CA2751478A1 - Derivatives of azaindoles as inhibitors of protein kinases abl and src - Google Patents
Derivatives of azaindoles as inhibitors of protein kinases abl and src Download PDFInfo
- Publication number
- CA2751478A1 CA2751478A1 CA2751478A CA2751478A CA2751478A1 CA 2751478 A1 CA2751478 A1 CA 2751478A1 CA 2751478 A CA2751478 A CA 2751478A CA 2751478 A CA2751478 A CA 2751478A CA 2751478 A1 CA2751478 A1 CA 2751478A1
- Authority
- CA
- Canada
- Prior art keywords
- group
- methyl
- pyrrolo
- optionally mono
- polysubstituted
- 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.)
- Abandoned
Links
- 239000003112 inhibitor Substances 0.000 title claims abstract description 58
- 102000001253 Protein Kinase Human genes 0.000 title claims abstract description 31
- 108060006633 protein kinase Proteins 0.000 title claims abstract description 31
- 125000005334 azaindolyl group Chemical group N1N=C(C2=CC=CC=C12)* 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 227
- 238000000034 method Methods 0.000 claims abstract description 40
- 238000004519 manufacturing process Methods 0.000 claims abstract description 12
- 229940126601 medicinal product Drugs 0.000 claims abstract description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 113
- 108091000080 Phosphotransferase Proteins 0.000 claims description 95
- 102000020233 phosphotransferase Human genes 0.000 claims description 95
- -1 phenyloxy Chemical group 0.000 claims description 86
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 81
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 70
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 64
- 238000002360 preparation method Methods 0.000 claims description 58
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 45
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 44
- 125000003545 alkoxy group Chemical group 0.000 claims description 43
- 125000001072 heteroaryl group Chemical group 0.000 claims description 43
- 125000005843 halogen group Chemical group 0.000 claims description 39
- 238000006243 chemical reaction Methods 0.000 claims description 36
- 125000003118 aryl group Chemical group 0.000 claims description 35
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 34
- 239000000203 mixture Substances 0.000 claims description 32
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 31
- 229910052794 bromium Inorganic materials 0.000 claims description 31
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 30
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 29
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 29
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 27
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 claims description 25
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims description 25
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 24
- 239000000460 chlorine Substances 0.000 claims description 24
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 23
- 229910052801 chlorine Inorganic materials 0.000 claims description 23
- 125000000565 sulfonamide group Chemical group 0.000 claims description 23
- 125000000217 alkyl group Chemical group 0.000 claims description 22
- 150000002148 esters Chemical group 0.000 claims description 22
- 239000002904 solvent Substances 0.000 claims description 22
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 claims description 20
- 125000004076 pyridyl group Chemical group 0.000 claims description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 19
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 19
- 229910052740 iodine Inorganic materials 0.000 claims description 19
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 18
- 125000000623 heterocyclic group Chemical group 0.000 claims description 17
- 229910052739 hydrogen Inorganic materials 0.000 claims description 17
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 17
- 150000001412 amines Chemical class 0.000 claims description 16
- 238000000746 purification Methods 0.000 claims description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 15
