Low molecular weight bicyclic thrombin inhibitors.

This invention relates to the discovery of heterocyclic competitive inhibitors of the enzyme thrombin having formula (i), their preparation and pharmaceutical compositions thereof. As well, this invention relates to the use of such compounds and compositions in vitro as anticoagulants and in vivo as agents for the treatment and prophylaxis of thrombotic disorders such as venous thrombosis, pulmonary embolism and arterial thrombosis resulting in acute ischemic events such as myocardial infarction or cerebral infarction. Moreover, these compounds and compositions have therapeutic utility for the prevention and treatment of coagulopathies associated with coronary bypass operations as well as restenotic events following transluminal angioplasty.

(QUINOLIN-2-YLMETHOXY) INDOLES AS INHIBITORS OF THE BIOSYNTHESIS OF LEUKOTRIENES

IMIDAZO 2,1-B -1,3,4-THIADIAZOLE of SULFONE AMIDE

(QUINOLIN-2-YLMETHOXY)INDOLES AS INHIBITORS OF THE BIOSYNTHESIS OF LEUKOTRIENES

Compounds having the formula I: I are inhibitors of leukotriene biosynthesis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents. They are also useful in treating diarrhea, hypertension, angina, platelet aggregation, cerebral spasm, premature labor, spontaneous abortion, dysmenorrhea, and migraine.

LOW MOLECULAR WEIGHT BICYCLIC-UREA TYPE THROMBIN INHIBITORS

This invention relates to heterocyclic inhibitors of the enzyme thrombin, their preparation, and pharmaceutical compositions thereof having general formula (I), wherein X, R2, R3, R4, R6, R7 and R8 are as defined herein. Also, the invention relates to the use of such compounds and compositions as anticoagulants and as agents for the treatment and prophylaxis or thrombotic disorders such as venous thrombosis, pulmonary embolism and arterial thrombosis resulting in acute ischemic events such as myocardial infarction or cerebral infarction.

(CHINOLIN-2-YLMETHOXY) - INDOLE AS LEUKOTRIENBIOSYNTHESE HEMMER.

An air conditioning duct fitting

(QUINOLIN-2-YLMETHOXY) INDOLES AS INHIBITORS OF THE BIOSYNTHESIS OF LEUKOTRIENES

... 75/DAM30 76/DAM31 17940IB TITLE OF THE INVENTION (QUINOLIN-2-YLMETHOXY)INDOLES AS INHIBITORS OF THE BIOSYNTHESIS OF LEUKOTRIENES. Compounds having the formula I: are inhibitors of leukotriene biosynthesis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents. They are also useful in treating diarrhea, hypertension, angina, platelet aggregation, cerebral spasm, premature labor, spontaneous abortion, dysmenorrhea, and migraine.

(QUINOLIN-2-YLMETHOXY)INDOLES AS INHIBITORS OF THE BIOSYNTHESIS OF LEUKOTRIENES

(QUINOLIN-2-YLMETHOXY) INDOLES AS INHIBITORS OF THE BIOSYNTHESIS OF LEUKOTRIENES

Compounds having the formula I: are inhibitors of leukotriene biosynthesis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents. They are also useful in treating diarrhea, hypertension, angina, platelet aggregation, cerebral spasm, premature labor, spontaneous abortion, dysmenorrhea, and migraine.

Intermediates of (quinolin-2-ylmethoxy)indoles

(QUINOLIN-2-YLMETHOXY) INDOLES AS INHIBITORS OF THE BIOSYNTHESIS OF LEUKOTRIENES

Compounds having the formula I: are inhibitors of leukotriene biosynthesis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents. They are also useful in treating diarrhea, hypertension, angina, platelet aggregation, cerebral spasm, premature labor, spontaneous abortion, dysmenorrhea, and migraine.

MULTI-PURPOSE PHYSICAL EXERCISE APPARATUS

A multi-purpose exercise machine in the "rowing machine" mode has a seat 14 slidable along a track 12 and levers 22 movable against resistance elements 24. The elements are pivoted at 26 at the foot of a mast, and alternative pivot points are provided at 20 at the top of the mast which, in conjunction with various alternative seat or user-support arrangements enables a wider range of exercises to be carried out. <IMAGE>

An air conditioning duct fitting

(quinolin-2-ylmethoxy)indoles as inhibitors of the biosynthesis of leukotrienes

HETEROCYCLIC KETO ARGININE PEPTIDES AS THROMBIN INHIBITORS

This invention relates to new and useful inhibitors of the enzyme thrombin of the formula (I): AS - X, and more particularly compound (1) in the preparation, and pharmaceutical compositions. As well, this invention relates to the use of such compounds and compositions in vitro as anticoagulants and in vivo as agents for the treatment and prophylaxis of thrombotic disorders such as venous thrombosis, pulmonary embolism and arterial thrombosis resulting in acute ischemic events such as myocardial infarction or cerebral infarction. Moreover, these compounds and compositions have therapeutic utility for the prevention and treatment of coagulopathis associated with coronary bypass operations as well as restenotic events following transluminal angioplasty.

