JP2013503139A5 - - Google Patents
Download PDFInfo
- Publication number
- JP2013503139A5 JP2013503139A5 JP2012526067A JP2012526067A JP2013503139A5 JP 2013503139 A5 JP2013503139 A5 JP 2013503139A5 JP 2012526067 A JP2012526067 A JP 2012526067A JP 2012526067 A JP2012526067 A JP 2012526067A JP 2013503139 A5 JP2013503139 A5 JP 2013503139A5
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- substituted
- methyl
- halo
- cyclopropyl
- 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.)
- Granted
Links
- -1 and R 1a is H Chemical group 0.000 claims description 23
- 150000001875 compounds Chemical class 0.000 claims description 22
- 150000003839 salts Chemical class 0.000 claims description 17
- 239000011780 sodium chloride Substances 0.000 claims description 17
- 125000006526 (C1-C2) alkyl group Chemical group 0.000 claims description 16
- 239000003814 drug Substances 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- 125000002947 alkylene group Chemical group 0.000 claims description 9
- 239000000203 mixture Substances 0.000 claims description 8
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 239000003112 inhibitor Substances 0.000 claims description 5
- 230000002401 inhibitory effect Effects 0.000 claims description 5
- GTIIVHODSNYECK-UHFFFAOYSA-N 1,1,1-trifluoropropane Chemical group [CH2]CC(F)(F)F GTIIVHODSNYECK-UHFFFAOYSA-N 0.000 claims description 3
- 125000006432 1-methyl cyclopropyl group Chemical group [H]C([H])([H])C1(*)C([H])([H])C1([H])[H] 0.000 claims description 3
- 125000006450 cyclopropyl cyclopropyl group Chemical group 0.000 claims description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 28
- 125000000217 alkyl group Chemical group 0.000 claims 16
- 229910052736 halogen Inorganic materials 0.000 claims 16
- 150000002367 halogens Chemical class 0.000 claims 16
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 13
- 125000001475 halogen functional group Chemical group 0.000 claims 13
- 125000006536 (C1-C2)alkoxy group Chemical group 0.000 claims 6
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 5
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 4
- 201000011510 cancer Diseases 0.000 claims 4
- 239000008194 pharmaceutical composition Substances 0.000 claims 4
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 2
- 208000003200 Adenoma Diseases 0.000 claims 2
- 206010001233 Adenoma benign Diseases 0.000 claims 2
- 206010005003 Bladder cancer Diseases 0.000 claims 2
- 206010009944 Colon cancer Diseases 0.000 claims 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 2
- 206010025650 Malignant melanoma Diseases 0.000 claims 2
- 208000008443 Pancreatic Carcinoma Diseases 0.000 claims 2
- 108091000081 Phosphotransferases Proteins 0.000 claims 2
- 102000001253 Protein Kinases Human genes 0.000 claims 2
- 239000004480 active ingredient Substances 0.000 claims 2
- 239000000730 antalgic agent Substances 0.000 claims 2
- 239000002260 anti-inflammatory agent Substances 0.000 claims 2
- 239000000935 antidepressant agent Substances 0.000 claims 2
- 239000002111 antiemetic agent Substances 0.000 claims 2
- 201000006484 bone marrow disease Diseases 0.000 claims 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 2
- 201000005202 lung cancer Diseases 0.000 claims 2
- 201000001441 melanoma Diseases 0.000 claims 2
