable salts, pharmaceutical compositions containing them, and their medical uses. The compounds of the invention have activity as Janus kinase (JAK) inhibitors and are useful in the in the treatment or control of inflammation, auto-immune diseases, cancer, and other disorders and indications where modulation of JAK would be desirable. Also described herein are methods of treating inflammation, auto-immune diseases, cancer, and other conditions susceptible to inhibition of JAK by administering a compound herein described.
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Paragraph 0187-0188; 0316-0318
(2020/12/01)
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- NON-LYSOSOMAL GLUCOSYLCERAMIDASE INHIBITORS AND USES THEREOF
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The invention provides compounds for inhibiting glucosylceramidases, prodrugs of the compounds, and pharmaceutical compositions including the compounds or prodrugs of the compounds.
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Paragraph 00167
(2020/12/01)
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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. The compounds include an IRAK binding moiety capable of binding to IRAK4 and a degradation inducing moiety (DIM). The DIM could be DTM a ligase binding moiety (LBM) or lysine mimetic. The compounds could be useful as IRAK protein kinase inhibitors and applied to IRAK mediated disorders.
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Paragraph 00920; 002259-002261
(2021/01/23)
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- Antibody drug conjugate, intermediate, preparation method, pharmaceutical composition and uses thereof
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Disclosed are an antibody drug conjugate IB, which uses ether linkages for connection, and improves the water solubility, stability and cytotoxicity in vivo and in intro, and an intermediate, a pharmaceutical composition, and uses of the antibody drug conjugate. The antibody drug conjugate has simple synthetic steps and a high yield.
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Page/Page column 121; 123
(2019/11/11)
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- HETEROARYLDIHYDROPYRIMIDINE DERIVATIVES AND METHODS OF TREATING HEPATITIS B INFECTIONS
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Provided herein are compounds useful for the treatment of HBV infection in a subject in need thereof, pharmaceutical compositions thereof, and methods of inhibiting, suppressing, or preventing HBV infection in the subject.
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Page/Page column 107; 108
(2019/01/17)
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- ANTIFIBRINOLYTIC COMPOUNDS
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The present invention provides novel antifibrinilytic compounds, processes for their preparation, pharmaceutical and veterinary compositions thereof, and their use in medicine, in particular for the treatment of bleeding.
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Page/Page column 26
(2016/07/11)
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- Hydroxypurine compound and use thereof
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The invention discloses a hydroxypurine compound and a use of the hydroxypurine compound as a PDE2 or TNFa inhibitor and concretely discloses a compound shown in the formula (I) and its tautomer or pharmaceutically acceptable salt.
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Paragraph 0394; 0395; 0396; 0397
(2016/10/08)
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- Cyclohexyl-4H,6H-5-oxa-2,3,10b-triaza-benzo[e]azulenes as V1a antagonists
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The present invention provides 4H,6H-5-oxa-2,3,10b-triaza-benzo[e]azulenes, which act as V1a receptor modulators, and in particular as V1a receptor antagonists, their manufacture, pharmaceutical compositions containing them and their use as medicaments. The active compounds of the present invention are useful as therapeutics acting peripherally and centrally in the conditions of dysmenorrhea, male or female sexual dysfunction, hypertension, chronic heart failure, inappropriate secretion of vasopressin, liver cirrhosis, nephrotic syndrome, anxiety, depressive disorders, obsessive compulsive disorder, autistic spectrum disorders, schizophrenia, and aggressive behavior.
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Paragraph 0166
(2014/08/19)
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- A NEW CLASS OF DIAZEPINE DERIVATIVE CHELATING AGENTS AND COMPLEXES WITH PARAMAGNETIC METALS THEREOF AS MRI CONTRAST AGENTS
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The present invention relates to a new class of diazepine-derivatives as chel ating agents for paramag netic metal ions, the process for their preparation, and use of such paramagnetic complexes as contrast agents, particularly suitable for Magnetic Resonance Imaging (MRI) analysis.
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Page/Page column 39; 40
(2013/09/26)
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- A new class of diazepine derivative chelating agents and complexes with paramagnetic metals as MRI contrast agents
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The present invention relates to a new class of diazepine-derivatives as chelating agents for paramagnetic metal ions, the process for their preparation, and use of such paramagnetic complexes as contrast agents, particularly suitable for Magnetic Resonance Imaging (MRI) analysis.
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Paragraph 0101; 0102
(2013/09/26)
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- SUBSTITUTED DIAZINE AND TRIAZINE SPLEEN TYROSINE KINASE (Syk) INHIBITORS
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The invention provides certain substituted diazine and triazine compounds of the Formula (I) (I) or pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, Rcy,Cy, and t are as d
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Paragraph 00215
(2014/01/09)
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- ORGANIC COMPOUNDS
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The present invention provides a compound of formula (I): wherein the variants R1, R2, R3, R4, R5, 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 73
(2009/05/28)
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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 55
(2010/11/26)
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