The present invention provides methods for treating and/or preventing conditions and diseases in humans and other mammals that are associated with and/or mediated by signal transduction pathways comprising platelet-derived growth factor receptor (PDGFR) by administering diaryl ureas of Formula I. Th
The present invention provides methods for treating and/or preventing conditions and diseases in humans and other mammals that are associated with and/or mediated by signal transduction pathways comprising platelet-derived growth factor receptor (PDGFR) by administering diaryl ureas of Formula I. The present invention also provides devices and methods for treating, ameliorating, preventing, or modulating restenosis following angioplastic surgery or other invasive procedures that affect or injure the vascular system, and graft rejection following transplantation of a donor tissue into a host, where a stent or other omplantable device comprises an effective amount of diaryl ureas of Formula I.
대표청구항▼
1. A method for treating a disease or condition in mammal, or a mammalian cell thereof, which is a tumor, chronic myeloid leukemia, inflammation, renal disease, diabetic nephropathy, mesangial proliferative glomerulonephritis, atherosclerosis, restenosis, hypertension-related arterosclerosis, venous
1. A method for treating a disease or condition in mammal, or a mammalian cell thereof, which is a tumor, chronic myeloid leukemia, inflammation, renal disease, diabetic nephropathy, mesangial proliferative glomerulonephritis, atherosclerosis, restenosis, hypertension-related arterosclerosis, venous bypass graft arterosclerosis, scleroderma, interstitial pulmonary disease, a synovial disorder, arthritis, leukemia or lymphoma mediated by platelet-derived growth factor receptor-beta, where a defect in the receptor itself is involved in “causing” the disease; or functional activity of PDGFR results in the disease symptom and/or phenotype when inappropriately expressed, said method comprising: administering to a subject in need thereof, an effective amount of an aryl urea compound of formula I, a salt form of a compound of Formula I, an isolated or mixed stereoisomer of a compound of Formula I, wherein: A is phenyl, optionally substituted 1, 2 or 3 times by R3, wherein each R3 is independently C1-C5 alkyl, C1-C5 haloalkyl, up to per-haloalkyl, C1-C5 alkoxy, C1-C5 haloalkoxy, up to per-haloalkoxy, halogen, cyano, or nitro; or A is a group of the formula: optionally substituted 1, 2, 3, 4, 5 or 6 times with R4 wherein each R4 is independently C1-C5 alkyl or halogen;B is phenylene, optionally substituted 1, 2 or 3 times by R2, or naphthylene, optionally substituted optionally substituted 1, 2 or 3 times by R2, wherein each R2 is independently C1-C5 alkyl, C1-C5 haloalkyl, up to per-haloalkyl, C1-C5 alkoxy, C1-C5 haloalkoxy up to per-haloalkoxyl, halogen, cyano or nitro; Q is cyano, —C(O)—Ra, or —C(O)—NRbRc, where each Ra, Rb and Rc is independently H or C1-C5 alkyl,L is —O— or —S—,m is an integer 0, 1, 2 or 3, andeach R1 is independently halogen, C1-5 alkyl, C1-5 haloalkyl, up to per-haloalkyl, C1-5 alkoxy, C1-5 haloalkoxy, up to per-haloalkoxy, N-oxo or N-hydroxy. 2. A method of claim 1 wherein for the compound of formula (I), each R2 is independently methyl, ethyl, propyl, butyl, isopropyl, tert-butyl, trifluoromethyl, methoxy, CN or NO2. 3. A method of claim 1 wherein for the compound of formula (I), each R3 is independently fluorine, chorine, bromine, methyl, ethyl, propyl, butyl, pentyl, isopropyl, iso-butyl, sec-butyl, tert-butyl, trifluoromethyl, methoxy, ethoxy, trifluoromethoxy, CN or NO2 and each R4 is independently fluorine, chorine, bromine or methyl. 4. A method of claim 1 wherein for the compound of formula (I), each R1 is independently methyl, ethyl, propyl, oxygen, cyano, n-oxo or n-hydroxy and each Ra, Rb and Rc is independently H or methyl. 5. A method of claim 1 wherein for the compound of formula (I), each Ra, Rb and Rc is independently H or methyl;each R1 is independently methyl, ethyl, propyl, oxygen, cyano, n-oxo or n-hydroxy;each R2 is independently methyl, ethyl, propyl, butyl, isopropyl, tert-butyl, trifluoromethyl, methoxy, CN or NO2;each R3 is independently fluorine, chorine, bromine, methyl, ethyl, propyl, butyl, pentyl, isopropyl, iso-butyl, sec-butyl, tert-butyl, trifluoromethyl, methoxy, ethoxy, trifluoromethoxy, CN or NO2; andeach R4 is independently fluorine, chorine, bromine or methyl. 