The present invention relates to compounds of Formula I or II, or pharmaceutically acceptable salts, esters, or prodrugs thereof: which relates to mophinan compounds useful as μ, δ and/or κ receptor opioid compounds and pharmaceuticals containing same that may be useful for mediating analgesia, combating drug addiction, alcohol addiction, drug overdose, mental illness, bladder dysfunctions, neurogenic bladder, interstitial cystitis, urinary incontinence, premature ejaculation, inflammatory pain, peripherally mediated and neuropathic pain, cough, lung edema, diarrhea, cardiac disorders, cardioprotection, depression, and cognitive, respiratory, diarrhea, irritable bowel syndrome and gastro-intestinal disorders, immunomodulation, and anti-tumor agents.

Disclosed are solid forms of 8-chloro-N-[(2-chloro-5-methoxyphenyl)sulfonyl]-6-(trifluoromethyl)-imidazo[1,2-a]pyridine-2-carboxamide (Compound 1). Methods for the preparation of solid forms of Compound 1 and for the conversion of one solid form of Compound 1 into another are disclosed. Disclosed are nematocidal compositions comprising a nematocidally effective amount of a solid form of Compound 1 and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid carriers. Compositions comprising a mixture of a solid form of Compound 1 and at least one other nematicide, insecticide and/or fungicide are also disclosed.Also disclosed are methods for protecting a plant from nematodes comprising applying to the plant, or portion, or seed thereof, or to the growing medium of the plant, a nematocidally effective amount of Compound 1 comprising the polymorph Form A.

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.

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.

The disclosure relates to BAX activators and therapeutic uses relates thereto. In certain embodiments, the disclosure relates to methods of treating or preventing cancer, such as lung cancer, comprising administering a therapeutically effective amount of a pharmaceutical composition comprising a compound disclosed herein or pharmaceutically acceptable salt to a subject in need thereof.

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.

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.

Herein are disclosed fluorescent dyes based around a framework for a ligand comprising a pyridyl group linked to a diaryl anilido unit. A variety of ligands based on this framework are disclosed. The ligands chelate to a BF2 center to produce the fluorescent dye. The disclosed dyes combine longer Stokes shifts (approximately 100 nm) with increased quantum yields. They are also photostable in aqueous and organic solutions for several hours. These dyes may be used in the labeling of biomolecules for bioimaging and assays. Also disclosed are methods for the synthesis of these dyes.

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 novel bicyclic thiazoles which are positive allosteric modulators of the metabotropic glutamate receptor subtype 5 (“mGluR5”) and which are useful for the treatment or prevention of disorders associated with glutamate dysfunction and diseases in which the mGluR5 subtype of receptors is involved. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which mGluR5 is involved.

A compound of formula (I) wherein R1 to R4 are, for example, each hydrogen, R5 is pyridyl, which has two or more substituents selected, for example, from halogen, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, and cyano; R6 is, for example, hydrogen; R7 is, for example, hydrogen, cyano, hydroxyl, formyl, C1-C4-alkyl, C1-C4-alkoxy, C2-C4-alkenyl, or C2-C4-alkynyl; and A1 to A5 are, independently selected, from, for example, N, and C—H; and its use as a pesticidal agent.

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.

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 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.

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.

A fastener includes a t-nut having a barrel and a flange. The flange includes an opening which leads to a threaded barrel. The threaded barrel extends from the opening in the flange to a distal end portion thereof. An end cap has an annular recess on a first side thereof and has a raised annular ridge on a second side thereof. The raised annular ridge of the end cap is affixed to the flange of the t-nut by welding the end cap to the flange. Dirt, water and moisture cannot enter the barrel because the end cap is sealed to the flange. Additionally, the barrel may be relatively short as it is fully threaded prior to the affixation of the end cap to the flange.

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.

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.

An anchor bolt locator is provided that is inexpensively manufactured on automatic die-press machines from sheet steel and a structural nut that does not require any welding, while also being easy to use and install with current, commonly-used building practices and anchor designs. The anchor bolt locator is made from a galvanized sheet metal chair and a structural nut attached to the chair by way of a friction fit.

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.

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.

The invention relates to a method for producing hollow body elements (200), for example, nut elements which are applied to components which are normally made of steel (280), in particular, for producing hollow body elements having an essentially quadratic or rectangular external profile (202). Said method consists of cutting individual elements of a profile in the form of a profile rod (1) or a winding after holes (204) have previously been stamped in the profile, a threaded cylinder (206) is subsequently, optionally, formed using a follow-on composite tool (10) which consists of several working stations. The invention is characterized in that a penetrating process and a punching process are carried out in the working station. The invention also relates to hollow body elements (200), components, follow-on composite tools (10) and rolling mills (600, 602).

