AU2004270699B2 - Heterocyclic inhibitors of MEK and methods of use thereof - Google Patents
Heterocyclic inhibitors of MEK and methods of use thereof Download PDFInfo
- Publication number
- AU2004270699B2 AU2004270699B2 AU2004270699A AU2004270699A AU2004270699B2 AU 2004270699 B2 AU2004270699 B2 AU 2004270699B2 AU 2004270699 A AU2004270699 A AU 2004270699A AU 2004270699 A AU2004270699 A AU 2004270699A AU 2004270699 B2 AU2004270699 B2 AU 2004270699B2
- Authority
- AU
- Australia
- Prior art keywords
- aryl
- heteroaryl
- heterocyclyl
- alkyl
- arylalkyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
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- 238000000034 method Methods 0.000 title claims abstract description 88
- 125000000623 heterocyclic group Chemical group 0.000 title claims description 307
- 239000003112 inhibitor Substances 0.000 title description 19
- 150000001875 compounds Chemical class 0.000 claims abstract description 202
- 229940002612 prodrug Drugs 0.000 claims abstract description 64
- 239000000651 prodrug Substances 0.000 claims abstract description 64
- 150000003839 salts Chemical class 0.000 claims abstract description 59
- 241000124008 Mammalia Species 0.000 claims abstract description 35
- 230000003463 hyperproliferative effect Effects 0.000 claims abstract description 19
- 125000001072 heteroaryl group Chemical group 0.000 claims description 263
- 125000003118 aryl group Chemical group 0.000 claims description 254
- 125000000217 alkyl group Chemical group 0.000 claims description 218
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 203
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 170
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 169
- 125000003342 alkenyl group Chemical group 0.000 claims description 125
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 121
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 120
- -1 heteroaiyl Chemical group 0.000 claims description 120
- 125000005843 halogen group Chemical group 0.000 claims description 104
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 101
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 99
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 98
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 92
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 88
- 125000000304 alkynyl group Chemical group 0.000 claims description 85
- 238000002360 preparation method Methods 0.000 claims description 72
- 229920006395 saturated elastomer Polymers 0.000 claims description 72
- 229910052739 hydrogen Inorganic materials 0.000 claims description 65
- 239000001257 hydrogen Substances 0.000 claims description 59
- 239000000203 mixture Substances 0.000 claims description 54
- 150000002431 hydrogen Chemical class 0.000 claims description 45
- 125000004043 oxo group Chemical group O=* 0.000 claims description 45
- 125000004429 atom Chemical group 0.000 claims description 39
- 125000002837 carbocyclic group Chemical group 0.000 claims description 38
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 32
- 239000012453 solvate Substances 0.000 claims description 23
- 229910019142 PO4 Inorganic materials 0.000 claims description 19
- 239000008194 pharmaceutical composition Substances 0.000 claims description 19
- 125000000539 amino acid group Chemical group 0.000 claims description 18
- 239000010452 phosphate Substances 0.000 claims description 18
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 16
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
- 102000004232 Mitogen-Activated Protein Kinase Kinases Human genes 0.000 claims description 14
- 108090000744 Mitogen-Activated Protein Kinase Kinases Proteins 0.000 claims description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- 230000002401 inhibitory effect Effects 0.000 claims description 11
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 10
- 230000000694 effects Effects 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 125000002757 morpholinyl group Chemical group 0.000 claims description 3
- 125000003386 piperidinyl group Chemical group 0.000 claims description 3
