JP2007507428A - 置換ベンズアゾールおよびＲａｆキナーゼのインヒビターとしてのその使用 - Google Patents
置換ベンズアゾールおよびＲａｆキナーゼのインヒビターとしてのその使用 Download PDFInfo
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- JP2007507428A JP2007507428A JP2006528331A JP2006528331A JP2007507428A JP 2007507428 A JP2007507428 A JP 2007507428A JP 2006528331 A JP2006528331 A JP 2006528331A JP 2006528331 A JP2006528331 A JP 2006528331A JP 2007507428 A JP2007507428 A JP 2007507428A
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- methyl
- substituted
- compound according
- amino
- heterocycloalkyl
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- 108010077182 raf Kinases Proteins 0.000 title claims abstract description 27
- 102000009929 raf Kinases Human genes 0.000 title claims abstract description 27
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical class C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 title abstract description 14
- 239000003112 inhibitor Substances 0.000 title description 8
- 239000000203 mixture Chemical class 0.000 claims abstract description 179
- 150000001875 compounds Chemical class 0.000 claims abstract description 156
- 238000000034 method Methods 0.000 claims abstract description 63
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 33
- 241001465754 Metazoa Species 0.000 claims abstract description 29
- 238000011282 treatment Methods 0.000 claims abstract description 23
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- 230000000694 effects Effects 0.000 claims abstract description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 14
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- 239000005556 hormone Substances 0.000 claims abstract description 8
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- 206010006187 Breast cancer Diseases 0.000 claims abstract description 5
- 208000026310 Breast neoplasm Diseases 0.000 claims abstract description 5
- 206010060862 Prostate cancer Diseases 0.000 claims abstract description 3
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims abstract description 3
- -1 amidoalkyl Chemical group 0.000 claims description 372
- 125000000217 alkyl group Chemical group 0.000 claims description 99
- 229910052739 hydrogen Inorganic materials 0.000 claims description 69
- 239000001257 hydrogen Substances 0.000 claims description 66
- 125000001072 heteroaryl group Chemical group 0.000 claims description 56
- 125000003118 aryl group Chemical group 0.000 claims description 53
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 39
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 38
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 36
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 36
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 28
- 150000002431 hydrogen Chemical class 0.000 claims description 28
- 150000003839 salts Chemical class 0.000 claims description 28
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 25
- 125000003545 alkoxy group Chemical group 0.000 claims description 24
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 22
- 150000002148 esters Chemical class 0.000 claims description 22
- 229940002612 prodrug Drugs 0.000 claims description 21
- 239000000651 prodrug Substances 0.000 claims description 21
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 16
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- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 14
- 229910052760 oxygen Inorganic materials 0.000 claims description 14
- 125000004076 pyridyl group Chemical group 0.000 claims description 14
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 14
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 13
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- 125000002252 acyl group Chemical group 0.000 claims description 12
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 12
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 12
- 125000003282 alkyl amino group Chemical group 0.000 claims description 11
- 239000012830 cancer therapeutic Substances 0.000 claims description 11
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- 125000002883 imidazolyl group Chemical group 0.000 claims description 10
- 230000002401 inhibitory effect Effects 0.000 claims description 10
