AU2001287901A1 - Imidazole derivatives as Raf kinase inhibitors - Google Patents

Imidazole derivatives as Raf kinase inhibitors

Info

Publication number: AU2001287901A1
Authority: AU; Australia
Prior art keywords: alkyl; formula; compound; hydrogen; optionally substituted
Prior art date: 2000-09-21
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.): Abandoned

Application number

AU2001287901A

Other languages

English (en)

Inventor

David Kenneth Dean

Andrew Kenneth Takle

David Matthew Wilson

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

SmithKline Beecham Ltd

Original Assignee

SmithKline Beecham Ltd

Priority date (The priority date 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 date listed.)

2000-09-21

Filing date

2001-09-19

Publication date

2002-04-02

2000-09-21 Priority claimed from GB0023196A external-priority patent/GB0023196D0/en

2000-09-21 Priority claimed from GB0023208A external-priority patent/GB0023208D0/en

2000-09-21 Priority claimed from GB0023193A external-priority patent/GB0023193D0/en

2000-09-21 Priority claimed from GB0023197A external-priority patent/GB0023197D0/en

2001-09-19 Application filed by SmithKline Beecham Ltd filed Critical SmithKline Beecham Ltd

2002-04-02 Publication of AU2001287901A1 publication Critical patent/AU2001287901A1/en