An air conditioning duct fitting

LOW MOLECULAR WEIGHT BICYCLIC THROMBIN INHIBITORS

This invention relates to the discovery of heterocyclic competitive inhibitors of the enzyme thrombin having formula (I), their preparation, and pharmaceutical compositions thereof. As well, this invention relates to the use of such compounds and compositions in vitro as anticoagulants and in vivo as agents for the treatment and prophylaxis of thrombotic disorders such as venous thrombosis, pulmonary embolism and arterial thrombosis resulting in acute ischemic events such as myocardial infarction or cerebral infarction. Moreover, these compounds and compositions have therapeutic utility for the prevention and treatment of coagulopathies associated with coronary bypass operations as well as restenotic events following transluminal angioplasty.

Neuroprotective and anti-proliferative compounds

Heterocyclic keto arginine peptides as thrombin inhibitors

IAP BIR DOMAIN BINDING COMPOUNDS

Disclosed herein is a compound of Formula 1: or a salt thereof, in which R1, R1a, R100, R100a, R2, R200, R3, R300, A, A1, Q, Q1 and BG are as defined herein. Also disclosed is the use of the compounds of Formula 1 to treat disorders of dysregulated apoptosis, such as cancer and cellular proliferative disorders.

(Chinolin-2-ylmethoxy)-indole als Leukotrienbiosynthese-Hemmer.

(Chinolin-2-ylmethoxy)-indole als Leukotrienbiosynthese-Hemmer.

(QUINOLIN-2-YLMETHOXY) INDOLES AS INHIBITOR OF THE BIOSYNTHESIS OF LEUCOTRIENES

NEW MATERIAL: Compounds of formula I [R1-R4 are each H, halogen, lower alkyl, etc.; R5 is H, CH3 etc.; R8 is H, X3-R9 (X3 is C(O), etc.; R9 is alkyl, etc.); R11 is H, lower alkyl, etc.; m is 0-1; n is 0-3; p is 0-3; v is 0, 1; Y is X1, X2 [X1 is O, etc.; X2 is C(O), etc.; Q is -CH2R12, etc.; (R12 is H, etc.)]] and their salts. EXAMPLE: 3-[N-(p-chlorobenzyl)-3-(t-butylthio)-5-(quinolin-2-ylmethoxy)indol-2- yl]-2,2-dimethylpropane acid. USE: Inhibitors for biosynthesis of leucotrienes, useful for anti-inflammation and anti-allergy, etc. PROCESS: A compound of formula I is obtained by reacting a compound of formula II (R10 is H, halogen, etc.), with a compound of formula III in a solvent such as DMF in the presence of a base (e.g. K2CO3) and hydrolyzing the obtained ester with a base. COPYRIGHT: (C)1991,JPO ...

IAP BIR DOMAIN BINDING COMPOUNDS

Disclosed is an isomer, enantiomer, diastereoisomer or tautomer of a compound represented by Formula I or II 156.-. (canceled)58. The method of claim 57 , wherein the cell is a cancer cell claim 57 , immune cell claim 57 , neutrophil claim 57 , monocyte claim 57 , or T-cell.59. The method of claim 57 , wherein the cell is in a subject claim 57 , and the cell is contacted with the compound of Formula I or salt thereof by administering the compound of Formula I or salt thereof to the subject.60. The method of claim 59 , further comprising administering to the subject a chemotherapeutic agent or death receptor agonist prior to claim 59 , simultaneously with claim 59 , or after administration of the compound of Formula I or salt thereof.61. The method of claim 60 , wherein the death receptor agonist is TRAIL or a TRAIL receptor antibody claim 60 , optionally in an amount that produces a synergistic effect.62. The method of claim 57 , in which the subject is a human.63. The method of claim 62 , wherein the subject is afflicted with a proliferative disease.64. The method of claim 63 , wherein the proliferative disease is cancer claim 63 , an autoimmune disease or inflammatory disorder.66. The method of claim 57 , wherein Rand Rare both CH.67. The method of claim 57 , wherein Rand Rare both C(CH).72. The method of claim 57 , wherein Q and Qare both NRR.73. The method of claim 57 , wherein A and Aare both CH.74. The method of claim 57 , wherein A and Aare both C═O.77. The method of claim 73 , wherein Q and Qare NRR.80. The method of claim 74 , wherein Q and Qare NRR.82. The method of claim 81 , wherein Ris C-Calkyl optionally substituted with one or more Rsubstituents or aryl optionally substituted with one or more Rsubstituents.87. The method of claim 57 , wherein the compound of Formula I or salt thereof is in a pharmaceutical composition comprising a pharmaceutically acceptable carrier claim 57 , diluents claim 57 , or excipient.88. The method of claim 87 , wherein the ...

