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The present invention provides heterocyclic compounds as selective inhibitors of fibroblast growth factor receptor 4 (FGFR4), pharmaceutical compositions containing the compounds, methods of preparingthe compounds, and methods of treating cell proliferative diseases, such as cancer, using the compounds of the invention.

The invention provides a pyrido[2,3-b]pyrazine-3(4H)-ketone derivative and application thereof. The structural general formula of the pyrido[2,3-b]pyrazine-3(4H)-ketone derivative is a formula V, andthe pyrido[2,3-b]pyrazine-3(4H)-ketone derivative comprises pharmaceutically acceptable salt, solvate, hydrate or crystal form thereof. The compound provided by the invention is an active ligand of afibroblast growth factor receptor (FGFR), and research shows that the compound shown in the structure V has good anti-proliferative activity on KATO III gastric cancer cells (FGFR2 amplification) andHuh-7 liver cancer cells (FGFR4 overexpression), and is applied to preparation of drugs for treating tumor-related diseases caused by FGFR abnormal activation as an FGFR inhibitor. The structural general formula V is shown in the description.

Kinetically stabilized nitrile N-oxides (NOs) have been regarded as viable tools for the postpolymerization functionalization of common polymers. However, thermal isomerization of NO to isocyanate restricts the applications of NO to industrial use. The re

This work discloses transamidation of primary and tertiary amides with a range of aryl, heteroaryl, and aliphatic amines using potassium tert-butoxide. The reaction proceeds at room temperature under transition-metal-free conditions providing secondary amides in high yields. Moreover, reaction of cyclopropyl amine with tertiary amides proceeds with ring-opening to provide a rapid access to enamides.

Aromatic donor-acceptor stacking involving electron-rich π-donors and electron-deficient π-acceptors has been utilized in a broad spectrum of diverse applications to great effect. We report the discovery of unprecedented donor-acceptor stacking from a non

A switchable oxidative coupling reaction of isocyanide and peroxide has been disclosed. In the presence of iron catalyst, the coupling reaction affords N-arylacetamides in good yields. By simply replacing the iron with copper catalyst, another different coupling reaction takes place in which peroxide can serve as alkoxylating source. This protocol represents a new fundamental coupling of two basic chemicals involving C?C and C?O bond-forming process. The unusual reactivity of an isocyano group in a radical reaction acting formally as an amidoyl synthon has also been well established. The experiment outcome reveals that aromatic isocyanides are particularly compatible reaction partners in present coupling reaction, whereas no desired products are observed when aliphatic isocyanides are used. (Figure presented.).

An efficient Fe(NO3)3·9H2O promoted ortho-nitration reaction of aniline derivatives has been developed. This reaction may go through a nitrogen dioxide radical (NO2) intermediate, which is generated by the thermal decomposition of iron(iii) nitrate. The practicality of the present method using nontoxic and inexpensive iron reagents has been shown by the broad substrate scope and applications.

Methods, compounds, pharmaceutical compositions, and methods of preparing medicaments for treating hepatocellular carcinoma having an altered FGFR4 and/or FGF19 status.

We provide FGFR inhibitors, their salts, methods of manufacture, and methods of use.

A heteroarylamine compound includes protein kinase inhibition activity, a pharmaceutically acceptable salt thereof and a pharmaceutical composition for preventing and treating a disease caused by abnormal cell growth, which contains the compound as an act

Identification of the novel (E)-N1-((2-chloro-7-methoxyquinolin-3-yl)methylene)-3-(phenylthio) propanehydrazide scaffold 18 has led to the development of a new series of biologically active hydrazide compounds. The parent compound 18 and new quinoline derivatives 19-26 were prepared from the corresponding quinoline hydrazones and substituted carboxylic acids using EDC-mediated peptide coupling reactions. Further modification of the parent compound 18 was achieved by replacement of the quinoline moiety with other aromatic systems. All the newly synthesized compounds were evaluated for their anti-cancer activity against the SH-SY5Y and Kelly neuroblastoma cell lines, as well as the MDA-MB-231 and MCF-7 breast adenocarcinoma cell lines. Analogues 19 and 22 significantly reduced the cell viability of neuroblastoma cancer cells with micromolar potency and significant selectivity over normal cells. The quinoline hydrazide 22 also induced G1 cell cycle arrest, as well as upregulation of the p27kip1 cell cycle regulating protein.