- KBOWEPWOSHLMGE-UHFFFAOYSA-N methyl 5-amino-1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound NC1=CN=C2NC(C(=O)OC)=CC2=C1 KBOWEPWOSHLMGE-UHFFFAOYSA-N 0.000 claims description 15
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 14
- 150000001408 amides Chemical class 0.000 claims description 14
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 14
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 14
- XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 claims description 14
- 238000010992 reflux Methods 0.000 claims description 14
- 125000004950 trifluoroalkyl group Chemical group 0.000 claims description 14
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 14
- 125000005412 pyrazyl group Chemical group 0.000 claims description 13
- WWCIKRATXUMSLS-UHFFFAOYSA-N methyl 5-nitro-1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound [O-][N+](=O)C1=CN=C2NC(C(=O)OC)=CC2=C1 WWCIKRATXUMSLS-UHFFFAOYSA-N 0.000 claims description 12
- 150000001263 acyl chlorides Chemical class 0.000 claims description 11
- 238000012512 characterization method Methods 0.000 claims description 11
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
- 125000001544 thienyl group Chemical group 0.000 claims description 10
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 9
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 9
- 239000001257 hydrogen Substances 0.000 claims description 9
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 9
- 206010006187 Breast cancer Diseases 0.000 claims description 8
- 208000026310 Breast neoplasm Diseases 0.000 claims description 8
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 8
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 8
- 125000004104 aryloxy group Chemical group 0.000 claims description 8
- 230000001684 chronic effect Effects 0.000 claims description 8
- 239000011737 fluorine Substances 0.000 claims description 8
- 229910052731 fluorine Inorganic materials 0.000 claims description 8
- 208000020816 lung neoplasm Diseases 0.000 claims description 8
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 8
- MVXVYAKCVDQRLW-UHFFFAOYSA-N 1h-pyrrolo[2,3-b]pyridine Chemical class C1=CN=C2NC=CC2=C1 MVXVYAKCVDQRLW-UHFFFAOYSA-N 0.000 claims description 7
- KCGKYAORRXGWMN-UHFFFAOYSA-N CNS(=O)=O Chemical compound CNS(=O)=O KCGKYAORRXGWMN-UHFFFAOYSA-N 0.000 claims description 7
- 208000014767 Myeloproliferative disease Diseases 0.000 claims description 7
- 102000001332 SRC Human genes 0.000 claims description 7
- 108060006706 SRC Proteins 0.000 claims description 7
- 230000001154 acute effect Effects 0.000 claims description 7
- 230000003197 catalytic effect Effects 0.000 claims description 7
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 7
- 230000003831 deregulation Effects 0.000 claims description 7
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 7
- OEYPDGZCSFPTBF-UHFFFAOYSA-N methyl 5-[(2-bromobenzoyl)amino]-1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound C=1N=C2NC(C(=O)OC)=CC2=CC=1NC(=O)C1=CC=CC=C1Br OEYPDGZCSFPTBF-UHFFFAOYSA-N 0.000 claims description 7
- 230000009467 reduction Effects 0.000 claims description 7
- 238000007127 saponification reaction Methods 0.000 claims description 7
- 239000000741 silica gel Substances 0.000 claims description 7
- 229910002027 silica gel Inorganic materials 0.000 claims description 7
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 6
- ZAHXYMFVNNUHCP-UHFFFAOYSA-N Naphazoline nitrate Chemical group O[N+]([O-])=O.C=1C=CC2=CC=CC=C2C=1CC1=NCCN1 ZAHXYMFVNNUHCP-UHFFFAOYSA-N 0.000 claims description 6
- 206010033128 Ovarian cancer Diseases 0.000 claims description 6
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 6
- 201000010099 disease Diseases 0.000 claims description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
- 201000005202 lung cancer Diseases 0.000 claims description 6
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical group CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 claims description 6