- 125000001424 substituent group Chemical group 0.000 claims 2
- 125000006442 t-butyl cyclopropyl group Chemical group 0.000 claims 2
- 201000005112 urinary bladder cancer Diseases 0.000 claims 2
- 102000010400 1-phosphatidylinositol-3-kinase activity proteins Human genes 0.000 claims 1
- 108040005185 1-phosphatidylinositol-3-kinase activity proteins Proteins 0.000 claims 1
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 claims 1
- 229940035676 ANALGESICS Drugs 0.000 claims 1
- 229940005513 ANTIDEPRESSANTS Drugs 0.000 claims 1
- 229940116904 ANTIINFLAMMATORY THERAPEUTIC RADIOPHARMACEUTICALS Drugs 0.000 claims 1
- 101700049227 CDK9 Proteins 0.000 claims 1
- 102100003972 CDK9 Human genes 0.000 claims 1
- 101700024891 EPHB2 Proteins 0.000 claims 1
- 101700011730 KINUA Proteins 0.000 claims 1
- 108091007472 MAP kinase family Proteins 0.000 claims 1
- 102000038027 MAP kinase family Human genes 0.000 claims 1
- 101700083887 MAPK1 Proteins 0.000 claims 1
- VDVHEBQEJCHLCN-UHFFFAOYSA-N N-[2-chloro-3-(2-cyclopropyl-5-pyrimidin-4-yl-1H-imidazol-4-yl)-5-fluorophenyl]-2,6-difluorobenzenesulfonamide Chemical compound ClC=1C(C2=C(NC(=N2)C2CC2)C=2N=CN=CC=2)=CC(F)=CC=1NS(=O)(=O)C1=C(F)C=CC=C1F VDVHEBQEJCHLCN-UHFFFAOYSA-N 0.000 claims 1
- XJNXDPBTZPNVPO-UHFFFAOYSA-N N-[2-chloro-3-(2-cyclopropyl-5-pyrimidin-4-yl-1H-imidazol-4-yl)-5-fluorophenyl]methanesulfonamide Chemical compound CS(=O)(=O)NC1=CC(F)=CC(C2=C(NC(=N2)C2CC2)C=2N=CN=CC=2)=C1Cl XJNXDPBTZPNVPO-UHFFFAOYSA-N 0.000 claims 1
- DMNKAFXXZZAQNF-UHFFFAOYSA-N N-[2-chloro-3-(2-cyclopropyl-5-pyrimidin-4-yl-1H-imidazol-4-yl)-5-fluorophenyl]propane-1-sulfonamide Chemical compound CCCS(=O)(=O)NC1=CC(F)=CC(C2=C(NC(=N2)C2CC2)C=2N=CN=CC=2)=C1Cl DMNKAFXXZZAQNF-UHFFFAOYSA-N 0.000 claims 1
- 229940074726 OPHTHALMOLOGIC ANTIINFLAMMATORY AGENTS Drugs 0.000 claims 1
- 102000029987 Phosphatidylethanolamine-binding protein Human genes 0.000 claims 1
- 108091000043 Phosphatidylethanolamine-binding protein Proteins 0.000 claims 1
- 206010060862 Prostate cancer Diseases 0.000 claims 1
- 102000003923 Protein Kinase C Human genes 0.000 claims 1
- 108090000315 Protein Kinase C Proteins 0.000 claims 1
- 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 claims 1
- 102000013530 TOR Serine-Threonine Kinases Human genes 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- 239000000654 additive Substances 0.000 claims 1
- 230000000996 additive Effects 0.000 claims 1
- 125000005119 alkyl cycloalkyl group Chemical group 0.000 claims 1
- 125000005466 alkylenyl group Chemical group 0.000 claims 1
- 230000000202 analgesic Effects 0.000 claims 1
- 230000001093 anti-cancer Effects 0.000 claims 1
- 230000001430 anti-depressive Effects 0.000 claims 1
- 230000003474 anti-emetic Effects 0.000 claims 1
- 229940121363 anti-inflammatory agents Drugs 0.000 claims 1
- 239000002246 antineoplastic agent Substances 0.000 claims 1
- 101700081248 byr1 Proteins 0.000 claims 1
- 239000000969 carrier Substances 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 230000001404 mediated Effects 0.000 claims 1
- 201000002510 thyroid cancer Diseases 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 description 11
