Abstract: This invention is in the area of synthesizing pyrimidine-based compounds useful in the treatment of disorders involving abnormal cellular proliferation, including but not limited to tumors and cancers.

Abstract: Provided is a composition comprising a polyglycolized glyceride and a compound having the following structure (I): or a pharmaceutically acceptable salt thereof. Also provided are crystalline forms of the compound of structure (I), or a pharmaceutically acceptable salt thereof. Methods of making the same, and methods for using the same in the treatment of cancer, autoimmune, inflammatory and other Pim kinase-associated diseases, disorders or conditions are also disclosed.

Abstract: Disclosed are compounds of Formula (I), methods of using the compounds for inhibiting ALK2 activity and pharmaceutical compositions comprising such compounds. The compounds are useful in treating, preventing or ameliorating diseases or disorders associated with ALK2 activity such as cancer.

Abstract: Small molecule inhibitors of neutral sphingomyelinase 2 (nSMase2) and their use for treating neurodegenerative diseases, such as, neurodegenerative diseases associated with high levels of ceramide, including, but not limited to Alzheimer's disease (AD), HIV-associated neurocognitive disorder (HAND), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS), and, in other aspects, for treating cancer, are provided.

Abstract: Disclosed are compounds of Formula (I), methods of using the compounds for inhibiting ALK2 activity and pharmaceutical compositions comprising such compounds. The compounds are useful in treating, preventing or ameliorating diseases or disorders associated with ALK2 activity such as cancer.

Abstract: The present invention relates to macrocyclic indole derivatives of general formula (I): in which R1, R2, R3, R4, R5, R6, A and L are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds, and the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular of hyperproliferative disorders, as a sole agent or in combination with other active ingredients.

Abstract: PI3K signalling is the most increased pathway in human cancers. The four isoforms of PI3K are thought to be activated by different redundant mechanisms leading to a common downstream signalling. The inventors questioned this concept, by mapping differential isoform-specific downstream signalling in response to their constant selective inhibition in pancreatic cancer, a disease currently without therapy. They identified common and specific signals activated by each PI3K isoform. These data make the rational for the development of highly selective PI3K isoform drugs used in combination, instead of compounds inhibiting all PI3Ks. In particular, the inventors showed that combined p110a and 110? inhibition is the most efficient strategy for pancreatic cancer patients.

Abstract: A method for preparing a refinery fuel composition having a target octane number, comprises: (i) blending fuel components in proportions which are designed to give a refinery fuel composition with an octane number which is greater than the target octane number by a margin of less than 1; and (ii) testing the octane number of the refinery fuel composition and, if the octane number falls below the target octane number, blending the refinery fuel composition with a non-metallic octane-boosting additive. A further method comprises: (a) passing a first refinery fuel composition comprising a non-metallic octane-boosting additive to a fuel handing system, and discharging the first refinery fuel composition from the fuel handing system; and (b) passing a second refinery fuel composition to the fuel handing system.

Abstract: The present invention relates to compounds of formula (I), or their isotopic forms, stereoisomers, tautomers or pharmaceutically acceptable salt (s) thereof as muscarinic M1 receptor positive allosteric modulators (M1 PAMs). The present invention describes the preparation, pharmaceutical composition and the use of compound formula (I).

Abstract: Compounds having the following Formula I and/or Formula II and methods of their use and preparation are disclosed:

Abstract: The present invention relates to: • combinations of: * a component A: which is a PI3K kinase inhibitor, such as copanlisib, or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a salt thereof, in particular a physiologically acceptable salt, or a mixture of same, for example; * a component B: which is an androgen receptor antagonist, such as darolutamide or enzalutamide for example; and, optionally, * one or more pharmaceutical agents C; in which optionally either or both of said components A and B are in the form of a pharmaceutical formulation which is ready for use to be administered simultaneously, concurrently, separately or sequentially; • use of such combinations: * in the treatment or prophylaxis of a cancer, particularly prostate cancer, or * for the preparation of a medicament for the treatment or prophylaxis of a cancer, particularly prostate cancer; • methods of treatment or prophylaxis of a cancer, particularly prostate cancer, in a subject, comprising administering to said subject

Abstract: Disclosed in the present invention are a thiazolidone spiro pyrimidine trione compound, a preparation method therefor and uses thereof, the compound having a structure represented by formula (I). In the formula, the definitions of the substituents are described in the specification and the claims. The thiazolidone spiro pyrimidine trione compound in the present invention has high in vivo and in vitro antibacterial activity, has better metabolic properties, and is obviously superior to existing compounds of the same kind.

Abstract: The present invention provides heterocyclic compounds of formula (I) that modulate biological metals and to pharmaceutical compositions containing such compounds. The invention particularly relates to compounds that modulate iron and to compounds for the treatment of diseases, particularly neurological diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), Alzheimer-type dementia, Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) and multiple system atrophy (MSA).