Hemming a Flange With Compression to Form a Sharp Edge

A tool and method of hemming a panel wherein the tool engages a flange to apply a compressive force with a stop initially preventing a distal end of the flange from moving inwardly. The hemming tool bends the intermediate portion of the flange between the flange bend and the distal end toward the panel. The stop is withdrawn to allow the flange to be progressively formed toward the panel until the distal end is aligned with the intermediate portion. 1. A tool for forming a hem on a panel comprising:a first hem die defining a cavity having a perimeter edge, the panel having a flange at an outer edge at a base of the flange;a second hem die that engages a distal end of the flange to compress the flange through the length of the flange into the perimeter edge while forming a hem bend on the flange.2. The tool of wherein a stop is provided on the second hem die that initially engages the flange and prevents the flange from moving inwardly while the second hem die moves towards the first hem die.3. The tool of wherein the stop is a block that moves inwardly as the second hem die moves inwardly.4. The tool of wherein the block has a face that extends parallel to the direction that the second hem die moves.5. The tool of wherein the second hem die has an inner portion and an outer portion that move independently toward the first hem die claim 2 , wherein the outer portion initially engages the distal edge of the flange claim 2 , and wherein the inner portion includes the stop that prevents the flange from moving inwardly as the outer portion bends an intermediate portion of the flange inwardly of the distal edge.6. The tool of wherein the outer portion clamps the intermediate portion of the flange while the inner portion forms the distal edge inwardly and into alignment with the intermediate portion of the flange.7. The tool of wherein the stop is a block that has an inwardly angled surface claim 2 , wherein the block is retracted into the second hem die as the second hem ...

Method to reduce tool marks in incremental forming

A method of incrementally forming workpiece is provided by the present disclosure. In one form, the method includes securing a sacrificial material layer to at least one surface of the workpiece, imparting a force directly to the sacrificial material layer with at least one forming tool, and incrementally forming the workpiece to a desired geometry based on a tool path of the forming tool.

Method of Hemming Sheet Metal Panels with Friction Element Applying a Counteraction Force to Prevent Hem Creep

A hemming tool for forming a hem securing an outer panel to an inner panel. The hemming tool includes a hemming die that has a first portion of a forming surface with a first coefficient of friction and a second portion that has a second coefficient of friction that is greater than the first portion. A flange on the outer panel is initially engaged by the first surface to begin forming the hem flange toward the inner panel. The flange is engaged by the second hemming surface to continue forming the flange toward the inner panel. A method of hemming a sheet metal assembly including an inner and an outer panel is also disclosed that utilizes the hemming die that has a forming surface with a second coefficient of friction that is greater than the first portion to reduce flange creep and roll-in during a hemming operation. 1. A hemming tool for forming a hem to secure an outer panel to an inner panel comprising:an anvil die that supports the inner panel on the outer panel inside a flange formed on the outer panel that extends away from the anvil die in an initial position; anda hemming die spaced from the flange in an initial position, the hemming die having a first portion of a forming surface that has a first coefficient of friction and a second portion that has a second coefficient of friction that is greater than the first portion, wherein the first portion engages the flange to begin forming the flange over the inner panel, and wherein the second portion subsequently engages the flange to continue forming the flange towards the inner panel.2. The hemming tool of further comprising a clamping pad that engages the inner panel and holds the inner panel against the outer panel on the anvil die.3. The hemming tool of wherein the flange is oriented at an oblique angle relative to the outer panel and further comprising a beveled surface outboard of the first portion of the forming surface claim 1 , and wherein the beveled surface contacts the flange before the first ...

Hemming a Flange with Compression to Form a Sharp Edge

A tool and method of hemming a panel wherein the tool engages a flange to apply a compressive force with a stop initially preventing a distal end of the flange from moving inwardly. The hemming tool bends the intermediate portion of the flange between the flange bend and the distal end toward the panel. The stop is withdrawn to allow the flange to be progressively formed toward the panel until the distal end is aligned with the intermediate portion. 1. A tool for forming a hem on a panel comprising:a first hem die defining a cavity having a perimeter edge, the panel having a flange at an outer edge at a base of the flange;a second hem die that engages a distal end of the flange to compress the flange through the length of the flange into the perimeter edge while forming a hem bend on the flange.2. The tool of wherein a stop is provided on the second hem die that initially engages the flange and prevents the flange from moving inwardly while the second hem die moves towards the first hem die.3. The tool of wherein the stop is a block that moves inwardly as the second hem die moves inwardly.4. The tool of wherein the block has a face that extends parallel to the direction that the second hem die moves.5. The tool of wherein the second hem die has an inner portion and an outer portion that move independently toward the first hem die claim 2 , wherein the outer portion initially engages the distal edge of the flange claim 2 , and wherein the inner portion includes the stop that prevents the flange from moving inwardly as the outer portion bends an intermediate portion of the flange inwardly of the distal edge.6. The tool of wherein the outer portion clamps the intermediate portion of the flange while the inner portion forms the distal edge inwardly and into alignment with the intermediate portion of the flange.7. The tool of wherein the stop is a block that has an inwardly angled surface claim 2 , wherein the block is retracted into the second hem die as the second hem ...

Electro-Hydraulic Trimming of a Part Perimeter with Multiple Discrete Pulses

A trim tool for trimming a part having a complex shape. The trim tool defines a plurality of electro-hydraulic cavities that are separated by walls in a lower die of the trim tool. Electrodes are discharged in the electro-hydraulic cavities to drive the panel into engagement with a trim steel edge. The discharge of the electrode severs the panel above the cavity and also across a portion of a wall separating adjacent cavities. Discharging an electrode in an adjacent cavity completes the trim operation above the wall.