6. A method of claim 1 wherein for the compound of formula (I), A is substituted phenyl. 7. A method of claim 1 wherein for the compound of formula (I), A is substituted phenyl; each Ra, Rb and Rc is independently H or methyl;each R1 is independently methyl, ethyl, propyl, oxygen, cyano, n-oxo or n-hydroxy;each R2 is independently methyl, ethyl, propyl, butyl, isopropyl, tert-butyl, trifluoromethyl, methoxy, CN or NO2; andeach R3 is independently fluorine, chorine, bromine, methyl, ethyl, propyl, butyl, pentyl, isopropyl, iso-butyl, sec-butyl, tert-butyl, trifluoromethyl, methoxy, ethoxy, trifluoromethoxy, CN or NO2. 8. A method of claim 1 wherein for the compound of formula (I), A is a group of the formula: optionally substituted 1, 2, 3 or 4 times with R4, wherein each R4 is independently chlorine or fluorine. 9. A method of claim 1 wherein for the compound of formula (I), A is a group of the formula: optionally substituted 1, 2, 3 or 4 times with R4, and whereineach Ra, Rb and Rc is independently H or methyl;each R1 is independently methyl, ethyl, propyl, oxygen, cyano, n-oxo or n-hydroxy;each R2 is independently methyl, ethyl, propyl, butyl, isopropyl, tert-butyl, trifluoromethyl, methoxy, CN or NO2; andeach R4 is independently fluorine or chorine. 10. A method of claim 1 wherein for the compound of formula (I), B is phenylene. 11. A method of claim 5 wherein for the compound of formula (I), B is phenylene. 12. A method of claim 1 wherein for the compound of formula (I), B is naphthylene. 13. A method of claim 5 wherein for the compound of formula (I), B is naphthylene. 14. A method of claim 1 wherein for the compound of formula (I), A is substituted phenyl and B is phenylene. 15. A method of claim 1 wherein for the compound of formula (I), A is substituted phenyl; B is phenylene, each Ra, Rb and Rc is independently H or methyl;each R1 is independently methyl, ethyl, propyl, oxygen, cyano, n-oxo or n-hydroxy;each R2 is independently methyl, ethyl, propyl, butyl, isopropyl, tert-butyl, trifluoromethyl, methoxy, CN or NO2 andeach R3 is independently fluorine, chorine, bromine, methyl, ethyl, propyl, butyl, pentyl, isopropyl, iso-butyl, sec-butyl, tert-butyl, trifluoromethyl, methoxy, ethoxy, trifluoromethoxy, CN or NO2. 16. A method of claim 1 wherein for the compound of formula (I), A is a group of the formula: optionally substituted 1, 2, 3 or 4 times with R4, wherein each R4 is independently chlorine or fluorine and B is phenylene. 17. A method of claim 1 wherein for the compound of formula (I), A is a group of the formula: optionally substituted 1, 2, 3 or 4 times with R4;B is phenylene;each Ra, Rb and Rc is independently H or methyl;each R1 is independently methyl, ethyl, propyl, oxygen, cyano, n-oxo or n-hydroxy;each R2 is independently methyl, ethyl, propyl, butyl, isopropyl, tert-butyl, trifluoromethyl, methoxy, CN or NO2; andeach R4 is independently fluorine or chlorine. 18. A method of claim 1 wherein for the compound of formula (I), L is oxygen. 19. A method of claim 5, wherein for the compound of formula (I), L is oxygen. 20. A method of claim 1, wherein for the compound of formula (I), A is substituted phenyl, and L is oxygen. 21. A method of claim 1, wherein for the compound of formula (I), B is phenylene and L is oxygen. 22. A method of claim 1, wherein for the compound of formula (I), B is naphthylene and L is oxygen. 23. A method of claim 1, wherein for the compound of formula (I), A is substituted phenyl; B is phenylene and L is oxygen. 24. A method of claim 23, wherein for the compound of formula (I), each Ra, Rb and Rc is independently H or methyl; each R1 is independently methyl, ethyl, propyl, oxygen, cyano, n-oxo or n-hydroxy;each R2 is independently methyl, ethyl, propyl, butyl, isopropyl, tert-butyl, trifluoromethyl, methoxy, CN or NO2; andeach R3 is independently fluorine, chorine, bromine, methyl, ethyl, propyl, butyl, pentyl, isopropyl, iso-butyl, sec-butyl, tert-butyl, trifluoromethyl, methoxy, ethoxy, trifluoromethoxy, CN or NO2. 25. A method of claim 1, wherein for the compound of formula (I), A is substituted phenyl; B is naphthylene and L is oxygen. 