Abstract: A compound or its acid addition salt of the general formula (I), wherein R1 represents phenyl substituted with one or two substituents selected from the group consisting of halogen and C1-C3 alkoxyl, or 6-membered heteroaryl with 1 or 2 nitrogen atoms, which is unsubstituted or substituted with a substituent selected from the group consisting of —NH2, halogen, alkyl C1-C4, alkoxyl C1-C3, and 6-membered heterocyclyl comprising 1 or 2 heteroatoms selected from the group consisting of N and O. The compound has the activity of kinase JAK1/JAK3 inhibitor and can find use in the treatment of chronic inflammatory and autoimmunological diseases.

Abstract: The present invention discloses compounds of Formula (I), and pharmaceutically acceptable salts thereof: which inhibit the protein(s) encoded by hepatitis B virus (HBV) or interfere with the function of the HBV life cycle of the hepatitis B virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HBV infection. The invention also relates to methods of treating an HBV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

Abstract: A fused tricyclic compound and use thereof as a medicament, in particular as a medicament for the treatment and/or prevention of hepatitis B. Specifically, a compound having Formula (I) or a stereoisomer, a tautomer, an N-oxide, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, wherein each variate is as defined in specification. The compound also includes a Formula (I) or a stereoisomer, a tautomer, an N-oxide, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof as a medicament, especially as a medicament for the treatment and/or prevention of hepatitis B.

Abstract: The present invention relates to novel compounds of formula (I), process for preparation of the same and composition comprising these compounds.

Abstract: The present invention relates to novel compounds of Formula I and their use in therapeutic treatments. The invention further relates to a novel chiral synthesis of 5,6,7,(8-substituted)-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazines using N-sp3 protective groups. The invention also provides intermediates for use in the synthesis of compounds of Formula I.

Abstract: The present invention provides a quinazoline derivative or its pharmaceutically acceptable salt, a process for the preparation thereof, a pharmaceutical composition comprising the same and a use thereof. The quinazoline derivative or its pharmaceutically acceptable salt has a selective inhibitory activity against the phosphatidylinositol 3-kinase delta subunit, and therefore can be usefully applied for preventing or treating cancer, along with avoiding side effects such as lymphopenia-associated inflammatory responses.

Abstract: Disclosed herein are compounds and methods for inhibiting Arf6. Pharmaceutical compositions and methods for treating a subject with an inhibitor of Arf6 are also disclosed herein.

Abstract: The present invention includes substituted pyridinone-containing tricyclic compounds, and compositions comprising the same, that can be used to treat or prevent hepatitis B virus (HBV) infection in a patient. In certain embodiments, the compounds and compositions of the invention inhibit and/or reduce HBsAg secretion.

Abstract: Compounds, methods of use, and processes for making inhibitors of complement Factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof wherein R12 or R13 on the A group is an aryl, heteroaryl or heterocycle (R32) are provided. The inhibitors of Factor D described herein reduce the excessive activation of complement.

Abstract: A compound having an antiviral activity for inhibiting release of an enveloped virus from a cell is disclosed, including methods of inhibiting release of an enveloped virus from a cell. The antiviral activity of the compound includes inhibiting formation of an associative complex or disrupting formation of an associative complex. The associative complex comprises an L-domain motif of the enveloped virus and at least one cellular polypeptide, or fragment thereof, capable of binding the L-domain motif of the enveloped virus.

Abstract: The present application relates to novel 2-phenyl-3-(piperazinomethyl)imidazo[1,2-a]pyridine derivatives, to processes for their preparation, to their use alone or in combinations for the treatment and/or prevention of diseases, and to their use for preparing medicaments for the treatment and/or prevention of diseases, in particular for treatment and/or prevention of respiratory disorders including, sleep-related respiratory disorders such as obstructive sleep apnoeas and central sleep apnoeas and snoring.

Abstract: The present invention relates to novel compounds of formula (I), process for preparation of the same and composition comprising these compounds.

Abstract: The present invention relates to pyrazolopyrimidinone compounds. The present invention also relates to pharmaceutical compositions containing these compounds and methods of treating autoimmune, inflammatory, and neurodegenerative diseases by administering these compounds and pharmaceutical compositions to subjects in need thereof. The present invention also relates to the use of such compounds for research or other non-therapeutic purposes.

Abstract: Disclosed are oral pharmaceutical compositions of neflamapimod that exhibit suitable exposure for administration in humans and/or that maintain a desirable dissolution profile under standard storage conditions.

