The present invention is directed to ethanamine compounds, pharmaceutical compositions comprising the same, and methods of treating depression by administering the ethanamine compound.

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 relates, inter alia, to metal complexes having improved solubility, to processes for the preparaion of the metal complexes, to devices comprising these metal complexes and to the use of the metal complexes.

This disclosure is directed to fused tetracyclic pyrido[4,3-b>]indole and pyrido[3,4-b]indole derivatives. Pharmaceutical compositions comprising the compounds are also provided, as are methods of using the compounds in a variety of therapeutic applications, including the treatment of a cognitive disorder, psychotic disorder, neurotransmitter-mediated disorder and/or a neuronal disorder.

The present disclosure relates to Oxime-Substituted Quinoxaline-Type Piperidine Compounds, such as those of Formula (I): and the pharmaceutically acceptable salts and solvates thereof, wherein R1, R2, R3, R4, R20, R21, Q, Y1, Z, A, B, and a are as defined herein; compositions comprising an effective amount of an Oxime-Substituted Quinoxaline-Type Piperidine Compound, and methods to treat or prevent a condition, such as pain, comprising administering to an animal in need thereof an effective amount of an Oxime-Substituted Quinoxaline-Type Piperidine Compound.

The present invention is directed to a compound of Formula (I) and to pharmaceutical compositions comprising compounds of Formula (I). Methods of making and using the compounds of Formula (I) are also within the scope of the invention.

The present invention features compounds having the Formula (Ia) and (Ib) (e.g., a compound of any of Formulas ((Ia-2)-(Ia-21)), including other tautomers, stereoisomers, E/Z stereoisomers, prodrugs, pharmaceutically acceptable salts, and compositions thereof. The invention also features methods for treating or preventing pain (e.g., neuropathic pain), inflammation, or epilepsy in a patient by administering an effective amount of a compound of Formula (Ia) or (Ib). The invention also features a method for treating or preventing pain (e.g., neuropathic pain), inflammation, or epilepsy in a patient that includes administering to a patient in need thereof an effective amount of a compound of Formula (IIa) or (IIb) (e.g., a compound of any of Formulas ((IIa-2)-(IIa-6)). The compounds described herein (e.g., a compound of Formulas (Ia), (Ib), (IIa), or (IIb)) can also be used as anticonvulsants.

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.

The invention provides novel substituted amino azaheterocyclic carboxamide compounds according to Formula (I), their manufacture and use for the treatment of hyperproliferative diseases, such as cancer.

Cyanine dye compounds having a substituted methine moiety that are nucleic acid stains, particularly for fluorescent staining of RNA, including compounds having the formula where R1 is a C1-C6 alkyl, sulfoalkyl, carboxyalkyl or C1-C6 alkoxy; each R2 is independently selected from the group consisting of H, C1-C6 alkyl, C1-C6 alkoxy, fused benzo, trifluoromethyl, amino, sulfo, carboxy and halogen, that is optionally further substituted; at least one of R3, R4, and R5 is an alkyl, aryl, heteroaryl, cyclic, or heterocyclic moiety that is optionally substituted by alkyl, amino, aminoalkyl, carboxy, nitro, or halogen; and the remaining R3, R4 or R5 are hydrogen; X is S, O, or Se; and D is a substituted or unsubstituted pyridinium, quinolinium or benzazolium moiety.

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.

There are provided compounds of formula (I), wherein R1, R6, R8, Q2, Q3, Q3a, Q4, L and A have meanings given in the description, and pharmaceutically-acceptable salts thereof, which compounds are useful in the treatment of diseases in which inhibition of the activity of a member of the MAPEG family is desired and/or required, and particularly in the treatment of inflammation and/or cancer.

The present invention relates to the use of selective adenosine A1 agonists, in particular the dicyanopyridines of formula (I), for the treatment and/or prophylaxis of glaucoma and ocular hypertension as well as the their use for the production of a medicament for the treatment and/or prophylaxis of glaucoma and ocular hypertension.

This invention relates to a method of preparing a benzoimidazole derivative at high purity and high yield so as to enable the production of the benzoimidazole derivative compound as an antagonist against a vanilloid reactor-1, and particularly to a method of preparing a benzoimidazole derivative at high purity and high yield, wherein the benzoimidazole derivative is synthesized using a novel intermediate, namely, benzaldehyde, and thereby the preparation process is simple so that it can be applied to production.

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.

A platinum complex of a formula (I): whereR1 and R2 are each fluoroalkyl,X is C—H or nitrogen, andL1 is a bidentate, nitrogen-containing heteroaromatic ligand.

