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A series of novel 4-[5-(substituted-1,2,4-oxadiazol-3-yl)phenylamine] derivatives at C-4 position of 6,7-dimethoxy-quinazolines were synthesized through multistep synthesis. The new compounds were tested for inhibition of vascular endothelial growth factor receptor II (VEGFR-2). Many compounds display VEGFR-2 inhibitory activity with an IC50 as low as 0.017 muM in an HTRF enzymatic assay. Compound 8j exhibited good antibacterial activity by inhibiting the growth of methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA) and ATCC 35218 Escherichia coli (MIC: 0.25-16.00 mug/mL).

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INDOLE DERIVATIVES

The present invention relates to the indole derivatives of formula (I), wherein R1- R6 and X are defined in the claims and optical antipodes or racemates and/or salts thereof which are selective antagonists of bradykinin B 1 to process for producing these compounds, pharmacological compositions containing them and to their use in therapy or prevention of painful and inflammatory conditions

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AMINE-SUBSTITUTED ARYL OR HETEROARYL COMPOUNDS AS EHMT1 AND EHMT2 INHIBITORS

The present disclosure relates to amine-substituted aryl or heteroaryl compounds. The present disclosure also relates to pharmaceutical compositions containing these compounds and methods of treating a disorder (e.g., sickle cell anemia) via inhibition of a methyltransferase enzyme selected from EHMT1 and EHMT2, by administering an amine-substituted aryl or heteroaryl compound disclosed herein or a pharmaceutical composition thereof to subjects in need thereof. The present disclosure also relates to the use of such compounds for research or other non-therapeutic purposes.

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INDOLE AMIDE DERIVATIVES AND RELATED COMPOUNDS FOR USE IN THE TREATMENT OF NEURODEGENERATIVE DISEASES

This invention provides novel compounds and the novel compounds for use as a medicine, more in particular for the prevention or treatment of neurodegenerative disorders, more specifically certain neurological disorders, such as disorders collectively known as tauopathies, and disorders characterised by cytotoxic alpha-synuclein amyloidogenesis. The present invention also relates to the use of said novel compounds for the manufacture of medicaments useful for treating such neurodegenerative disorders. The present invention further relates to pharmaceutical compositions including said novel compounds and to methods for the preparation of said novel compounds.

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COMPOUNDS AND USES THEREOF

The present invention features compounds useful in the treatment of neurological disorders. The compounds of the invention, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing neurological disorders.

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Facile synthesis of 9-(arenethenyl)purines via Heck reaction of 9-vinylpurines and aryl halides

The first example of a Heck reaction with 9-vinylpurines and aryl halides is described. It gives exclusively E-9-(arenethenyl)purines in high yields. Subsequent hydrogenation furnishes 9-(arenethyl)purines quantitatively.

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SUBSTITUTED PYRROLIDINE COMPOUNDS

The present disclosure provides substituted pyrrolidine compounds having Formula (I): and the pharmaceutically acceptable salts and solvates thereof, wherein R1, B, X, and Z are defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula (I) to treat a disorder responsive to the blockade of SMYD proteins such as SMYD3 or SMYD2. Compounds of the present disclosure are especially useful for treating cancer.

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COMPOUNDS, COMPOSITIONS AND METHODS

The present disclosure relates generally to eukaryotic initiation factor 2B modulators, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers or prodrug thereof, and methods of making and using thereof.

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Synthesis and structure?activity relationship study of pyrazolo[3,4-d]pyrimidines as tyrosine kinase RET inhibitors

Three series of pyrazolo[3,4-d]pyrimidine derivatives were synthesized and evaluated as RET kinase inhibitors. Compounds 23a and 23c were identified to show significant activity both in the biochemical and the BaF3/CCDC6-RET cell assays. Compound 23c was found to significantly inhibit RET phosphorylation and down-stream signaling in BaF3/CCDC6-RET cells, confirming its potent cellular RET-targeting profile. Different from other RET inhibitors with equal potency against KDR that associated with severe toxicity, 23c did not show significant KDR-inhibition even at the concentration of 1?muM. These results demonstrated that 23c is a potent and selective RET inhibitor.

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SUBSTITUTED NAPHTHYRIDINONE COMPOUNDS USEFUL AS T CELL ACTIVATORS

Disclosed are compounds of Formula (I) or a salt thereof, wherein: R1, R2, R3, R4, R5, and m are defined herein. Also disclosed are methods of using such compounds to inhibit the activity of one or both of diacylglycerol kinase alpha (DGKalpha) and diacylglycerol kinase zeta (DGKzeta), and pharmaceutical compositions comprising such compounds. These compounds are useful in the treatment of viral infections and proliferative disorders, such as cancer.

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