Status Abandoned legal-status Critical Current

Links

102000009929 raf Kinases Human genes 0.000 title abstract description 8
108010077182 raf Kinases Proteins 0.000 title abstract description 8
229940043355 kinase inhibitor Drugs 0.000 title abstract description 4
239000003757 phosphotransferase inhibitor Substances 0.000 title abstract description 4
150000002460 imidazoles Chemical class 0.000 title description 5
229940079865 intestinal antiinfectives imidazole derivative Drugs 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 142
238000011282 treatment Methods 0.000 claims abstract description 21
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 9
239000003814 drug Substances 0.000 claims abstract description 9
206010007572 Cardiac hypertrophy Diseases 0.000 claims abstract description 7
208000006029 Cardiomegaly Diseases 0.000 claims abstract description 7
208000019695 Migraine disease Diseases 0.000 claims abstract description 7
206010028980 Neoplasm Diseases 0.000 claims abstract description 7
208000002193 Pain Diseases 0.000 claims abstract description 7
206010027599 migraine Diseases 0.000 claims abstract description 7
201000010099 disease Diseases 0.000 claims abstract description 6
201000011510 cancer Diseases 0.000 claims abstract description 5
-1 Cj.6alkyl Chemical group 0.000 claims description 35
125000000623 heterocyclic group Chemical group 0.000 claims description 31
229910052739 hydrogen Inorganic materials 0.000 claims description 30
239000001257 hydrogen Substances 0.000 claims description 29
125000003118 aryl group Chemical group 0.000 claims description 21
150000003839 salts Chemical class 0.000 claims description 18
125000001072 heteroaryl group Chemical group 0.000 claims description 15
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 15
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 13
125000001424 substituent group Chemical group 0.000 claims description 13
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 10
241000124008 Mammalia Species 0.000 claims description 9
229910052736 halogen Inorganic materials 0.000 claims description 9
150000002367 halogens Chemical class 0.000 claims description 9
150000002431 hydrogen Chemical group 0.000 claims description 9
238000004519 manufacturing process Methods 0.000 claims description 9
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 8
229910052717 sulfur Inorganic materials 0.000 claims description 8
229910052760 oxygen Inorganic materials 0.000 claims description 7
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 6
125000004432 carbon atom Chemical group C* 0.000 claims description 6
230000000069 prophylactic effect Effects 0.000 claims description 6
230000001225 therapeutic effect Effects 0.000 claims description 6
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 5
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 5
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
239000003937 drug carrier Substances 0.000 claims description 5
125000005842 heteroatom Chemical group 0.000 claims description 5
239000008194 pharmaceutical composition Substances 0.000 claims description 5
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
125000004442 acylamino group Chemical group 0.000 claims description 3
125000004423 acyloxy group Chemical group 0.000 claims description 3
125000004658 aryl carbonyl amino group Chemical group 0.000 claims description 3
125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 3
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 3
230000001684 chronic effect Effects 0.000 claims description 3
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
229930194542 Keto Natural products 0.000 claims description 2
229910052799 carbon Inorganic materials 0.000 claims description 2
229910002091 carbon monoxide Inorganic materials 0.000 claims description 2
125000002541 furyl group Chemical group 0.000 claims description 2
125000000468 ketone group Chemical group 0.000 claims description 2
125000005936 piperidyl group Chemical group 0.000 claims description 2
125000004076 pyridyl group Chemical group 0.000 claims description 2
125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
230000000063 preceeding effect Effects 0.000 claims 1
230000006726 chronic neurodegeneration Effects 0.000 abstract description 4
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 57
239000000047 product Substances 0.000 description 54
239000000203 mixture Substances 0.000 description 48
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 42
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
239000000243 solution Substances 0.000 description 39
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 32
238000000034 method Methods 0.000 description 26
239000007787 solid Substances 0.000 description 25
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
150000002923 oximes Chemical group 0.000 description 20
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 18
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 17
238000006243 chemical reaction Methods 0.000 description 17
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 16
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 14
101100381978 Mus musculus Braf gene Proteins 0.000 description 14
238000010898 silica gel chromatography Methods 0.000 description 14
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 13
239000003112 inhibitor Substances 0.000 description 13
KKVYYGGCHJGEFJ-UHFFFAOYSA-N 1-n-(4-chlorophenyl)-6-methyl-5-n-[3-(7h-purin-6-yl)pyridin-2-yl]isoquinoline-1,5-diamine Chemical compound N=1C=CC2=C(NC=3C(=CC=CN=3)C=3C=4N=CNC=4N=CN=3)C(C)=CC=C2C=1NC1=CC=C(Cl)C=C1 KKVYYGGCHJGEFJ-UHFFFAOYSA-N 0.000 description 12
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 11
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 11
235000011114 ammonium hydroxide Nutrition 0.000 description 11
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 11
229910052938 sodium sulfate Inorganic materials 0.000 description 11
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
239000012074 organic phase Substances 0.000 description 10
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 9
229910000030 sodium bicarbonate Inorganic materials 0.000 description 9
235000017557 sodium bicarbonate Nutrition 0.000 description 9
108091000080 Phosphotransferase Proteins 0.000 description 8
229910052786 argon Inorganic materials 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
239000003921 oil Substances 0.000 description 8
235000019198 oils Nutrition 0.000 description 8
102000020233 phosphotransferase Human genes 0.000 description 8
125000006239 protecting group Chemical group 0.000 description 8
239000003446 ligand Substances 0.000 description 7
229910052943 magnesium sulfate Inorganic materials 0.000 description 7
230000008569 process Effects 0.000 description 7
238000011321 prophylaxis Methods 0.000 description 7
239000011541 reaction mixture Substances 0.000 description 7
229920006395 saturated elastomer Polymers 0.000 description 7
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
235000011152 sodium sulphate Nutrition 0.000 description 6
238000005160 1H NMR spectroscopy Methods 0.000 description 5
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
102000004232 Mitogen-Activated Protein Kinase Kinases Human genes 0.000 description 5
108090000744 Mitogen-Activated Protein Kinase Kinases Proteins 0.000 description 5
239000007832 Na2SO4 Substances 0.000 description 5
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 5
QNXSIUBBGPHDDE-UHFFFAOYSA-N alpha-indanone Natural products C1=CC=C2C(=O)CCC2=C1 QNXSIUBBGPHDDE-UHFFFAOYSA-N 0.000 description 5
238000007796 conventional method Methods 0.000 description 5
239000013058 crude material Substances 0.000 description 5
230000006378 damage Effects 0.000 description 5
239000007788 liquid Substances 0.000 description 5
235000019341 magnesium sulphate Nutrition 0.000 description 5
