Abstract: This invention relates to pyrrolopyrimidine derivatives of formula (I): where R1, X, p, R4, R2 and R3 are as defined herein, and their use as pharmaceuticals.

Abstract: The present invention provides compounds of Formula (I) and pharmaceutically acceptable salts thereof; as further described herein. The present invention further provides pharmaceutical compositions comprising these compounds, and combinations comprising these compounds combined with or used with a therapeutic co-agent, as well as therapeutic uses of these compounds and compositions. These are useful in the treatment of diseases such as cancer that are associated with activation of ERK1 and/or ERK2, and especially for MAPK pathway dependent cancers showing resistance to Raf and/or MEK inhibitory cancer therapeutics.

Abstract: The present invention provides hydroxyl, keto, and glucuronide derivatives of 3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile.

Abstract: Fused cyclic pyrimidine compounds, including tautomers thereof, and pharmaceutically acceptable salts, prodrugs, solvates and hydrates thereof, are disclosed having the general Formula 1: These compounds are useful in methods for treating cancer, selectively targeting cancerous cells via the proton coupled folate transporter, folate receptor alpha, and/or folate receptor beta pathways, inhibiting GARFTase in cancerous cells, and selectively targeting activated macrophages in a patient having an autoimmune disease, such as rheumatoid arthritis.

Abstract: The present invention is directed to piperidinone carboxamide indane derivatives which are antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which the CGRP is involved, such as migraine. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

Abstract: The invention encompasses a novel process for making piperidinone carboxamide indane and azainane derivatives, which are CGRP receptor antagonists useful for the treatment of migraine, utilizing a highly effective spiroacid synthesis.

Abstract: Compounds of formulae I, II or III, and pharmaceutically acceptable salts thereof, are useful as CDK inhibitors.

Abstract: A method for treating cancer tumors, particularly ovarian cancer tumors, is described, where fused cyclic pyrimidine having a cancer treating ability is selectively delivered to an FR expressing cancerous tumor.

Abstract: A pharmaceutical composition of Pemetrexed represented by formula (I), which is a liquid ready to use solution formulation or a lyophilized pharmaceutical composition for parenteral administration comprising a pharmaceutically acceptable organic amine, an inert gas and optionally containing at least one or more pharmaceutically acceptable excipients. Also provided are processes for preparation of the ready to use solution formulation or lyophilized pharmaceutical composition of the present invention.

Abstract: The present invention relates to a bisulfate of a Janus kinase (JAK) inhibitor and a preparation method therefor. More specifically, the present invention relates to a (3aR,5s,6aS)—N-(3-methoxyl-1,2,4-thiadiazole-5-group)-5-(methyl(7H-pyrrolo[2,3-d]pyrimidine-4-group)amino)hexahydrocyclopenta[c]pyrrole-2(1H)-formamide bisulfate shown in the formula (I), a preparation method therefor, and an application thereof. The bisulfate shown in the formula (I) can be well suitable as a Janus kinase (JAK) inhibitor in clinical work for treating rheumatism or rheumatoid arthritis.

Abstract: Disclosed are compound of Formula (Ia), wherein R1, R2, and R3 are as defined in the specification, and pharmaceutically acceptable salts thereof. The compounds may be used as agents in the treatment of diseases, including cancer. Also provided are pharmaceutical compositions, comprising one or more compounds of Formula (Ia).

Abstract: A compound having the Formula as follows: wherein R, R1 and R2 are selected from hydrogen, aryl, fused aryl, heteroaryl, saturated carbocylclic, partially saturated carbocyclic, saturated heterocyclic, partially saturated heterocyclic, C1-10 alkyl, haloalkyl, alkenyl, alkynyl, arylalkyl, arylalkenyl, arylalkynyl, heteroarylalkyl, heteroarylalkenyl, alkenylalkyl, alkynylalkyl, carbocycloalkyl, heterocycloalkyl, hydroxyalkyl, aminoalkyl, carboxyalkyl, nitroalkyl, cyanoalkyl, acetamidoalkyl, and acyloxyalkyl. A process for the preparation thereof is also provided.

Abstract: The present invention relates to compounds of formula (I) or pharmaceutically acceptable salts thereof, wherein Q, G, ring A, ring B, R1, R2, R3, R4, R5, R5a, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15, R16, R17, R18, R19, R20, R21, R22, R23, R24, and m are defined herein. The novel purine derivatives are useful in the treatment of abnormal cell growth, such as cancer, in mammals. Additional embodiments relate to pharmaceutical compositions containing the compounds and to methods of using the compounds and compositions in the treatment of abnormal cell growth in mammals.