- XEKOWRVHYACXOJ-UHFFFAOYSA-N acetic acid ethyl ester Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 239000010410 layer Substances 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- XKRFYHLGVUSROY-UHFFFAOYSA-N argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- 239000012267 brine Substances 0.000 description 4
- 235000019439 ethyl acetate Nutrition 0.000 description 4
- 238000003818 flash chromatography Methods 0.000 description 4
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 4
- IMNFDUFMRHMDMM-UHFFFAOYSA-N n-heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N HCl Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- JBGGFYZUDGDHMN-UHFFFAOYSA-N 3-bromo-2,5-difluoroaniline Chemical compound NC1=CC(F)=CC(Br)=C1F JBGGFYZUDGDHMN-UHFFFAOYSA-N 0.000 description 2
- WFFDTMNHOINATE-UHFFFAOYSA-N 5-chloro-2-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC(Cl)=CC(N)=C1F WFFDTMNHOINATE-UHFFFAOYSA-N 0.000 description 2
- 229960001433 Erlotinib Drugs 0.000 description 2
- AAKJLRGGTJKAMG-UHFFFAOYSA-N Erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 description 2
- 239000005551 L01XE03 - Erlotinib Substances 0.000 description 2
- 239000002136 L01XE07 - Lapatinib Substances 0.000 description 2
- BCFGMOOMADDAQU-UHFFFAOYSA-N Lapatinib Chemical compound O1C(CNCCS(=O)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=C(Cl)C(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 BCFGMOOMADDAQU-UHFFFAOYSA-N 0.000 description 2
- 229910004298 SiO 2 Inorganic materials 0.000 description 2
- MFRIHAYPQRLWNB-UHFFFAOYSA-N Sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 2
- 108010010691 Trastuzumab Proteins 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- WEVYAHXRMPXWCK-UHFFFAOYSA-N acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- 229960004891 lapatinib Drugs 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N methylene dichloride Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- YXFVVABEGXRONW-UHFFFAOYSA-N toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 2
- 229960000575 trastuzumab Drugs 0.000 description 2
- ZMANZCXQSJIPKH-UHFFFAOYSA-N triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 2
- QTZSKHCRRPXONC-UHFFFAOYSA-N 1,3-dibromo-2,5-difluorobenzene Chemical compound FC1=CC(Br)=C(F)C(Br)=C1 QTZSKHCRRPXONC-UHFFFAOYSA-N 0.000 description 1
- QKWVGDAAZHJCLH-UHFFFAOYSA-N 2,5-difluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC(F)=CC(N)=C1F QKWVGDAAZHJCLH-UHFFFAOYSA-N 0.000 description 1
- BPXKZEMBEZGUAH-UHFFFAOYSA-N 2-(chloromethoxy)ethyl-trimethylsilane Chemical compound C[Si](C)(C)CCOCCl BPXKZEMBEZGUAH-UHFFFAOYSA-N 0.000 description 1
- PWCZPJXBQQJUTN-UHFFFAOYSA-N 2-[(4,5-dibromo-2-cyclobutylimidazol-1-yl)methoxy]ethyl-trimethylsilane Chemical compound C[Si](C)(C)CCOCN1C(Br)=C(Br)N=C1C1CCC1 PWCZPJXBQQJUTN-UHFFFAOYSA-N 0.000 description 1
- YHSRGCNBSMCVBR-UHFFFAOYSA-N 3-[[4-[5-(3-amino-5-chloro-2-fluorophenyl)-2-cyclopropyl-3-(2-trimethylsilylethoxymethyl)imidazol-4-yl]pyrimidin-2-yl]amino]propanenitrile Chemical compound C[Si](C)(C)CCOCN1C(C2CC2)=NC(C=2C(=C(N)C=C(Cl)C=2)F)=C1C1=CC=NC(NCCC#N)=N1 YHSRGCNBSMCVBR-UHFFFAOYSA-N 0.000 description 1
- FHEFXECHHOBHIQ-UHFFFAOYSA-N 3-[[4-[5-bromo-2-cyclopropyl-3-(2-trimethylsilylethoxymethyl)imidazol-4-yl]pyrimidin-2-yl]amino]propanenitrile Chemical compound C[Si](C)(C)CCOCN1C(C2CC2)=NC(Br)=C1C1=CC=NC(NCCC#N)=N1 FHEFXECHHOBHIQ-UHFFFAOYSA-N 0.000 description 1