238000002360 preparation method Methods 0.000 description 5
238000000746 purification Methods 0.000 description 5
239000002904 solvent Substances 0.000 description 5
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 5
KSONICAHAPRCMV-UHFFFAOYSA-N 5-bromo-2,3-dihydroinden-1-one Chemical compound BrC1=CC=C2C(=O)CCC2=C1 KSONICAHAPRCMV-UHFFFAOYSA-N 0.000 description 4
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 4
YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 4
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
102000043136 MAP kinase family Human genes 0.000 description 4
108091054455 MAP kinase family Proteins 0.000 description 4
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
208000027418 Wounds and injury Diseases 0.000 description 4
239000002253 acid Substances 0.000 description 4
210000004556 brain Anatomy 0.000 description 4
230000030833 cell death Effects 0.000 description 4
125000000392 cycloalkenyl group Chemical group 0.000 description 4
125000000753 cycloalkyl group Chemical group 0.000 description 4
239000002552 dosage form Substances 0.000 description 4
230000000694 effects Effects 0.000 description 4
150000002148 esters Chemical class 0.000 description 4
125000000524 functional group Chemical group 0.000 description 4
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229910052757 nitrogen Inorganic materials 0.000 description 4
239000012044 organic layer Substances 0.000 description 4
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
238000003756 stirring Methods 0.000 description 4
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238000003786 synthesis reaction Methods 0.000 description 4
238000012360 testing method Methods 0.000 description 4
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238000005481 NMR spectroscopy Methods 0.000 description 3
102000001253 Protein Kinase Human genes 0.000 description 3
208000006011 Stroke Diseases 0.000 description 3
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235000019257 ammonium acetate Nutrition 0.000 description 3
210000004027 cell Anatomy 0.000 description 3
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208000035475 disorder Diseases 0.000 description 3
239000000284 extract Substances 0.000 description 3
230000000971 hippocampal effect Effects 0.000 description 3
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230000001537 neural effect Effects 0.000 description 3
210000002569 neuron Anatomy 0.000 description 3
230000026731 phosphorylation Effects 0.000 description 3
238000006366 phosphorylation reaction Methods 0.000 description 3
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UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Chemical group COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
125000006413 ring segment Chemical group 0.000 description 3
239000012047 saturated solution Substances 0.000 description 3
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RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
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WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 2
208000032382 Ischaemic stroke Diseases 0.000 description 2
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
KZSAHWNTHDQGCV-UHFFFAOYSA-N N-[2-[4-(1-hydroxyimino-2,3-dihydroinden-5-yl)-5-pyridin-4-yl-1H-imidazol-2-yl]-2-methylpropyl]methanesulfonamide Chemical compound C=1C=C2C(=NO)CCC2=CC=1C=1NC(C(C)(CNS(C)(=O)=O)C)=NC=1C1=CC=NC=C1 KZSAHWNTHDQGCV-UHFFFAOYSA-N 0.000 description 2
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical group N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
229930006000 Sucrose Natural products 0.000 description 2
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
125000003342 alkenyl group Chemical group 0.000 description 2
125000000217 alkyl group Chemical group 0.000 description 2
229910000147 aluminium phosphate Inorganic materials 0.000 description 2
150000001408 amides Chemical class 0.000 description 2
150000001412 amines Chemical class 0.000 description 2
125000003277 amino group Chemical group 0.000 description 2
238000013459 approach Methods 0.000 description 2
238000003556 assay Methods 0.000 description 2
125000002619 bicyclic group Chemical group 0.000 description 2
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239000012267 brine Substances 0.000 description 2
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238000010494 dissociation reaction Methods 0.000 description 2
230000005593 dissociations Effects 0.000 description 2
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XNXVOSBNFZWHBV-UHFFFAOYSA-N hydron;o-methylhydroxylamine;chloride Chemical compound Cl.CON XNXVOSBNFZWHBV-UHFFFAOYSA-N 0.000 description 2
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238000001727 in vivo Methods 0.000 description 2
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AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical group C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
230000001404 mediated effect Effects 0.000 description 2
239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
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125000005646 oximino group Chemical group 0.000 description 2
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USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical compound C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 description 2
125000000719 pyrrolidinyl group Chemical group 0.000 description 2
238000010992 reflux Methods 0.000 description 2
230000019491 signal transduction Effects 0.000 description 2
229910000029 sodium carbonate Inorganic materials 0.000 description 2
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
239000005720 sucrose Substances 0.000 description 2
238000001356 surgical procedure Methods 0.000 description 2
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CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 2
SGUQXLLGHZISLF-UHFFFAOYSA-N tert-butyl-dimethyl-(pyridin-4-ylmethoxy)silane Chemical compound CC(C)(C)[Si](C)(C)OCC1=CC=NC=C1 SGUQXLLGHZISLF-UHFFFAOYSA-N 0.000 description 2
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229910052723 transition metal Inorganic materials 0.000 description 2
150000003624 transition metals Chemical class 0.000 description 2
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
HFVMEOPYDLEHBR-UHFFFAOYSA-N (2-fluorophenyl)-phenylmethanol Chemical compound C=1C=CC=C(F)C=1C(O)C1=CC=CC=C1 HFVMEOPYDLEHBR-UHFFFAOYSA-N 0.000 description 1
125000006700 (C1-C6) alkylthio group Chemical group 0.000 description 1
CSJXMGWIFCRNGY-UHFFFAOYSA-N 1-(1-methoxyimino-2,3-dihydroinden-5-yl)-2-pyridin-4-ylethane-1,2-diol Chemical compound C=1C=C2C(=NOC)CCC2=CC=1C(O)C(O)C1=CC=NC=C1 CSJXMGWIFCRNGY-UHFFFAOYSA-N 0.000 description 1
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VNWIGGFRGGOBHZ-UHFFFAOYSA-N tert-butyl 4-[4-(1-methoxyimino-2,3-dihydroinden-5-yl)-5-pyridin-4-yl-1h-imidazol-2-yl]piperidine-1-carboxylate Chemical compound C=1C=C2C(=NOC)CCC2=CC=1C=1N=C(C2CCN(CC2)C(=O)OC(C)(C)C)NC=1C1=CC=NC=C1 VNWIGGFRGGOBHZ-UHFFFAOYSA-N 0.000 description 1
JYUQEWCJWDGCRX-UHFFFAOYSA-N tert-butyl 4-formylpiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(C=O)CC1 JYUQEWCJWDGCRX-UHFFFAOYSA-N 0.000 description 1
PXYSKRPXLWMCMU-UHFFFAOYSA-N tert-butyl n-(2,2-dimethyl-3-oxopropyl)carbamate Chemical compound CC(C)(C)OC(=O)NCC(C)(C)C=O PXYSKRPXLWMCMU-UHFFFAOYSA-N 0.000 description 1
ACNRTYKOPZDRCO-UHFFFAOYSA-N tert-butyl n-(2-oxoethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCC=O ACNRTYKOPZDRCO-UHFFFAOYSA-N 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/0019—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules
- A61K49/0021—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules the fluorescent group being a small organic molecule
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings

AU2001287901A 2000-09-21 2001-09-19 Imidazole derivatives as Raf kinase inhibitors Abandoned AU2001287901A1 (en)

Applications Claiming Priority (9)

Application Number	Priority Date	Filing Date	Title
GB0023196		2000-09-21
GB0023208		2000-09-21
GB0023193		2000-09-21
GB0023196A GB0023196D0 (en)	2000-09-21	2000-09-21	Compouds
GB0023208A GB0023208D0 (en)	2000-09-21	2000-09-21	Compounds
GB0023197		2000-09-21
GB0023193A GB0023193D0 (en)	2000-09-21	2000-09-21	Compounds
GB0023197A GB0023197D0 (en)	2000-09-21	2000-09-21	Compounds
PCT/GB2001/004195 WO2002024680A1 (en)	2000-09-21	2001-09-19	Imidazole derivatives as raf kinase inhibitors

Publications (1)

Publication Number	Publication Date
AU2001287901A1 true AU2001287901A1 (en)	2002-04-02

Family

ID=27447885

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
AU2001287901A Abandoned AU2001287901A1 (en)	2000-09-21	2001-09-19	Imidazole derivatives as Raf kinase inhibitors

Country Status (21)

Country	Link
US (2)	US7199137B2 (de)
EP (1)	EP1318992B1 (de)
JP (1)	JP2004509882A (de)
KR (1)	KR20030030027A (de)
CN (1)	CN1471523A (de)
AT (1)	ATE300529T1 (de)
AU (1)	AU2001287901A1 (de)
BR (1)	BR0114023A (de)
CA (1)	CA2423154A1 (de)
CY (1)	CY1105251T1 (de)
CZ (1)	CZ2003793A3 (de)
DE (1)	DE60112312T2 (de)
DK (1)	DK1318992T3 (de)
ES (1)	ES2242767T3 (de)
HU (1)	HUP0301181A2 (de)
IL (1)	IL154949A0 (de)
MX (1)	MXPA03002449A (de)
NO (1)	NO20031270L (de)
PL (1)	PL361397A1 (de)
PT (1)	PT1318992E (de)
WO (1)	WO2002024680A1 (de)

