Abstract: The present invention provides compounds inhibiting eIF4E activity, and compositions and methods of using thereof. Compounds of the present invention, and pharmaceutically acceptable compositions thereof, are useful for treating a variety of diseases, disorders or conditions, associated with eIF4E. Such diseases, disorders, or conditions include cellular proliferative disorders (e.g., cancer) such as those described herein.

Abstract: The present disclosure provides pyrrolopyrimidine nucleoside analogs of the Formula I, Formula IA, Formula IB, or Formula II and phospholipid conjugates and pharmaceutical compositions thereof wherein Rc and A are defined herein. Also presented are methods of treating and/or preventing viral infection and/or viral infection-associated disease or disorder with one or more compounds of Formula I, Formula IA, Formula IB, or Formula II.

Abstract: The present invention relates to novel mesylate salt of N-(5-(4-(4-((dimethylamino)methyl)-3-phenyl-1H-pyrazol-1-yl)pyrimidine-2-ylamino)-4-methoxy-2-morpholinophenyl)acrylamide, a novel crystalline form thereof, and a process for preparing the same. More specifically, the present invention relates to mesylate salt of N-(5-(4-(4-((dimethylamino)methyl)-3-phenyl-1H-pyrazol-1-yl)pyrimidine-2-ylamino)-4-methoxy-2-morpholinophenyl)acrylamide, which is excellent in stability, solubility, and bioavailability when it is administered not only alone but also in combination with other drugs and which has a high purity, a crystalline form thereof, and a process for preparing the same.

Abstract: Bifunctional compounds, which find utility as modulators of leucine-rich repeat kinase 2 (LRRK2), are described herein. In particular, the hetero-bifunctional compounds of the present disclosure contain on one end a moiety that binds to the cereblon E3 ubiquitin ligase and on the other end a moiety which binds LRRK2, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The hetero-bifunctional compounds of the present disclosure exhibit a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aberrant regulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

Abstract: Provided are aminopyridine compounds and pharmaceutically acceptable compositions thereof which exhibit inhibition activity against certain mutated forms of EGFR.

Abstract: The invention provides a compound of formula (0): or a pharmaceutically acceptable salt, N-oxide or tautomer thereof; wherein: n is 1 or 2; X is CH or N; Y is selected from CH and C—F; Z is selected from C—Rz and N; R1 is selected from: -(Alk1)t-Cyc1; wherein t is 0 or 1; Optionally substituted C1-6 acyclic hydrocarbon groups R2 is selected from hydrogen; halogen; and C1-3 hydrocarbon groups optionally substituted with one or more fluorine atoms; R3 is hydrogen or a group L1-R7; R4 is selected from hydrogen; methoxy; and optionally substituted C1-3 alkyl; and R4a is selected from hydrogen and a C1-3 alkyl group; wherein Rz, Alk1, Cyc1, L1 and R7 are defined herein; provided that the compound is other than 6-benzyl-3-{2-[(2-methylpyrimidin-4-yl)amino]pyridin-4-yl}-7,8-dihydro-1,6-naphthyridin-5(6H)-one and 3-{2-[(2-methylpyrimidin-4-yl)amino]pyridin-4-yl}-7,8-dihydro-1,6-naphthyridin-5(6H)-one and salts and tautomers thereof.

Abstract: Biochemically active PASTA kinase inhibitors which exploit subtle structural differences between human kinases and bacterial PASTA kinases to improve specificity and inhibitor activity.

Abstract: The present invention provides a compound of general formula (I) (wherein X is as described in the present description and claims), or a pharmacologically acceptable salt thereof, and a pharmaceutical composition containing that compound.

Abstract: Crystalline forms of Compound (I): are disclosed. Pharmaceutical compositions comprising the same, methods of treating disorders and conditions mediated by BTK activity using the same, and methods for making Compound (I) and crystalline forms thereof are also disclosed.

Abstract: The present invention provides an improved process for preparing an aminopyrimidine derivative or pharmaceutically acceptable salt thereof having a selective inhibitory activity against protein kinases, especially against the protein kinases for mutant epidermal growth factor receptors. Additional, the present invention provides novel intermediates useful for said process and processes for preparing the same.

Abstract: The present invention provides a compound having the structure: wherein R1, R2, R3, R4, and R5 are each independently H, halogen, CF3 or C1-C4 alkyl, wherein two or more of R1, R2, R3, R4, or R5 are other than H; R6 is H, OH, or halogen; and B is a substituted or unsubstituted heterobicycle, wherein when R1 is CF3, R2 is H, R3 is F, R4 is H, and R5 is H, or R1 is H, R2 is CF3, R3 is H, R4 is CF3, and R5 is H, or R1 is Cl, R2 is H, R3 is H, R4 is F, and R5 is H, or R1 is CF3, R2 is H, R3 is F, R4 is H, and R5 is H, or R1 is CF3, R2 is F, R3 is H, R4 is H, and R5 is H, or R1 is Cl, R2 is F, R3 is H, R4 is H, and R5 is H, then B is other than or a pharmaceutically acceptable salt thereof.