- 125000002987 valine group Chemical group [H]N([H])C([H])(C(*)=O)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims 5
- 125000005865 C2-C10alkynyl group Chemical group 0.000 claims 2
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims 1
- 239000004474 valine Substances 0.000 claims 1
- 238000011282 treatment Methods 0.000 abstract description 39
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- 206010028980 Neoplasm Diseases 0.000 abstract description 25
- 201000010099 disease Diseases 0.000 abstract description 22
- 201000011510 cancer Diseases 0.000 abstract description 13
- 229910052721 tungsten Inorganic materials 0.000 abstract description 9
- 229910052727 yttrium Inorganic materials 0.000 abstract description 9
- 239000002829 mitogen activated protein kinase inhibitor Substances 0.000 abstract description 5
- 206010061218 Inflammation Diseases 0.000 abstract description 2
- 230000004054 inflammatory process Effects 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 146
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 144
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 132
- 238000006243 chemical reaction Methods 0.000 description 92
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 87
- 230000015572 biosynthetic process Effects 0.000 description 83
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 81
- 239000000047 product Substances 0.000 description 81
- 238000003786 synthesis reaction Methods 0.000 description 81
- 238000005481 NMR spectroscopy Methods 0.000 description 71
- 239000000243 solution Substances 0.000 description 69
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 66
- 235000019439 ethyl acetate Nutrition 0.000 description 64
- 239000011541 reaction mixture Substances 0.000 description 63
- 239000007787 solid Substances 0.000 description 62
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 54
- HHAMGFVBGIBWEJ-UHFFFAOYSA-N methyl 2-(2-chloroanilino)-3,4-difluoro-5-(2-trimethylsilylethynyl)benzoate Chemical compound COC(=O)C1=CC(C#C[Si](C)(C)C)=C(F)C(F)=C1NC1=CC=CC=C1Cl HHAMGFVBGIBWEJ-UHFFFAOYSA-N 0.000 description 45
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 42
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 40
- 239000012267 brine Substances 0.000 description 40
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 40
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 38
- YHNRUSMOYCDMJS-UHFFFAOYSA-N o-(cyclopropylmethyl)hydroxylamine Chemical compound NOCC1CC1 YHNRUSMOYCDMJS-UHFFFAOYSA-N 0.000 description 36
- 239000011734 sodium Substances 0.000 description 35
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
- 239000012044 organic layer Substances 0.000 description 31
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
- 150000001732 carboxylic acid derivatives Chemical group 0.000 description 30
- 238000000746 purification Methods 0.000 description 28
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 27
- 150000002148 esters Chemical class 0.000 description 25
- 238000003818 flash chromatography Methods 0.000 description 25
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 24
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- 239000002253 acid Substances 0.000 description 24
- 238000003756 stirring Methods 0.000 description 24
- 239000000725 suspension Substances 0.000 description 24
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 22
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 22
- WWWTWPXKLJTKPM-UHFFFAOYSA-N 2-aminooxyethanol Chemical compound NOCCO WWWTWPXKLJTKPM-UHFFFAOYSA-N 0.000 description 20
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 16
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 16
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 16
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 15
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 14
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 14
- 150000001412 amines Chemical class 0.000 description 14
- 230000008878 coupling Effects 0.000 description 14
- 238000010168 coupling process Methods 0.000 description 14
- 238000005859 coupling reaction Methods 0.000 description 14
