Abstract: Selenophene compounds of formula (I) are described herein. In the compounds of Formula (I), ring A is a 6-membered aromatic fused ring, optionally containing one, two or three nitrogen atoms; a 5-membered heteroaromatic fused ring; or a mono- or bicyclic saturated heterocyclic fused ring having at least one ring member selected from the group consisting of N, O, S, SO and SO2; Y in ring B is nitrogen or substituted carbon; X is NR6, O, S, S(O), or S(O)2. R1, R2, R3, R4, and R6 are defined in the specification. Selenophene compounds of formula (I) may be used in methods of treating cell proliferative disorders, particularly cancer. Pharmaceutical compositions containing selenophene compounds of formula (I) may be used for treatment, inhibition, or control of cancer.

Abstract: The present invention provides a 4-aminoquinazoline derivative having the chemical structure of the following formula, and the use thereof. It is demonstrated by the pharmacological experiment that, the compound or a salt thereof according to the present invention not only has distinct inhibitory effect on histone deacetylases, but also has stronger differentiation induction and anti-proliferative activities for certain tumor cells. It can be used in the treatment of cancers and diseases related to cell differentiation and proliferation. Excellent efficacy is observed especially for leukemia and a solid tumor. As demonstrated by the animal test, the compound or a salt thereof according to the present invention is less toxic.

Abstract: The present invention is directed to novel quinazolines, their derivatives, pharmaceutically acceptable salts, solvates, prodrug, stereoisomer, tautomer, metabolite and hydrates thereof. The compounds and compositions of the present invention have protein kinases inhibitory activities and are expected to be useful for the treatment of protein kinases mediated diseases and conditions.

Abstract: Methods are disclosed for preventing toxic drug-drug interactions during combination cancer therapy with a drug that is an anti-ErbB3 agent, such as an anti-ErbB3 antibody, together with a drug that is a tyrosine kinase inhibitor and/or a drug that binds to alpha-1 acid glycoprotein (e.g., erlotinib). Health care practitioners obtaining any one of the drugs are warned that when co-administering the drug that is an anti-ErbB3 agent with either or both of a drug that is a tyrosine kinase inhibitor and a drug that binds to alpha-1 acid glycoprotein, at least one of the co-administered drugs should be administered using a reduced dosage to prevent toxicity. In a reduced dosage, the amount of drug administered per unit time is reduced as compared to a dose that would be administered if the drug was administered as monotherapy. The reduced dosage can be, for example, a reduced drug dose or a reduced drug dosing frequency, or both. Compositions useful in practicing the disclosed methods are also provided.

Abstract: The present invention relates to compounds useful as inhibitors of voltage-gated sodium channels. The invention also provides pharmaceutically acceptable compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various disorders.

Abstract: The present invention relates to the field of medicine. Provided herein are aminoquinazoline derivatives, their salts and pharmaceutical formulations useful in modulating the protein tyrosine kinase activity, and in modulating inter- and/or intra-cellular signaling. Also provided herein are pharmaceutically acceptable compositions comprising the aminoquinazoline compounds and methods of using the compositions in the treatment of hyperproliferative disorders in mammals, especially humans.

Abstract: The present invention relates to quinazoline containing zinc-binding moiety based derivatives of Formula (IV) below. These compounds have enhanced and unexpected properties as inhibitors of epidermal growth factor receptor tyrosine kinase (EGFR-TK) and are useful in the treatment of EGFR-TK related diseases and disorders such as cancer. These compounds may further act as HDAC inhibitors.

Abstract: The invention provides quinazoline-7-ether derivatives, particularly 4-anilinyl-6-butenamido-quinazoline-7-ether derivatives that are inhibitors of the receptor protein tyrosine kinases (RTK). The compounds are useful in the treatment of diseases and disorders where RTK activity is implicated such as a hyperproliferative diseases (e.g., cancer). Also provided are methods of preparation of the quinazoline derivatives and methods of use as therapeutic agents alone or in a drug combination.