- 125000002103 4,4'-dimethoxytriphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)(C1=C([H])C([H])=C(OC([H])([H])[H])C([H])=C1[H])C1=C([H])C([H])=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 1
- VSYNJLZSZQQECA-UHFFFAOYSA-N 4,5-dibromo-2-cyclobutyl-1H-imidazole Chemical compound N1C(Br)=C(Br)N=C1C1CCC1 VSYNJLZSZQQECA-UHFFFAOYSA-N 0.000 description 1
- AOJJSUZBOXZQNB-TZSSRYMLSA-N ADRIAMYCIN Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 1
- 229940100198 ALKYLATING AGENTS Drugs 0.000 description 1
- 229940030495 ANTIANDROGEN SEX HORMONES AND MODULATORS OF THE GENITAL SYSTEM Drugs 0.000 description 1
- 229940100197 ANTIMETABOLITES Drugs 0.000 description 1
- 229940064005 Antibiotic throat preparations Drugs 0.000 description 1
- 229940083879 Antibiotics FOR TREATMENT OF HEMORRHOIDS AND ANAL FISSURES FOR TOPICAL USE Drugs 0.000 description 1
- 229940042052 Antibiotics for systemic use Drugs 0.000 description 1
- 229940042786 Antitubercular Antibiotics Drugs 0.000 description 1
- MLDQJTXFUGDVEO-UHFFFAOYSA-N BAY-43-9006 Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 MLDQJTXFUGDVEO-UHFFFAOYSA-N 0.000 description 1
- MUALRAIOVNYAIW-UHFFFAOYSA-N BINAP Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 1
- RWCCWEUUXYIKHB-UHFFFAOYSA-N Benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 description 1
- 108010005144 Bevacizumab Proteins 0.000 description 1
- 229960004562 Carboplatin Drugs 0.000 description 1
- OLESAACUTLOWQZ-UHFFFAOYSA-L Carboplatin Chemical compound O=C1O[Pt]([N]([H])([H])[H])([N]([H])([H])[H])OC(=O)C11CCC1 OLESAACUTLOWQZ-UHFFFAOYSA-L 0.000 description 1
- 108010022830 Cetuximab Proteins 0.000 description 1
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N Docetaxel Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 1
- 229960004679 Doxorubicin Drugs 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- XGALLCVXEZPNRQ-UHFFFAOYSA-N Gefitinib Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- 229940093922 Gynecological Antibiotics Drugs 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N Intaxel 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
- 239000005411 L01XE02 - Gefitinib Substances 0.000 description 1
- 239000005511 L01XE05 - Sorafenib Substances 0.000 description 1
- SLOWBIWRFDGYFV-UHFFFAOYSA-N N-[5-chloro-3-[5-[2-(2-cyanoethylamino)pyrimidin-4-yl]-2-cyclopropyl-1H-imidazol-4-yl]-2-fluorophenyl]methanesulfonamide Chemical compound CS(=O)(=O)NC1=CC(Cl)=CC(C2=C(NC(=N2)C2CC2)C=2N=C(NCCC#N)N=CC=2)=C1F SLOWBIWRFDGYFV-UHFFFAOYSA-N 0.000 description 1
- 229960001592 Paclitaxel Drugs 0.000 description 1
- 108010061219 Panitumumab Proteins 0.000 description 1
- QFJCIRLUMZQUOT-HPLJOQBZSA-N Sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 1
- BPEGJWRSRHCHSN-UHFFFAOYSA-N Temodal Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 description 1
- 229940024982 Topical Antifungal Antibiotics Drugs 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 239000004037 angiogenesis inhibitor Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000002280 anti-androgenic Effects 0.000 description 1
- 230000003388 anti-hormone Effects 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 230000001028 anti-proliferant Effects 0.000 description 1