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 present invention provides processes for the preparation of saturated ketone morphinan compounds. In particular, the invention provides processes for the conversion of a morphinan comprising an allyl alcohol ring moiety into a morphinan comprising a saturated ketone ring moiety by an isomerization reaction catalyzed by an inorganic salt of a late transition metal.

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 present invention relates to a novel method for producing a pyridazinone compound and an intermediate thereof as shown in the following scheme: wherein the symbols are as defined in the specification.

Disclosed are compounds which inhibit the activity of anti-apoptotic Bcl-2 or Bcl-xL proteins, compositions containing the compounds and methods of treating diseases during which are expressed anti-apoptotic Bcl-2 protein.

The present invention is concerned with a process for preparing 5-(2{[6-(2,2-difluoro-2-phenylethoxy)hexyl]amino}-1(R)-hydroxyethyl)-8-hydroxyquinolin-2(1H)-one or a pharmaceutically acceptable salt thereof.

An objective of the present invention is to provide a process for producing 4-carbonyl oxyquinoline derivatives useful as agricultural and horticultural pesticides and fungicides. The objective can be attained by a process for producing 4-carbonyl oxyquinoline derivatives represented by general formula (1), the process including reacting a quinolone derivative with a halogenated compound or an acid anhydride in the presence of a phase transfer catalyst and a base.

The present invention relates to electronic devices, in particular organic electroluminescent devices, comprising compounds of the formula (1), and the corresponding compounds.

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.

A fastening assembly includes a connecting member, a mounting member mounted to the connecting member, and a sliding member. The mounting member includes a first fixing portion. The sliding member is slidably received in the mounting member and the connecting member. The sliding member includes a first end exposed out of the first fixing portion, and a second end slidably received in the connecting member. The second end of the sliding member is operable to be extended out of or substantially coplanar with an end of the connecting member. The fastening assembly can be utilized to mount a heat sink to a board.

The invention includes a method, and a component made according to the method having at least one thread pattern formed thereon from a stamping method. The invention includes a tubular member comprising a body having a wall formed from a wrapped sheet of stock to define an interior wall and an exterior wall, a seam in the wall defining a first and second end of the wrapped sheet of stock, and a thread pattern stamped on the exterior wall. The method comprises the steps of forming a blank from sheet of stock having a first surface. A thread pattern is formed onto the first surface while in a substantially sheet-like form. A bending operation then forms the sheet stock into a tubular member such that the thread pattern, located on the tube's external surface, is substantially aligned about its circumference.

An electronic device includes, a circuit board including a through hole, a member including a screw hole, a screw including a screw body having an outer diameter smaller than an inner diameter of the through hole and a screw head having an outer diameter larger than the inner diameter of the through hole, wherein the screw body penetrates through the through hole to engage with the screw hole and the screw head is disposed on an opposite side of the circuit board to the member, and a first washer provided between the screw head and the circuit board, the first washer including a first washer body and a plurality of first washer legs extending from the first washer body toward the circuit board, the first washer legs being in contact with the circuit board and having a characteristic of reducing stress on the circuit board upon being heated.

A method of manufacturing fastenings or fasteners with radial outer contours, especially screws or threaded bolts, made of solid metal is performed by a device. The method manufactures the fastenings or fasteners preferably on a multi-stage press. Several recesses running in an axial direction at a fixed radial distance are formed in the shank-shaped section of a blank. The prefabricated blank with the recesses is inserted into a multi-part split mold within a multi-stage press, whose die stocks have an inner profiling forming the outer contour, and are opened in the starting position, that at the places where the die stocks are opened, there are the recesses. During the closing movement of the die stocks, at least one radial outer contour is pressed on the shank-shaped section of the blank by radial action of forces, with the recesses preventing material from getting between the die stocks during the pressing process.

The present invention is premised upon method of manufacturing rolled pierce nuts having a predetermined profile from a metal rod, more particularly to a method and apparatus delivering greater manufacturing flexibility through the use of multiple stations with flexible inputs and outputs.

The present invention provides a method for manufacturing a fitting that has a configuration where a fitting plate and a blind nut are integrally formed and also provides a tap tool for use in this method. According to the present invention, performing tap processing to an internal diameter portion to integrally form a portion corresponding to the blind nut, when a tap tool having a protrusion at an end thereof is utilized to be inserted into the bag-like blind hole at a planned part of the blind nut and the tap processing is carried out, the protrusion provided at the end of the tap tool comes into contact with an inner wall at the end of the bag-like blind hole, and a pressed material thereby forms a convex shape on an outer side of the bag-like blind hole.