- KTUFNOKKBVMGRW-UHFFFAOYSA-N imatinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 claims description 9
- 125000001041 indolyl group Chemical group 0.000 claims description 9
- 239000005517 L01XE01 - Imatinib Substances 0.000 claims description 8
- 150000005347 biaryls Chemical group 0.000 claims description 8
- 125000002541 furyl group Chemical group 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
- 125000001624 naphthyl group Chemical group 0.000 claims description 8
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 8
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- RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 claims description 7
- 235000010290 biphenyl Nutrition 0.000 claims description 7
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 7
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 7
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 7
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 claims description 7
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 7
- 125000002757 morpholinyl group Chemical group 0.000 claims description 7
- 125000006501 nitrophenyl group Chemical group 0.000 claims description 7
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 7
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 6
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 6
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims description 6
- 125000005036 alkoxyphenyl group Chemical group 0.000 claims description 6
- HSMPSHPWCOOUJH-UHFFFAOYSA-N anilinyl Chemical group [NH]C1=CC=CC=C1 HSMPSHPWCOOUJH-UHFFFAOYSA-N 0.000 claims description 6
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- 239000004305 biphenyl Substances 0.000 claims description 6
- 125000004799 bromophenyl group Chemical group 0.000 claims description 6
- 125000000068 chlorophenyl group Chemical group 0.000 claims description 6
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims description 6
- 229960004316 cisplatin Drugs 0.000 claims description 6
- WVIIMZNLDWSIRH-UHFFFAOYSA-N cyclohexylcyclohexane Chemical group C1CCCCC1C1CCCCC1 WVIIMZNLDWSIRH-UHFFFAOYSA-N 0.000 claims description 6
- DLAHAXOYRFRPFQ-UHFFFAOYSA-N dodecyl benzoate Chemical compound CCCCCCCCCCCCOC(=O)C1=CC=CC=C1 DLAHAXOYRFRPFQ-UHFFFAOYSA-N 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 125000001207 fluorophenyl group Chemical group 0.000 claims description 6
- 229960002949 fluorouracil Drugs 0.000 claims description 6
- 125000004464 hydroxyphenyl group Chemical group 0.000 claims description 6
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 6
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 6
- 125000006303 iodophenyl group Chemical group 0.000 claims description 6
- 229960004768 irinotecan Drugs 0.000 claims description 6
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 6
- NAYYNDKKHOIIOD-UHFFFAOYSA-N phthalamide Chemical compound NC(=O)C1=CC=CC=C1C(N)=O NAYYNDKKHOIIOD-UHFFFAOYSA-N 0.000 claims description 6
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 6
- 229960004641 rituximab Drugs 0.000 claims description 6
- 125000005329 tetralinyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims description 6
- 229930192474 thiophene Natural products 0.000 claims description 6
- QERYCTSHXKAMIS-UHFFFAOYSA-M thiophene-2-carboxylate Chemical compound [O-]C(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-M 0.000 claims description 6
- 125000004360 trifluorophenyl group Chemical group 0.000 claims description 6
- VVIAGPKUTFNRDU-UHFFFAOYSA-N 6S-folinic acid Natural products C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-UHFFFAOYSA-N 0.000 claims description 5
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 5
- 229940123237 Taxane Drugs 0.000 claims description 5
- 229940122803 Vinca alkaloid Drugs 0.000 claims description 5
- 229940045799 anthracyclines and related substance Drugs 0.000 claims description 5
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 claims description 5
- 229960004562 carboplatin Drugs 0.000 claims description 5
- 229960004397 cyclophosphamide Drugs 0.000 claims description 5
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 5
