Abstract: The present invention relates to substituted benzene compounds. The present invention also relates to pharmaceutical compositions containing these compounds and methods of treating cancer 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: The present invention relates to CCR3 inhibitors of formula 1, wherein R1 is H, C1-6-alkyl, C0-4-alkyl-C3-6-cycloalkyl, C1-6-haloalkyl; R2 is H, C1-6-alkyl; X is an anion selected from the group consisting of chloride or ½ dibenzoyltartrate j is 1 or 2. for use as a medicament for the treatment of diseases selected from dry age-related macular degeneration (dAMD), wet age-related macular degeneration (wAMD), retinopathy of prematurity (ROP), central retinal vein occlusion (CRVO), nasal polyposis, eosinophilic esophagitis, eosinophillic gastroenteritis (e.g. eosinophilic gastritis and eosinophilic ententeritis), hypereosinophilic syndrome and Churg Strauss syndrome.

Abstract: The instant invention describes compounds having metalloenzyme modulating activity, and methods of treating diseases, disorders or symptoms thereof mediated by such metalloenzymes.

Abstract: A method for treating cancer with a mutation in ROS or RET, comprising identifying a subject with a cancer with a mutation in ROS or RET, and administering to the subject an effective amount of a compound according to formulae (I) OR (la) or a tautomer, or a pharmaceutically acceptable salt thereof, wherein the variables structural formulae are defined herein.

Abstract: Provided herein are antagonists of prostaglandin EP3 receptor, processes to make said antagonists, and methods comprising administering said antagonists to a mammal in need thereof.

Abstract: Compounds of formula (I) have checkpoint kinase 1 (CHK1) inhibitory activity: wherein R1, R2, R5 and R6 are independently selected from hydrogen, hydroxy, methyl, trifluoromethyl, hydroxymethyl, methoxy, trifluoromethoxy, methylamino and dimethylamino; R3, and R4 are independently selected from hydrogen, hydroxy, C1-C3 alkyl, fluoro-(C1-C3)-alkyl, hydroxy-(C1-C3)-alkyl, C1-C3 alkoxy, fluoro-(C1-C3)-alkoxy, hydroxy-(C1-C3)-alkoxy, —N(R11)—R12, -Alk-N(R11)—R12, —O-Alk-N(R11)—R12, —C(?O)OH, carboxy-(C1-C3)-alkyl, or —C(?O)—NH—R13; Alk is a straight or branched chain divalent C1-C6 alkylene radical; R7 and R8 are independently selected from hydrogen, hydroxy, or C1-C3 alkoxy; X is a straight chain divalent C1-C3 alkylene radical, optionally substituted on one or more carbons by R9 and/or R10; W is selected from —C(?O)—N(—R16)— or —N(—R17)—C(?O)—; Y is hydrogen, C1-C3 alkyl, C1-C3 alkoxy, or halo; and Q is selected from optionally substituted phenyl, optionally substituted cyclohexyl, or an optionally substitu

Abstract: The present invention relates to compounds and pharmaceutically acceptable salts of Formulas A and B: wherein A, B, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R10 are as defined above. The invention further relates to pharmaceutical compositions comprising the compounds and pharmaceutically acceptable salts and to methods of treating diabetes mellitus and its complications, cancer, ischemia, inflammation, central nervous system disorders, cardiovascular disease, Alzheimer's disease and dermatological disease pression, virus diseases, inflammatory disorders, or diseases in which the liver is a target organ.

Abstract: The present invention relates to organic molecules capable of modulating tyrosine kinase signal transduction in order to regulate, modulate and/or inhibit abnormal cell proliferation.

Abstract: The invention relates to piperidinyl compounds of Formula (I): or a pharmaceutically acceptable salt, prodrug, or solvate thereof, wherein R1-R3 and Z are defined as set forth in the specification. The invention is also directed to an assay useful for identifying such compounds as N-type calcium channel modulators or blockers. The invention is also directed to the compounds of Formula (I) and compounds identified by the above assay, and the use of such compounds to treat, prevent or ameliorate a disorder responsive to the blockade of calcium channels, and particularly N-type calcium channels. Compounds of the present invention are especially useful for treating pain.

Abstract: The present invention relates to compounds of Formula (I) that are useful for treating, preventing and/or managing the diseases, disorders, syndromes or conditions associated with the modulation of GPR119 receptor activity. The invention also relates to the process for preparation of the compounds, pharmaceutical compositions thereof. The invention further relates to methods of treating, preventing and/or managing diseases, disorders syndromes or conditions associated with the modulation of GPR119 receptor by using either alone or in combinations of Formula (I).