Abstract: In order to identify a gene that can serve as an indicator for predicting the effectiveness of a drug treatment of cancer and to provide a novel method for predicting the effectiveness of a drug treatment targeting said gene, lung adenocarcinomas were subjected to whole-transcriptome sequencing. As a result, in-frame fusion transcripts between the KIF5B gene and the RET gene were identified. The KIF5B-RET gene fusions were detected in 6 out of 319 (2%) LADC specimens from Japanese individuals and 1 out of 80 (1%) LADC specimens from U.S.A. individuals. None of the seven subjects revealed known activating mutations such as EGFR, KRAS or ALK oncogenes; thus, said gene fusions were found to be responsible mutations (driver mutations) for oncogenesis. Since said gene fusions are considered to induce constitutive activation of RET tyrosine kinase protein, it was found that treatments with RET tyrosine kinase inhibitors are effective in patients with detection of said gene fusions.

Abstract: Disclosed are compounds having the formula (Formula I)): wherein R1, R2, R3 and Z are as defined herein, and methods of making and using the same.

Abstract: The present invention provides a method for treating a thrombotic or an inflammatory disorder administering to a patient in need thereof a therapeutically effective amount of at least one compound of Formula (I) or Formula (V): or a stereoisomer or pharmaceutically acceptable salt or solvate form thereof, wherein the variables A, L, Z, R3, R4, R6, R11, X1, X2, and X3 are as defined herein. The compounds of Formula (I) are useful as selective inhibitors of serine protease enzymes of the coagulation cascade and/or contact activation system; for example thrombin, factor Xa, factor XIa, factor IXa, factor VIIa and/or plasma kallikrein. In particular, it relates to compounds that are selective factor XIa inhibitors. This invention also provides compounds within the scope of Formula I and relates to pharmaceutical compositions comprising these compounds.

Abstract: Disclosed are as represented by Formula (I) a quinazoline derivative and a pharmaceutical acceptable salt thereof, or, an enantiomer, a non-enantiomer, a tautomer, a racemate, a solvate, a metabolic precursor, or a prodrug of both. Also disclosed are a preparation method therefor, an intermediate, a pharmaceutical composition having the quinazoline derivative, and an application thereof. The quinazoline derivative of the present invention is provided with improved anti-tumor activity.

Abstract: A compound for treating protein kinase-related disease or disorder having a structure of formula (A): wherein X is N or CH; Y is NH, O, or CH2; Z is an aryl or a heteroaryl; and R1, R2, R3, and R4 are independently H, halo, nitro, cyano, aryl, heteroaryl, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, —ORa, —C(O)Ra, —C(O)NRaRb, —NRaC(O)Rb, —NRaRb, —S(O)2Ra, —S(O)2NRaRb, —NRaS(O)2Rb, —N?CRaRb, or —NRaC(O)NHRb, wherein each of Ra and Rb, independently, is H, alkyl, alkenyl, alkynyl, aryl, aryloxy, alkoxy, hydroxy, heteroaryl, cycloalkyl, heterocycloalkyl, cycloalkenyl, or heterocycloalkenyl, or Ra and Rb, together with the nitrogen atom to which they are bonded, form heteroaryl, heterocycloalkyl, or heterocycloalkenyl; or R3 and R4 are as defined above, and R1 and R2 together with the carbons, to which they are attached, form a heterocycloalkenyl or heteroaryl.

Abstract: A process for the preparation of a salt of N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)quinazolin-4-amine comprising reacting a 4-halo-6,7-bis(2-methoxyethoxy)quinazoline with 3-aminophenyl acetylene or an acid salt thereof under acidic conditions to form the corresponding acid salt of N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)quinazolin-4-amine, the process optionally further comprising converting the acid salt of N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)quinazolin-4-amine to N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)quinazolin-4-amine.

Abstract: A method of preparing a compound of formula (I), A method for treating cancer or inhibiting growth of cancer cells including administering to a patient mammal in need thereof a pharmaceutical preparation including the compound. A method of treating or preventing a physiological disorder caused by abnormal protein tyrosine kinase activity in a mammal including administering to a mammal a pharmaceutical preparation including the compound.

Abstract: Quinazoline derivatives are provided that specifically inhibit proliferation of T cells without affecting the level of IL-2 secreted from said T cells. These compounds as well as pharmaceutical composition comprising them are useful for the treatment of indications mediated by T cell proliferation.