- 230000000259 anti-tumor Effects 0.000 description 1
- 239000000051 antiandrogen Substances 0.000 description 1
- 108090001123 antibodies Proteins 0.000 description 1
- 102000004965 antibodies Human genes 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 229960000397 bevacizumab Drugs 0.000 description 1
- 230000003115 biocidal Effects 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- 125000006440 butyl cyclopropyl group Chemical group 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 229960005395 cetuximab Drugs 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- 239000002254 cytotoxic agent Substances 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- LCGLNKUTAGEVQW-UHFFFAOYSA-N dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 1
- SXZIXHOMFPUIRK-UHFFFAOYSA-N diphenylmethanimine Chemical compound C=1C=CC=CC=1C(=N)C1=CC=CC=C1 SXZIXHOMFPUIRK-UHFFFAOYSA-N 0.000 description 1
- 239000003534 dna topoisomerase inhibitor Substances 0.000 description 1
- 229960003668 docetaxel Drugs 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 229960002584 gefitinib Drugs 0.000 description 1
- 229960005277 gemcitabine Drugs 0.000 description 1
- 239000008079 hexane Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 1
- 239000000367 immunologic factor Substances 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 229940079866 intestinal antibiotics Drugs 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000000394 mitotic Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 229940005935 ophthalmologic Antibiotics Drugs 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 229960001972 panitumumab Drugs 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 229960002087 pertuzumab Drugs 0.000 description 1
- 108010042024 pertuzumab Proteins 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229960002930 sirolimus Drugs 0.000 description 1
- BZKBCQXYZZXSCO-UHFFFAOYSA-N sodium hydride Inorganic materials [H-].[Na+] BZKBCQXYZZXSCO-UHFFFAOYSA-N 0.000 description 1
- 229960003787 sorafenib Drugs 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 229930003347 taxol Natural products 0.000 description 1
- 229960004964 temozolomide Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- LXZZYRPGZAFOLE-UHFFFAOYSA-L transplatin Chemical compound [H][N]([H])([H])[Pt](Cl)(Cl)[N]([H])([H])[H] LXZZYRPGZAFOLE-UHFFFAOYSA-L 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US23808309P | 2009-08-28 | 2009-08-28 | |
US61/238,083 | 2009-08-28 | ||
US31306110P | 2010-03-11 | 2010-03-11 | |
US61/313,061 | 2010-03-11 | ||
PCT/EP2010/062495 WO2011023773A1 (en) | 2009-08-28 | 2010-08-26 | Compounds and compositions as protein kinase inhibitors |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2013503139A JP2013503139A (ja) | 2013-01-31 |
JP2013503139A5 true JP2013503139A5 (US07794700-20100914-C00125.png) | 2013-07-04 |
JP5726190B2 JP5726190B2 (ja) | 2015-05-27 |
Family
ID=42829939
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2012526067A Active JP5726190B2 (ja) | 2009-08-28 | 2010-08-26 | タンパク質キナーゼ阻害剤としての化合物および組成物 |
Country Status (19)
Families Citing this family (22)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AR077975A1 (es) | 2009-08-28 | 2011-10-05 | Irm Llc | Derivados de pirazol pirimidina y composiciones como inhibidores de cinasa de proteina |
