The invention encompasses compounds having formula I and the compositions and methods using these compounds in the treatment of conditions in which modulation of the JAK pathway or inhibition of JAK kinases are therapeutically useful.

The present invention relates to compounds of formula (I) wherein X1 to X5, Y, Z1 to Z3, and R have the meaning as cited in the description and the claims. Said compounds are useful as JAK inhibitors for the treatment or prophylaxis of immunological, inflammatory, autoimmune, allergic disorders, and immunologically-mediated diseases. The invention also relates to pharmaceutical compositions including said compounds, the preparation of such compounds as well as the use as medicaments.

The invention relates to quinazoline derivatives of formula (I), wherein m is an integer from 1 to 3; R1 represents halogeno or C1-3alkyl; X1 represents —O—; R2 is selected from one of the following three groups: 1) C1-5alkylR3, wherein R3 is piperidinyl-4-yl which may bear one or two substituents selected from hydroxy, halogeno, C1-4alkyl, C1-4hydroxyalkyl and C1-4alkoxy; 2) C2-5alkenylR3, wherein R3 is as defined herein; 3) C2-5alkynylR3, wherein R3 is as defined herein; and wherein any alkyl, alkenyl or alkynyl group may bear one or more substituents selected from hydroxy, halogeno and amino; and salts thereof; processes for their preparation; pharmaceutical compositions containing a compound of formula (I) or a pharmaceutically acceptable salt thereof as an active ingredient.

This invention relates to novel 5-[(hydroxymethyl)aryl]-substituted pyrrolo[2,1-f][1,2,4]triazin-4-amines of formula (I), to processes for the preparation of such compounds, to pharmaceutical compositions containing such compounds, and to the use of such compounds or compositions for treating angiogenesis-related disorders, in particular angiogenesis-related ocular disorders.

Derivatives of 2,5-piperazinedione of formula (I) are apoptotic peptidase activating factor 1 (Apaf-1) inhibitors, therefore they are useful as active pharmaceutical ingredients for the prophylaxis and/or treatment of a pathological and/or physiological condition associated with an increase of apoptosis.

Disclosed are methods for producing rubber-containing bituminous mixtures by pressurizing mixtures of bituminous materials, crumb rubber, and one or more suspension agents with a gas, and then reducing the pressure, creating bubbles of the gas in the mixture. Also disclosed are methods of introducing gas into such mixture by rapid mixing. Mixtures produced by the disclosed methods, such as rubber-containing asphalt mixtures and paving compositions thereof, and their use are also disclosed.

A method for decoding and checking a tail-biting convolutional code is provided. The method fully utilizes structural features of the tail-biting convolutional code to re-sort Log-Likelihood Ratio (LLR) values input into a decoder, and by reconstructing a derivative generator polynomial of a convolutional code, allows the decoder to output in serial according to a normal ordering of information bits during backtracking, that is, a first bit of an information sequence is first decoded successfully. Thus, CRC checking may be activated as soon as possible, so that part of the backtracking process and the CRC checking may be performed in parallel, thereby achieving the objective of reducing a processing time delay in decoding and checking the tail-biting convolutional code.

The invention relates to the use of polymers, containing between 1 and 100 mol % of structural units of the formula (1), wherein R1 means hydrogen or C1-C6 alkyl, A means C2-C4 alkylene groups, and B means C2-C4 alkylene groups, with the stipulation that A is different from B, and x and y mean an integer from 1 to 100 independent of each other, in amounts of 0.01 to 2 wt % relative to the water phase, as gas hydrate inhibitors.

The invention provides for the use of copolymers comprising 1 to 99 mol % of structural units of the formula (1) in which R1 is hydrogen or C1-C6-alkyl, A is C2-C4-alkylene groups and B is C2-C4-alkylene groups, with the proviso that A is different than B, and x, y are each independently an integer of 1-100, and 1 to 99 mol % of structural units of the formula (3) in which R6 is hydrogen or C1-C6-alkyl, D is C2-C4-alkylene groups and z is an integer of 1-50, in amounts of 0.01 to 2% by weight, based on the water phase, as gas hydrate inhibitors.