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2001
- 2001-09-19 CA CA002423154A patent/CA2423154A1/en not_active Abandoned
- 2001-09-19 BR BR0114023-0A patent/BR0114023A/pt not_active Application Discontinuation
- 2001-09-19 AU AU2001287901A patent/AU2001287901A1/en not_active Abandoned
- 2001-09-19 CN CNA018182135A patent/CN1471523A/zh active Pending
- 2001-09-19 WO PCT/GB2001/004195 patent/WO2002024680A1/en active IP Right Grant
- 2001-09-19 PL PL01361397A patent/PL361397A1/xx not_active Application Discontinuation
- 2001-09-19 IL IL15494901A patent/IL154949A0/xx unknown
- 2001-09-19 KR KR10-2003-7004109A patent/KR20030030027A/ko not_active Application Discontinuation
- 2001-09-19 HU HU0301181A patent/HUP0301181A2/hu unknown
- 2001-09-19 DE DE60112312T patent/DE60112312T2/de not_active Expired - Fee Related
- 2001-09-19 EP EP01967528A patent/EP1318992B1/de not_active Expired - Lifetime
- 2001-09-19 MX MXPA03002449A patent/MXPA03002449A/es unknown
- 2001-09-19 JP JP2002529090A patent/JP2004509882A/ja active Pending
- 2001-09-19 CZ CZ2003793A patent/CZ2003793A3/cs unknown
- 2001-09-19 US US10/380,891 patent/US7199137B2/en not_active Expired - Fee Related
- 2001-09-19 AT AT01967528T patent/ATE300529T1/de not_active IP Right Cessation
- 2001-09-19 DK DK01967528T patent/DK1318992T3/da active
- 2001-09-19 ES ES01967528T patent/ES2242767T3/es not_active Expired - Lifetime
- 2001-09-19 PT PT01967528T patent/PT1318992E/pt unknown
2003
- 2003-03-19 NO NO20031270A patent/NO20031270L/no not_active Application Discontinuation
2005
- 2005-09-06 CY CY20051101069T patent/CY1105251T1/el unknown
2007
- 2007-01-22 US US11/625,406 patent/US20070135433A1/en not_active Abandoned

Also Published As

Publication number	Publication date
CA2423154A1 (en)	2002-03-28
HUP0301181A2 (en)	2007-02-28
ATE300529T1 (de)	2005-08-15
US20040038964A1 (en)	2004-02-26
DE60112312T2 (de)	2005-12-29
EP1318992A1 (de)	2003-06-18
DE60112312D1 (de)	2005-09-01
ES2242767T3 (es)	2005-11-16
MXPA03002449A (es)	2003-06-19
PL361397A1 (en)	2004-10-04
US7199137B2 (en)	2007-04-03
BR0114023A (pt)	2004-02-03
US20070135433A1 (en)	2007-06-14
CN1471523A (zh)	2004-01-28
JP2004509882A (ja)	2004-04-02
DK1318992T3 (da)	2005-11-21
PT1318992E (pt)	2005-11-30
EP1318992B1 (de)	2005-07-27
NO20031270D0 (no)	2003-03-19
KR20030030027A (ko)	2003-04-16
CY1105251T1 (el)	2010-03-03
WO2002024680A1 (en)	2002-03-28
IL154949A0 (en)	2003-10-31
NO20031270L (no)	2003-05-19
CZ2003793A3 (cs)	2004-04-14

Publication	Publication Date	Title
EP1318992B1 (de)	2005-07-27	Imidazolderivate als raf-kinase-inhibitoren
EP1397354B1 (de)	2005-10-26	Imidazol-2-carbonsäureamid derivate als raf-kinase-inhibitoren
US6987119B2 (en)	2006-01-17	Imidazol-2-carboxamide derivatives as raf kinase inhibitors
US7235658B2 (en)	2007-06-26	Imidazol derivatives as Raf kinase inhibitors
EP1232153B1 (de)	2004-11-03	Imidazolderivate und deren verwendung als raf kinase inhibitoren
US7375105B2 (en)	2008-05-20	Pyridine substituted furan derivatives as Raf kinase inhibitors
JP2005504794A (ja)	2005-02-17	Ｒａｆキナーゼ阻害剤としてのピリジン誘導体
US7297694B2 (en)	2007-11-20	Pyridylfurans and pyrroles as Raf kinase inhibitors
US7297693B2 (en)	2007-11-20	Nitrogen-containing heterocyclic compounds and their use as Raf inhibitors
WO2003022837A1 (en)	2003-03-20	Heterocycle-carboxamide derivatives as raf kinase inhibitors