A magnetized nut for fastening a compressor wheel of an exhaust turbocharger to a turbo shaft. The nut has a base body made of a non-magnetic material forming a hollow space for accommodating a magnetic material, and a method for the production of the magnetized nut. In order to provide a magnetized nut that is produced in a simple and cost-effective manner and ensures as equal a distribution of mass as possible with regard to the rotational axis of the nut, the magnetic material is introduced into the hollow space using injection molding.

There is provided a nut having a thread portion having a female thread, a metallic plate portion having a base segment, and a hardness gradient portion provided between the thread portion and the metallic plate portion. The thread portion, metallic plate portion and the hardness gradient portion are monolithic each other, a metallographic structure of the metallic plate portion differs from a metallographic structure of the thread portion and a hardness of the hardness gradient portion is lower than a hardness of the thread portion and lowers from the thread portion toward the metallic plate portion.

A thread forming tap having a complete thread portion, formed with a predetermined back taper with that decreases rotational torque during tapping work, which reduces load acting on first complete protruding portions, formed at an extreme leading end of the complete thread portion, and thereby suppressing degradation in service life of the tool due to wear.

The invention relates to a profile-rolling machine for rolling a profile in a blank, wherein the profile-rolling machine has a first and a second profile-rolling jaw. The second profile-rolling jaw (126) is guided—held by a carriage (124)—in a guide track (130) relative to the first profile-rolling jaw (110) for the purpose of rolling the profile into the blank. The carriage (124) has a carriage slide plate (122) and the guide track (130) has a guide slide plate (132). The two slide plates together form a sliding pairing and slide on each other. In order to render said sliding pairing less susceptible to dirty lubricant and less susceptible to wear, it is proposed according to the invention to manufacture the guide slide plate (132) and/or the carriage slide plate (122) at least partially from ceramic or from a non-metallic material or to coat the same with such materials.

A rolling machine comprises parallel guides delimiting a workpiece conveying channel extending from a plurality of per se known rolling tools to a machined workpiece unloading arrangement, wherein, upstream of the workpiece unloading arrangement, one of the channel delimiting guides is operatively coupled to a structural element swingably supported by a pivot pin, the structural element being integral with the piston rod of a cylinder-piston unit slidably driving the structural element together with the channel delimiting guide, thereby providing a side unloading opening for the workpiece.

A full-round head nail having an offset head is configured with a gusset formed integrally between an undersurface of the offset head and a superior portion of a shank. The head of the nail is relatively thin, and the shank is positioned radially off center of the round head such that no heel is formed at a point tangential to both the head and the shank. The gusset has a lofted surface tapering radially from a roundness at the zero heel to a taper at the toe. The gusset reinforces the junction of the shank with the head, supports the toe of the head, and distributes the force of a load on the head through a longitudinal axis of the shank, preventing the toe from bending or yielding and prevents the shank from yielding to the stresses of the load applied.

A set of tooling for making pointed headed bolts of a given diameter in numerous lengths with roll thread ready threaded to the head and partially threaded shanks in a four forming station forming machine, the tools being configured to work on wire stock as received at the first station of a diameter larger than or substantially the same as the roll diameter and not greater than the nominal diameter of the bolt, including at least two sequential head forming tools for mounting on the slide, an extrusion pointing tool for mounting on the die breast, a roll diameter extrusion tool for mounting on the die breast and a head support tool mountable in a station on the slide at multiple axial positions corresponding to standard lengths of the bolts being made, the head support tool being arranged to work at either the extrusion pointing station or the roll diameter extrusion station.

Provided is a method for manufacturing an FRP member with insert which enables to reduce a machining time to improve productivity. First, a threaded hole 11 is formed in an insert 3. An FRP member 2 where at least the threaded hole 11 of the insert 3 is covered with a coating 4 made of FRP is molded. A counter-bored hole 31 that penetrates the coating 4 of the FRP member 2 to communicate with the threaded hole 11 of the insert 3 is formed, to thereby obtain an FRP component 1 with insert. Accordingly, a machining step after molding the FRP member 2 in which dry machining is required includes only the boring step of forming the counter-bored hole 31 in the FRP member 2. Thus, the machining time can be reduced, and the productivity can be improved.

In FIG. 2, a diameter Dd of drilling edges of a drill is selected smaller than a valley diameter d1 of a male thread of a tap portion, and an inner diameter D1 of a female thread is defined by the valley diameter d1 of the male thread. Therefore, a predetermined radial gap is formed between the male thread 30 formed by the tap portion and the drill. When a tap with the drill is reversely rotated to be pulled out from the female thread after cutting the female thread, the tap released from the restriction may deflectively displace in the diameter direction upon pulling out the male thread of the tap portion from the female thread. However, the drill hardly contacts with the female thread, so that the occurrence of the defective product due to the contact is suppressed.