Abstract: The invention described herein relates to certain pyrimidinetrione N-substituted glycine derivatives of formula (I) which are antagonists of HIF prolyl hydroxylases and are useful for treating diseases benefiting from the inhibition of this enzyme, anemia being one example.

Abstract: A compound which has a superior control effect on arthropod pests is provided. In particular, a compound represented by formula (I) is provided, wherein the variable groups are as defined in the specification. Also provided is a composition containing the compound represented by formula (I), and uses thereof for controlling harmful arthropods.

Abstract: Disclosed are compounds active towards nuclear receptors, pharmaceutical compositions containing the compounds and use of the compounds in therapy.

Abstract: The present invention provides an improved process for preparing an aminopyrimidine derivative or pharmaceutically acceptable salt thereof having a selective inhibitory activity against protein kinases, especially against the protein kinases for mutant epidermal growth factor receptors. Additional, the present invention provides novel intermediates useful for said process and processes for preparing the same.

Abstract: Compounds of formula (I) which are inhibitors of Bub 1 kinase, processes for their production and their use as pharmaceuticals.

Abstract: Pyrimidine derivatives of formula (I) wherein: Z is a direct bond or —(CH2)n— wherein n is 1 or 2; one of X and Y is N, CH or CF, and the other of X and Y is CH; one of R1 and R2 is selected from —NHR, —NR2, —OR, —SR, —S(O)R, —S(O)2R and a group of the following formula (A) and the other of R1 and R2 is selected from —NHR?, —OH, —OR? and a group of the above formula (A); R is unsubstituted C1-C6 alkyl; R? is a group selected from C1-C6 alkyl, 5- to 12-membered aryl and C3-C6 cycloalkyl, which group is unsubstituted or substituted; W is —(CH2)m—, —CH2—O—CH2—, —CH2—S—CH2— or —CH2—S(O)2—CH2—; p is 1, q is an integer of 1-6 and V is N; or p is 1, q is 0 and V is CH; or p is 0, q is 0 and V is N; r is 0 or 1; and R3 is —(CH2)s—NH2 or —(CH2)s—OH wherein s is 0 or an integer of 1 to 4; and the pharmaceutically acceptable salts thereof are inhibitors of RSV and can therefore be used to treat or prevent an RSV infection.

Abstract: Disclosed herein are compounds that are inhibitors of BRD4 and their use in the treatment of cancer. Methods of screening for selective inhibitors of BRD4 are also disclosed. In certain aspects, disclosed are compounds of Formula I-IV.

Abstract: The present invention relates to a novel method of preparing copanlisib, copanlisib dihydrochloride, or hydrates of copanlisib dihydrochloride, to novel intermediate compounds, and to the use of said novel intermediate compounds for the preparation of said copanlisib, copanlisib dihydrochloride, or hydrates of copanlisib dihydrochloride. The present invention also relates to copanlisib dihydrochloride hydrates as compounds.

Abstract: The present invention relates to a phenyl amino pyrimidine compound or a polymorph of a salt thereof, specifically, to N-(cyanomethyl)-4-(2-((4-(2?,2?,6?,6?-d4-morpholino)phenyl)amino)pyrimidin-4-yl)benzamide, or a pharmaceutically acceptable salt thereof, or a polymorph of a solvate thereof, that is, a compound shown in formula I or salt thereof, or a polymorph of a solvate thereof. The polymorph is suitable for preparing a pharmaceutical composition for suppressing non-receptor tyrosine kinases (such as JAK kinase).

Abstract: Compounds of formula (I) which are inhibitors of Bub 1 kinase, processes for their production and their use as pharmaceuticals.

Abstract: This document relates to inhibitors of G protein coupled receptor 6 kinase (GRK6) polypeptides as well as methods and materials for using such inhibitors to treat hematological malignancies, inflammation diseases, and autoimmune disorders.

Abstract: The invention is directed to a formula (I): or a pharmaceutically acceptable salt thereof, wherein R1, R2a, R2b and R3-R7 are herein. The invention is also directed to compositions containing a compound of formula (I) and to the use of such compounds in the inhibition of mutant IDH proteins having a neomorphic activity. The invention is further directed to the use of a compound of formula (I) in the treatment of diseases or disorders associated with such mutant IDH proteins including, but not limited to, cell-proliferation disorders, such as cancer.