Abstract: The ectopic expression of Mer receptor tyrosine kinase (Mer) has been identified as a tumor cell survival gene product in Acute Lymphoblastic Leukemia (ALL) cells and a potential cause of ALL chemoresistance. Hence, we investigated whether the development of small molecule Mer inhibitors was possible. A first aspect of the present invention is a compound (sometimes referred to as an “active compound” herein) of Formula I, IA, or IB.

Abstract: Compounds Formula I: and salts thereof, formulations thereof, conjugates thereof, derivatives thereof, forms thereof and uses thereof are described. In certain aspects and embodiments, the described compounds or salts thereof, formulations thereof, conjugates thereof, derivatives thereof, forms thereof are active on at least one of Fms protein kinase or Kit protein kinase.

Abstract: Described is a device comprising a substrate, and a quorum sensor array on the substrate. The quorum sensor array comprises quorum sensors that release signal molecules in response to one or more environmental signals being sense by the quorum sensors to thereby amplify the one or more environmental signals by causing a signal chain reaction in neighboring quorum sensors of the quorum sensor array. Each of the quorum sensors comprises a lipid multilayer structure. Also described is a method comprising providing data for changes in optical properties of at least part of the quorum sensor array in response to exposing the quorum sensor array to one or more environmental signals, and determining the presence of the one or more environmental signals based on the data.

Abstract: The present invention is directed to fused heterocyclic azaindane carboxamide derivatives which are antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which the CGRP is involved, such as migraine. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

Abstract: The present invention discloses pharmaceutical combination therapies for the treatment or prevention of diseases in a mammal comprising a Janus Kinase inhibitor or a pharmaceutically acceptable salt thereof and a HMG-CoA reductase inhibitor or a pharmaceutically acceptable salt thereof. Pharmaceutical compositions containing the same and kits for achieving a therapeutic effect in a mammal comprising pharmaceutical combination therapies are further described.

Abstract: Described herein is pyrrolo{2,3-d}pyrimidine compounds, their use as Janus Kinase (JAK) inhibitors, pharmaceutical compositions containing this compounds, and methods for the preparation of these compounds.

Abstract: The present invention relates to compounds of formula (I) or pharmaceutically acceptable salts thereof, wherein Q, T, V, W, X, Y, Z, ring A, R1, R2, R3, R4, R5, R5a, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15, R16, R17 and m are defined herein. There novel pyrrolopyrimidine and purine derivatives are useful in the treatment of abnormal cell growth, such as cancer, in mammals. Additional embodiments relate to pharmaceutical compositions containing the compounds and to methods of using the compounds and compositions in the treatment of abnormal cell growth in mammals.

Abstract: The present invention provides pharmacological compounds including an effector moiety conjugated to a binding moiety that directs the effector moiety to a biological target of interest. Likewise, the present invention provides compositions, kits, and methods (e.g., therapeutic, diagnostic, and imaging) including the compounds. The compounds can be described as a protein interacting binding moiety-drug conjugate (SDC-TRAP) compounds, which include a protein interacting binding moiety and an effector moiety. For example, in certain embodiments directed to treating cancer, the SDC-TRAP can include an Hsp90 inhibitor conjugated to a cytotoxic agent as the effector moiety.

Abstract: The present invention provides heterocyclic-substituted pyrrolopyridines and pyrrolopyrimidines of Formula I: wherein X, Y, Z, L, A, R5, n, m, and r are defined above, as well as their compositions and methods of use, that modulate the activity of Janus kinases (JAKs) and are useful in the treatment of diseases related to the activity of JAKs including, for example, inflammatory disorders, autoimmune disorders, cancer, and other diseases.

Abstract: The present invention relates to certain pyrrolopyrimidine derivatives, pharmaceutical compositions containing them, and methods of using them, including methods for the treatment of tumors and related diseases related to the dysregulation of kinase (such as EGFR (including HER), Alk, PDGFR, but not limited to) pathways.

Abstract: The present invention relates to pharmaceutical compounds, compositions and methods, especially as they are related to compositions and methods for the treatment and/or prevention of a proliferation disorder, a cancer, a tumor, an inflammatory disease, an autoimmune disease, psoriasis, dry eye or an immunologically related disease, and in some embodiments diseases or disorders related to the dysregulation of kinase such as, but not limited to, EGFR (including HER), Alk, PDGFR, BLK, BMX/ETK, FLT3(D835Y), ITK, TEC, TXK, BTK, or JAK, and the respective pathways.

Abstract: A method for treating cancer tumors, particularly ovarian cancer tumors, is described, where fused cyclic pyrimidine having a cancer treating ability is selectively delivered to an FR expressing cancerous tumor.