The invention relates to polymers that can be obtained by polymerizing the monomers (A), (B), and (D), and optionally (C), where (A) is a monomer of formula (I), wherein A stands for C2 to C4 alkylene, B stands for a C2 to C4 alkylene different from A, R stands for hydrogen or methyl, m stands for a number from 1 to 500, n stands for a number from 1 to 500, (B) is an ethylenically unsaturated monomer that contains at least one carboxylic acid function, (C) is optionally a further ethylenically unsaturated monomer different from (A) and (B), (D) is a monomer of formula (II), wherein D stands for C2 to C4 alkylene, E stands for a C2 to C4 alkylene group different from D, F stands for a C2 to C4 alkylene group different from E, R stands for hydrogen or methyl, o stands for a number from 1 to 500, p stands for a number from 1 to 500, q stands for a number from 1 to 500, and wherein the weight fraction of the monomers is 35 to 99% for the macromonomer (A), 0.5 to 45% for the monomer (B), 0 to 20% for the monomer (C), and 1 to 20% for the monomer (D), and to the use of said polymers as defoamers for inorganic solid suspensions.

Gemini surfactants of bis-N-alkyl polyether, bis-N-alkenyl polyether, bis-N-cycloalkyl polyether, bis-N-aryl polyether bis-beta or alpha-amino acids or their salts, are produced for use as multifunctional corrosion inhibitors, which protect and prevent corrosion of ferrous metals exposed to acidic, basic and neutral liquids when transporting or storing crude oil and liquid fuels. The surfactants are also used to inhibit corrosion of equipment and pipes used in cooling systems in petroleum and petrochemical equipment. The Gemini surfactants have the structural formula:

The present invention provides compounds for the inhibition of soluble epoxide hydrolase and associated disease conditions.

A cytosine analog, a method of preparation of a cytosine analog, a DNA methyltransferase 1 inhibitor, and a method for DNA methylation inhibition, is provided for the treatment of diseases associated with deviations from normal DNA methylation. The analog of cytosine may be comprised of 1, N4, 5 and 6-substituted derivatives of cytosine or 5,6-dihydrocytosine, wherein the analog can be described by the chemical formula where R1 is H, R3, R4, 2'-deoxyribosyl, R4 is alkyl or aryl, X is N or C, wherein if X in the analog of formula I is N, then R5 is no substituent and if X in the analog of formula I and/or II is C or if X in the analog of formula II is N, then R5 and R6 are independently alkyl, aryl, hydroxyalkyl, aminoalkyl, hydroxyl, carboxyl, amino group, alkoxyl, aryloxyl, aminoalkyl, aminoaryl, thio group, sulfonyl, sulfinyl or halogen.

RNA interference is provided for inhibition of Frizzled Related Protein-1 mRNA expression, in particular, for treating patients having glaucoma or at risk of developing glaucoma.

The present invention relates to the field of cardiology. More specifically, the present invention provides methods and compositions for inducing proliferation of cardiomyocytes. In a specific embodiment, a method for inducing proliferation of cardiomyocytes comprises the step of administering an effective amount of an ALMS1 inhibitor.

A composition comprising an SL0101 [kaempferol 3-O-(3″,4″-di-O-acetyl-α-L-rhamnopyranoside)] derivative compound that has enhanced ability to inhibit RSK activity, relative to the parent compound is provided. The compounds have utility for treating any disease or conditions characterized or associated with excess or undesirable RSK activity. For example the RSK inhibitors of the present invention can be used to reduce the proliferation of neoplastic cells or for inhibiting the establishment or maintenance of an intracellular pathogenic infection by pathogens whose pathogenicity derives in part from the pathogen's ability to impede endosomal/phagosomal maturation in the host cell.

The subject of the present invention are novel esters of (acyloxymethyl)acrylamide, a pharmaceutical composition containing them and their use in the production of drugs for the prophylaxis or treatment of oncogenic diseases and diseases connected with increased cell proliferation.

A method for inhibiting the crystal growth rate of an amide compound present in a molten polyolefin-based resin and a method for producing a polyolefin-based resin molded article are provided. A phenol compound is incorporated into an amide compound-containing polyolefin-based resin such that a weight ratio, amide compound:phenol compound, is 60:40 to 10:90.

The present invention relates to organometallic compounds useful in the treatment of metastasis. The organometallic compounds comprise a ligand that is covalently bound to a bioactive compound, which is an inhibitor of a resistance pathway or a derivative thereof. Preferably, the organometallic compounds are half-sandwich (“piano-stool”) compounds. The compounds of the present invention offer a high variability with respect to the bioactive compound and to the nature of the ligand bound to a central transition metal.

A compound with a diphenylmethane moiety having an inhibitory activity against sodium-dependent glucose cotransporter 2 (SGLT2) being present in the intestine and kidney is disclosed. A pharmaceutical composition including the compound as an active ingredient, which is useful for preventing or treating metabolic disorders, particularly diabetes is disclosed. A method for preparing the compound, and a method for preventing or treating metabolic disorders, particularly diabetes, by using the compound is provided.