26. A method of claim 25, wherein for the compound of formula (I), each Ra, Rb and Rc is independently H or methyl; each R1 is independently methyl, ethyl, propyl, oxygen, cyano, n-oxo or n-hydroxy;each R2 is independently methyl, ethyl, propyl, butyl, isopropyl, tert-butyl, trifluoromethyl, methoxy, CN or NO2; andeach R3 is independently fluorine, chorine, bromine, methyl, ethyl, propyl, butyl, pentyl, isopropyl, iso-butyl, sec-butyl, tert-butyl, trifluoromethyl, methoxy, ethoxy, trifluoromethoxy, CN or NO2. 27. A method of claim 1, wherein for the compound of formula (I), A is a group of the formula: optionally substituted 1, 2, 3 or 4 times with R4, B is phenylene and L is oxygen, wherein each R4 is independently chlorine or fluorine. 28. A method of claim 27 wherein for the compound of formula (I), each Ra, Rb and Rc is independently H or methyl;each R1 is independently methyl, ethyl, propyl, oxygen, cyano, n-oxo or n-hydroxy;each R2 is independently methyl, ethyl, propyl, butyl, isopropyl, tert-butyl, trifluoromethyl, methoxy, CN or NO2; andeach R4 is independently fluorine or chorine. 29. A method of claim 1 wherein for the compound of formula (I), L is oxygen; B is naphthylene, A is a group of the formula: optionally substituted 1, 2, 3 or 4 times with R4;each Ra, Rb and Rc is independently H or methyl;each R1 is independently methyl, ethyl, propyl, oxygen, cyano, n-oxo or n-hydroxy;each R2 is independently methyl, ethyl, propyl, butyl, isopropyl, tert-butyl, trifluoromethyl, methoxy, CN or NO2; andeach R4 is independently fluorine or chorine. 30. A method of claim 29 wherein for the compound of formula (I), each Ra, Rb and Rc is independently H or methyl;each R1 is independently methyl, ethyl, propyl, oxygen, cyano, n-oxo or n-hydroxy;each R2 is independently methyl, ethyl, propyl, butyl, isopropyl, tert-butyl, trifluoromethyl, methoxy, CN or NO2; andeach R4 is independently fluorine or chorine. 31. A method of claim 15 wherein for the compound of formula (I), each R3 is chlorine, bromine, tert-butyl, trifluoromethyl or methoxy. 32. A method of claim 24 wherein for the compound of formula (I), each R3 is chlorine, bromine, tert-butyl, trifluoromethyl or methoxy. 33. A method of claim 26 wherein for the compound of formula (I), each R3 is chlorine, bromine, tert-butyl, trifluoromethyl or methoxy. 34. A method for treating a disease or condition in mammal, or a mammalian cell thereof, which is a tumor, chronic myeloid leukemia, inflammation, renal disease, diabetic nephropathy, mesangial proliferative glomerulonephritis, atherosclerosis, restenosis, hypertension-related arterosclerosis, venous bypass graft arterosclerosis, scleroderma, interstitial pulmonary disease, a synovial disorder, arthritis, leukemia or lymphoma mediated by platelet-derived growth factor receptor-beta where a defect in the receptor itself is involved in “causing” the disease or functional activity of PDGFR results in the disease symptom and/or phenotype when inappropriately expressed, said method comprising: administering to a subject in need thereof, an effective amount of an aryl urea compound of formulae X, Y, ZA, ZB, or ZD, a salt form of a compound of formulae X, Y, ZA, ZB, or ZD, or an isolated or mixed stereoisomer of a compound of formulae X, Y, ZA, ZB, or ZD, wherein each R3 is independently halogen or trifluoromethyl and each R2 is independently methyl, trifluoromethyl, methoxy, CN or NO2 the variable n is 0, 1, 2, 3 or 4 and the variable p is 0, 1 or 2. 35. A method of claim 1 wherein a pharmaceutically acceptable basic salt of an organic acid of formula (I) is administered. 36. A method of claim 34 wherein a pharmaceutically acceptable basic salt of an organic acid of formula (I) is administered. 