The present invention relates to bicyclic heterocycles, and pharmaceutical compositions of the same, that are inhibitors of the FGFR4 enzyme and are useful in the treatment of FGFR4-associated diseases such as cancer.

Provided herein are compounds of Formula I useful as FGFR4 inhibitors, as well as methods of use of the same.

A mild and efficient chemoselective N-deacetylation using the Schwartz reagent at room temperature in rapid time is described. The mild and neutral conditions enable orthogonal N-deacetylation in the presence of some of the common protecting groups (viz. Boc, Fmoc, Cbz, Ts). The deprotection conditions did not induce any epimerization at the chiral amino centre.

The present invention relates to compounds useful as inhibitors of protein kinases, containing a cysteine residue in the ATP binding site. The invention further provides for pharmaceutically acceptable compositions comprising therapeutically effective amounts of one or more of the protein kinase inhibitor compounds and methods of using said compositions in the treatment of cancers and carcinomas.

Most azobenzene-based photoswitches use UV light for photoisomerization. This can limit their application in biological systems, where UV light can trigger unwanted responses, including cellular apoptosis. We have found that substitution of all four ortho positions with methoxy groups in an amidoazobenzene derivative leads to a substantial (～35 nm) red shift of the n-π* band of the trans isomer, separating it from the cis n-π* transition. This red shift makes trans-to-cis photoswitching possible using green light (530-560 nm). The cis state is thermally stable with a half-life of ～2.4 days in the dark in aqueous solution. Reverse (cis-to-trans) photoswitching can be accomplished with blue light (460 nm), so bidirectional photoswitching between thermally stable isomers is possible without using UV light at all.

A novel series of N-aryl-N′-pyrimidin-4-yl ureas has been optimized to afford potent and selective inhibitors of the fibroblast growth factor receptor tyrosine kinases 1, 2, and 3 by rationally designing the substitution pattern of the aryl ring. On the b

A convenient and efficient method for the construction of indole skeleton was developed via Pd-catalyzed C-H activation of N-aryl amides and subsequent coupling with alkynes. Both stoichiometric and catalytic versions have been successfully achieved.

The invention relates to new quinoxaline derivative compounds, to pharmaceutical compositions comprising said compounds, to processes for the preparation of said compounds and to the use of said compounds in the treatment of diseases, e.g. cancer.

Recently, the rhodium(III)-complex [Cp*RhCl2]2 1 has provided exciting opportunities for the efficient synthesis of aromatic heterocycles based on a rhodium-catalyzed C-H bond functionalization event. In the present report, the use of complexes 1 and its dicationic analogue [Cp*Rh(MeCN)3][SbF6]2 2 have been employed in the formation of indoles via the oxidative annulation of acetanilides with internal alkynes. The optimized reaction conditions allow for molecular oxygen to be used as the terminal oxidant in this process, and the reaction may be carried out under mild temperatures (60 °C). These conditions have resulted in an expanded compatibility of the reaction to include a range of new internal alkynes bearing synthetically useful functional groups in moderate to excellent yields. The applicability of the method is exemplified in an efficient synthesis of paullone 3, a tetracyclic indole derivative with established biological activity. A mechanistic investigation of the reaction, employing deuterium labeling experiments and kinetic analysis, has provided insight into issues of reactivity for both coupling partners as well as aided in the development of conditions for improved regioselectivity with respect to meta-substituted acetanilides. This reaction class has also been extended to include the synthesis of pyrroles. Catalyst 2 efficiently couples substituted enamides with internal alkynes at room temperature to form trisubstituted pyrroles in good to excellent yields. The high functional group compatibility of this reaction enables the elaboration of the pyrrole products into a variety of differentially substituted pyrroles.