- VVIAGPKUTFNRDU-ABLWVSNPSA-N folinic acid Chemical compound C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-ABLWVSNPSA-N 0.000 claims description 5
- 235000008191 folinic acid Nutrition 0.000 claims description 5
- 239000011672 folinic acid Substances 0.000 claims description 5
- 229960005277 gemcitabine Drugs 0.000 claims description 5
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 claims description 5
- 229960002411 imatinib Drugs 0.000 claims description 5
- 229960001691 leucovorin Drugs 0.000 claims description 5
- DKPFODGZWDEEBT-QFIAKTPHSA-N taxane Chemical class C([C@]1(C)CCC[C@@H](C)[C@H]1C1)C[C@H]2[C@H](C)CC[C@@H]1C2(C)C DKPFODGZWDEEBT-QFIAKTPHSA-N 0.000 claims description 5
- 229950006410 tezacitabine Drugs 0.000 claims description 5
- GFFXZLZWLOBBLO-ASKVSEFXSA-N tezacitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(=C/F)/[C@H](O)[C@@H](CO)O1 GFFXZLZWLOBBLO-ASKVSEFXSA-N 0.000 claims description 5
- 229960000303 topotecan Drugs 0.000 claims description 5
- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 claims description 5
- 229960000575 trastuzumab Drugs 0.000 claims description 5
- 125000005885 heterocycloalkylalkyl group Chemical group 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 2
- NIHNNTQXNPWCJQ-UHFFFAOYSA-N fluorene Chemical compound C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 claims 10
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 claims 5
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 claims 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 5
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims 5
- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 claims 5
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims 5
- 230000002489 hematologic effect Effects 0.000 claims 1
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- 230000001404 mediated effect Effects 0.000 abstract description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 419
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 299
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- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 127
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 105
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 97
- 239000012044 organic layer Substances 0.000 description 94
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- 239000007787 solid Substances 0.000 description 89
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 80
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 55
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 52
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- 238000002360 preparation method Methods 0.000 description 51
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- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 42
- 239000000725 suspension Substances 0.000 description 40
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- 238000004237 preparative chromatography Methods 0.000 description 35
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 34
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- 238000000746 purification Methods 0.000 description 32
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- 125000000623 heterocyclic group Chemical group 0.000 description 14
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- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
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- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- 229940063683 taxotere Drugs 0.000 description 1
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- BCCIQUYKSACFJY-UHFFFAOYSA-N tert-butyl n-[(4-phenylphenyl)methyl]carbamate Chemical compound C1=CC(CNC(=O)OC(C)(C)C)=CC=C1C1=CC=CC=C1 BCCIQUYKSACFJY-UHFFFAOYSA-N 0.000 description 1
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- CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 125000005309 thioalkoxy group Chemical group 0.000 description 1
- NONOKGVFTBWRLD-UHFFFAOYSA-N thioisocyanate group Chemical group S(N=C=O)N=C=O NONOKGVFTBWRLD-UHFFFAOYSA-N 0.000 description 1
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- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