- 208000035475 disorder Diseases 0.000 description 14
- 239000003960 organic solvent Substances 0.000 description 14
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 13
- 210000004027 cell Anatomy 0.000 description 13
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 13
- 238000007363 ring formation reaction Methods 0.000 description 13
- 238000010561 standard procedure Methods 0.000 description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 12
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 12
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 12
- 230000002159 abnormal effect Effects 0.000 description 12
- 239000002585 base Substances 0.000 description 12
- 230000010261 cell growth Effects 0.000 description 12
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 12
- 238000010992 reflux Methods 0.000 description 12
- HSFNEBWXUWQGNW-UHFFFAOYSA-N 7-(4-bromo-2-chloroanilino)-8-chloro-n-(2-hydroxyethoxy)imidazo[1,2-a]pyridine-6-carboxamide Chemical compound OCCONC(=O)C1=CN2C=CN=C2C(Cl)=C1NC1=CC=C(Br)C=C1Cl HSFNEBWXUWQGNW-UHFFFAOYSA-N 0.000 description 11
- 239000004480 active ingredient Substances 0.000 description 11
- 239000000284 extract Substances 0.000 description 11
- 238000001914 filtration Methods 0.000 description 11
- 235000021317 phosphate Nutrition 0.000 description 11
- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 10
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- YLPFLKCGZGXPFI-UHFFFAOYSA-N methyl 6-amino-4-(4-bromo-2-chloroanilino)-5-chloropyridine-3-carboxylate Chemical compound COC(=O)C1=CN=C(N)C(Cl)=C1NC1=CC=C(Br)C=C1Cl YLPFLKCGZGXPFI-UHFFFAOYSA-N 0.000 description 10
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- 125000001424 substituent group Chemical group 0.000 description 10
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 9
- 238000005160 1H NMR spectroscopy Methods 0.000 description 9
- 102000043136 MAP kinase family Human genes 0.000 description 9
- 108091054455 MAP kinase family Proteins 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
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- 239000007788 liquid Substances 0.000 description 9
- 229910052763 palladium Inorganic materials 0.000 description 9
- XQIATTAAVBLNAN-UHFFFAOYSA-N 5-bromo-2,3,4-trifluorobenzoic acid Chemical compound OC(=O)C1=CC(Br)=C(F)C(F)=C1F XQIATTAAVBLNAN-UHFFFAOYSA-N 0.000 description 8
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 8
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 8
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- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 8
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 8
- 239000007858 starting material Substances 0.000 description 8
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 7
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- 102100024193 Mitogen-activated protein kinase 1 Human genes 0.000 description 7
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 7
- 125000004432 carbon atom Chemical group C* 0.000 description 7
- 239000003054 catalyst Substances 0.000 description 7
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- 238000004293 19F NMR spectroscopy Methods 0.000 description 6
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- ILMIEWNDXAKVNI-UHFFFAOYSA-N 4,6-dichloropyridine-3-carboxylic acid Chemical compound OC(=O)C1=CN=C(Cl)C=C1Cl ILMIEWNDXAKVNI-UHFFFAOYSA-N 0.000 description 6
- RZRBEUMGDQTYNA-UHFFFAOYSA-N 4-(4-bromo-2-chloroanilino)-5,6-dichloropyridine-3-carboxylic acid Chemical compound OC(=O)C1=CN=C(Cl)C(Cl)=C1NC1=CC=C(Br)C=C1Cl RZRBEUMGDQTYNA-UHFFFAOYSA-N 0.000 description 6
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- PXAJQJMDEXJWFB-UHFFFAOYSA-N acetone oxime Chemical compound CC(C)=NO PXAJQJMDEXJWFB-UHFFFAOYSA-N 0.000 description 6
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- UPXZTUASRXFGEX-UHFFFAOYSA-N methyl 2-(2-chloroanilino)-5-cyano-3,4-difluorobenzoate Chemical compound COC(=O)C1=CC(C#N)=C(F)C(F)=C1NC1=CC=CC=C1Cl UPXZTUASRXFGEX-UHFFFAOYSA-N 0.000 description 6