37. A method of claim 1 wherein a pharmaceutically acceptable basic salt of an organic acid of formula (I) is administered, selected from hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, methanesulfonic acid, trifluoromethanesulfonic acid, benzenesulfonic acid, p-toluene sulfonic acid (tosylate salt), 1-napthalene sulfonic acid, 2-napthalene sulfonic acid, acetic acid, trifluoroacetic acid, malic acid, tartaric acid, citric acid, lactic acid, oxalic acid, succinic acid, fumaric acid, maleic acid, benzoic acid, salicylic acid, phenylacetic acid, or mandelic acid. 38. A method of claim 34 wherein a pharmaceutically acceptable basic salt of an organic acid of formula (I) is administered, selected from hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, methanesulfonic acid, trifluoromethanesulfonic acid, benzenesulfonic acid, p-toluene sulfonic acid (tosylate salt), 1-napthalene sulfonic acid, 2-napthalene sulfonic acid, acetic acid, trifluoroacetic acid, malic acid, tartaric acid, citric acid, lactic acid, oxalic acid, succinic acid, fumaric acid, maleic acid, benzoic acid, salicylic acid, phenylacetic acid, or mandelic acid. 39. A method of claim 15 wherein a pharmaceutically acceptable basic salt of an organic acid of formula (I) is administered, selected from hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, methanesulfonic acid, trifluoromethanesulfonic acid, benzenesulfonic acid, p-toluene sulfonic acid (tosylate salt), 1-napthalene sulfonic acid, 2-napthalene sulfonic acid, acetic acid, trifluoroacetic acid, malic acid, tartaric acid, citric acid, lactic acid, oxalic acid, succinic acid, fumaric acid, maleic acid, benzoic acid, salicylic acid, phenylacetic acid, or mandelic acid. 40. A method of claim 24 wherein a pharmaceutically acceptable basic salt of an organic acid of formula (I) is administered, selected from hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, methanesulfonic acid, trifluoromethanesulfonic acid, benzenesulfonic acid, p-toluene sulfonic acid (tosylate salt), 1-napthalene sulfonic acid, 2-napthalene sulfonic acid, acetic acid, trifluoroacetic acid, malic acid, tartaric acid, citric acid, lactic acid, oxalic acid, succinic acid, fumaric acid, maleic acid, benzoic acid, salicylic acid, phenylacetic acid, or mandelic acid. 41. A method of claim 26 wherein a pharmaceutically acceptable basic salt of an organic acid of formula (I) is administered, selected from hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, methanesulfonic acid, trifluoromethanesulfonic acid, benzenesulfonic acid, p-toluene sulfonic acid (tosylate salt), 1-napthalene sulfonic acid, 2-napthalene sulfonic acid, acetic acid, trifluoroacetic acid, malic acid, tartaric acid, citric acid, lactic acid, oxalic acid, succinic acid, fumaric acid, maleic acid, benzoic acid, salicylic acid, phenylacetic acid, or mandelic acid. 42. A method of claim 28 wherein a pharmaceutically acceptable basic salt of an organic acid of formula (I) is administered, selected from hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, methanesulfonic acid, trifluoromethanesulfonic acid, benzenesulfonic acid, p-toluene sulfonic acid (tosylate salt), 1-napthalene sulfonic acid, 2-napthalene sulfonic acid, acetic acid, trifluoroacetic acid, malic acid, tartaric acid, citric acid, lactic acid, oxalic acid, succinic acid, fumaric acid, maleic acid, benzoic acid, salicylic acid, phenylacetic acid, or mandelic acid. 43. A method of claim 34 wherein a pharmaceutically acceptable basic salt of an organic acid of formula (I) is administered, selected from hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, methanesulfonic acid, trifluoromethanesulfonic acid, benzenesulfonic acid, p-toluene sulfonic acid (tosylate salt), 1-napthalene sulfonic acid, 2-napthalene sulfonic acid, acetic acid, trifluoroacetic acid, malic acid, tartaric acid, citric acid, lactic acid, oxalic acid, succinic acid, fumaric acid, maleic acid, benzoic acid, salicylic acid, phenylacetic acid, or mandelic acid. 44. A method of claim 1 wherein the compound of formula I, is a hydrochloride, benzenesulfonate, or methanesulfonate salt of N-(4-chloro-3-(trifluoromethyl)phenyl)-N′-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl)urea. 45. The method of claim 1 wherein the compound of formula (I), is a tosylate salt of N-(4-chloro-3-(trifluoromethyl)phenyl-N′-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl)urea. 46. A method of claim 1 wherein for the compound of formula (I), A is 4-chloro-3-trifluoromethylphenyl, 4-fluoro-3-trifluoromethylphenyl, 4-bromo-3-trifluoromethylphenyl, or 2,2,4,4-tetrafluoro-4H-benzo[1,3]dioxin-6-yl;B is phenylene;L is —O—;andQ is cyano, C(O)—NH2, or C(O)—NHMe. 47. A method of claim 1 wherein the compound of formula (I), is: N-(4-chloro-3-(trifluoromethyl)phenyl)-N′-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl)urea,N-(4-bromo-3-(trifluoromethyl)phenyl)-N′-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl)urea,N-(4-chloro-3-(trifluoromethyl)phenyl)-N′-(4-(2-carbamoyl-4-pyridyloxy)phenyl)urea,N-(4-chloro-3-(trifluoromethyl)phenyl)-N′-(4-(1-hydroxy-2-carbamoyl-4-pyridyloxy) phenyl)urea,N-(4-chloro-3-(trifluoromethyl)phenyl)-N′-(4-(1-hydroxy-2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl)urea, orN-(6-(2,2,4,4-tetrafluoro-4H-bezo[1,3]dioxinyl))-N′-(4-(2-cyano-4-pyridyloxy)phenyl)urea. 48. A method of claim 1 comprising administering an additional pharmaceutical agent with the compound of formula (I) to a patient in need thereof. 49. A method of claim 1 wherein said compound of formula (I) is administered to a patient in need thereof at an oral, intramuscular, intravenous, subcutaneous, or parenteral dosage which can range from about 0.1 to about 300 mg/kg of total body weight. 50. A method of claim 1, wherein said disease or condition is chronic myeloid leukemia, renal disease, diabetic nephropathy, mesangial proliferative glomerulonephritis, atherosclerosis, hypertension-related arterosclerosis, venous bypass graft arterosclerosis, scleroderma, interstitial pulmonary disease, a synovial disorder, arthritis, leukemia, lymphoma or restenosis following angioplasty. 51. A method of claim 1, wherein said disease or condition is graft rejection following transplantation of a donor tissue into a host. 52. A method of claim 5, wherein said disease or condition is chronic myeloid leukemia, renal disease, diabetic nephropathy, mesangial proliferative glomerulonephritis, atherosclerosis, hypertension-related arterosclerosis, venous bypass graft arterosclerosis, scleroderma, interstitial pulmonary disease, a synovial disorder, arthritis, leukemia, lymphoma or restenosis following angioplasty. 53. A method of claim 5, wherein said disease or condition is graft rejection following transplantation of a donor tissue into a host. 54. A method of claim 34, wherein said disease or condition is a tumor, chronic myeloid leukemia, renal disease, diabetic nephropathy, mesangial proliferative glomerulonephritis, atherosclerosis, hypertension-related arterosclerosis, venous bypass graft arterosclerosis, scleroderma, interstitial pulmonary disease, a synovial disorder, arthritis, leukemia, lymphoma or restenosis following angioplasty. 55. A method of claim 34, wherein said disease or condition is graft rejection following transplantation of a donor tissue into a host.
Vladi{acute over (m)}ir Oremus SK; Vendelin {haeck over (S)}mahovsky SK; Viera Faberova SK; Ivan Kakalik SK; {haeck over (L)}udmila Schmidtova SK; Marian Zemanek SK, 1,3-disubstituted ureas as ACAT inhibitors, and method of preparing thereof.
Aldrich Paul Edward (Wilmington DE) Berezin Gilbert Harvey (West Chester PA) Dittmar Bruce Ivor (Wilmington DE), 1-Tertiary-alkyl-3-(substituted thienyl)ureas and 1-tertiary-alkyl-3-(substituted thietyl)ureas as antihypertensive agen.
Paolo Pevarello IT; Paolo Orsini IT; Gabriella Traquandi IT; Mario Varasi IT; Edward L. Fritzen ; Martha A. Warpehoski ; Betsy S. Pierce, 3(5)-ureido-pyrazole derivatives process for their preparation and their use as antitumor agents.
Kanno Hisashi,JPX ; Yoshida Kazuo,JPX ; Sato Tsutomu,JPX ; Sato Koki,JPX ; Kanda Yoichi,JPX, 6-phenoxy picolinic acid alkylidene hydrazide derivative, process for producing the same and herbicide using the same.
Dixon James S. (Malvern PA) Hall Raplh F. (Villanova PA) Marshall Lisa A. (Wyndmoor PA) Chilton ; III Floyd H. (Pilot Mountain NC) Mayer Ruth J. (Wayne PA) Winkler James D. (Fort Washington PA), Anti-inflammatory compounds.
John C. Lee ; Jerry L. Adams ; Timothy F. Gallagher ; David W. Green ; John Richard Heys ; Peter C. McDonnell ; Dean E. McNulty ; Peter R. Young ; James E. Strickler, Antibodies produced against cytokine suppressive anti-inflammatory drug binding proteins.
O\Doherty George O. P. (Greenfield IN) Clinton Albert J. (Indianapolis IN), Anticoccidial combinations comprising polyether antibiotics and carbanilides.
O\Doherty George O. P. (Greenfield IN) Clinton Albert J. (Indianapolis IN), Anticoccidial combinations comprising polyether antibiotics and carbanilides.