BR112012021411A2 (pt) | 2010-02-25 | 2017-04-18 | Dana Farber Cancer Inst Inc | mutações braf que conferem resistência a inibidores braf. |
WO2013059634A1 (en) | 2011-10-20 | 2013-04-25 | The Regents Of The University Of California | Use of cdk9 inhibitors to reduce cartilage degradation |
EP2776037B1 (en) | 2011-11-11 | 2019-01-09 | Novartis AG | Method of treating a proliferative disease |
KR102091295B1 (ko) | 2011-11-23 | 2020-03-19 | 어레이 바이오파마 인크. | 제약 제제 |
US9408885B2 (en) | 2011-12-01 | 2016-08-09 | Vib Vzw | Combinations of therapeutic agents for treating melanoma |
US20150232452A1 (en) * | 2012-09-19 | 2015-08-20 | Ruga Corporation | Novel raf kinase inhibitors |
US9242969B2 (en) | 2013-03-14 | 2016-01-26 | Novartis Ag | Biaryl amide compounds as kinase inhibitors |
WO2014194127A1 (en) * | 2013-05-30 | 2014-12-04 | Plexxikon Inc. | Compounds for kinase modulation, and indications therefor |
AR096721A1 (es) | 2013-06-25 | 2016-01-27 | Bristol Myers Squibb Co | Compuestos de tetrahidrocarbazol y carbazol carboxamida sustituidos |
AU2014302550A1 (en) | 2013-06-25 | 2016-02-11 | Bristol-Myers Squibb Company | Carbazole carboxamide compounds useful as kinase inhibitors |
LT3038622T (lt) * | 2013-08-28 | 2018-07-25 | Medivation Technologies Llc | Heterocikliniai junginiai ir jų naudojimo būdai |
GB2517988A (en) * | 2013-09-09 | 2015-03-11 | Redx Pharma Ltd | Compounds |
UY36294A (es) | 2014-09-12 | 2016-04-29 | Novartis Ag | Compuestos y composiciones como inhibidores de quinasa |
US10300073B2 (en) | 2014-10-14 | 2019-05-28 | The Regents Of The University Of California | Use of CDK9 and BRD4 inhibitors to inhibit inflammation |
CN104402920B (zh) * | 2014-11-27 | 2018-04-03 | 河南科技学院 | 一种合成2‑卤代‑3‑频那醇硼酸酯‑5‑氯苯胺的方法 |
AU2017329090B9 (en) | 2016-09-19 | 2019-09-05 | Novartis Ag | Therapeutic combinations comprising a RAF inhibitor and a ERK inhibitor |
WO2018146253A1 (en) | 2017-02-10 | 2018-08-16 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for the treatment of cancers associated with activation of the mapk pathway |
US11725185B2 (en) | 2017-12-28 | 2023-08-15 | University Of Houston System | Stem cell culture systems for columnar epithelial stem cells, and uses related thereto |
WO2020124397A1 (en) * | 2018-12-19 | 2020-06-25 | Inventisbio Shanghai Ltd. | C-terminal src kinase inhibitors |
US20230303551A1 (en) * | 2020-08-13 | 2023-09-28 | Albert Einstein College Of Medicine | N-cyclyl-sulfonamides useful for inhibiting raf |
WO2023240024A1 (en) | 2022-06-08 | 2023-12-14 | Nikang Therapeutics, Inc. | Sulfamide derivatives as cyclin-dependent kinase 2 inhibitors |
Family Cites Families (25)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2659739A (en) | 1950-04-14 | 1953-11-17 | Eastman Kodak Co | 1-hydroxy-4-beta-cyanopropylamino-anthraquinone and process for preparing same |
US6358932B1 (en) | 1994-05-31 | 2002-03-19 | Isis Pharmaceticals, Inc. | Antisense oligonucleotide inhibition of raf gene expression |
US6391636B1 (en) | 1994-05-31 | 2002-05-21 | Isis Pharmaceuticals, Inc. | Antisense oligonucleotide modulation of raf gene expression |
US6037136A (en) | 1994-10-24 | 2000-03-14 | Cold Spring Harbor Laboratory | Interactions between RaF proto-oncogenes and CDC25 phosphatases, and uses related thereto |