- NHHCTYLYMAUZHD-UHFFFAOYSA-N methyl 5-bromo-2-(2-chloroanilino)-3,4-difluorobenzoate Chemical compound COC(=O)C1=CC(Br)=C(F)C(F)=C1NC1=CC=CC=C1Cl NHHCTYLYMAUZHD-UHFFFAOYSA-N 0.000 description 6
- VHNBCNJMJRBOAN-UHFFFAOYSA-N methyl 7-(4-bromo-2-chloroanilino)-8-chloroimidazo[1,2-a]pyridine-6-carboxylate Chemical compound COC(=O)C1=CN2C=CN=C2C(Cl)=C1NC1=CC=C(Br)C=C1Cl VHNBCNJMJRBOAN-UHFFFAOYSA-N 0.000 description 6
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- AAUBVINEXCCXOK-UHFFFAOYSA-N ethyl 4,6-dichloropyridine-3-carboxylate Chemical compound CCOC(=O)C1=CN=C(Cl)C=C1Cl AAUBVINEXCCXOK-UHFFFAOYSA-N 0.000 description 5
- MUTLQOJUSJVKRM-UHFFFAOYSA-N ethyl 4-(4-bromo-2-chloroanilino)-5-chloro-6-hydrazinylpyridine-3-carboxylate Chemical compound CCOC(=O)C1=CN=C(NN)C(Cl)=C1NC1=CC=C(Br)C=C1Cl MUTLQOJUSJVKRM-UHFFFAOYSA-N 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 5
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- 230000007062 hydrolysis Effects 0.000 description 5
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/20—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings condensed with carbocyclic rings or ring systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10/654,580 | 2003-09-03 | ||
| US10/654,580 US7144907B2 (en) | 2003-09-03 | 2003-09-03 | Heterocyclic inhibitors of MEK and methods of use thereof |
| US10/929,295 | 2004-08-30 | ||
| US10/929,295 US7230099B2 (en) | 2003-09-03 | 2004-08-30 | Heterocyclic inhibitors of MEK and methods of use thereof |
| PCT/US2004/028649 WO2005023759A2 (en) | 2003-09-03 | 2004-09-01 | Heterocyclic inhibitors of mek and methods of use thereof |
Publications (2)
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| AU2004270699A1 AU2004270699A1 (en) | 2005-03-17 |
| AU2004270699B2 true AU2004270699B2 (en) | 2011-11-10 |
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| AU2004270699A Ceased AU2004270699B2 (en) | 2003-09-03 | 2004-09-01 | Heterocyclic inhibitors of MEK and methods of use thereof |
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|---|---|
| US (5) | US7144907B2 (enExample) |
| EP (1) | EP1673339B1 (enExample) |
| JP (1) | JP4131741B2 (enExample) |
| KR (1) | KR20060070558A (enExample) |
| CN (1) | CN1874769A (enExample) |
| AR (1) | AR046081A1 (enExample) |
| AU (1) | AU2004270699B2 (enExample) |
| BR (1) | BRPI0414111A (enExample) |
| CA (1) | CA2537321A1 (enExample) |
| IL (4) | IL173936A (enExample) |
| IS (1) | IS8392A (enExample) |
| MX (1) | MXPA06002466A (enExample) |
| NO (1) | NO20061506L (enExample) |
| PT (1) | PT1673339E (enExample) |
| RU (1) | RU2006109599A (enExample) |
| TW (1) | TW200526607A (enExample) |
| WO (1) | WO2005023759A2 (enExample) |
| ZA (1) | ZA200602581B (enExample) |
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-
2003
- 2003-09-03 US US10/654,580 patent/US7144907B2/en not_active Expired - Fee Related
-
2004
- 2004-08-30 US US10/929,295 patent/US7230099B2/en not_active Expired - Fee Related
- 2004-09-01 KR KR1020067004505A patent/KR20060070558A/ko not_active Withdrawn
- 2004-09-01 EP EP04783028.6A patent/EP1673339B1/en not_active Expired - Lifetime
- 2004-09-01 RU RU2006109599/04A patent/RU2006109599A/ru not_active Application Discontinuation
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- 2004-09-01 CN CNA2004800326551A patent/CN1874769A/zh active Pending
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- 2004-09-01 PT PT47830286T patent/PT1673339E/pt unknown
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- 2006-03-31 IS IS8392A patent/IS8392A/is unknown
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- 2006-04-24 US US11/410,343 patent/US7271178B2/en not_active Expired - Fee Related
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2012
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0602242A1 (en) * | 1991-08-22 | 1994-06-22 | Yoshitomi Pharmaceutical Industries, Ltd. | Benzisoxazole compound and use thereof |
| JP2000204079A (ja) * | 1999-01-13 | 2000-07-25 | Warner Lambert Co | ジアリ―ルアミン |
| US20050049276A1 (en) * | 2003-07-23 | 2005-03-03 | Warner-Lambert Company, Llc | Imidazopyridines and triazolopyridines |
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