Abstract: A compound according to Formula I: wherein R1, LA, CyA, RA, R2, R3, and R4 are as described herein. The present invention relates to novel compounds according to Formula I that antagonize GPR84, a G-protein-coupled receptor that is involved in inflammatory conditions, and methods for the production of these novel compounds, pharmaceutical compositions comprising these compounds, and methods for the prevention and/or treatment of inflammatory conditions, pain, neuroinflammatory conditions, neurodegenerative conditions, infectious diseases, autoimmune diseases, endocrine and/or metabolic diseases, cardiovascular diseases, leukemia, and/or diseases involving impairment of immune cell functions by administering a compound of the invention.

Abstract: The present invention relates to a process for providing the compound of formula I, comprising the step of reacting a compound of formula VII with a base in the presence of an alkaline- or alkaline earth metal salt (MX), wherein LG is a leaving group. The presence of an alkaline- or alkaline earth metal salt was surprisingly found to render said reaction highly reliable in terms of the yield and purity of the compound of formula I obtained. In a further aspect, the present invention relates to the compound of formula I, having less than an amount of 1.50% or less than an amount of 1.25% or less than an amount of 1.00% or less than an amount of 0.75% or less than an amount of 0.50% or less than an amount of 0.25% or less than an amount of 0.10% of the compound of formula VIII.

Abstract: The disclosure relates to aryl hydrocarbon receptor antagonists, such as substituted imidazopyridines and imidazopyrazines, as well as methods of expanding hematopoietic stem cells by culturing hematopoietic stem or progenitor cells in the presence of these agents. Additionally, the disclosure provides methods of treating various pathologies in a patient by administration of expanded hematopoietic stem cells. The disclosure further provides methods of synthesizing aryl hydrocarbon receptor antagonists, such as substituted imidazopyridines and imidazopyrazines, as well as kits containing aryl hydrocarbon receptor antagonists that can be used for the expansion of hematopoietic stem cells.

Abstract: The present invention provides a compound of Formula I: or a pharmaceutically acceptable salt thereof, useful as a BACE1 inhibitor.

Abstract: Compounds of formula (I) defined herein are p38 MAPK inhibitors and are useful as anti-inflammatory agents in the treatment of, inter alia, diseases of the respiratory tract.

Abstract: The disclosure relates to aryl hydrocarbon receptor antagonists, such as substituted imidazopyridines and imidazopyrazines, as well as methods of expanding hematopoietic stem cells by culturing hematopoietic stem or progenitor cells in the presence of these agents. Additionally, the disclosure provides methods of treating various pathologies in a patient by administration of expanded hematopoietic stem cells. The disclosure further provides methods of synthesizing aryl hydrocarbon receptor antagonists, such as substituted imidazopyridines and imidazopyrazines, as well as kits containing aryl hydrocarbon receptor antagonists that can be used for the expansion of hematopoietic stem cells.

Abstract: The present invention relates to substituted 4,5,6,7-tetrahydro-pyrazolo[1,5-a]pyrimidine derivatives and 2,3-dihydro-1H-imidazo[1,2-b]pyrazole derivatives of formula (I) and also compounds of formula (I?) wherein the variables have the meaning defined in the claims. The compounds according to the present invention are useful as ROS1 inhibitors. The invention further relates to processes for preparing novel compounds of the present invention, pharmaceutical compositions comprising compounds of the present invention as an active ingredient as well as the use of compounds of the present invention as a medicament.

Abstract: Disclosed are methods for the treatment of cancer in patients in need of such treatment. The methods comprise administering to such a patient an ubiquitin-activating enzyme (UAE) inhibitor such as ((1R,2R,3S,4R)-2,3-dihydroxy-4-(2-(3-(trifluoromethylthio) phenyl)pyrazolo[1,5-a]pyrimidin-7-ylamino)cyclopentyl)methyl sulfamate (Compound 1) or a pharmaceutically acceptable salt in combination with radiation. Also disclosed are medicaments for use in the treatment of cancer.

Abstract: The present disclosure pertains to a pharmaceutical combination comprising (a) an alpha-isoform specific PI3K inhibitor, (b) a cyclin dependent kinase 4/6 (CDK4/6) inhibitor, and (c) an antimetabolite antineoplastic agent; combined preparations and pharmaceutical compositions thereof; the uses of such a combination in the treatment or prevention of cancer; and methods of treating or preventing cancer in a subject comprising administering a therapeutically effective amount of such combination.

Abstract: The present invention provides a method of treating or ameliorating a neurodegenerative disease in a mammal, the method comprising administering to the mammal a therapeutically effective amount of a neurodegenerative disease drug, wherein the drug is a substrate of an ABC transporter inhibitor, wherein the mammal is further administered a therapeutically effective amount of an ABC transporter inhibitor, whereby the neurodegenerative disease is treated in the mammal. In certain embodiments, the neurodegenerative disease comprises at least one selected from the group consisting of spinal cord injury, Alzheimer's disease, Parkinson's disease, Huntington's disease, prion disease, amyotrophic lateral sclerosis, a tauopathy, and chronic traumatic encephalopathy.