In our efforts to minimize the side effects associated with low selectivity against the other PDE isozymes, a novel class of 2-phenylquinazolin-4(3H)-one derivatives were designed and prepared as potent PDE5 inhibitors with high selectivity against PDE6.

A series of quinoline derivatives were synthesized and their immunosuppressive activity and cytotoxicity were evaluated with a T-cell functional assay and MTT method, respectively. Most of 5,7-dimethoxyquinolin-4-yl ortho-substituted benzoate derivatives

The invention relates to compounds of formula (I), wherein R1, R2, R1a, R2a, R3, R4, A, B, X, W and n are as defined in the description, and pharmaceutically acceptable salts of such compounds. These compounds are useful as calcium channel blockers.

The oxidative synthesis of highly functionalized indoles from simple anilines and internal alkynes mediated by a rhodium(III) catalyst is described. Good yields are obtained for a variety of aniline substrates, and good regioselectivity is obtained for the more sterically accessible position when meta-substituted anilines are used. Symmetrical and unsymmetrical alkynes react efficiently with high (>40:1) C2/C3 regioselectivity when aryl/alkyl substituted alkynes are used. Copyright

The invention provides a novel class of compounds of the Formula (I): in which the symbols have the meanings given in the description and claims, to pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prev

The invention relates to heteroaryl aryl ureas of the formula (IA), wherein the radicals and symbols have the meanings as defined herein, the use of such compounds in the treatment of protein kinase dependent diseases; to pharmaceutical preparations comprising said heteroaryl aryl ureas, to processes for the manufacture of such novel compounds and to methods of treatment comprising the use of such heteroaryl aryl ureas.

A compound selected from those of formula (I): 1 wherein: X and Y represent a group selected from hydrogen, halogen, hydroxy, alkoxy, nitro, cyano, alkyl, trihaloalkyl and NRaRb, wherein Ra and Rb are as defined in the description R1 represents hydrogen or alkyl R2 represents a group selected from hydrogen, alkyl, —OR″a, —NR′aR′b, -Ta-O″a, —N″a-Ta-NR′aR′b, —N″a—C(O)-TaH, —O—C(O) TaH, Ta-NR′aR′b, —NR″a-Ta-OR″a, —NR″a-Ta-CO2R″a and —N″a—C(O)-Ta-NR′aR′b, wherein R′a, R″a, R′b and Ta are as defined in the description R3 and R4 represent hydrogen or alkyl A represents a group of formula —CH(R5)CH(R6), —CH=C(R7)—, —C(R7)=CH—, —C(O)CH(R8) or —CH(R8)—C(O), wherein R5, R6, R7 and R8 are as defined in the description its isomers, N-oxides, and addition salts thereof with a pharmaceutically acceptable acid or base, and medicinal products containing the same which are useful in the treatment of cancer.

Activated acetophenones were deacetylated by treatment with an excess of tin(IV) chloride in 1,2-dichloroethane.

Novel imidazoquinoxalines and salts thereof, pharmaceutical compositions containing such compounds, and methods of using such compounds in the treatment of protein tyrosine kinase-associated disorders such as immunologic disorders.

Two new synthetic routes to pyridocarbazoles are described.In the first, Goldberg-type coupling of various aryl sulfonamides with aryl bromides in the presence of copper and potassium carbonate gives N,N-diaryl sulfonamides.UV irradiation of these, in ethanol, removes the toluene-p-sulfonyl protecting groups and cyclises the diphenylamine moiety to the corresponding carbazoles.These carbazoles are established intermediates in the synthesis of several ellipticines (5,11-dimethylpyridocarbazoles).In a complementary route, a series of substituted acetanilides are similarly coupled under Goldberg conditions with 2-bromo-5-cyanotoluene to give the corresponding cyanodiphenylamines and diphenylamides.Hydrolysis of the latter gives the diphenylamines which are then oxidatively cyclised to 3-cyano-1-methylcarbazoles.Reduction of the cyanocarbazoles leads to 3-formylcarbazoles which are known intermediates for the synthesis of 5-methylpyridocarbazoles.