IAP BIR Domain Binding Compounds

A compound of Formula I 2. The compound claim 1 , according to claim 1 , wherein the compound is a pharmaceutically acceptable salt of Formula I.3. The compound claim 1 , according to claim 1 , wherein the compound is an HCl salt of Formula I.6. The compound claim 2 , according to claim 2 , in which Rand Rare both CH.7. The compound claim 2 , according to claim 2 , in which Rand Rare both C(CH).12. The compound claim 2 , according to claim 2 , in which Q and Qare both NRR.13. The compound claim 2 , according to claim 2 , in which A and Aare both CH.14. The compound claim 2 , according to claim 2 , in which A and Aare both C═O.15. The compound claim 2 , according to claim 2 , in which A and Aare both C═O claim 2 , and Q and Qare both NRR claim 2 , wherein Ris H and{'sup': '5', 'claim-text': [{'sub': 1', '6, '1) C-Calkyl,'}, {'sub': 2', '6, '2) C-Calkenyl,'}, {'sub': 2', '4, '3) C-Calkynyl,'}, {'sub': 3', '7, '4) C-Ccycloalkyl,'}, {'sub': 3', '7, '5) C-Ccycloalkenyl,'}, '6) aryl,', '7) heteroaryl,', '8) heterocyclyl, or', '9) heterobicyclyl,, 'Ris'}{'sup': 6', '10, 'wherein the alkyl, alkenyl, alkynyl, cycloalkyl, and cycloalkenyl are optionally substituted with one or more Rsubstituents; and wherein the aryl, heteroaryl, heterocyclyl, and heterobicyclyl are optionally substituted with one or more Rsubstituents.'}17. The compound claim 13 , according to claim 13 , wherein Q and Qare NRR.20. The compound claim 14 , according to claim 14 , wherein Q and Qare NRR.22. The compound claim 21 , according to claim 21 , wherein Ris C-Calkyl optionally substituted with one or more Rsubstituents or aryl optionally substituted with one or more Rsubstituents.32. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable carrier claim 2 , diluent or excipient. This patent application is a divisional of copending U.S. patent application Ser. No. 13/672,637, filed Nov. 8, 2012, which is a divisional of U.S. patent application Ser. No. 12/619,979, filed ...

結合於細胞凋亡抑制蛋白（ｉａｐ）之桿狀病毒ｉａｐ重複序列（ｂｉｒ）區域之化合物

IAP BIR domenebindende forbindelser

Det beskrives en isomer, enantiomer, diastereoisomer eller tautomer av en forbindelse representert ved formel I eller II: (I) (II) eller et salt derav, hvor R1, R2, R3, R100, R200, R300, A, A1, BG, Q og Q1 er substituenter beskrevet her. Det beskrives også anvendelse av forbindelser med formel I og II for å behandle proliferative lidelser så som kreft.

(quinolin-2-ylmethoxy)heterotetrahydrocarbazoles as inhibitors of the biosynthesis of leukotrienes

(Quinolin-2-ylmethoxy)Heterotetrahydrocarbazoles as inhibitors of the biosynthesis of leukotrienes useful in the treatment of asthma and eye inflamation.

Cyclohept[b]indolealkanoic acids

TITLE OF THE INVENTION CYCLOHEPT[b]INDOLEALKANOIC ACIDS ABSTRACT OF THE DISCLOSURE Cyclohept[b]indolealkanoic acids and acid derivatives are disclosed. The compounds act as prostaglandin and thromboxane antagonists and are useful in treating asthma, diarrhea, hypertension, angina, platelet aggregation, cerebral spasm, premature labor, spontaneous abortion, dysmenorrhea and nephrotoxicity caused by cyclosporin A and as cytoprotective agents.

Imidazo[2,1-b]-1,3,4-thiadiazole sulfoxides and sulfones

This invention relates to novel imidazo[2,1-b]-1,3,4-thiadiazole sulfoxide and sulfone compounds of Formula (I) and the use of compounds of Formula (I) in the treatment of neuronal disorders of the central and peripheral nervous systems and for the treatment of proliferative diseases such as cancer.

(Quinolin-2-ylmethoxy)indoles as inhibitors of the biosynthesis of leukotrienes

Compounds having the formula I: ##STR1## are inhibitors of leukotriene biosynthesis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents. They are also useful in treating diarrhea, hypertension, angina, platelet aggregation, cerebral spasm, premature labor, spontaneous abortion, dysmenorrhea, and migraine. RELATED APPLICATION

5-lipoxygenase activating protein

An 18kD protein (FLAP) has been isolated from rat and human cells which is necessary for production of leukotrienes from arachidonic acid in mammalian cells containing 5-lipoxygenase. The gene (cDNA) encoding for FLAP has also been produced.

Hemming a flange with compression to form a sharp edge

A tool and method of hemming a panel wherein the tool engages a flange to apply a compressive force with a stop initially preventing a distal end of the flange from moving inwardly. The hemming tool bends the intermediate portion of the flange between the flange bend and the distal end toward the panel. The stop is withdrawn to allow the flange to be progressively formed toward the panel until the distal end is aligned with the intermediate portion.

Tetrahydrocarbazole esters

TITLE OF THE INVENTION TETRAHYDROCARBAZOLE ESTERS ABSTRACT OF THE DISCLOSURE Tetrahydrocarbazole esters are disclosed. The compounds act as prostaglandin and thromboxane antagonists and are useful in treating asthma, diarrhea, hypertension, angina, platelet aggregation cerebral spasm, premature labor, spontaneous abortion and dysmenorrhea and nephrotoxicity casued by cyclosporin A and as cytoprotective agents.