- 150000003335 secondary amines Chemical class 0.000 claims description 6
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 6
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 5
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 5
- 206010009944 Colon cancer Diseases 0.000 claims description 5
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 5
- 230000009471 action Effects 0.000 claims description 5
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 5
- 239000012298 atmosphere Substances 0.000 claims description 5
- 238000009903 catalytic hydrogenation reaction Methods 0.000 claims description 5
- 125000000723 dihydrobenzofuranyl group Chemical group O1C(CC2=C1C=CC=C2)* 0.000 claims description 5
- 238000005984 hydrogenation reaction Methods 0.000 claims description 5
- 239000011630 iodine Substances 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- 125000003368 amide group Chemical group 0.000 claims description 4
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
- 125000004185 ester group Chemical group 0.000 claims description 4
- 239000012280 lithium aluminium hydride Substances 0.000 claims description 4
- IPNPIHIZVLFAFP-UHFFFAOYSA-N phosphorus tribromide Chemical compound BrP(Br)Br IPNPIHIZVLFAFP-UHFFFAOYSA-N 0.000 claims description 4
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 4
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 4
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 claims description 3
- OPMOBCCZILYPTP-UHFFFAOYSA-N 2-bromo-n-[2-[(4-hydroxyanilino)methyl]-1h-pyrrolo[2,3-b]pyridin-5-yl]benzamide Chemical compound C1=CC(O)=CC=C1NCC1=CC2=CC(NC(=O)C=3C(=CC=CC=3)Br)=CN=C2N1 OPMOBCCZILYPTP-UHFFFAOYSA-N 0.000 claims description 3
- DHIHZLGSYHTLMS-UHFFFAOYSA-N 3-methoxy-1h-indazole Chemical compound C1=CC=C2C(OC)=NNC2=C1 DHIHZLGSYHTLMS-UHFFFAOYSA-N 0.000 claims description 3
- 150000001298 alcohols Chemical class 0.000 claims description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 3
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 claims description 3
- FCDMJPPRJSFFRX-UHFFFAOYSA-N methyl 5-[(2-fluoro-6-methoxybenzoyl)amino]-1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound C=1N=C2NC(C(=O)OC)=CC2=CC=1NC(=O)C1=C(F)C=CC=C1OC FCDMJPPRJSFFRX-UHFFFAOYSA-N 0.000 claims description 3
- 229910052763 palladium Inorganic materials 0.000 claims description 3
- 238000005897 peptide coupling reaction Methods 0.000 claims description 3
- 150000003140 primary amides Chemical class 0.000 claims description 3
- 125000005495 pyridazyl group Chemical group 0.000 claims description 3
- DZJWVPHWQSPJDD-UHFFFAOYSA-N 2-bromo-n-[2-(1h-pyrrol-2-ylmethyl)-1h-pyrrolo[2,3-b]pyridin-5-yl]benzamide Chemical compound BrC1=CC=CC=C1C(=O)NC1=CN=C(NC(CC=2NC=CC=2)=C2)C2=C1 DZJWVPHWQSPJDD-UHFFFAOYSA-N 0.000 claims description 2
- 238000004090 dissolution Methods 0.000 claims description 2
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
- ZWXCSTVTBKAEAD-UHFFFAOYSA-N 2-bromo-n-[2-(methoxymethyl)-1h-pyrrolo[2,3-b]pyridin-5-yl]benzamide Chemical compound C=1N=C2NC(COC)=CC2=CC=1NC(=O)C1=CC=CC=C1Br ZWXCSTVTBKAEAD-UHFFFAOYSA-N 0.000 claims 1
- CYOZJGAFKCEXBD-UHFFFAOYSA-N 5-[(2-bromobenzoyl)amino]-n-[3-(dimethylamino)propyl]-1h-pyrrolo[2,3-b]pyridine-2-carboxamide Chemical compound C=1N=C2NC(C(=O)NCCCN(C)C)=CC2=CC=1NC(=O)C1=CC=CC=C1Br CYOZJGAFKCEXBD-UHFFFAOYSA-N 0.000 claims 1
- 229910020667 PBr3 Inorganic materials 0.000 claims 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 181
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 123
- 238000004128 high performance liquid chromatography Methods 0.000 description 78
- 239000007787 solid Substances 0.000 description 71
- 238000004949 mass spectrometry Methods 0.000 description 69
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 68
- 230000002829 reductive effect Effects 0.000 description 60
- 239000000047 product Substances 0.000 description 55
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 50
- 238000005481 NMR spectroscopy Methods 0.000 description 49