The invention relates to a process for preparing 1-aryl-pyrazol-3-one intermediates, tautomers, and salts thereof, to novel intermediates, and to the use of the intermediates in the preparation of sigma receptor inhibitors.

Disclosed in the present invention is a novel histone deacetylase inhibitor of benzamides and use thereof. The inhibitor has good efficacy in treating diseases caused by abnormal gene expression, such as tumors, endocrine disorders, immune system diseases, genetic diseases and nerve system diseases. The histone deacetylase inhibitor of benzamides is a compound of the following general chemical structural formula (I) or a salt thereof.

The present invention is directed to a novel process for the preparation of compounds having inhibitory activity against sodium-dependent glucose transporter (SGLT) being present in the intestine or kidney.

Compounds having drug and bio-affecting properties, their pharmaceutical compositions and methods of use are set forth. In particular, C-17 bicyclic amines of triterpenoids that possess unique antiviral activity are provided as HIV maturation inhibitors, as represented by compounds of Formulas I, II and III: These compounds are useful for the treatment of HIV and AIDS.

Compounds having drug and bio-affecting properties, their pharmaceutical compositions and methods of use are set forth. In particular, C-3 cycloalkenyl triterpenoids that possess unique antiviral activity are provided as HIV maturation inhibitors, as represented by compounds of Formulas I, II, III and IV: wherein X can be a C4-8 cycloalkyl, C4-8 cycloalkenyl, C4-9 spirocycloalkyl, C4-9 spirocycloalkenyl, C4-8 oxacycloalkyl, C4-8 dioxacycloalkyl, C6-8 oxacycloalkenyl, C6-8 dioxacycloalkenyl, C6-9 oxaspirocycloalkyl, or C6-9 oxaspirocycloalkenyl ring. These compounds are useful for the treatment of HIV and AIDS.

An inhibitor for tobacco axillary bud growth, the inhibitor containing one or more cell division inhibitors selected from pyridine-based compounds and benzamide-based compounds. This inhibitor may further include an aliphatic alcohol having 6 to 20 carbon atoms in combination with the one or more cell division inhibitors.

This invention relates to novel compounds which are inhibitors of the Rearranged during Transfection (RET) kinase, to pharmaceutical compositions containing them, to processes for their preparation, and to their use in therapy, alone or in combination, for the normalization of gastrointestinal sensitivity, motility and/or secretion and/or abdominal disorders or diseases and/or treatment related to diseases related to RET dysfunction or where modulation of RET activity may have therapeutic benefit including but not limited to all classifications of irritable bowel syndrome (IBS) including diarrhea-predominant, constipation-predominant or alternating stool pattern, functional bloating, functional constipation, functional diarrhea, unspecified functional bowel disorder, functional abdominal pain syndrome, chronic idiopathic constipation, functional esophageal disorders, functional gastroduodenal disorders, functional anorectal pain, inflammatory bowel disease, proliferative diseases such as non-small cell lung cancer, hepatocellular carcinoma, colorectal cancer, medullary thyroid cancer, follicular thyroid cancer, anaplastic thyroid cancer, papillary thyroid cancer, brain tumors, peritoneal cavity cancer, solid tumors, other lung cancer, head and neck cancer, gliomas, neuroblastomas, Von Hippel-Lindau Syndrome and kidney tumors, breast cancer, fallopian tube cancer, ovarian cancer, transitional cell cancer, prostate cancer, cancer of the esophagus and gastroesophageal junction, biliary cancer, adenocarcinoma, and any malignancy with increased RET kinase activity.

The invention relates to compounds represented by Structural Formula I, which can bind to CCR9 receptors and block the binding of a ligand (e.g., TECK) to the receptors. The invention also relates to a method of inhibiting a function of CCR9, and to the use compounds represented by Structural Formula I in research, therapeutic, prophylactic and diagnostic methods.

The present invention relates to novel synthetic substituted heterocyclic compounds and pharmaceutical compositions containing the same that are capable of inhibiting or antagonizing a family of receptor tyrosine kinases, Tropomysosin Related Kinases (Trk), in particular the nerve growth factor (NGF) receptor, TrkA. The invention further concerns the use of such compounds in the treatment and/or prevention of pain, cancer, restenosis, atherosclerosis, psoriasis, thrombosis, or a disease, disorder or injury relating to dysmyelination or demyelination or the disease or disorder associated with abnormal activities of NGF receptor TrkA.