Abstract: Disclosed herein are methods for controlling the activity of hypoxia-inducible transcription factor 1-alpha (HIF-1?) and diseases, conditions, or syndromes related thereto, inter alia, Peripheral Vascular Disease (PVD), Coronary Artery Disease (CAD), heart failure, ischemia, and anemia. Further disclosed are pharmaceutical compositions comprising HIF-1? prolyl hydroxylase inhibitors useful in treating diseases, conditions, and/or syndromes related thereto the activity of HIF-1?.

Abstract: Disclosed are the ERK inhibitors of formula (1): and the pharmaceutically acceptable salts thereof, wherein: A is a five membered monocyclic heteroaryl ring; and B is a monocyclic heterocycloalkyl ring, or a monocyclic heterocycloalkenyl ring, or a bridged monocyclic heterocycloalkyl ring, or a fused (monocyclic heterocycloalkyl ring) cyclopropyl ring. Also disclosed are methods of treating cancer using the compounds of formula (1).

Abstract: A method of reducing or inhibiting kinase activity of C-KIT in a cell or a subject, and the use of such compounds for preventing or treating in a subject a cell proliferative disorder and/or disorders related to C-KIT using a compound of the present invention: or a solvate, hydrate, tautomer or pharmaceutically acceptable salt thereof. The present invention is further directed to methods for treating conditions such as cancers and other cell proliferative disorders.

Abstract: The present invention belongs to the medicinal chemistry field, and specifically discloses a [1,3,4]oxadiazole derivative with the structure of general formula (I) and pharmaceutically acceptable salt thereof. The compound can be used to prepare a medicine for preventing or treating a disease of the central nervous system.

Abstract: The invention relates to the compounds of formula I or its pharmaceutical acceptable salts, as well as polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of formula I, and methods for the treatment of severe pain may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be used to treatment of postoperative pain, cancer pain, kidney stones pain, fractures, local pain, chronic pain, chemotherapy induced pain, neuropathic pain, post herpetic neuralgia, neuralgia, motor neurone disease, diabetic neuropathy, postherpetic neuralgia, injury, post-operative pain, osteoarthritis, rheumatoid arthritis, multiple sclerosis, spinal cord injury, migraine, HIV related neuropathic pain, cancer pain and lower back pain.

Abstract: The invention relates to novel substituted piperidines, to processes for their preparation, to their use for the treatment and/or prophylaxis of diseases and to their use for preparing medicaments for the treatment and/or prophylaxis of diseases, in particular of cardiovascular disorders and tumor disorders.

Abstract: Disclosed are substituted pyridine compounds as well as pharmaceutical compositions and methods of use. One embodiment is a compound having the structure wherein E, J, T, the ring system denoted by “B”, T, R3, R4, w and x are as described herein. In certain embodiments, a compound disclosed herein activates the AMPK pathway, and can be used to treat metabolism-related disorders and conditions.

Abstract: The present invention is concerned with novel substituted triazolyl piperazine and triazolyl piperidine derivatives of Formula (I) wherein R1, R2, R3, R4a, R4b, R5, X, Y1, Y2, L1, and L2 have the meaning defined in the claims. The compounds according to the present invention are useful as gamma secretase modulators. The invention further relates to processes for preparing such novel compounds, pharmaceutical compositions comprising said compounds as an active ingredient as well as the use of said compounds as a medicament.

Abstract: The present invention provides a compound of formula (A): as described herein, and pharmaceutically acceptable salts, enantiomers, rotamers, tautomers, or racemates thereof. Also provided are methods of treating a disease or condition mediated by PIM kinase using the compounds of Formula I, and pharmaceutical compositions comprising such compounds.

Abstract: This invention relates to certain heteroaryl compounds for use as medicaments, more specifically as medicaments for treating animals. The medicament can be used for the treatment of helminth infections and the treatment of parasitosis caused by helminth infections. This invention also relates to uses of the compounds to make medicaments and treatments comprising the administration of the compounds to animals in need of the treatments. This invention also relates to pharmaceutical compositions and kits comprising the compounds.

Abstract: The present invention provides for compounds of Formula I and various embodiments thereof, and compositions comprising compounds of Formula I and various embodiments thereof. In compounds of Formula I, the groups R1, R2, R3, R4, R5, R6, m, n and the C-linked Ring have the meaning as described herein. The present invention also provides for methods of using compounds of Formula I and compositions comprising compounds of Formula I as DLK inhibitors and for treating neurodegeneration diseases and disorders.

Abstract: Compounds are provided that act as potent antagonists of the CCR9 receptor, and which have been further confirmed in animal testing for inflammation, one of the hallmark disease states for CCR9. The compounds are generally aryl sulfonamide derivatives and are useful in pharmaceutical compositions, methods for the treatment of CCR9-mediated diseases, and as controls in assays for the identification of CCR9 antagonists.

Abstract: Disclosed are substituted pyridine compounds as well as pharmaceutical compositions and methods of use. One embodiment is a compound having the structure wherein E, J, T, the ring system denoted by “B”, T, R3, R4, w and x are as described herein. In certain embodiments, a compound disclosed herein activates the AMPK pathway, and can be used to treat metabolism-related disorders and conditions.