- 230000000694 effects Effects 0.000 description 44
- 230000015572 biosynthetic process Effects 0.000 description 34
- 239000000243 solution Substances 0.000 description 33
- 238000003786 synthesis reaction Methods 0.000 description 32
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 32
- SIOXPEMLGUPBBT-UHFFFAOYSA-M picolinate Chemical compound [O-]C(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-M 0.000 description 29
- 230000005764 inhibitory process Effects 0.000 description 27
- 239000012074 organic phase Substances 0.000 description 27
- 210000004027 cell Anatomy 0.000 description 25
- 229910052938 sodium sulfate Inorganic materials 0.000 description 25
- 235000011152 sodium sulphate Nutrition 0.000 description 25
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 24
- 239000005517 L01XE01 - Imatinib Substances 0.000 description 23
- 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 description 23
- 238000005160 1H NMR spectroscopy Methods 0.000 description 22
- 239000008346 aqueous phase Substances 0.000 description 22
- 229960002411 imatinib Drugs 0.000 description 22
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
- 238000012360 testing method Methods 0.000 description 16
- WEVYNIUIFUYDGI-UHFFFAOYSA-N 3-[6-[4-(trifluoromethoxy)anilino]-4-pyrimidinyl]benzamide Chemical compound NC(=O)C1=CC=CC(C=2N=CN=C(NC=3C=CC(OC(F)(F)F)=CC=3)C=2)=C1 WEVYNIUIFUYDGI-UHFFFAOYSA-N 0.000 description 14
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 14
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
- 150000003254 radicals Chemical class 0.000 description 14
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 13
- 230000002401 inhibitory effect Effects 0.000 description 13
- 238000011282 treatment Methods 0.000 description 13
- 206010028980 Neoplasm Diseases 0.000 description 12
- 238000000338 in vitro Methods 0.000 description 12
- 239000011541 reaction mixture Substances 0.000 description 12
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 11
- 238000006268 reductive amination reaction Methods 0.000 description 11
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- 239000003153 chemical reaction reagent Substances 0.000 description 10
- 239000003480 eluent Substances 0.000 description 10
- 238000010898 silica gel chromatography Methods 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 9
- 150000001299 aldehydes Chemical class 0.000 description 9
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 9
- 208000032839 leukemia Diseases 0.000 description 9
- JNPZKGOLYSCSEL-UHFFFAOYSA-N methyl 5-amino-2-methylbenzoate Chemical compound COC(=O)C1=CC(N)=CC=C1C JNPZKGOLYSCSEL-UHFFFAOYSA-N 0.000 description 9
- 229910052757 nitrogen Inorganic materials 0.000 description 9
- 229910052760 oxygen Inorganic materials 0.000 description 9
- HBEDSQVIWPRPAY-UHFFFAOYSA-N 2,3-dihydrobenzofuran Chemical compound C1=CC=C2OCCC2=C1 HBEDSQVIWPRPAY-UHFFFAOYSA-N 0.000 description 8
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 8
- 201000011510 cancer Diseases 0.000 description 8
- 239000012047 saturated solution Substances 0.000 description 8
- 102000009076 src-Family Kinases Human genes 0.000 description 8
- 108010087686 src-Family Kinases Proteins 0.000 description 8
- JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 7
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 239000012300 argon atmosphere Substances 0.000 description 7
- 239000008280 blood Substances 0.000 description 7
- 210000004369 blood Anatomy 0.000 description 7
- 230000008878 coupling Effects 0.000 description 7
- 238000010168 coupling process Methods 0.000 description 7
- 238000005859 coupling reaction Methods 0.000 description 7
- CSDQQAQKBAQLLE-UHFFFAOYSA-N 4-(4-chlorophenyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine Chemical compound C1=CC(Cl)=CC=C1C1C(C=CS2)=C2CCN1 CSDQQAQKBAQLLE-UHFFFAOYSA-N 0.000 description 6
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 6