Techniques for reinforcing concrete using rebar are disclosed. Some example embodiments may include prestressed concrete structures reinforced by twisted, threaded reinforcing bars. An example reinforcing bar for a prestressed concrete structure may include an elongated, generally cylindrical rod; an external thread disposed on the generally cylindrical rod, the external thread formed from an elongated, generally nonlinear channel wrapped about a radial surface of the generally cylindrical rod in a generally helical fashion. A base portion of the nonlinear channel may be disposed substantially against the radial surface of the generally cylindrical rod and/or an upstanding portion of the nonlinear channel may extend generally orthogonally from the radial surface of the generally cylindrical rod.

Disclosed is a tap driver and tap driver system for rigid tapping, which includes a unique flexure system. In some embodiments, an integrated flexure component and housing configuration provides and may provide both a more economical and a universal configuration of the tap driver flexure component that allows the central body to be integrated with and into different types of tap drivers.

A form tap for tapping an article may include a longitudinal shank having a mounting end opposite a tip, the shank having a shank length, and a thread portion with a plurality of threads for engaging a surface of the article. The thread portion includes a first region, a second region and a third region. The form tap includes a plurality of lobes extending though the first and second regions from the tip to the second region end, the lobes being spaced circumferentially around the shank and lying on a crest circumference. Each lobe may be disposed between respective first and second convex relief portions and each relief portion may be spaced radially inward from the crest circumference. Each lobe has a lobe width, the lobe width at the second region end being greater than the lobe width at the tip. The third region is free of lobes.

A clinch-type fastener is formed by simultaneously creating an undercut during the same forging that creates the head and displacer of the fastener. A fastener blank is compressed end-to-end between top and bottom dies whereby the axial compression of a blank causes the outward bulging of the shank at its midline. Simultaneously, a tapered end point and a tangential interference band are formed provided by a curvilinear-shaped bulge in the shank. As the bulge is formed an undercut is created between the bulge and a shoulder which extends downwardly from a head of the fastener. This method of formation and the fastener produced thereby are particularly suited to the manufacture of small clinch pins having a diameter in the range of 1.0 mm.

A process for producing hollow bolts including a longitudinal bore with the hollow bolts being provided with circumferential notches. The hollow bolts are provided with longitudinal grooves extending between elevations determining the bolt diameter, wherein circumferential notches are rolled onto the hollow bolts provided with the longitudinal grooves and the elevations, the longitudinal grooves being of such cross-section that some of the material displaced during rolling-on of the notches flows into the longitudinal grooves.

A testing method for the bolt to be used under the conditions of excessive wind force by which bolts made of Cr—Mo steel can be separated into a group of bolts usable in cold areas and a group of bolts unusable in cold areas without conducting Charpy impact test involving complicated operation, specifically, a testing method for determining whether bolts made of heat-treated Cr—Mo steel are usable or unusable in cold areas, wherein the determination is conducted on the basis of both J parameter calculated by formula: J=(Si %+Mn %) (P %+Sn %) 104 (wherein P %, Si %, Mn % and Sn % are contents (mass %) of phosphorus (P), silicon (Si), manganese (Mn) and tin (Sn) respectively as disclosed in the inspection certificate of the Cr—Mo steel) and bolt diameter.

A radial tapping attachment for a motor-driven tool includes an enclosed, box-shaped housing, a main shaft assembly adapted to retain a tap, a drive mechanism rotatably driven by the tool and a guide member assembly for supporting an object to be tapped. The main shaft assembly includes a main shaft rotatably coupled to the housing by a pair of bearings, a pair of spaced apart discs fixedly mounted on the main shaft, and a pair of axially mounted compression springs that allow for slight, bi-directional, axial displacement of the main shaft relative to the housing. The drive mechanism includes a drive shaft rotatably coupled to the housing at an approximate right angle relative to the main shaft and a drive wheel mounted on the drive shaft that selectively engages the pair of discs to rotate the main shaft in either direction when an axial force is applied to the tap.

Embodiments of the present invention are directed to improved designs of railroad spikes and improved methods of manufacturing the same. According to one exemplary embodiment, a method for manufacturing a railroad spike may comprise the steps of: preparing a metal blank having a substantially circular cross-section; subjecting the metal blank to at least one cold heading process and at least one cold extrusion process to form a railroad spike having (a) a circular head with a fillet at its bottom side that is angled to engage a railroad tie plate or rail base and (b) a non-threaded shank with a substantially square cross-section and a chiseled tip; and coating the railroad spike with an anti-corrosion material.