Abstract: The present invention is directed to novel aminopyrrolidines of formula I pharmaceutically acceptable salts thereof, metabolites thereof, isomers thereof, stereoisomers thereof or pro-drugs thereof, wherein the variables are as defined herein. The compounds of formula (I) are useful as chemokine receptor antagonists and as such would be useful in treating certain conditions and diseases, especially inflammatory conditions and diseases and proliferative disorders and conditions, for example, cancers.

Abstract: The invention relates to a quinazoline derivative represented by the general formula (I), a pharmaceutical acceptable salt and a stereoisomer thereof as tyrosine kinase inhibitor, wherein R1, R2, R3, R3?, R4, R5, R6, X, L, T, Z and q are as defined in the specification. The invention also relates to a process for preparing the same, a pharmaceutical composition and a pharmaceutical formulation containing the derivative, use of the derivative for treating excessive proliferative diseases and chronic obstructive pulmonary disease and use of the derivative in the manufacture of a medicament for treating excessive proliferative diseases and chronic obstructive pulmonary disease.

Abstract: Compounds, compositions, and methods for specific inhibition of activated cdc42-associated kinase 1 (Ack1) are provided.

Abstract: The present invention relates to three novel crystalline forms of Erlotinib hydrochloride and method of preparation thereof. Erlotinib hydrochloride is N-(3-ethynylphenyl)-6,7-bis(2 -methoxy ethoxy)-4-quinazolinamine hydrochloride of formula-(I): The present invention provides stable novel crystalline forms of Erlotinib hydrochloride designated as Form-M, Form-N and Form-P, and processes for the preparation of the same. Erlotinib hydrochloride can be used as medicament for the treatment of hyperproliferative disorders, such as cancers, in humans.

Abstract: The present invention relates to quinazoline containing zinc-binding moiety based derivatives of Formula (I) below. These compounds have enhanced and unexpected properties as inhibitors of epidermal growth factor receptor tyrosine kinase (EGFR-TK) and are useful in the treatment of EGFR-TK related diseases and disorders such as cancer. These compounds may further act as HDAC inhibitors.

Abstract: The present invention provides compounds, including resolved enantiomers, diastereomers, solvates and pharmaceutically acceptable salts thereof, comprising the Formula: A-L-CR where CR is a cyclical core group, L is a linking group and A is as defined herein. Also provided are methods of using the compounds of this invention as AKT protein kinase inhibitors and for the treatment of hyperproliferative diseases such as cancer.

Abstract: The invention concerns quinazoline derivatives of the Formula I, or pharmaceutically acceptable salts thereof: wherein each of R1, R2, R3, R4 and m are as defined in the description; processes for their preparation; pharmaceutical compositions containing them and their use in the manufacture of a medicament for providing an anti-proliferative effect. The quinazoline derivatives of Formula I are expected to be useful in the treatment of diseases such as certain cancers mediated by erbB receptor tyrosine kinases, and, for example, EGFR tyrosine kinase.

Abstract: This invention relates to novel sulfoximine substituted quinazoline derivatives of formula I wherein Ar, R1 and R2 are as defined herein, and their use as MNK1 (MNK1a or MNK1b) and/or MNK2 (MNK2a or MNK2b) kinase inhibitors, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment or amelioration of MNK1 (MNK1a or MNK1b) and/or MNK2 (MNK2a or MNK2b) mediated disorders.

Abstract: The present invention relates to bicyclic heterocycles of general formula wherein Ra to Rc, A to E and X are defined as in claim 1, the tautomers, stereoisomers and salts thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases which have valuable pharmacological properties, in particular an inhibitory effect on signal transduction mediated by tyrosine kinases, their use in the treatment of diseases, especially tumoral diseases and diseases of the lungs and airways, and the preparation thereof.

Abstract: The invention provides alkyne substituted quinazoline compounds, such as compounds of the formula (I), which are irreversible ErbB kinase inhibitors. The compounds are useful in the treatment of diseases and disorders where ErbB kinase activity is implicated such as a hyperproliferative disorder (e.g., cancer).