Tetrahydrocarbazole esters

TETRAHYDROCARBAZOLESTES AND PHARMACEUTICAL PREPARATIONS CONTAINING SUCH A CONNECTION

PROCESS FOR THE PREPARATION OF TETRAHYDROCARBAZOLE-1-ALCANOIC ACIDS

TETRAHYDROCABAZOLE-1-ALKANIC ACID AND PHARMACEUTICAL PREPARATION CONTAINING SUCH A COMPOUND

(Quinolin-2-ylmethoxy) indoles as inhibitors of the biosynthesis of leukotrienes

5-lipoxygenase activating protein

An 18kD protein (FLAP) has been isolated from rat and human cells which is necessary for production of leukotrienes from arachidonic acid in mammalian cells containing 5-lipoxygenase. The gene (cDNA) encoding for FLAP has also been produced.

(quinolin-2-ylmethoxy)heterotetrahydrocarbazoles as inhibitors of the biosynthesis of leukotrienes

(quinolin-2-ylmethoxy)heterotetrahydrocarbazoles as inhibitors of the biosynthesis of leukotrienes

Compounds having the formula I: (See Formula I) are inhibitors of leukotriene biosynthesis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents. They are also useful in treating diarrhea, hypertension, angina, platelet aggregation, cerebral spasm, premature labor, spontaneous abortion, dysmenorrhea, and migraine.

(Bicyclic-hetero-arylmethoxy)indoles as inhibitors of leukotriene biosynthesis

Compounds having the formula I: ##STR1## are inhibitors of leukotriene biosynthesis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents. They are also useful in treating diarrhea, hypertension, angina, platelet aggregation, cerebral spasm, premature labor, spontaneous abortion, dysmenorrhea, and migraine.

(quinolin-2-ylmethoxy)tetrahydrocarbazoles as inhibitors of the biosynthesis of leukotrienes

Compounds having tho Formula I: (see formula I) are inhibitors of leukotriene biosynthesis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents. They are also useful in treating diarrhea, hypertension, angina, platelet aggregation, cerebral spasm, premature labor, spontaneous abortion, dysmenorrhea, and migraine.

1,9-DISUBSTITUTED 1,2,3,4-TETRAHYDROCARBAZOLES AND PHARMACEUTICAL PREPARATIONS CONTAINING SUCH COMPOUNDS

Tetrahydrocarbazole 1-alkanoic acids are disclosed. The compounds act as prostaglandin and thromboxane antagonists and are useful in treating asthma, diarrhea, hypertension, angina, platelet aggregation. cerebral spasm, premature labor, spontaneous abortion and dysmenorrhea and as cytoprotective agents.

TETRAHYDROCARBAZOLE ESTER.

Tetrahydrocarbazole esters are disclosed. The compounds act as prostaglandin and thromboxane antagonists and are useful in treating asthma, diarrhea, hypertension, angina, platelet aggregation, cerebral spasm, premature labor, spontaneous abortion and dysmenorrhea and as cytoprotective agents.

TETRAHYDROCARBAZOLESTES AND PHARMACEUTICAL PREPARATIONS CONTAINING SUCH A CONNECTION

Tetrahydrocarbazole 1-alkanoic acids and pharmaecutical compositions

Tetrahydrocarbazole 1-alkanoic acids are disclosed. The compounds act as prostaglandin and thromboxane antagonists and are useful in treating asthma, diarrhea, hypertension, angina, platelet aggregation, cerebral spasm, premature labor, spontaneous abortion and dysmenorrhea and as cytoprotective agents.

Low molecular weight bicyclic thrombin inhibitors

This invention relates to the discovery of heterocyclic competitive inhibitors of the enzyme thrombin having formula (I), their preparation, and pharmaceutical compositions thereof. As well, this invention relates to the use of such compounds and compositions in vitro as anticoagulants and in vivo as agents for the treatment and prophylaxis of thrombotic disorders such as venous thrombosis, pulmonary embolism and arterial thrombosis resulting in acute ischemic events such as myocardial infarction or cerebral infarction. Moreover, these compounds and compositions have therapeutic utility for the prevention and treatment of coagulopathies associated with coronary bypass operations as well as restenotic events following transluminal angioplasty.

Low molecular weight bicyclic fibrin element inhibitors

3-(indol-1-yl)-4-(indol-3-yl)-pyrrole-2,5-diones,3-(benzimidazol-1-yl)-4-(indol-3-yl)-pyrrole-2,5-diones, and 3-(indolin-1-yl)-4-(indol-3-yl)-pyrrole-2,5-diones; their preparation and use as modulators of apoptosis

This invention features compounds of formula (I), (II) and (III), which are useful in the treatment of proliferative disorders characterized by loss of growth or cellular differentiation control including, but not limited to, cancer and inflammation. Formulas (I), (II), (III) have functional groups designated as A1, A2, B1, B2, X1-X9 and Rl -R8 as defined further.

(Quinolin-2-ylmethoxy)indoles as inhibitors of the biosynthesis of leukotrienes

Compounds having the formula I: ##STR1## are inhibitors of leukotriene biosynthesis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents. They are also useful in treating diarrhea, hypertension, angina, platelet aggregation, cerebral spasm, premature labor, spontaneous abortion, dysmenorrhea, and migraine.