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- 108700012359 toxins Proteins 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
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- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 230000004565 tumor cell growth Effects 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 1
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 1
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
- 125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N urethane group Chemical group NC(=O)OCC JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
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- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C04—CEMENTS; CONCRETE; ARTIFICIAL STONE; CERAMICS; REFRACTORIES
- C04B—LIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
- C04B35/00—Shaped ceramic products characterised by their composition; Ceramics compositions; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products
- C04B35/622—Forming processes; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products
- C04B35/626—Preparing or treating the powders individually or as batches ; preparing or treating macroscopic reinforcing agents for ceramic products, e.g. fibres; mechanical aspects section B
- C04B35/63—Preparing or treating the powders individually or as batches ; preparing or treating macroscopic reinforcing agents for ceramic products, e.g. fibres; mechanical aspects section B using additives specially adapted for forming the products, e.g.. binder binders
- C04B35/632—Organic additives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
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- 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
- 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
- C07D401/12—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 linked by a chain containing hetero atoms as chain links
-
- 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
- C07D405/02—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 two hetero rings
- C07D405/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
- C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Health & Medical Sciences (AREA)
- Ceramic Engineering (AREA)
- Manufacturing & Machinery (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Materials Engineering (AREA)
- Structural Engineering (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10/675,927 US8299108B2 (en) | 2002-03-29 | 2003-09-29 | Substituted benzazoles and methods of their use as inhibitors of raf kinase |
| PCT/US2004/032161 WO2005032548A1 (en) | 2003-09-29 | 2004-09-29 | Substituted benzazoles and use thereof as inhibitors of raf kinase |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2007507428A true JP2007507428A (ja) | 2007-03-29 |
| JP2007507428A5 JP2007507428A5 (OSRAM) | 2007-08-30 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2006528331A Withdrawn JP2007507428A (ja) | 2003-09-29 | 2004-09-29 | 置換ベンズアゾールおよびＲａｆキナーゼのインヒビターとしてのその使用 |
Country Status (13)
| Country | Link |
|---|---|
| US (2) | US8299108B2 (OSRAM) |
| EP (1) | EP1675584A1 (OSRAM) |
| JP (1) | JP2007507428A (OSRAM) |
| KR (1) | KR20060089232A (OSRAM) |
| CN (1) | CN1913884A (OSRAM) |
| AU (1) | AU2004277405A1 (OSRAM) |
| BR (1) | BRPI0414908A (OSRAM) |
| CA (1) | CA2539748A1 (OSRAM) |
| EA (1) | EA011890B1 (OSRAM) |
| IL (1) | IL174431A0 (OSRAM) |
| MX (1) | MXPA06003435A (OSRAM) |
| WO (1) | WO2005032548A1 (OSRAM) |
| ZA (1) | ZA200603418B (OSRAM) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010064611A1 (ja) * | 2008-12-01 | 2010-06-10 | 武田薬品工業株式会社 | 複素環化合物およびその用途 |
| JP2020526547A (ja) * | 2017-07-12 | 2020-08-31 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | 心不全の治療のためのｒｏｃｋの５員アミノヘテロ環および５，６−または６，６員二環式アミノヘテロ環の阻害剤 |
| JP2023554392A (ja) * | 2020-12-16 | 2023-12-27 | アイエフエム デュー インコーポレイテッド | Ｓｔｉｎｇ活性に関連する状態を治療するための化合物および組成物 |
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| US8124630B2 (en) | 1999-01-13 | 2012-02-28 | Bayer Healthcare Llc | ω-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors |
| CA2359244C (en) | 1999-01-13 | 2013-10-08 | Bayer Healthcare Llc | .omega.-carboxy aryl substituted diphenyl ureas as p38 kinase inhibitors |