Abstract: The present invention discloses an improved and efficient process for preparing Erlotinib hydrochloride suitable as a cancer drug.

Abstract: This disclosure relates to processes and reagents for making diaryliodonium salts, which are useful for the preparation of fluorinated, iodinated, astatinated and radiofluorinated aromatic compounds.

Abstract: The invention provides novel bicyclic azaheterocyclic carboxamide compounds according to Formula (I), their manufacture and use for the treatment of hyperproliferative diseases, such as cancer.

Abstract: A compound of formula (X): which can be used as an intermediate to make lapatinib or its pharmaceutically acceptable salt.

Abstract: A series of mono- and di-substituted quinazoline and pyrimidine derivatives based on the skeleton of erlotinib (an EGFR inhibitor) were synthesized and their bioactivities against hepatocellular carcinoma and human lung adenocarcinoma were evaluated.

Abstract: The present invention provides a novel and stable hydrated form of erlotinib free base, and a process for its preparation thereof. The present invention also provides a process for preparation of erlotinib hydrochloride crystalline polymorph a substantially free of polymorph B. The present invention further relates to erlotinib hydrochloride crystalline particles having mean particle size (D50) ranging from about 4 ?m to 15 ?m and 90 volume-% of the particles (D90) ranging from about 14 ?m to 30 ?m, to the methods for the manufacture of said crystalline particles, and to pharmaceutical compositions comprising said crystalline particles.

Abstract: The present invention relates to an improved and novel process for the preparation of high purity crystalline base of Lapatinib of formula-(1) having chemical name N-{3-chloro-4-[(3-fluorobenzyloxy]phenyl}-6-[5-({[2-(methanesulfonyl)ethyl]amino}methyl]-2-furyl]-4-quin-azolinamine and its pharmaceutically acceptable salts. The present invention further relates to intermediates according to formula (8) and formula (9) used in this process.

Abstract: Afatinib salts and crystalline forms thereof are described in the present application and processes for their preparation. Crystalline forms of Afatinib are also described in the present application and processes for their preparation. The present invention also includes pharmaceutical compositions of such Afatinib salts and crystalline forms thereof or crystalline forms of Afatinib, methods of their preparation and the use thereof in the treatment of a patient in need thereof.

Abstract: A novel crystal of antitumor drug erlotinib base and its preparation method are provided in the present invention. A preparation method of erlotinib hydrochloride with high-purity is also provided in the present invention.

Abstract: The invention relates to the compounds and methods for inhibiting the Cyclin-Dependent Kinase Inhibitor (CDKI) pathway. More particularly, the invention relates to compounds and methods for inhibiting the CDKI pathway for studies of and intervention in senescence-related and other CDKI-related diseases. The invention provides new compounds having improved solubility and/or potency, and methods for their use. In various aspects, the invention relates to the treatment of cancer. The invention provides methods for chemoprevention and prevention of tumor recurrence or metastasis. The invention further provides diagnostic techniques for treatment for certain cancer types. The invention utilizes specific inhibitors of CDK8/19 and/or measurement of CDK8 levels in a patient.

Abstract: A process for the preparation of a salt of N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)quinazolin-4-amine comprising reacting a 4-halo-6,7-bis(2-methoxyethoxy) quinazoline with 3-aminophenyl acetylene or an acid salt thereof under acidic conditions to form the corresponding acid salt of N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)quinazolin-4-amine, the process optionally further comprising converting the acid salt of N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)quinazolin-4-amine to N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)quinazolin-4-amine.

Abstract: A compound of formula I wherein A, X, Y, Z, R1 and R24 are described herein. The compounds are useful as inhibitors of potassium channel function and in the treatment and prevention of arrhythmia, IKur-associated disorders, and other disorders mediated by ion channel function.

Abstract: A compound of formula (X): which can be used as an intermediate to make lapatinib or its pharmaceutically acceptable salt.

Abstract: There is provided processes for preparing Lapatinib and pharmaceutically acceptable salts thereof by the reductive amination of the aldehyde of Formula II by treatment with 2-methanesulphonylethylamine followed by catalytic hydrogenation in the presence of a suitable hydrogenation catalyst.