Leukotriene antagonists

Compounds having the formula: ##STR1## are antagonists of leukotrienes of C 4 , D 4 E 4 and the slow reacting substance of anaphylaxis. As such, these compounds will be useful as anti-asthmatic, anti-allergic, anti-inflammatory and cytoprotective agents.

Indole-2-alkanoic acids

ABSTRACT OF THE DISCLOSURE Indole-2-alkanoic acids are disclosed. The compounds have the following general formula: I The compounds act as prostaglandin and thromboxane antagonists and are useful in treating asthma, inflammation, diarrhea, hypertension, angina, platelet aggregation, cerebral spasm, premature labor, spontaneous abortion and dismenorrhea and as cytoprotective agents.

Tetrahydrocarbazole 1-alkanoic acid derivatives and pharmaceutical compositions thereof

Tetrahydrocarbazole 1-alkanoic acids are disclosed. The compounds act as prostaglandin and thromboxane antagonists and are useful in treating asthma, diarrhea, hypertension, angina, platelet aggregation. cerebral spasm, premature labor, spontaneous abortion and dysmenorrhea and as cytoprotective agents.

PROCESS FOR THE PREPARATION OF (QUINOLIN-2-ILMETOXI) INDOLES AS BIOSAFETY INHIBITORS OF LEUCOTYRIENES

Cyclohept(B)indolealkanoic acids, pharmaceutical compositions and use

Cyclohept[b]indolealkanoic acids and acid derivatives are disclosed. The compounds act as prostaglandin and thromboxane antagonists and are useful in treating asthma, diarrhea, hypertension, angina, platelet, aggregation, cerebral spasm, premature labor, spontaneous abortion, dysmenorrhea and nephrotoxicity caused by cyclosporin A and as cytoprotective agents.

(polycyclic-arylmethoxy)indoles as inhibitors of leukotriene biosynthesis

TITLE OF THE INVENTION (POLYCYCLIC-ARYLMETHOXY)lNDOLES AS INHIBITORS OF LEUKOTRIENE BIOSYNTHESIS ABSTRACT OF THE DISCLOSURE Compounds having the formula I: I are inhibitore of leukotriene biosynthesis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents. They are also useful in treating diarrhea, hypertension, angina, platelet aggregation, cerebral spasm, premature labor, spontaneous abortion, dysmenorrhea, and migraine.

PROCESS FOR PREPARING TETRAHYDROCARBOZOLE 1-ALKANOIC ACIDS

Method for differentiating between multiple sclerosis subtypes

Disclosed herein is a method for differentiating between multiple sclerosis subtypes in a patient. The method comprises a) determining an amount of an IAP gene expression level in a blood sample obtained from the patient; and b) correlating the amount of the IAP gene expression level in the blood sample with the presence of a multiple sclerosis subtype in the patient.

Pyranylphenyl hydroxyalkylnaphthoic acids as inhibitors of leukotriene biosynthesis

Compounds having the formula I: are inhibitors of leukotriene biosynthesis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents. They are also useful in treating angina, cerebral spasm, glomerular nephritis, hepatitis, endotoxemia, uveitis and allograft rejection and in preventing the formation of atherosclerotic plaques.

(azaarylmethoxy)indoles as inhibitors of leukotriene biosynthesis

Compounds having the formula I: (see formula I) are inhibitors of leukotriene biosynthesis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents. They are also useful in treating diarrhea, hypertension, angina, platelet aggregation, cerebral spasm, premature labor, spontaneous abortion, dysmenorrhea, and migraine.

Imidazo(2,1-b)thiadiazole sulfonamides

This invention relates to novel compounds of Formula I and the use of compounds of Formula I as neuroprotective agents in the treatment of neuronal disorders of the central and peripheral nervous systems. In Formula I, R6 can be represented by W.