| US7351834B1 (en) | 1999-01-13 | 2008-04-01 | Bayer Pharmaceuticals Corporation | ω-Carboxyaryl substituted diphenyl ureas as raf kinase inhibitors |
| US20030216396A1 (en) | 2002-02-11 | 2003-11-20 | Bayer Corporation | Pyridine, quinoline, and isoquinoline N-oxides as kinase inhibitors |
| EP2324825A1 (en) | 2002-02-11 | 2011-05-25 | Bayer Healthcare LLC | Aryl ureas with angiogenesis inhibiting activity |
| ATE447404T1 (de) * | 2002-03-29 | 2009-11-15 | Novartis Vaccines & Diagnostic | Substituierte benzazole und ihre verwendung als raf-kinase-hemmer |
| UY28213A1 (es) | 2003-02-28 | 2004-09-30 | Bayer Pharmaceuticals Corp | Nuevos derivados de cianopiridina útiles en el tratamiento de cáncer y otros trastornos. |
| US7902192B2 (en) | 2003-05-15 | 2011-03-08 | Arqule, Inc. | Inhibitors of P38 and methods of using the same |
| DE602004007382T2 (de) | 2003-05-20 | 2008-04-17 | Bayer Pharmaceuticals Corp., West Haven | Diaryl-harnstoffe für durch pdgfr vermittelte krankheiten |
| DK1663978T3 (da) | 2003-07-23 | 2008-04-07 | Bayer Pharmaceuticals Corp | Fluorsubstitueret omega-carboxyaryl-diphenylurinstof til behandling og forebyggelse af sygdomme og lidelser |
| JP4755991B2 (ja) * | 2003-10-16 | 2011-08-24 | ノバルティス バクシンズ アンド ダイアグノスティックス，インコーポレーテッド | Ｒａｆキナーゼインヒビターとしての置換ベンゾアゾールおよびその使用 |
| WO2006010082A1 (en) * | 2004-07-08 | 2006-01-26 | Arqule, Inc. | 1,4-disubstituted naphtalenes as inhibitors of p38 map kinase |
| EP2258704A1 (en) * | 2004-10-19 | 2010-12-08 | ArQule, Inc. | Synthesis of imidazooxazole and imidazothiazole inhibitors of p38 map kinase |
| WO2006078907A1 (en) * | 2005-01-20 | 2006-07-27 | Amgen Inc. | 2-substituted benzimidazole derivatives as vanilloid receptor ligands and their use in treatments |
| TWI370820B (en) * | 2005-04-27 | 2012-08-21 | Takeda Pharmaceutical | Fused heterocyclic compounds |
| TW200804345A (en) * | 2005-08-30 | 2008-01-16 | Novartis Ag | Substituted benzimidazoles and methods of preparation |
| WO2007047397A2 (en) * | 2005-10-13 | 2007-04-26 | Smithkline Beecham Corporation | Phenol ethers as modulators of the opioid receptors |
| AU2007215247B2 (en) * | 2006-02-10 | 2012-12-13 | Transtech Pharma, Llc | Benzazole derivatives, compositions, and methods of use as Aurora kinase inhibitors |
| DK2010528T3 (en) | 2006-04-19 | 2018-01-15 | Novartis Ag | 6-O-Substituted Benzoxazole and Benzothiazole Compounds and Methods for Inhibiting CSF-1R Signaling |
| KR20090033904A (ko) | 2006-07-21 | 2009-04-06 | 노파르티스 아게 | 벤즈이미다졸릴 피리딜 에테르의 제제 |
| PE20130814A1 (es) * | 2006-08-30 | 2013-08-08 | Novartis Ag | Sales de benzimidazolil piridil eteres y formulaciones que las contienen |
| BRPI0809643A2 (pt) * | 2007-04-05 | 2014-11-11 | Daiichi Sankyo Co Ltd | Derivados de heteroarila bicíclica fundida |
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| UA101166C2 (ru) | 2007-09-21 | 2013-03-11 | Аррей Биофарма Инк. | Производные пиридин-2-иламино-1,2,4-тиадиазола как активаторы глюкокиназы для лечения сахарного диабета |
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| WO2010064611A1 (ja) * | 2008-12-01 | 2010-06-10 | 武田薬品工業株式会社 | 複素環化合物およびその用途 |
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| JP2020526547A (ja) * | 2017-07-12 | 2020-08-31 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | 心不全の治療のためのｒｏｃｋの５員アミノヘテロ環および５，６−または６，６員二環式アミノヘテロ環の阻害剤 |
| JP7234201B2 (ja) | 2017-07-12 | 2023-03-07 | ブリストル－マイヤーズ スクイブ カンパニー | 心不全の治療のためのｒｏｃｋの５員アミノヘテロ環および５，６－または６，６員二環式アミノヘテロ環の阻害剤 |
| JP2023554392A (ja) * | 2020-12-16 | 2023-12-27 | アイエフエム デュー インコーポレイテッド | Ｓｔｉｎｇ活性に関連する状態を治療するための化合物および組成物 |
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| BRPI0414908A (pt) | 2006-11-07 |
| US20040122237A1 (en) | 2004-06-24 |
| EP1675584A1 (en) | 2006-07-05 |
| ZA200603418B (en) | 2007-07-25 |
| WO2005032548A1 (en) | 2005-04-14 |
| US20120288501A1 (en) | 2012-11-15 |
| AU2004277405A1 (en) | 2005-04-14 |
| IL174431A0 (en) | 2006-08-01 |
| US8299108B2 (en) | 2012-10-30 |
| EA200600689A1 (ru) | 2006-08-25 |
| CN1913884A (zh) | 2007-02-14 |
| CA2539748A1 (en) | 2005-04-14 |
| KR20060089232A (ko) | 2006-08-08 |
| MXPA06003435A (es) | 2006-06-20 |
| EA011890B1 (ru) | 2009-06-30 |
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