Abstract: This invention relates to L-tartaric acid complexes, acid addition salts, base addition salts of the compound named (S)-4-(((R)-6-(2-chloro-4-fluorophenyl)-5-(methoxycarbonyl)-2-(thiazol-2-yl)-3,6-dihydropyrimidin-4-yl)methyl) morpholine-3-carboxylic acid or tautomer thereof and pharmaceutical compositions thereof, and further relates to use of the compounds or the pharmaceutical compositions in the manufacture of a medicament, especially for use in preventing, managing, treating or lessening a HBV infection. The complex, acid addition salt or base addition salt of the present invention is crystalline form, substantially crystalline form, polymorphism, amorphism, hydrate or solvate.

Abstract: The invention described herein relates to certain pyrimidinetrione N-substituted glycine derivatives of formula (I) which are antagonists of HIF prolyl hydroxylases and are useful for treating diseases benefiting from the inhibition of this enzyme, anemia being one example.

Abstract: The present invention relates to a novel method of preparing copanlisib, and copanlisib dihydrochloride, to novel intermediate compounds, and to the use of said novel intermediate compounds for the preparation of said copanlisib.

Abstract: An ALK kinase inhibitor compound as represented by Formula I, pharmaceutical composition containing the compound, and preparation method and use thereof in the preparation of drugs serving as an ALK inhibitor for treating cancer.

Abstract: The present invention relates to the novel regioselective syntheses of 2,4-disubstituted pyrimidines through sequential nucleophilic aromatic substitutions.

Abstract: The present invention provides 2,4-diaminopyrimidines, and/or pharmaceutically acceptable compositions thereof, as kinase inhibitors.

Abstract: In compounds of formula I: R1 to R5, Ar and X1 to X3 have defined meanings. The compounds have anti-inflammatory activity (e.g., through inhibition of one or more of members of: the family of p38 mitogen-activated protein kinase enzymes; Syk kinase; and members of the Src family of tyrosine kinases) and have use in therapy, including in pharmaceutical combinations, especially in the treatment of inflammatory diseases, including inflammatory diseases of the lung, eye and intestines.

Abstract: The invention is directed to a formula (I): or a pharmaceutically acceptable salt thereof, wherein R1, R2a, R2b and R3-R7 are herein. The invention is also directed to compositions containing a compound of formula (I) and to the use of such compounds in the inhibition of mutant IDH proteins having a neomorphic activity. The invention is further directed to the use of a compound of formula (I) in the treatment of diseases or disorders associated with such mutant IDH proteins including, but not limited to, cell-proliferation disorders, such as cancer.

Abstract: Compounds of formula (I), processes for their preparation and their use as pharmaceuticals.

Abstract: The present invention relates to novel amidopyridine derivatives. More specifically, the present invention provides a medicinal agent which is useful as a prophylactic or therapeutic agent for diseases based on the production of cytokines from T cells, comprising as the active ingredient an amidopyridine derivative or a pharmacologically acceptable salt thereof. Provided are an amidopyridine derivative of the following general formula (I): wherein each symbol has the same meaning as defined in the description, or a pharmacologically acceptable salt thereof.

Abstract: The present invention relates to oxazolidin-2-one substituted pyrimidine compounds that act as PI3K (phosphatidylinositol-3-kinase) inhibitors, as well as pharmaceutical compositions thereof, methods for their manufacture and uses for the treatment of conditions, diseases and disorders dependent on PI3K.

Abstract: The invention is directed to a formula (I): or a pharmaceutically acceptable salt thereof, wherein R1, R2a, R2b and R3-R7 are herein. The invention is also directed to compositions containing a compound of formula (I) and to the use of such compounds in the inhibition of mutant IDH proteins having a neomorphic activity. The invention is further directed to the use of a compound of formula (I) in the treatment of diseases or disorders associated with such mutant IDH proteins including, but not limited to, cell-proliferation disorders, such as cancer.

Abstract: The present invention is directed to novel cyclic amines which inhibit the P2X7 receptor.

Abstract: The present invention provides compounds of Formula (I): (I) as defined in the specification and compositions comprising any of such novel compounds. These compounds are endothelial lipase inhibitors which may be used as medicaments.

Abstract: The invention provides certain substituted phenyl compounds of the Formula (I) or pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, Rcy, and t are as defined herein. The invention also provides pharmaceutical compositions comprising such compounds, and methods of using the compounds for treating diseases or conditions mediated by Spleen Tyrosine Kinase (Syk).