Regan John R. ; Cirillo Pier F. ; Hickey Eugene R. ; Moss Neil ; Cywin Charles L. ; Pargellis Christopher ; Gilmore Thomas A., Aromatic heterocyclic compounds and their use as anti-inflammatory agents.
Regan John R. ; Cirillo Pier F. ; Hickey Eugene R. ; Moss Neil ; Cywin Charles L. ; Pargellis Christopher ; Gilmore Thomas A., Aromatic heterocyclic compounds and their use as anti-inflammatory agents.
Cirillo, Pier Francesco; Dinallo, Roger; Regan, John Robinson; Riska, Paul S.; Swinamer, Alan David; Tan, Zhulin; Walter, Brian Andrew, Aromatic heterocyclic compounds as antiinflammatory agents.
Reel Jon K. (Carmel IN) Simon Richard L. (Greenwood IN) Whitesitt Celia A. (Greenwood IN), Chemical compounds as inhibitors of amyloid beta protein production.
Lehureau Jean-Claude,FRX ; Loiseaux Brigitte,FRX ; Joubert Cecile,FRX, Color display device in which the area of a spherical lens equals the area of a set of RGB sub-pixels.
Sirrenberg ; Wilhelm ; Alles ; Hans-Ulrich ; Hammann ; Ingeborg ; Stend el ; Wilhelm, Combating arthropods with 3-(2,2,4,4-tetrafluoro-benz-1,3-dioxin-6-yl)-1-(substituted benzoyl)-ureas.
Johnston Howard (Walnut Creek CA), Composition and method of controlling undesired plant growth with substituted pyridinyloxy(thio)phenyl -acetamides, -ure.
Petrie Charles ; Orme Mark W. ; Baindur Nand ; Robbins Kirk G. ; Kontoyianni Maria ; Mundy Gregory R., Compositions and methods for treating bone deficit conditions.
Steffen Breitfelder ; Pier F. Cirillo ; Thomas A. Gilmore ; Eugene R. Hickey ; John R. Proudfoot ; John R. Regan ; Alan D. Swinamer ; Hidenori Takahashi, Compounds useful as anti-inflammatory agents.
Lee John C. ; Adams Jerry L. ; Gallagher Timothy F. ; Green David W. ; Heys John Richard ; McDonnell Peter C. ; McNulty Dean E. ; Strickler James E. ; Young Peter R., Cytokine suppressive anit-inflammatory drug binding proteins.
Charles R. Petrie ; Patricia A. McKernan ; Emma E. Moore ; John M. Ostresh ; Jean-Philippe Meyer ; Richard A. Houghten ; Clemencia Pinilla, Dialkyl ureas as calcitonin mimetics.
Acker Rolf-Dieter (Leimen DEX) Rossy Phillip A. (Ludwigshafen DEX) Hamprecht Gerhard (Weinheim DEX) Wuerzer Bruno (Otterstadt DEX), Dihydrothiophenecarboxylates and their use for controlling undersirable plant growth.
Tracey, Kevin J.; Cohen, Pamela; Bukrinsky, Michael; Schmidtmayerova, Helena, Guanylhydrazones useful for treating diseases associated with T cell activation.
Widdowson Katherine Louisa ; Veber Daniel Frank ; Jurewicz Anthony Joseph ; Hertzberg Robert Philip ; Rutledge ; Jr. Melvin Clarence, IL-8 receptor antagonists.
Widdowson Katherine Louisa ; Veber Daniel Frank ; Jurewicz Anthony Joseph ; Hertzberg Robert Philip ; Rutledge ; Jr. Melvin Clarence, IL-8 receptor antagonists.
Widdowson Katherine Louisa ; Veber Daniel Frank ; Jurewicz Anthony Joseph ; Hertzberg Robert Philip ; Rutledge ; Jr. Melvin Clarence, IL-8 receptor antagonists.
Widdowson Katherine Louisa ; Veber Daniel Frank ; Jurewicz Anthony Joseph ; Hertzberg Robert Philip ; Rutledge ; Jr. Melvin Clarence, IL-8 receptor antagonists.
Widdowson Katherine Louisa ; Veber Daniel Frank ; Jurewicz Anthony Joseph ; Hertzberg Robert Phillip ; Rutledge ; Jr. Melvin Clarence, IL-8 receptor antagonists.
Adams Jerry Leroy (Wayne PA) Gallagher Timothy Francis (Harleysville PA) Sisko Joseph (Hatfield PA) Peng Zhi-Qiang (King of Prussia PA) Osifo Irennegbe Kelly (Eagleville PA) Boehm Jeffrey Charles (Ki, Imidazole compounds, compositions and use.