Indole-2-alkanoic acids and their use as prostaglandin antagonists

Tetrahydrocarbazole 1-alkanoic acids

TITLE OF THE INVENTION ABSTRACT OF THE DISCLOSURE Tetrahydrocarbazole 1-alkanoic acids are disclosed. The compounds act as prostaglandin and thromboxane antagonists and are useful in treating asthma, diarrhea, hypertension, angina, platelet aggregation, cerebral spasm, premature labor, spontaneous abortion and dysmenorrhea and as cytoprotective agents, and have the following general formula: I wherein: R1, R2, R3, R4, R5 and R6 are each independently selected from: (1) hydrogen; (2) alkyl having 1 to 6 carbon atoms; (3) alkenyl having 2 to 6 carbon atoms; (4) -(CH2)nM wherein n is O to 3 and M is a) OR13; b) halogen; c) CF3; d) SR13; e) phenyl or substituted phenyl wherein substituted phenyl i s as defined below in the definition of R13; f) COOR14; g) -?-R15; h) -NH-?-R16 wherein R16 is C1 to C6 alkyl, benzyl or phenyl; i) -NR14R14; j) -NHSO2R17 wherein R17 is C1 to C6 alkyl, 4-methylphenyl, phenyl, or CF3; k) -?-CH2OH; l) -SOR13; CONR14R14; n) -SO2NR14R14; o) -SO2R13; p) NO2 ; q) -O-?-R15; r) -O-?-NR14R14; s) - O-?-OR16; t) CN; u) N3; R7 is H or alkyl of 1 to 6 carbons; R8 is H or alkyl of 1 to 6 carbon atoms; each R9 is independently H, OH, C1 to C4-O-alkyl or alkyl of 1 to 4 carbons; R10 is COOH; CH2OH; CHO; NHSO2R11 wherein R11 is OH, alkyl or alkoxy of 1 to 6 carbons, perhaloalkyl of 1 to 6 carbons, phenyl or phenyl substituted by alkyl or alkoxy groups of 1 to 3 carbons, halogen, hydroxy, COOH, CN, formyl or acyl to 1 to 6 carbons; CONHSO2R11; hydroxymethylketone; CN; or CON(R9)2; r is 1 to 6; each R13 independently is H; C1 to C6 alkyl; benzyl; phenyl or substituted phenyl wherein the substituents are C1 to C3 alkyl, halogen, CN, CF3, COOR14, CH2COOR14, C1 to C3 alkoxy, or C1 to C4 perfluoroalkyl; each R14 is independently H, phenyl, benzyl or C1 to C6 alkyl; and, each R15 independently is H, (CH2)mCOOR14 wherein m is 0 to 4, C1 to C6 alkyl, CF3, phenyl, or substituted phenyl wherein substituted phenyl is as defined above in the definition of R13; or a ...

Tetrahydrocarbazole 1-alkanoic acids

Tetrahydrocarbazole 1-alkanoic acids are disclosed. The compounds act as prostaglandin and thromboxane antagonists and are useful in treating asthma, diarrhea, hypertension, angina, platelet aggregation. cerebral spasm, premature labor, spontaneous abortion and dysmenorrhea and as cytoprotective agents.

(quinolin-2-ylmethoxy)tetrahydrocarbazoles as inhibitors of the biosynthesis of leukotrienes

Compounds having the Formula I: ##STR1## are inhibitors of leukotriene biosynthesis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents. They are also useful in treating diarrhea, hypertension, angina, platelet aggregation, cerebral spasm, premature labor, spontaneous abortion, dysmenorrhea, and migraine.

IMIDAZO- (2,1-B) -1,3,4-TIADIAZOL SULFONAMIDS.

Un compuesto de imidazo[2,1-b]-1,3,4-tiadiazol sulfonamida de acuerdo con la Fórmula I: **(Ver fórmula)** o una sal farmacéuticamente aceptable del mismo, en la que: R1 y R2 se seleccionan individualmente entre H y alquilo C(1-8); R5 se selecciona entre H, halógeno, alquilo C(1-8) sin sustituir, arilo sin sustituir y heteroarilo sin sustituir; y R6 se selecciona entre alquilo C(1-8) sustituido, fluoroalquilo C(1-8), arilo C(6-16) sustituido y sin sustituir, heteroarilo sustituido y sin sustituir, coumarinilo sustituido y sin sustituir, adamantilo y **(Ver fórmula)** en la que n representa 0 ó 1; en la que el sistema de anillos que contiene X7-X11 representa un sistema de anillos aromático o heteroaromático, de 5 ó 6 miembros (n = 0 ó 1, respectivamente), en el que cada uno de X7-X11 se elige independientemente entre C, N, S y O; en la que cada uno de X7-X11, cuando representa independientemente C, tiene un grupo R7-R11 respectivo seleccionado entre: a) H, Halógeno, nitro, ciano, alquilo C(1-8) sustituido y sin sustituir, fluoroalquilo, arilo sustituido y sin sustituir, heteroarilo sustituido y sin sustituir, alquilcarbonilo C(1-8) sustituido y sin sustituir; c) SOnR18 en la que n = 0,1 ó 2, y en la que R18 se selecciona entre el grupo constituido por alquilo C(1-8), arilo sustituido y sin sustituir y heteroarilo sustituido y sin sustituir; d) OR19 en la que R19 se selecciona entre el grupo constituido por alquilo sustituido y sin sustituir, fluoroalquilo, arilo sustituido y sin sustituir, heteroarilo sustituido y sin sustituir, alquilcarbonilo C(1-8) sustituido y sin sustituir, arilcarbonilo sustituido y sin sustituir, heteroarilcarbonilo sustituido y sin sustituir, alquilaminocarbonilo C(1-8) y arilaminocarbonilo sustituido y sin sustituir; e) NR14R15 en la que R14 y R15 se definen como alquilo C(1-8) o se unen para formar un sistema de anillos alquilo o heteroalquilo sustituido o sin sustituir; y en la que cada uno de X7-X11, cuando representa independientemente N ...

(quinolin-2-ylmethoxy)indoles as inhibitors of the biosynthesis of leukotrienes

Compounds having formula (I) are inhibitors of leukotriene biosynthesis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents. They are also useful in treating diarrhea, hypertension, angina, platelet aggregation, cerebral spasm, premature labor, spontaneous abortion, dysmenorrhea, and migraine.

(quinolin-2-ylmethoxy)heterotetrahydrocarbazoles as inhibitors of the biosynthesis of leukotrienes

Compounds having the formula I: (See Formula I) are inhibitors of leukotriene biosynthesis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents. They are also useful in treating diarrhea, hypertension, angina, platelet aggregation, cerebral spasm, premature labor, spontaneous abortion, dysmenorrhea, and migraine.