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 150000004982 aromatic amines Chemical class 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 235000011167 hydrochloric acid Nutrition 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- 238000002953 preparative HPLC Methods 0.000 description 6
- 238000006722 reduction reaction Methods 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- 241000238631 Hexapoda Species 0.000 description 5
- 108091008606 PDGF receptors Proteins 0.000 description 5
- 102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 238000011161 development Methods 0.000 description 5
- HKSZLNNOFSGOKW-UHFFFAOYSA-N ent-staurosporine Natural products C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1C1CC(NC)C(OC)C4(C)O1 HKSZLNNOFSGOKW-UHFFFAOYSA-N 0.000 description 5
- 230000002496 gastric effect Effects 0.000 description 5
- 230000002440 hepatic effect Effects 0.000 description 5
- 230000007170 pathology Effects 0.000 description 5
- 239000003208 petroleum Substances 0.000 description 5
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Substances [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 5
- 230000035755 proliferation Effects 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- HKSZLNNOFSGOKW-FYTWVXJKSA-N staurosporine Chemical compound C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1[C@H]1C[C@@H](NC)[C@@H](OC)[C@]4(C)O1 HKSZLNNOFSGOKW-FYTWVXJKSA-N 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 239000000758 substrate Substances 0.000 description 5
- YDTDKKULPWTHRV-UHFFFAOYSA-N 1H-indazol-3-amine Chemical compound C1=CC=C2C(N)=NNC2=C1 YDTDKKULPWTHRV-UHFFFAOYSA-N 0.000 description 4
- PBIXGSYVMDNMKP-UHFFFAOYSA-N 2-(methoxymethyl)-1h-pyrrolo[2,3-b]pyridin-5-amine Chemical compound NC1=CN=C2NC(COC)=CC2=C1 PBIXGSYVMDNMKP-UHFFFAOYSA-N 0.000 description 4
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- ZBNZXTGUTAYRHI-UHFFFAOYSA-N Dasatinib Chemical compound C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1Cl ZBNZXTGUTAYRHI-UHFFFAOYSA-N 0.000 description 4
- 239000002067 L01XE06 - Dasatinib Substances 0.000 description 4
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
- 102000016971 Proto-Oncogene Proteins c-kit Human genes 0.000 description 4
- 108010014608 Proto-Oncogene Proteins c-kit Proteins 0.000 description 4
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 4
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 4
- 235000011114 ammonium hydroxide Nutrition 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- 150000007942 carboxylates Chemical class 0.000 description 4
- 230000004663 cell proliferation Effects 0.000 description 4
- 229960002448 dasatinib Drugs 0.000 description 4
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 4
- JPFAEMAZJNUMME-UHFFFAOYSA-N methyl 2-methyl-5-[[4-[(4-methylpiperazin-1-yl)methyl]benzoyl]amino]benzoate Chemical compound C1=C(C)C(C(=O)OC)=CC(NC(=O)C=2C=CC(CN3CCN(C)CC3)=CC=2)=C1 JPFAEMAZJNUMME-UHFFFAOYSA-N 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- 238000006467 substitution reaction Methods 0.000 description 4
- 150000003512 tertiary amines Chemical group 0.000 description 4
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 3
- GWRSATNRNFYMDI-UHFFFAOYSA-N 4-[(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-8h-pyrimido[4,5-b][1,4]diazepin-2-yl)amino]-2-fluoro-5-methoxy-n-(1-methylpiperidin-4-yl)benzamide Chemical compound FC=1C=C(NC=2N=C3N(C4CCCC4)CC(F)(F)C(=O)N(C)C3=CN=2)C(OC)=CC=1C(=O)NC1CCN(C)CC1 GWRSATNRNFYMDI-UHFFFAOYSA-N 0.000 description 3
- CAPKAYDTKWGFQB-UHFFFAOYSA-N 4-methyl-3-(trifluoromethyl)benzoic acid Chemical compound CC1=CC=C(C(O)=O)C=C1C(F)(F)F CAPKAYDTKWGFQB-UHFFFAOYSA-N 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
- 239000005536 L01XE08 - Nilotinib Substances 0.000 description 3
- 239000012448 Lithium borohydride Substances 0.000 description 3
- 101150038994 PDGFRA gene Proteins 0.000 description 3
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 3
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 3
- 238000007080 aromatic substitution reaction Methods 0.000 description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 125000004122 cyclic group Chemical group 0.000 description 3