Gerald Ranges ; William Scott ; Michael Bombara ; Deborah Rauner ; Aniko Redman ; Roger Smith ; Holger Paulsen DE; David Gunn ; Jinshan Chen ; Joel Renick, Inhibition of p38 kinase activity by aryl ureas.
Dodge Jeffrey A. ; Sato Masahiko ; Vlahos Chris J., Inhibition of phosphatidylinositol 3-kinase with viridin, demethoxyviridin, viridiol, demethoxyviridiol, virone, wortma.
Bonjouklian Rosanne (Zionsville IN) Vlahos Chris J. (Carmel IN) Powis Garth (Tucson AZ), Inhibition of phosphatidylinositol 3-kinase with wortmannin and analogs thereof.
Wood Jill E ; Wild Hanno,DEX ; Rogers Daniel H ; Lyons John ; Katz Michael ; Caringal Yolanda ; Dally Robert ; Lee Wendy ; Smith Roger A. ; Blum Cheri, Inhibition of raf kinase activity using aryl ureas.
Armistead David M. ; Badia Michael C. ; Bemis Guy W. ; Bethiel Randy S. ; Frank Catharine A. ; Novak Perry M. ; Ronkin Steven M. ; Saunders Jeffrey O., Inhibitors of IMPDH enzyme.
Heinz Lawrence J. ; Panetta Jill A. ; Phillips Michael L. ; Reel Jon K. ; Shadle John K. ; Simon Richard L. ; Whitesitt Celia A., Inhibitors of amyloid beta-protein production.
Kabbe Hans-Joachim (Leverkusen DEX) Klauke Erich (Odenthal DEX) Krause Hans P. (Wuppertal DEX) Mardin Mithat (Wuppertal DEX) Sitt Rdiger (Wuppertal DEX), Medicaments for the treatment of disorders of lipometabolism and their use.
Warenius, Hilmar Meek; Seabra, Laurence Anthony, Methods for determining chemosensitivity of cancer cells based upon expression of negative and positive signal transduction factors.
Dodge Jeffrey A. (Indianapolis IN) Sato Masahiko (Carmel IN), Methods for inhibiting bone loss and cartilage degradation using wortmannin and its analogs.
Tang Peng C. ; McMahon Gerald ; Weinberger Heinz,DEX ; Kutscher Bernhard,DEX ; App Harald, Methods of modulating serine/thereonine protein kinase function with quinazoline-based compounds.
Foulkes J. Gordon ; Leichtfried Franz ; Pieler Christian ; Stephenson John R., Methods of specifically transcriptionally modulating the expression of gene of interest.
Bger Manfred (Weil am Rhein DEX) Ehrenfreund Josef (Allschwil CHX) Martin Pierre (Rheinfelden CHX) Steiner Eginhard (Fllinsdorf CHX), N-(2-Pyridyloxyphenyl)-N′-benzoyl ureas, pesticidal compositions containing same and pesticidal methods of use.
Hisashi Kanno JP; Yoshikazu Kubota JP; Tsutomu Sato JP; Koki Sato JP, N-(unsubstituted or substituted)-4-substituted-6-(unsubstituted or substituted)phenoxy-2-pyridinecarboxamides or thiocarboxamides, processes for producing the same, and herbicides.
Husermann Walter (Ollon CHX) Maurer Max (Murten CHX) Friedel Thomas (N.S.W. AUX), N-3-(5-trifluoromethylpyridyl-2-oxy)phenyl-N′-benzoylureas for controlling helminths in productive livestock.
Ko, Soo S.; DeLucca, George V.; Duncia, John V.; Santella, III, Joseph B.; Gardner, Daniel S., N-ureidoalkyl-piperidines as modulators of chemokine receptor activity.
Lepage Francis (Creteil FRX) Hublot Bernard (Paris FRX), Novel isoxazole and isoxazoline compounds with anticonvulsant activity process for their preparation and therapeutic com.
Goulet Mark (Westfield NJ) Parsons William H. (Edison NJ) Sinclair Peter J. (Highland Park NJ) Wong Frederick (Glen Ridge NJ) Wyvratt Matthew J. (Mountainside NJ), O-aryl, O-alkyl, O-alkenyl and O-alkynylrapamycin derivatives.
Lee John C. ; Adams Jerry L. ; Gallagher Timothy F. ; Green David W. ; Heys John Richard ; McDonnell Peter C. ; McNulty Dean E. ; Young Peter R. ; Strickler James E., Oligonucleotides comprising a region of a cytokine suppressive anti-inflammatory drug binding protein.
Hider Robert C. (Clacton GB2) Kontoghiorghes George (London GB2) Silver Jack (London GB2) Stockham Michael A. (Saffron Walden GB2), Pharmaceutical compositions.