US5717100A (en) | 1995-10-06 | 1998-02-10 | Merck & Co., Inc. | Substituted imidazoles having anti-cancer and cytokine inhibitory activity |
GB2306108A (en) * | 1995-10-13 | 1997-04-30 | Merck & Co Inc | Treatment of Raf-mediated cancers with imidazole derivatives |
WO1997044058A1 (en) | 1996-05-23 | 1997-11-27 | Applied Research Systems Ars Holding N.V. | Compounds that inhibit the binding of raf-1 or 14-3-3 proteins to the beta chain of il-2 receptor, and pharmaceutical compositions containing same |
AR012634A1 (es) | 1997-05-02 | 2000-11-08 | Sugen Inc | Compuesto basado en quinazolina, composicion famaceutica que lo comprende, metodo para sintetizarlo, su uso, metodos de modulacion de la funcion deserina/treonina proteinaquinasa con dicho compuesto y metodo in vitro para identificar compuestos que modulan dicha funcion |
US6187799B1 (en) | 1997-05-23 | 2001-02-13 | Onyx Pharmaceuticals | Inhibition of raf kinase activity using aryl ureas |
GB9716557D0 (en) | 1997-08-06 | 1997-10-08 | Glaxo Group Ltd | Benzylidene-1,3-dihydro-indol-2-one derivatives having anti-cancer activity |
US6022884A (en) | 1997-11-07 | 2000-02-08 | Amgen Inc. | Substituted pyridine compounds and methods of use |
US6204467B1 (en) | 1998-03-24 | 2001-03-20 | Ford Global Technologies, Inc. | Method and apparatus for resistive welding |
ME00275B (me) | 1999-01-13 | 2011-02-10 | Bayer Corp | ω-KARBOKSIARIL SUPSTITUISANI DIFENIL KARBAMIDI KAO INHIBITORI RAF KINAZE |
WO2002018654A1 (en) | 2000-08-30 | 2002-03-07 | The Board Of Trustees Of The University Of Arkansas | Induction of ldl receptor expression by extracellular-signal regulated kinase, erk-1/2 |
HUE025767T2 (en) | 2002-03-13 | 2016-05-30 | Array Biopharma Inc | N3-alkylated benzimidazole derivatives as MEK inhibitors |
US6644516B1 (en) | 2002-11-06 | 2003-11-11 | Continental Afa Dispensing Company | Foaming liquid dispenser |
AU2006217742A1 (en) | 2005-02-25 | 2006-08-31 | Kudos Pharmaceuticals Limited | Hydrazinomethyl, HYDR zonomethyl and 5-membered heterocylic compounds which act as MTOR inhibitors and their use as anti cancer agents |
AU2006217744A1 (en) | 2005-02-25 | 2006-08-31 | Kudos Pharmaceuticals Limited | 2,4-diamino-pyridopyrimidine derivatives and their use as MTOR inhibitors |
CA2628920C (en) | 2005-11-22 | 2015-12-29 | Kudos Pharmaceuticals Limited | Pyrido-,pyrazo- and pyrimido-pyrimidine derivatives as mtor inhibitors |
CA2635997A1 (en) | 2006-01-11 | 2007-07-19 | Astrazeneca Ab | Morpholino pyrimidine derivatives and their use in therapy |
MY148688A (en) | 2006-08-23 | 2013-05-31 | Kudos Pharm Ltd | 2-methylmorpholine pyrido-, pyrazo- and pyrimido-pyrimidine derivatives as mtor inhibitors |
TW200922582A (en) | 2007-08-20 | 2009-06-01 | Organon Nv | N-benzyl, N'-arylcarbonylpiperazine derivatives |
US8129394B2 (en) * | 2008-03-21 | 2012-03-06 | Novartis Ag | Heteroaryl-substituted imidazole compounds and uses thereof |
UA103319C2 (en) | 2008-05-06 | 2013-10-10 | Глаксосмитклайн Ллк | Thiazole- and oxazole-benzene sulfonamide compounds |
ATE557015T1 (de) | 2008-07-24 | 2012-05-15 | Nerviano Medical Sciences Srl | 3,4-diarylpyrazole als proteinkinaseinhibitoren |
-
2010
- 2010-08-24 US US12/862,418 patent/US8242260B2/en not_active Expired - Fee Related