Abstract: The present invention relates to quinazoline containing zinc-binding moiety based derivatives of formula I that have enhanced and unexpected properties as inhibitors of epidermal growth factor receptor tyrosine kinase (EGFR-TK) and their use in the treatment of EGFR-TK related diseases and disorders such as cancer.

Abstract: The purpose of the present invention is to provide a retardation film which has high retardation developability, good mechanical strength and good durability. This retardation film contains a cellulose derivative and at least one compound represented by general formula (1), wherein each of R1 and R2 independently represents an alkyl group, a cycloalkyl group, an aryl group or a heterocyclic group; X1 represents a single bond, —NR4—, —O— or —S—; X2 represents a single bond, —NR5—, —NR5—(C?O)—, —O— or —S—; each of R4 and R5 independently represents a hydrogen atom, an alkyl group, a cycloalkyl group, an aryl group or a heterocyclic group; R3 represents a substituent; n represents an integer of 0-4; and when n is 2 or more, a plurality of R3s may be the same or different and adjacent R3s may be joined together to form a ring).

Abstract: An alternative method for the preparation of Erlotinib through a new chemical reaction for the preparation of the 4-(3-aminophenyl)-2-methyl-3-butyn-2-ol key intermediate of formula (IV) according to the following scheme.

Abstract: The invention generally relates to biomarkers associated with NSCLC, and methods and compositions for the detection and diagnosis of non-small cell lung cancer in a human subject.

Abstract: The present invention relates to quinazoline containing zinc-binding moiety based derivatives of Formula (IV) below. These compounds have enhanced and unexpected properties as inhibitors of epidermal growth factor receptor tyrosine kinase (EGFR-TK) and are useful in the treatment of EGFR-TK related diseases and disorders such as cancer. These compounds may further act as HDAC inhibitors.

Abstract: The invention relates to compounds for inhibiting the Cyclin-Dependent Kinase Inhibitor (CDKI) pathway. More particularly, the invention relates to compounds for inhibiting the CDKI pathway for studies of and intervention in senescence-related and other CDKI-related diseases.

Abstract: The present invention comprises compounds of Formula I. wherein: R1, R2, R4, J, Q, and A are as defined in the specification. The invention also comprises a method of preventing, treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is type II diabetes, obesity and asthma. The invention also comprises a method of inhibiting CCR2 activity in a mammal by administration of a therapeutically effective amount of at least one compound of Formula I.

Abstract: A pharmaceutical formulation comprising the compound of formula

Abstract: A compound of general formula I wherein: Ra is a benzyl, 1-phenylethyl, or 3-chloro-4-fluorophenyl group; Rb is a dimethylamino, N-methyl-N-ethylamino, diethylamino, N-methyl-N-isopropylamino, N-methyl-N-cyclopropylamino, N-methyl-N-(2-methoxyethyl)amino, N-ethyl-N-(2-methoxyethyl)amino, bis(2-methoxyethyl)amino, morpholino, N-methyl-N-(tetra-hydrofuran-3-yl)amino, N-methyl-N-(tetrahydrofuran-2-ylmethyl)amino, N-methyl-N-(tetra-hydrofuran-3-ylmethyl)amino, N-methyl-N-(tetrahydropyran-4-yl)amino, or N-methyl-N-(tetrahydropyran-4-ylmethyl)amino group; and Rc is a cyclopropylmethoxy, cyclobutyloxy, cyclopentyloxy, tetrahydrofuran-3-yloxy, tetrahydrofuran-2-ylmethoxy, tetrahydrofuran-3-ylmethoxy, tetrahydropyran-4-yloxy, or tetrahydropyran-4-ylmethoxy group, or a tautomer, stereoisomer, or salt thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases which have valuable pharmacological properties, in particular an inhibitory effect on signal transduction

Abstract: The present invention relates to a pharmaceutical composition comprising N-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-[5[[[2-(methylsulfonyl)ethyl]amino]methyl]-2-furyl]-4-quinazolinamine as active pharmaceutical ingredient and a process of preparing such composition.