The present invention generally relates to use of compounds and compositions as a chemosensitizers and/or radiosensitizers and/or inhibitors of PNKP phosphatase activity. The present invention provides pharmaceutical combinations and/or a pharmaceutically acceptable salt thereof, kits containing such compounds and/composition and methods of using such compounds and/or compositions.

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.

Many GTPases such as Ras, Ral and Rho require post-translational farnestylation or geranylgeranylation for mediating malignant transformation. Dual farnesyltransferase (FT) (FTI) and geranylgeranyltransferase-I (GGT-1) inhibitors (GGTI) were developed as anticancer agents from based on an ethylenediamine scaffold. On the basis of a 4-fold substituted ethylenediamine scaffold, the inhibitors are structurally simple and readily derivatized, facilitating extensive structure-activity relationship studies. The most potent inhibitor is compound exhibited an in vitro hFTase IC50 value of 25 nM and a whole cell H-Ras processing IC50 value of 90 nM. Several of the inhibitors proved highly selective for hFTase over the related prenyltransferase enzyme geranylgeranyltransferase-I (GGTase-I). A crystal structure of an inhibitor cocrystallized with farnesyl pyrophosphate in the active site of rat FTase illustrates that the para-benzonitrile moiety is stabilized by a π-π stacking interaction with the Y361β residue, suggesting an importance of this component of the inhibitors.

The invention provides a chemical entity of Formula (I) wherein R1, R2, R3, R4, Y and Z have any of the values described herein, and compositions comprising such chemical entities; methods of making them; and their use in a wide range of methods, including metabolic and reaction kinetic studies, detection and imaging techniques, and radioactive treatments; and therapies, including inhibiting PDE4, enhancing neuronal plasticity, treating neurological disorders, providing neuroprotection, treating a cognitive impairment associated with a CNS disorder, enhancing the efficiency of cognitive and motor training, providing neurorecovery and neurorehabilitation, enhancing the efficiency of non-human animal training protocols, and treating peripheral disorders, including inflammatory and renal disorders.

Compounds according to Formula I and Formula II are potent inhibitors of Arginase I and II activity: where R1, R2, R3, R4, R5, R6, R7, R8, R9, D, M, X, and Y are defined as set forth in the specification. The invention also provides pharmaceutical compositions of the compounds and methods of their use for treating or preventing a disease or a condition associated with arginase activity.

The invention provides novel inhibitors of IAP that are useful as therapeutic agents for treating malignancies where the compounds have the general formula I: wherein A, Q, X1, X2, Y, R1, R2, R3, R4, R4', R5, R6 and R6' are as described herein.

The invention provides a chemical entity of Formula (I) wherein R1, R2, R3, Y, and n have any of the values described herein and compositions comprising such chemical entities; methods of making them; and their use in a wide range of methods, including metabolic and reaction kinetic studies, detection and imaging techniques, and radioactive treatments; and therapies, including inhibiting MAO, and MAO-B selectively, enhancing neuronal plasticity, treating neurological disorders, providing neuroprotection, treating a cognitive impairment associated with a CNS disorder, enhancing the efficiency of cognitive and motor training, providing neurorecovery and neurorehabilitation, enhancing the efficiency of non-human animal training protocols, and treating treating peripheral disorders (including obesity, diabetes, and cardiometabolic disorders) and their associated co-morbidities.

The invention relates to a lubricant in the form of grease or thick lubricating gel or transmission oil, as well as motor or universal oils with a myriad of applications. As a result of its contents presented in the patent application is characteristic of low coefficient of friction ranging from 0.055 to 0.062. As the main component, the contents of the discussed lubricant includes three or four stearates of metals or hydroxistearates of metals, which interact and cause a noticeable reduction of friction drag on the lubricated surfaces. Additionally, these substances may include a number of other solid or liquid elements, which maintain low friction drags and, furthermore, improve the lubricant through increasing its load capacity, antirust characteristics, shear strength, etc. The lubricant made according to the invention underwent comparative tests against other greases and greasing oils, the accounts of which are included in the application as diagrams, descriptions of research tests and examples of the contents of the lubricant products.

A machine tool is provided with a chain-type bit-storing apparatus which includes a frame, two sprockets, a chain and a pivoting unit. The frame includes a cutout. The sprockets are placed in the frame. The chain is driven by the sprockets. The chain includes links each including a socket for containing a bit, two plates for supporting the socket, first and second blocks placed between the plates, first and second bearing units for rotationally supporting the first and second blocks on the plates, and a connecting unit for pivotally connecting the first block thereof to the second block of an adjacent link. The pivoting unit is used to pivot the socket of a selected one of the links to move an open end of the socket out of the frame through the cutout.