A spiral fluted tap is provided which includes a threaded portion having an external thread corresponding to an internal thread to be cut and a cutting edge formed along a spiral flute formed to divide the external thread, and being screwed into a prepared hole that is provided on a workpiece to cut an internal thread by the cutting edge on an inner circumferential surface of the prepared hole with discharging chips toward a shank via the spiral flute, the spiral flute having a stepped portion at a rear end of a chamfer portion or in a portion on a shank side from the rear end of the chamfer portion in the threaded portion, and a flute bottom diameter on a distal end side of the spiral fluted tap from the stepped portion being smaller than a flute bottom diameter on a shank side from the stepped portion.

In various embodiments, a tapered thread roll, a set of tapered thread rolls, a thread rolling tool, and a thread rolling method are provided for rolling angled or tapered threads onto a workpiece to create a threaded workpiece. In at least one embodiment, the threaded workpiece may comprise a polished rod or a polished rod precursor as specified by the American Petroleum Institute for use in an oil-field sucker-type pump, for example.

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 pivoting split thread chasing die with fastener is disclosed. In one example, the fastener can include a retainer that captures the fastener within one half of the thread chasing die. The thread chasing die may make it easier for a user to refurbish threads of large bolts and studs.

A slotted inverse tap, compressible for insertion past damaged entry threads in blind holes. (FIG. 1 thru FIG. 5) The tool can be made to smaller sizes than that of prior art. An elongate slot (23) proceeds through a first threaded end (21), then well into a reduced diameter cylindrical body (25). After insertion to the hole bottom, a tabbed shim (28) is inserted to the slot from its side, then pressed down until stopped. The shim (28) enforces mating engagement with undamaged internal threads. A second end of hex and/or squared or other configuration facilitates use of a tap wrench or other tool for rotational extraction. Damaged threads are reformed/re-cut upon rotational withdrawal.

A fastener suitable for use in airplane manufacture or repair that is coated with a pre-mixed moisture cure sealant. The sealant layer is coated with a frangible moisture barrier that will break apart when the fastener is installed, thus exposing the sealant to atmospheric moisture. Once exposed to moisture, the sealant will begin to cure. Preferred embodiments also provide a moisture indicator that provides a visual indication that the outer moisture resistant layer has been damaged.

An apparatus to produce a self-piercing and clinch nut includes a first forging die assembly, a second forging die assembly, a third forging die assembly, a transfer mechanism, and a controller. The first forging die assembly is configured to subject a blank to first processing. The second forging die assembly is adjacent to the first forging die assembly and configured to subject the blank to second processing after the blank has undergone the first processing in the first forging die assembly. The third forging die assembly is adjacent to the second forging die assembly and configured to subject the blank to third processing after the blank has undergone the second processing in the second forging die assembly. The controller is configured to control the first forging die assembly, the second forging die assembly, the third forging die assembly, and the transfer mechanism to operate.

A releasable lock nut assembly for securing a bearing on a threaded hub may include a thrust washer including a disk portion and a peripheral skirt extending axially away from the disk portion, the peripheral skirt having a plurality of openings and a characteristic diameter measured at an axial location of the openings, and a protuberance proximate to at least one of the openings. The assembly may also include a lock ring inserted into the thrust washer, where the lock ring includes a plurality of tangs that extend beyond a lock ring major diameter such that the tangs fit within the openings of the thrust washer. The protuberance may be deformed such that all of the peripheral skirt is within the characteristic diameter, and the protuberance may define an internal envelope of the thrust washer where the internal envelope is larger than the major diameter of the lock ring.

A locking device for preventing unauthorized retraction of a telescopic prop is made up of an adjustable clamp which can be fitted round the outer circumference of the prop together with a fastener for tightening the clamp, such as a nut and bolt with anti-tamper heads and a shield to prevent access to the head with a gripping instrument. The device can be placed around the outer circumference of an extended prop adjacent to the collar such that once the clamp is tightened the collar is sandwiched between the locking device and the pin. Alternatively the device can be placed around the outer circumference of the inner tube of the prop adjacent to and abutting the end of the outer tube of the prop in order to prevent unauthorized retraction of the prop.

A nail-forming apparatus and method to rapidly form nails typically with circular heads is provided. One aspect relates to a sequential wire piece positioner configured for sequentially positioning wire pieces respectively adjacent a plurality of nail head formers. The wire piece positioner may include several carriages related to moving and forming the wire pieces.

Disclosed herein is a method for manufacturing a screw comprising a continuous thread with a variable thread pitch, in which method a blank is rolled between two rolling dies, wherein in each rolling die a rolling profile is formed that comprises a host of curved non-parallel depressions. The depressions are designed and arranged in such a manner that during rolling no volume transport, or as little volume transport as possible, in the axial direction takes place, or a volume transport from a region of the blank where a thread section with a larger thread pitch is to be formed, to a region in which a thread section with a smaller thread pitch is to be formed takes place.