- 2010-08-26 MX MX2012002542A patent/MX2012002542A/es active IP Right Grant
- 2010-08-26 JP JP2012526067A patent/JP5726190B2/ja active Active
- 2010-08-26 PL PL10745280T patent/PL2470528T3/pl unknown
- 2010-08-26 AU AU2010288455A patent/AU2010288455B2/en not_active Ceased
- 2010-08-26 WO PCT/EP2010/062495 patent/WO2011023773A1/en active Application Filing
- 2010-08-26 BR BR112012004448A patent/BR112012004448A2/pt not_active Application Discontinuation
- 2010-08-26 ES ES10745280.7T patent/ES2527176T3/es active Active
- 2010-08-26 JO JOP/2010/0298A patent/JO3007B1/ar active
- 2010-08-26 CN CN201080038235.XA patent/CN102596937B/zh active Active
- 2010-08-26 IN IN869DEN2012 patent/IN2012DN00869A/en unknown
- 2010-08-26 PT PT107452807T patent/PT2470528E/pt unknown
- 2010-08-26 CA CA2771673A patent/CA2771673C/en not_active Expired - Fee Related
- 2010-08-26 AR ARP100103125A patent/AR077977A1/es unknown
- 2010-08-26 EP EP10745280.7A patent/EP2470528B1/en active Active
- 2010-08-26 EA EA201200323A patent/EA020479B1/ru not_active IP Right Cessation
- 2010-08-26 KR KR1020127007838A patent/KR101714107B1/ko active IP Right Grant
- 2010-08-27 UY UY0001032859A patent/UY32859A/es not_active Application Discontinuation
- 2010-08-27 TW TW099128938A patent/TWI487701B/zh not_active IP Right Cessation
-
2012
- 2012-05-16 US US13/473,230 patent/US8563553B2/en active Active
-
2013
- 2013-09-10 US US14/022,540 patent/US8859548B2/en active Active
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP2013503139A5 (US07794700-20100914-C00125.png) | ||
TWI679201B (zh) | 吡唑并嘧啶化合物 | |
RU2018119173A (ru) | Производное бензофурана, способ его получения и его применение в медицине | |
JP2019517487A5 (US07794700-20100914-C00125.png) | ||
RU2007116987A (ru) | Новые соединения | |
RU2018138828A (ru) | Уменьшение массы опухоли путем введения ccr1 антагонистов в комбинации с pd-1 ингибиторами или pd-l1 ингибиторами | |
JP2014508811A5 (US07794700-20100914-C00125.png) | ||
RU2020102453A (ru) | Фармацевтические композиции | |
HRP20151410T1 (hr) | Derivati pikolinamida kao inhibitori kinaze | |
RU2014115847A (ru) | Пирролопиримидиновые соединения для лечения злокачественной опухоли | |
KR20170049604A (ko) | Bub1 억제제로서의 벤질 치환된 인다졸 | |
RU2008128568A (ru) | (1-азабицикло[3,3,1]нон-4-ил)-[н-индол-5-ил)-гетероарил]-амины, как холинергические лиганды n-achr, предназначенные для лечения психотических и нейродегенеративных нарушений | |
JP2016504365A5 (US07794700-20100914-C00125.png) | ||
RU2007143507A (ru) | Производные фенилацетилена, обладающие сродством к рецептору mglur 5 | |
CA2669680A1 (en) | Compounds for inhibiting mitotic progression | |
RU2010126056A (ru) | Органические соединения | |
JP6380777B2 (ja) | PI3K、mTOR阻害薬としての縮合キノリン化合物 | |
JP2017531041A5 (US07794700-20100914-C00125.png) | ||
RU2007143509A (ru) | Производные ацетилена | |
ES2617878T3 (es) | Inhibidores de tubulina basados en la pirazina | |
JP2020506951A5 (US07794700-20100914-C00125.png) | ||
RU2007146769A (ru) | Бициклические производные и их применение в качестве модуляторов ионых каналов | |
RU2011133128A (ru) | Противоопухолевые соединения дигидропиран-2-она | |
RU2010113358A (ru) | Гуанидинсодержащие соединения, применимые в качестве антагонистов мускариновых рецепторов | |
EA200801536A1 (ru) | Новые тиенопирсульфоновые производные |