Caldwell, William Scott; Bencherif, Merouane; Dull, Gary Maurice; Crooks, Peter Anthony; Lippiello, Patrick Michael, Pharmaceutical compositions and methods for effecting dopamine release.
Widdowson Katherine Louisa ; Veber Daniel Frank ; Jurewicz Anthony Joseph ; Hertzberg Robert Philip ; Rutledge ; Jr. Melvin Clarence, Phenyl urea antagonists of the IL-8 receptor.
Barbachyn Michael Robert ; Homa Fred L. ; Monge Antonio,ESX ; Santiago Esteban,ESX ; Martinez-Irujo Juan J.,ESX ; Font Maria,ESX, Polyaromatic antiviral compositions.
Lee John C. ; Adams Jerry L. ; Gallagher Timothy F. ; Green David W. ; Heys John Richard ; McDonnell Peter C. ; McNulty Dean E. ; Strickler James E. ; Young Peter R., Polynucleotides encoding cytokine suppressive anti-inflammatory drug binding proteins.
Kissener Wolfram (Bergisch Gladbach DEX) Franke Joachim (Cologne DEX) Fiege Helmut (Leverkusen DEX) Wedemeyer Karlfried (Cologne DEX), Process for the preparation of N,N-diaryl-ureas.
Trk Sandor (Budapest HUX) Vrshazy Lajos (Budapest HUX) Galambos Peter (Budapest HUX) Daroczi Ivan (Budapest HUX) Ormenyi Zoltan (Budapest HUX), Process for the preparation of N-aryl-N′-(mono- or di substituted)-urea derivatives.
Myers Michael R. ; Spada Alfred P. ; Maguire Martin P. ; Persons Paul E., Protein tyrosine kinase aryl and heteroaryl quinazoline compounds having selective inhibition of HER-2 autophosphorylati.
Lee John Cheung-Lun ; Adams Jerry Leroy ; Gallagher Timothy Francis ; Green David W. ; Heys John Richard ; McDonnell Peter Colon ; McNulty Dean Edward ; Strickler James E. ; Young Peter Ronald, Screening methods using cytokine suppressive anti-inflammatory drug (CSAID) binding proteins.
Kleemann Heinz-Werner (Bischofsheim DEX) Lang Hans-Jochen (Hofheim DEX) Schwark Jan-Robert (Frankfurt DEX) Weichert Andreas (Egelsbach DEX) Scholz Wolfgang (Eschborn DEX) Albus Udo (Florstadt DEX), Substituted N-heteroaroylguanidines, a process for their preparation, their use as a medicament or diagnostic agent, and.
Peter Charles Astles GB; David Edward Clark GB; Alan John Collis GB; Paul Joseph Cox GB; Paul Robert Eastwood GB; Neil Victor Harris GB; Justine Yeun Quai Lai GB; Andrew David Morley GB; Barr, Substituted anilides.
Ashton Wallace T. (Clark NJ) Chang Linda L. (Wayne NJ) Greenlee William J. (Teaneck NJ) Hutchins Steven M. (Iselin NJ) Rivero Ralph A. (Tinton Falls NJ), Substituted carbamoyl and oxycarbonyl derivatives of biphenylmethylamines.
Hallenbach Werner (Langenfeld DEX) Lindel Hans (Leverkusen DEX) Berschauer Friedrich (Wuppertal DEX) Scheer Martin (Wuppertal DEX) de Jong Anno (Wuppertal DEX), Thienooxazinones, processes for their preparation, and their use as growth promoters.
Nishiyama, Ryuzo; Fujikawa, Kanichi; Yokomichi, Isao; Haga, Takahiro; Nagatani, Kuniaki; Hayashi, Kouji, Trifluoromethyl-2-pyridinone or pyridinthione compounds and process for the preparation of the same.
Ullrich Axel,DEX ; Risau Werner,DEX ; Millauer Birgit,DEX, Use of organic compounds for the inhibition of Flk-1 mediated vasculogenesis and angiogenesis.
Hallenbach Werner (Langenfeld DEX) Lindel Hans (Leverkusen DEX) Brandes Wilhelm (Leichlingen DEX), Use of thienylurea derivatives as selective fungicides.
Stiehl, Juergen; Heilmann, Werner; Lögers, Michael; Rehse, Joachim; Gottfried, Michael; Wichmann, Saskia, Process for the preparation of 4-{4-[({[4 chloro-3-(trifluoromethyl)-phenyl]amino}carbonyl)amino]-3-fluorphenoxy-N-ethylpyridie-carboxamide, its salts and monohydrate.
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