- 238000002866 fluorescence resonance energy transfer Methods 0.000 description 3
- 102000037865 fusion proteins Human genes 0.000 description 3
- 108020001507 fusion proteins Proteins 0.000 description 3
- 201000011243 gastrointestinal stromal tumor Diseases 0.000 description 3
- 238000002868 homogeneous time resolved fluorescence Methods 0.000 description 3
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 3
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 3
- HHZIURLSWUIHRB-UHFFFAOYSA-N nilotinib Chemical compound C1=NC(C)=CN1C1=CC(NC(=O)C=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)=CC(C(F)(F)F)=C1 HHZIURLSWUIHRB-UHFFFAOYSA-N 0.000 description 3
- 229960001346 nilotinib Drugs 0.000 description 3
- 239000013641 positive control Substances 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- JWEQRJSCTFBRSI-PCLIKHOPSA-N rboxylate Chemical compound COC(=O)C1C(N2C3=O)C4=CC=CC=C4OC1(C)N=C2S\C3=C\C(C=1)=CC=C(OC)C=1COC1=CC=CC=C1C JWEQRJSCTFBRSI-PCLIKHOPSA-N 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- DXMRZBGFYBCTLR-UHFFFAOYSA-N 1h-pyrrolo[2,3-b]pyridine-2-carboxylic acid Chemical compound C1=CN=C2NC(C(=O)O)=CC2=C1 DXMRZBGFYBCTLR-UHFFFAOYSA-N 0.000 description 2
- HLCPWBZNUKCSBN-UHFFFAOYSA-N 2-aminobenzonitrile Chemical compound NC1=CC=CC=C1C#N HLCPWBZNUKCSBN-UHFFFAOYSA-N 0.000 description 2
- GNGMKJGQYROQBT-UHFFFAOYSA-N 2-fluoro-n-[2-(morpholine-4-carbonyl)-1h-pyrrolo[2,3-b]pyridin-5-yl]-5-nitrobenzamide Chemical compound [O-][N+](=O)C1=CC=C(F)C(C(=O)NC=2C=C3C=C(NC3=NC=2)C(=O)N2CCOCC2)=C1 GNGMKJGQYROQBT-UHFFFAOYSA-N 0.000 description 2
- ZQOCDOFDUXPNGM-UHFFFAOYSA-N 3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)benzoic acid Chemical compound C1=NC(C)=CN1C1=CC(C(O)=O)=CC(C(F)(F)F)=C1 ZQOCDOFDUXPNGM-UHFFFAOYSA-N 0.000 description 2
- SYVNVEGIRVXRQH-UHFFFAOYSA-N 3-fluorobenzoyl chloride Chemical compound FC1=CC=CC(C(Cl)=O)=C1 SYVNVEGIRVXRQH-UHFFFAOYSA-N 0.000 description 2
- JJYPMNFTHPTTDI-UHFFFAOYSA-N 3-methylaniline Chemical compound CC1=CC=CC(N)=C1 JJYPMNFTHPTTDI-UHFFFAOYSA-N 0.000 description 2
- NVKJOXRVEKMMHS-UHFFFAOYSA-N 5-nitro-1,2,4-triazol-3-one Chemical compound [O-][N+](=O)C1=NC(=O)N=N1 NVKJOXRVEKMMHS-UHFFFAOYSA-N 0.000 description 2
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 2
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 108090000461 Aurora Kinase A Proteins 0.000 description 2
- 102100032311 Aurora kinase A Human genes 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 238000006646 Dess-Martin oxidation reaction Methods 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- 206010051066 Gastrointestinal stromal tumour Diseases 0.000 description 2
- 239000002145 L01XE14 - Bosutinib Substances 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- 241001181114 Neta Species 0.000 description 2
- 108700020796 Oncogene Proteins 0.000 description 2
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 2
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 2
- 229940124639 Selective inhibitor Drugs 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- 239000005864 Sulphur Substances 0.000 description 2
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-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
- 238000003556 assay Methods 0.000 description 2
- 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 2
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- UBPYILGKFZZVDX-UHFFFAOYSA-N bosutinib Chemical compound C1=C(Cl)C(OC)=CC(NC=2C3=CC(OC)=C(OCCCN4CCN(C)CC4)C=C3N=CC=2C#N)=C1Cl UBPYILGKFZZVDX-UHFFFAOYSA-N 0.000 description 2
- 229960003736 bosutinib Drugs 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- JINWVMKLXKAPRV-UHFFFAOYSA-N carbonic acid;3-(ethyliminomethylideneamino)-n,n-dimethylpropan-1-amine Chemical compound OC(O)=O.CCN=C=NCCCN(C)C JINWVMKLXKAPRV-UHFFFAOYSA-N 0.000 description 2
- 150000001735 carboxylic acids Chemical class 0.000 description 2
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