Abstract: The invention relates to compounds and methods for treating cell proliferation disorders.

Abstract: Compounds of the present invention, and pharmaceutically acceptable compositions thereof, are useful as modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator (“CFTR”). The present invention also relates to methods of treating ABC transporter mediated diseases using compounds of the present invention.

Abstract: A method for treating a tumor by combining a piperidine compound of formula (I) or salt thereof and a microtubule-targeting drug, in which the microtubule-targeting drug is administered once per 7 days or more one cycle, and the piperidine compound is administered once or more per day for 4 days or more: R1 represents a carboxyl group, —C(?O)NR5R6, or an oxadiazolyl group optionally substituted with a C1-C6 alkyl group or trifluoromethyl group; R2 represents a halogen atom or C1-C6 alkoxy group; R3 represents a phenyl group optionally having 1 to 3 groups, selected from a halogen atom, and a C1-C6 alkyl, C1-C6 alkoxy, or trifluoromethyl group; R4 represents a hydrogen atom or C1-C6 alkyl group; and R5 and R6, each represent a hydrogen atom, a C1-C6 alkyl or C3-C6 cycloalkyl group; or R5 and R6, together with a nitrogen atom, optionally form a 3 to 6-membered nitrogen-containing saturated heterocyclic group.

Abstract: It has been discovered that pharmacological inhibition of K+ channels (using the FDA-approved broad-spectrum K+ channel antagonist 4-AP) positively benefitted smn mutant phenotypes, a result that is consistent with the defective excitability of motor circuits by their interneuron or sensory neuron inputs being a critical consequence of SMN depletion. Based on these observations, certain embodiments of the invention are directed to methods of treatment of SMA by administering therapeutically effective amounts of one or more potassium channel antagonists, including 4-aminopyridine, 4-(dimethylamino)pyridine, 4-(methylamino)pyridine, and 4-(aminomethyl)pyridine. Other embodiments are directed to new pharmaceutical formulations comprising two or more potassium channel antagonists.

Abstract: The present invention provides organic compounds of the following structure; A-L1-B-C-D-L2-E that are useful for treating or preventing conditions or disorders associated with DGAT1 activity in animals, particularly humans.

Abstract: This invention comprises the novel compounds of formula (I) wherein n, m, t, R1, R2, L, Q, X, Y, Z and have defined meanings, having histone deacetylase inhibiting enzymatic activity; their preparation, compositions containing them and their use as a medicine.

Abstract: The present invention is directed to N-linked lactam compounds of general formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimer's disease, schizophrenia, pain or sleep disorders. The invention is also directed to pharmaceutical compositions comprising the compounds, and to the use of the compounds and compositions in the treatment of diseases mediated by the M1 receptor.

Abstract: The present invention relates to novel carboxamide compounds and their use for the manufacture of a medicament. The carboxamide compounds are inhibitors of calpain (calcium dependant cysteine proteases). The invention therefore also relates to the use of these carboxamide compounds for treating a disorder associated with an elevated calpain activity.

Abstract: The present disclosure relates to compositions and methods for treating acne and other conditions. In particular, the compositions and methods are useful for the treatment of sebum associated conditions.

Abstract: The present invention relates to picolinamide derivatives which have blocking activities of voltage gated sodium channels as the TTX-S channels, and which are useful in the treatment or prevention of disorders and diseases in which voltage gated sodium channels are involved. The invention also relates to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which voltage gated sodium channels are involved.

Abstract: Embodiments of the invention are directed to compounds that are positive allosteric modulators of AMPA receptors.

Abstract: The present disclosure provides methods of that include detecting in a biological sample from a patient having or suspected of having cancer the presence of a polypeptide having ROS1 kinase activity or a polynucleotide encoding the same and detecting in the biological sample the presence of a mutant EGFR polypeptide or a polynucleotide encoding the same. In some aspects, the disclosure provides methods of treating a patient for cancer that include determining that a biological sample from a tumor in the patient includes a polypeptide having ROS1 kinase activity or a polynucleotide encoding the same and a mutant EGFR polypeptide or a polynucleotide encoding the same and administering to the patient a therapeutically effective amount of a ROS1 inhibitor and an EGFR inhibitor, thereby treating the patient for cancer.

Abstract: Amido compounds are disclosed that have a formula represented by the following: and wherein Cy1, Cy2, n1, n2, R1a, R1b, R2, R3, R4, R5, and R6 are as described herein. The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, inflammatory conditions, autoimmune disorders, cancer, and graft-versus-host disease.

Abstract: The present invention provides compounds of Formula (Ia): or stereoisomers, tautomers, or pharmaceutically acceptable salts thereof, wherein all the variables are as defined herein. These compounds are selective factor XIa inhibitors or dual inhibitors of FXIa and plasma kallikrein. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and/or inflammatory disorders using the same.