Abstract: The invention relates to the novel products of formula (I) with p, q=0, 1 or 2; R1=phenyl, pyridyl; —(CH2)m—Ra; alkylene; cycloalkyl; heterocycloalkyl; alkyl; —SO2 —Rb; —CO—Re; m=1 or 2; Ra=aryl, heteroaryl, —CO-cycloalkyl, —CO-heterocycloalkyl, —CO—Rb, —C(Rb)?N—ORc, —CO 2 Rd, —CONRxRy; Rb=alkyl, aryl, heteroaryl; Rc=H, alkyl; Rd=alkyl, cycloalkyl; Re=alkyl, cycloalkyl, aryl, heteroaryl; NRxRy with Rx,Ry=H, alkyl, cycloalkyl, alkoxy, phenyl, or form with N a ring with optionally O, N; R2, R3=H, alkyl, CF 3, or form with C a ring with optionally O, S and N; R4=H, F, Cl, CH3 or CN; the morpholine is substituted with Me, and optionally substituted with F, OH; or is (Formula 1a) and the isomer of configuration R,R (Formula 1b) these products being in all the isomer forms and the salts, as medicaments, in particular as anticancer medicaments.

Abstract: The present invention relates to novel compounds of formula (I), process for preparation of the same and composition comprising these compounds.

Abstract: Disclosed are compounds of Formula (I) or a salt thereof, wherein: X is N; W is: (i) —(CR3R3)1-4—; (ii) —(CR3R3)x—Y—(CR3R3)y—; Or (iii) —Y—(CR3R3)2—Y—; and Y, R1, R2, R3, R5, R6, R8, x, and y are defined herein. Also disclosed are methods of using such compounds as modulators of TNF?, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating inflammatory and autoimmune diseases.

Abstract: Disclosed herein are methods determining susceptibility of bacteria in a sample from a subject suspected of having an infection to a plurality of antibiotics simultaneously, wherein the sample is tested without first isolating the bacteria from the sample.

Abstract: The invention concerns novel substituted tricyclic pyrazolo pyrimidine compounds of formula (I-a) or (I-b) having antiviral activity, in particular, having an inhibitory activity on the replication of the respiratory syncytial virus (RSV). The invention further concerns the preparation of such novel compounds, compositions comprising these compounds, and the compounds for use in the treatment of respiratory syncytial virus infection.

Abstract: Described herein are IRE1? inhibitors, compositions containing such inhibitors, and methods of treatment that include administration of such compounds. Exemplary compounds are provided throughout the application.

Abstract: Disclosed are compounds of Formula (I) or a salt thereof, wherein: X is CR6 or N; W is: (i) —(CR3R3)1-4— or (ii) —(CR3R3)x-Y—(CR3R3)y-; and Y, R1, R2, R3, R5, R6, R7, x, and y are define herein. Also disclosed are methods of using such compounds as modulators of TNF?, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating inflammatory and autoimmune diseases.

Abstract: This disclosure is directed to agonists of the apelin receptor (APJ) and uses of such agonists.

Abstract: This invention is in the area of improved compounds, compositions and methods of transiently protecting healthy cells, and in particular hematopoietic stem and progenitor cells (HSPC) as well as renal cells, from damage associated with DNA damaging chemotherapeutic agents. In one aspect, improved protection of healthy cells is disclosed using disclosed compounds that act as highly selective and short, transiently-acting cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors when administered to subjects undergoing DNA damaging chemotherapeutic regimens for the treatment of proliferative disorders.

Abstract: This invention is in the area of improved compounds for and methods of treating selected RB-positive cancers and other Rb-positive abnormal cellular proliferative disorders while minimizing the deleterious effects on healthy cells, for example healthy Hematopoietic Stem Cells and Progenitor Cells (HSPCs), associated with current treatment modalities. In one aspect, improved treatment of select RB-positive cancers is disclosed using specific compounds disclosed herein. In certain embodiments, the compounds described herein act as highly selective and, in certain embodiments, short, transiently-acting cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors when administered to subjects.

Abstract: A series of substituted [1,2,4]triazolo[4,3-b]pyridazine derivatives of formula (I), being potent modulators of human TNFa activity, are accordingly of benefit in the treatment and/or prevention of various human ailments, including autoimmune and inflammatory disorders; neurological and neurodegenerative disorders; pain and nociceptive disorders; cardiovascular disorders; metabolic disorders; ocular disorders; and oncological disorders.

Abstract: Provided herein are 2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-substituted-pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ols and 1-(2,4-difluorophenyl)-2,2-difluoro-2-(5-substituted-pyridin-2-yl)ethanones and processes for their preparation.

Abstract: The invention provides compositions and methods for utilizing human epididymal secretion protein E4 (HE4) in the prevention and treatment of cancer and other human diseases.