A system and method are disclosed for transporting deterministic traffic in a gigabit passive optical network. A system that incorporates teachings of the present disclosure may include, for example, an Optical Line Termination (OLT) for exchanging data traffic in a Gigabit Passive Optical Network (GPON) having a controller programmed to generate a timeslot schedule for transport of a desired bandwidth of constant bit rate (CBR) data traffic by selecting one or more timeslots from periodic frame clusters operating according to a GPON Transmission Convergence (GTC) protocol. Additional embodiments are disclosed.

A wound dressing including a hydrophilic layer and a hydrophobic layer is described. The hydrophilic layer absorbs exudate from a wound and the hydrophobic layer absorbs the exudate from the hydrophilic layer and traps the exudate. Because the hydrophilic layer is used adjacent to the wound, the exudate is readily absorbed thereby reducing the risk of maceration and infection of the wound tissue by the exudate. The hydrophobic layer receives the absorbed exudate from the hydrophilic layer and traps the exudate through an interaction that in turn prevents lateral diffusion of the exudate through the bandage to healthy portions of the skin. The hydrophilic and hydrophobic layers are fabricated from polymer fibers that can be spun to include components that facilitate wound healing, such as poly(hexamethylene biguanide) and/or hyaluronic acid.

A breast cancer resistance protein (BCRP/ABCG2) inhibitor. The BCRP inhibitor contains, as an active ingredient, an acrylonitrile derivative or a salt thereof.

The disclosure generally relates to the novel compounds of formula I, including their salts, which inhibit HIV integrase and prevent viral integration into human DNA. This action makes the compounds useful for treating HIV infection and AIDS. The invention also encompasses pharmaceutical compositions and methods for treating those infected with HIV.

Novel radiopharmaceuticals that are useful in diagnostic imaging and therapeutic treatment of disease characterized by over expression of CA-IX comprise a complex that contains a sulfonamide moiety which is capable of binding the active catalytic site of CA-IX, and a radionuclide adapted for radioimaging and/or radiotherapy:

Classes of compounds that exhibit effective inhibition of autotaxin enzymes are provided. Such classes include thioureas, diphenyldiazerenes, xanthenes, and isoindoles and exhibit reactivity with autotaxin to ultimately reduce the size of the reactive sites thereon to prevent conversion of lysophosphatidyl choline to lysophophatidic acid. Furthermore, such compounds can be incorporated within delivery forms for human ingestion. As such, these compounds accord an excellent manner of potentially reducing generation of certain cancers attributable to the presence of naturally occurring autotaxin within the human body. Methods of inactivating autotaxin to certain degrees therewith such compounds are encompassed within invention as well.

Described herein are pharmaceutical compositions and medicaments, and methods of using such pharmaceutical compositions and medicaments in the treatment of cancer.

Disclosed herein are compounds that inhibit Hsp90 interactions with IAP proteins, such as Survivin, XIAP, cIAP1, or cIAP2, and methods for identifying and using such compounds.

A chimeric protein containing neutrophil inhibitory factor and hirugen, the chimeric protein having an amino acid sequence that includes FPRPGSGG (SEQ ID NO:21) Also provided is a pharmaceutical composition comprising the chimeric protein, which can be used for treating or preventing cerebral injury and cerebral edema, or for inhibiting platelet aggregation.

This invention relates to compositions and methods comprising “lymphotoxin-β-receptor blocking agents”, which block lymphotoxin-β receptor signalling. Lymphotoxin-β receptor blocking agents are useful for treating lymphocyte-mediated immunological diseases, and more particularly, for inhibiting Th1 cell-mediated immune responses. This invention relates to soluble forms of the lymphotoxin-β receptor extracellular domain that act as lymphotoxin-β receptor blocking agents. This invention also relates to the use of antibodies directed against either the lymphotoxin-β receptor or its ligand, surface lymphotoxin, that act as lymphotoxin-β receptor blocking agents. A novel screening method for selecting soluble receptors, antibodies and other agents that block LT-β receptor signalling is provided.

The present invention relates to compositions and methods for inhibiting the activity of an enzyme, for example, Protein Kinase B, p70S6K and/or Abl using the catalytic subunit of Protein Kinase A (PKAc), or at least one PKAc fragment or variant PKAc fragment thereof. In this regard, methods for preventing or treating cancer or a neurodegenerative disease or disorder are also provided.

A method of treating a disease or condition in which up-regulating GAGs is therapeutically beneficial is disclosed, in particular osteoarthritis and skin diseases. The method comprises locally administering to a subject a therapeutically effective amount of an agent capable of down-regulating activity or expression of a component of the renin-angiotensin system.