Abstract: The present invention relates to the 1H-indazole-3-carboxamide compounds having the following general formula (I) as glycogen synthase kinase 3 beta (GSK-3?) inhibitors and to their use in the treatment of GSK-3p-related disorders such as, for example, (i) insulin-resistance disorders; (ii) neurodegenerative diseases; (iii) mood disorders; (iv) schizophrenic disorders; (v) cancerous disorders; (vi) inflammation, (vii) substance abuse disorders; (viii) epilepsies; and (ix) neuropathic pain.

Abstract: Compounds, compositions, and methods for modulation of Hec1/Nek2 interaction are provided. Especially preferred compounds disrupt Nek2/Hec1 binding and are therefore useful as chemotherapeutic agent for neoplastic diseases.

Abstract: The present disclosure provides substituted piperidines or pyrrolidines having Formula IA: and the pharmaceutically acceptable salts and solvates thereof, wherein R1, R2a, R2b, R6, A, X, m and n are defined as set forth in the specification. In certain embodiments, Compounds of the present disclosure are useful for treating pain. The present disclosure is also directed to the use of Compounds of the present disclosure to treat a disorder responsive to blockade of one or more sodium channels.

Abstract: 8-Substituted-2,6-methano-3-benzazocines of general structure are useful as analgesics, anti-diarrheal agents, anticonvulsants, antitussives and anti-addiction medications.

Abstract: The present invention provides novel substituted pyrazolone compounds, pharmaceutical acceptable salts and formulations thereof useful in modulating the protein tyrosine kinase activity, and in modulating cellular activities such as proliferation, differentiation, apoptosis, migration and invasion. The invention also provides pharmaceutically acceptable compositions comprising such compounds and methods of using the compositions in the treatment of hyperproliferative disorders in mammals, especially humans.

Abstract: The invention, in a first aspect relates to compounds of formula (I) or a pharmaceutically acceptable salt thereof, wherein R is a 6-membered aromatic ring, or a 5- or 6-membered heteroaromatic ring comprising 1 to 3 heteroatoms selected from S, O and N, or a 6-membered benzocondensed heteroaromatic ring containing N as heteroatom, optionally each of said rings being substituted with one or two substituents selected from the group consisting of (C1-C3)alkyl, (C3-C5)cycloalkyloxy, (C1-C3)alkylcarbonyl, cyano, trifluoromethyl, dimethylamino, or phenyl which optionally is substituted with one or more halogen atoms, or a 5- or 6-membered heterocycle containing from one to three nitrogen atoms; X is O or N; P is pyridyl, pyrimidyl, pyrazyl, or pyridazyl, each being optionally substituted with one or more substituents selected from the group consisting of (C1-C3)alkyl, halogen, trifluoromethyl, and cyano, and use thereof as pharmaceuticals.

Abstract: Compounds which modulate the CB2 receptor are disclosed. The compounds are useful for treating CB2 receptor-mediated diseases such as pain.

Abstract: This document discloses molecules having the following formula (“Formula I”):

Abstract: Compounds having the following formula: (I) wherein: A is an optionally substituted triazole, or a stereoisomer or a pharmaceutically-acceptable salt thereof, are useful as kinase modulators, including IRAK-4 modulation.

Abstract: Described herein are compounds and pharmaceutical compositions containing such compounds, which inhibit the activity of histone deacetylase 8 (HDAC8). Also described herein are methods of using such HDAC8 inhibitors, alone and in combination with other compounds, for treating diseases or conditions that would benefit from inhibition of HDAC8 activity.

Abstract: In accordance with the present invention, there are provided formulations of gamma secretase modulators (GSMs) which are suitable for oral delivery and have improved transport properties relative to prior art formulations thereof. Also provided are methods for the preparation of such improved formulations and uses thereof for the delivery of GSMs to subjects in need thereof.

Abstract: A novel compound which has an excellent aurora A-selective inhibitory action and is useful as an orally administrable anticancer agent is provided. Also, a novel agent for potentiation of anti-tumor effect of microtubule agonists, which include a taxane anticancer agent, and a combination therapy are provided.

Abstract: The invention relates to compounds that modulate the glucagon-like peptide 1 (GLP-1) receptor, methods of their synthesis, and methods of their therapeutic and/or prophylactic use. Such compounds are act as modulators or potentiators of GLP-1 receptor on their own, or with receptor ligands including GLP-1 peptides GLP-1(7-36) and GLP-1(9-36), or with peptide-based therapies, such as exenatide and liraglutide, and have the following general structure (where “” represents either or both the R and S form of the compound): where A, B, C, Y1, Y2, Z, R1, R2, R3, R4, R5, W1, n, p and q are as defined herein.