Abstract: A novel inhibitor of Rac activity based on the structure of the established Rac/Rac-GEF inhibitor NSC23766 is discloses. The compound EHop-016, with an IC50 of 1.1 ?M, is a 100-fold more efficient inhibitor of Rac activity than NSC23766. EHop-016 is specific for Rac1 and Rac3 at concentrations ?5 mM. At higher concentrations, EHop-016 inhibits the close homolog Cdc42. In MDA-MB-435 cells, EHop-016 (?5 mM) inhibits the association of the Rac-GEF Vav2 with a nucleotide-free Rac1(G15A), which has a high affinity for activated GEFs. EHop-016 does not affect the association of the Rac-GEF Tiam-1 with Rac1(G15A) at similar concentrations. EHop-016 also inhibits the Rac activity of MDA-MB-231 metastatic breast cancer cells and reduces Rac-directed lamellipodia formation in both cell lines. EHop-016 decreases Rac-downstream effects of p21-activated kinase (PAK)1 activity and directed migration of metastatic cancer cells. At low concentrations (<5 ?M), EHop-016 does not affect cell viability.

Abstract: Compounds of formula (I) which are inhibitors of Bub1 kinase, processes for their production and their use as pharmaceuticals.

Abstract: The present invention relates to ethynyl derivatives of formula I wherein Y is N or CH R1 is fluoro or chloro R2 is hydrogen or methyl or to a pharmaceutically acceptable acid addition salt, to a racemic mixture, or to its corresponding enantiomer and/or optical isomer and/or stereoisomer thereof. It has now surprisingly been found that the compounds of general formula I are metabotropic glutamate receptor antagonists (negative allosteric modulators) for use in the treatment of anxiety and pain, depression, Fragile-X syndrome, autism spectrum disorders, Parkinson's disease, and gastroesophageal reflux disease (GERD).

Abstract: The present invention provides an agent for the prophylaxis or treatment of autoimmune diseases (e.g., psoriasis, rheumatoid arthritis, inflammatory bowel disease, Sjogren's syndrome, Behcet's disease, multiple sclerosis, systemic lupus erythematosus etc.) and the like, which has a superior Tyk2 inhibitory action. The present invention relates to a compound represented by the formula wherein each symbol is as defined in the specification, or a salt thereof.

Abstract: The present invention relates to novel chemical compounds derived from pyrimidines, to the method for preparing same, to the novel intermediates obtained, to the use thereof as drugs, to the pharmaceutical compositions containing same, and to the therapeutic use thereof as AKT inhibitors.

Abstract: 5-Membered heterocyclic amides and related compounds are provided, of the Formula: wherein variables are as described herein. Such compounds are ligands that may be used to modulate specific receptor activity in vivo or in vitro, and are particularly useful in the treatment of conditions associated with pathological receptor activation in humans, domesticated companion animals and livestock animals. Pharmaceutical compositions and methods for using such compounds to treat such disorders are provided, as are methods for using such ligands for receptor localization studies.

Abstract: The invention provides certain substituted pyridines of the Formula (I) or pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, Rcy, Cy, and t are as defined herein. The invention also provides pharmaceutical compositions comprising such compounds, and methods of using the compounds for treating diseases or conditions mediated by Spleen Tyrosine Kinase (Syk) kinase.

Abstract: The invention is directed to novel substituted benzylamino quinolines, compounds comprising substituted benzylamino quinolines, methods of making substituted benzylamino quinolines, the use of substituted benzylamino quinolines for treating or preventing a variety of conditions or diseases associated with lipoprotein metabolism, and the use of substituted benzylamino quinolines as cholesterol ester-transfer protein inhibitors.

Abstract: The invention relates compounds of general formula (I) and pharmaceutically acceptable salts and solvates thereof wherein R1 is halogen, vinylene-aryl, substituted aryl, heteroaryl or a benzo[1,3]dioxolil group, W is a group of formula —NH—SO2—R2 or heteroaryl group or NHR3 group where R3 is hydrogen or heteroaryl; and n is 1, 2, 3 or 4. Furthermore, the present invention is directed to pharmaceutical composition containing at least one compound of general formula (I) and/or pharmaceutically acceptable salts or solvates thereof and for the use of them for the preparation of pharmaceutical compositions for the prophylaxis and/or the treatment of protein kinase related, especially CDK9-related diseases e.g. cell proliferative disease, infectious disease, pain, cardiovascular disease and inflammation.

Abstract: Compounds of formula (I), processes for their production and their use as Bub1 kinase inhibitors for the treatment of hyperproliferative diseases and/or disorders responsive to induction of cell death.

Abstract: The present invention provides compounds of Formula (I) for the treatment of cancer, rheumatoid arthritis and other diseases.

Abstract: The present invention is directed to benzyl urea compounds, which are tropomyosin-related kinase (Trk) family protein kinase inhibitors, and hence may be useful in the treatment of pain, inflammation, cancer, restenosis, atherosclerosis, psoriasis, thrombosis, a disease, disorder, injury, or malfunction relating to dysmyelination or demyelination or a disease or disorder associated with abnormal activities of nerve growth factor (NGF) receptor Trk-A, Trk-B and/or Trk-C.