PROCEDURE FOR THE PREPARATION OF (KINOLIN-2-YLMETHOXY) INDOLES.

Compounds having the formula I: <CHEM> are inhibitors of leukotriene biosynthesis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents. They are also useful in treating diarrhea, hypertension, angina, platelet aggregation, cerebral spasm, premature labor, spontaneous abortion, dysmenorrhea, and migraine.

5-lipoxygenase activating protein

An 18kD protein (FLAP) has been isolated from rat and human cells which is necessary for production of leukotrienes from arachidonic acid in mammalian cells containing 5-lipoxygenase. The gene (cDNA) encoding for FLAP has also been produced.

Device to reduce tool marks in incremental forming

A device for incrementally forming a plurality of workpieces includes a frame configured to receive a workpiece, at least one clamp configured to secure the workpiece to the frame, a first sacrificial material layer configured to be secured to at least one surface of the workpiece, and a first forming tool configured to impart a first force directly to the first sacrificial material layer and incrementally form the workpiece to a desired geometry based on a tool path of the first forming tool. The frame, the at least one clamp, the first sacrificial material layer, and the first forming tool are configured to impart a first force directly to the first sacrificial material layer secured to at least one surface of a first workpiece with the first forming tool and incrementally form the first workpiece to a desired geometry based on a tool path of the first forming tool.

(bicyclische heteroarylmethoxy)indole als inhibitore leukotriene biosynthese

Elektrohydraulisches Formwerkzeug sowie Verfahren zum Formen eines Blechzuschnitts unter Verwendung desselben

Die Erfindung betrifft ein elektrohydraulisches Formwerkzeug (EHF-Werkzeug) sowie ein Verfahren zum Formen eines Blechzuschnitts in einem EHF-Arbeitsvorgang. Das Werkzeug (10) kann ein Paar von Elektroden (16, 18) aufweisen und mit einer Flüssigkeit gefüllt werden. Eine Hochspannungsentladung kann zwischen den Elektroden (16, 18) in solcher Weise erzeugt werden, dass eine Schockwelle innerhalb des Fluids induziert wird. Die Schockwelle kann eine ausreichende Kraft innerhalb der Flüssigkeit zum Formen des Zuschnitts (20) gegen eine Matrize (24) erzeugen.

Imidazo 2,1-b -1,3,4-thiadiazole sulfonamides

Einrichtung mit integrierter baugruppe aus elektromagnetischer spule und saugbecher zum abstapeln eines stapels von rohlingen

Die vorliegende Offenbarung stellt eine Einrichtung mit einer integrierten Baugruppe aus elektromagnetischer Spule und Saugbecher zum Abstapeln eines Stapels von Rohlingen bereit. Eine Einrichtung zum Abstapeln eines Rohlings von einem Stapel von Rohlingen beinhaltet eine elektromagnetische Saugvorrichtung, die eine primäre Saugvorrichtung und eine elektromagnetische Vorrichtung beinhaltet, wobei die primäre Saugvorrichtung in die elektromagnetische Vorrichtung integriert ist. Die Vorrichtung beinhaltet eine Hilfssaugvorrichtung in der Nähe der elektromagnetischen Saugvorrichtung.

Improvements in and relating tothe manufacture of flexible tubing

Connector means for connecting flexible tubing conduit orthe like

Heteroarylnaphthalene hydroxy acids as inhibitors of leukotriene biosynthesis

Improvements in and relating tothe manufacture of flexible tubing

Heteroarylnaphthalene lactones as inhibitors of leukotriene biosynthesis

Connector means for connecting flexible tubing conduit orthe like

Neuroprotective and anti-proliferative compounds

This invention features ring-substituted pyrrolo-β-carboline derivatives and ring-substitution and structural derivatives of 3-(1H-indol-3-yl)-1H-pyrrole-2,5-dione of formulas (I - III), which are useful as neuroprotective and anti-proliferative compounds. Also disclosed are methods for the preparation of these compounds, selected biological profiles and uses of these compounds in the treatment of various neurodegenerative and inflammatory diseases of the human nervous system and in the treatment of various other proliferative disorders characterized by loss of growth or cellular differentiation control including, but not limited to, cancer and inflammation.

Improved electric conduit fittings

Mixing valve

Heterocyclic keto arginine peptided as thrombin inhibitors

Neuroprotective and anti-proliferative compounds

Neuroprotective and anti-proliferative compounds

This invention features ring-substituted pyrrolo-β-carboline derivatives and ring-substitution and structural derivatives of 3-(1H-indol-3-yl)-1H-pyrrole-2,5-dione of formulas (I - III), which are useful as neuroprotective and anti-proliferative compounds. Also disclosed are methods for the preparation of these compounds, selected biological profiles and uses of these compounds in the treatment of various neurodegenerative and inflammatory diseases of the human nervous system and in the treatment of various other proliferative disorders characterized by loss of growth or cellular differentiation control including, but not limited to, cancer and inflammation.

Heterocyclic keto arginine peptides as thrombin inhibitors

Low molecular weight bicyclic thrombin inhibitors

Heterociclic peptides of the ceto-arginine, asinhibitors of the tromb