Abstract: [Problem] On the basis of a cathepsin S inhibitory effect, an excellent agent for treating or preventing autoimmune disease, allergic disease, graft rejection of an organ, bone marrow or tissue, systemic lupus erythematosus, or the like is provided. [Means for Solution] It was found that a nitrogen-containing bicyclic heterocyclic compound has the excellent cathepsin S inhibitory effect, thereby completing the invention. The compound of the present invention has the cathepsin S inhibitory effect, and can be used as an agent for preventing and/or treating autoimmune disease, allergic disease, graft rejection of an organ, bone marrow or tissue, systemic lupus erythematosus, or the like.

Abstract: The present invention provides a method for treating allergic dermatitis, atopic dermatitis, or one or more symptoms thereof in a mammal in need, which method comprises administering to the mammal a first therapeutically effective dose of a Janus Kinase (JAK) inhibitor twice a day for a number of days sufficient to ease or eliminate one or more clinical signs in the mammal, followed by a second therapeutically effective dose of the JAK inhibitor at a reduced frequency.

Abstract: Disclosed are compounds of Formula 1, N-oxides, and salts thereof, wherein Z is O or S; A1, A2, A3 and A4 are independently N or CR1, provided that only one of A1, A2, A3 and A4 is N; and R1, R2, R3 and Q are as defined in the disclosure. Also disclosed are compositions containing the compounds of Formula 1 and methods for controlling a parasitic nematode comprising contacting the parasitic nematode or its environment with a biologically effective amount of a compound or a composition of the invention.

Abstract: Disclosed herein are markers whose mutational status is associated with sensitivity to treatment with NAE inhibitors. Mutational status is determined by measurement of characteristics of markers associated with the marker genes. Compositions and methods are provided to assess markers of marker genes to predict response to NAE inhibition treatment.

Abstract: A compound having the Formula as follows: wherein R, R1 and R2 are selected from hydrogen, aryl, fused aryl, heteroaryl, saturated carbocylclic, partially saturated carbocyclic, saturated heterocyclic, partially saturated heterocyclic, C1-10 alkyl, haloalkyl, alkenyl, alkynyl, arylalkyl, arylalkenyl, arylalkynyl, heteroarylalkyl, heteroarylalkenyl, alkenylalkyl, alkynylalkyl, carbocycloalkyl, heterocycloalkyl, hydroxyalkyl, aminoalkyl, carboxyalkyl, nitroalkyl, cyanoalkyl, acetamidoalkyl, and acyloxyalkyl. A process for the preparation thereof is also provided.

Abstract: A pharmaceutical composition of Pemetrexed represented by formula (I), which is a liquid ready to use solution formulation or a lyophilized pharmaceutical composition for parenteral administration comprising a pharmaceutically acceptable organic amine, an inert gas and optionally containing at least one or more pharmaceutically acceptable excipients. Also provided are processes for preparation of the ready to use solution formulation or lyophilized pharmaceutical composition of the present invention.

Abstract: The present invention provides substituted pyrrolo-, furano-, and cyclopentylpyrimidine bicyclic compounds of Formula III, and Formula IV, and pharmaceutically acceptable salts, solvates, and hydrates thereof, having antimitotic activity, anti-multidrug resistance activity, such as for example P-glycoprotein inhibition, and antitumor activity, and which inhibit paclitaxel sensitive and resistant tumor cells. Also provided are methods of utilizing these compounds and pharmaceutical compositions for treating tumor cells and inhibiting mitosis of cancerous cells.

Abstract: The present application relates to novel substituted annellated pyrimidines, methods for production thereof, use thereof alone or in combinations for treating and/or preventing diseases and use thereof for the production of medicinal products for treating and/or preventing diseases, in particular for treating and/or preventing cardiovascular diseases.

Abstract: Disclosed herein are markers whose mutational status is associated with sensitivity to treatment with NAE inhibitors. Mutational status is determined by measurement of characteristics of markers associated with the marker genes. Compositions and methods are provided to assess markers of marker genes to predict response to NAE inhibition treatment.

Abstract: The invention is directed to novel pyrrolopyrimidine compounds of formula (1) wherein R1, R2y, R4, R8-R11, A and L are defined herein and to salts, including pharmaceutically acceptable salts thereof. The compounds of the present invention are CDK4/6 inhibitors and could be useful in the treatment of diseases and disorders mediated by CDK4/6, such as cancer, including mantle cell lymphoma, liposarcoma, non small cell lung cancer, melanoma, squamous cell esophageal cancer and breast cancer. The invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting CDK4/6 activity and to the treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

Abstract: There are disclosed novel compounds of formula (I) wherein R1, R12, L, X and Y are as defined in the specification, and pharmaceutically acceptable salts thereof; together with processes for their preparation, compositions containing them and their use in therapy. The compounds are inhibitors of the enzyme MPO and are thereby particularly useful in the treatment or prophylaxis of neuroinflammatory disorders, cardiovascular disorders and respiratory disorders.

Abstract: The present invention relates to a corticotropin releasing hormone receptor type 1 (CRHR1) antagonist for use in the treatment of depressive symptoms and/or anxiety symptoms in a novel group of patients, i.e. patients having corticotropin releasing hormone (CRH) overactivity.

Abstract: The instant invention provides compounds of formula I which are JAK3 inhibitors. Specifically, the compounds of formula I are pyrrolo[2,3-d]pyrimidine derivative compounds. The instant invention also provides methods of treating JAK-mediated diseases such as rheumatoid arthritis, asthma, COPD and cancer, by administering the pyrrolo[2,3-d]pyrimidine-derivative compounds of formula I.

Abstract: The present invention is related to processes for preparing chiral substituted pyrazolyl pyrrolo[2,3-d]pyrimidines of Formula III, and related synthetic intermediate compounds. The chiral substituted pyrazolyl pyrrolo[2,3-d]pyrimidines are useful as inhibitors of the Janus Kinase family of protein tyrosine kinases (JAKs) for treatment of inflammatory diseases, myeloproliferative disorders, and other diseases.

Abstract: The present invention provides chemical entities or compounds and pharmaceutical compositions thereof that are capable of modulating lipid kinases such PI3 kinases, tyrosine kinases and protein kinases such as mTOR. For example, the invention provides compounds of Formula: Also provided in the present invention are methods of using these compositions to modulate these kinases especially for therapeutic applications.

Abstract: The present invention relates to cyclobutane and methylcyclobutane derivatives, as well as their salts, compositions, and methods of use, which are Janus kinase (JAK) inhibitors useful in the treatment of JAK-associated diseases including, for example, inflammatory and autoimmune disorders, as well as cancer and myeloproliferative disorders.

Abstract: The present invention provides methods of predicting response to a cancer therapy based on the methylation status of the ERBB2 gene. One aspect of the invention provides a method of predicting response to an EGFR inhibitor therapy based on the methylation status of the ERBB2 gene.

Abstract: The present invention provides cyclobutyl substituted pyrrolopyrimidines and pyrrolopyridines of Formula I: wherein X, Y, Z, L, A, R5, n and m are defined above, as well as their compositions and methods of use, that modulate the activity of Janus kinases (JAKs) and are useful in the treatment of diseases related to the activity of JAKs including, for example, inflammatory disorders, autoimmune disorders, cancer, and other diseases.

Abstract: The present invention discloses certain new solid state forms of (S)-4-amino-N-(1-(4-chlorophenyl)-3-hydroxypropyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide, processes for preparing such forms, pharmaceutical compositions comprising them, and the use of such forms in therapy.

Abstract: Methods to improve hematopoiesis and increase white blood cell counts in subjects and patients using pyrimidine-based inhibitors of Bruton's tyrosine kinase (Btk) are disclosed.

Abstract: Described herein is pyrrolo{2,3-d}pyrimidine compounds, their use as Janus Kinase (JAK) inhibitors, pharmaceutical compositions containing this compounds, and methods for the preparation of these compounds.

Abstract: The present invention relates to veterinary compositions in a form of an orally deliverable tablet, and more particularly to a controlled-release composition that provides sufficiently long duration to permit once daily administration.

Abstract: The compounds of Formula (I), wherein R1, R2, R21, R22, R23, R24, Y and R3 have the meanings as given in the description, the salts thereof, the stereoisomers of the compounds and the salts thereof are effective inhibitors of the type 5 phosphodiesterase and are useful for treating or preventing idiopathic pulmonary lung fibrosis.

Abstract: The current disclosure provides for specific peptides, and derived ionization characteristics of the peptides, from the KRT5, KRT7, NapsinA, TTF1, TP63, and/or MUC1 proteins that are particularly advantageous for quantifying the KRT5, KRT7, NapsinA, TTF1, TP63, and/or MUC1 proteins directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or what can also be termed as Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological samples are chemically preserved and fixed wherein said biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded.

Abstract: A stable ready-to-use pharmaceutical composition comprising pemetrexed or pharmaceutically acceptable salts thereof, wherein the composition is free from antioxidants, amino acids and chelating agents. Also provided is a process for preparing a stable ready-to-use pharmaceutical composition comprising the steps: i) purging inert gas into a parenterally acceptable aqueous solvent until the dissolved oxygen content of the solvent comes to less than 7 mg/L, preferably less than 3 mg/L; ii) adding pemetrexed disodium under stirring; iii) adjusting the pH of the resulting solution to between 4 to 9; iv) optionally adding additional aqueous solvent; wherein the composition is purged with inert gas throughout the entire process.