- ZOOSILUVXHVRJE-UHFFFAOYSA-N cyclopropanecarbonyl chloride Chemical compound ClC(=O)C1CC1 ZOOSILUVXHVRJE-UHFFFAOYSA-N 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 238000007429 general method Methods 0.000 description 2
- 230000003394 haemopoietic effect Effects 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- 238000000021 kinase assay Methods 0.000 description 2
- 230000003211 malignant effect Effects 0.000 description 2
- YSGIJTXCUYNTID-UHFFFAOYSA-N methyl 2-methyl-5-[[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)benzoyl]amino]benzoate Chemical compound C1=C(C)C(C(=O)OC)=CC(NC(=O)C=2C=C(C=C(C=2)N2C=C(C)N=C2)C(F)(F)F)=C1 YSGIJTXCUYNTID-UHFFFAOYSA-N 0.000 description 2
- UKKQILPRRXWYFY-UHFFFAOYSA-N methyl 5-(4-iodoanilino)-1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound C=1N=C2NC(C(=O)OC)=CC2=CC=1NC1=CC=C(I)C=C1 UKKQILPRRXWYFY-UHFFFAOYSA-N 0.000 description 2
- VFIDNKBEBGLRQT-UHFFFAOYSA-N methyl 5-[[2-(trifluoromethoxy)benzoyl]amino]-1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound C=1N=C2NC(C(=O)OC)=CC2=CC=1NC(=O)C1=CC=CC=C1OC(F)(F)F VFIDNKBEBGLRQT-UHFFFAOYSA-N 0.000 description 2
- MPKPLIIMXGFXDA-UHFFFAOYSA-N methyl 5-[[2-methyl-5-[[4-[(4-methylpiperazin-1-yl)methyl]benzoyl]amino]phenyl]methylamino]-1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound C=1N=C2NC(C(=O)OC)=CC2=CC=1NCC(C(=CC=1)C)=CC=1NC(=O)C(C=C1)=CC=C1CN1CCN(C)CC1 MPKPLIIMXGFXDA-UHFFFAOYSA-N 0.000 description 2
- KFBZGRLLFITJKG-UHFFFAOYSA-N methyl 5-benzamido-1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound C=1N=C2NC(C(=O)OC)=CC2=CC=1NC(=O)C1=CC=CC=C1 KFBZGRLLFITJKG-UHFFFAOYSA-N 0.000 description 2
- 150000004702 methyl esters Chemical class 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- ZPHVCXQPVIQNAF-UHFFFAOYSA-N n-(3-formyl-4-methylphenyl)-3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)benzamide Chemical compound C1=NC(C)=CN1C1=CC(C(=O)NC=2C=C(C=O)C(C)=CC=2)=CC(C(F)(F)F)=C1 ZPHVCXQPVIQNAF-UHFFFAOYSA-N 0.000 description 2
- AWXYGPZHSNSOHC-UHFFFAOYSA-N n-(3-formyl-4-methylphenyl)-4-[(4-methylpiperazin-1-yl)methyl]benzamide Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(C=O)C(C)=CC=2)C=C1 AWXYGPZHSNSOHC-UHFFFAOYSA-N 0.000 description 2
- 230000002611 ovarian Effects 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 125000003367 polycyclic group Chemical group 0.000 description 2
- 150000003138 primary alcohols Chemical class 0.000 description 2
- 150000003141 primary amines Chemical group 0.000 description 2
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 2
- MVILWLLYYQVYNH-UHFFFAOYSA-N pyridine-2-carboxamide Chemical compound NC(=O)C1=CC=CC=N1.NC(=O)C1=CC=CC=N1 MVILWLLYYQVYNH-UHFFFAOYSA-N 0.000 description 2
- UTEQROVYZDJSOO-UHFFFAOYSA-N quinoxaline-6-carbonyl chloride Chemical compound N1=CC=NC2=CC(C(=O)Cl)=CC=C21 UTEQROVYZDJSOO-UHFFFAOYSA-N 0.000 description 2
- 230000011514 reflex Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 210000000130 stem cell Anatomy 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- 229930192474 thiophene Natural products 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- PQDJYEQOELDLCP-UHFFFAOYSA-N trimethylsilane Chemical compound C[SiH](C)C PQDJYEQOELDLCP-UHFFFAOYSA-N 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- FRDZGSBXKJXGNR-HTQZYQBOSA-N (1r,2r)-2-n,2-n-dimethylcyclohexane-1,2-diamine Chemical compound CN(C)[C@@H]1CCCC[C@H]1N FRDZGSBXKJXGNR-HTQZYQBOSA-N 0.000 description 1
- PXHHIBMOFPCBJQ-UHFFFAOYSA-N 1,2-dimethylpyrrolidine Chemical compound CC1CCCN1C PXHHIBMOFPCBJQ-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- ZNTAXEMTUMCOTJ-UHFFFAOYSA-N 1-methyl-2-nitropyrrole Chemical compound CN1C=CC=C1[N+]([O-])=O ZNTAXEMTUMCOTJ-UHFFFAOYSA-N 0.000 description 1
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- KRQUFUKTQHISJB-YYADALCUSA-N 2-[(E)-N-[2-(4-chlorophenoxy)propoxy]-C-propylcarbonimidoyl]-3-hydroxy-5-(thian-3-yl)cyclohex-2-en-1-one Chemical compound CCC\C(=N/OCC(C)OC1=CC=C(Cl)C=C1)C1=C(O)CC(CC1=O)C1CCCSC1 KRQUFUKTQHISJB-YYADALCUSA-N 0.000 description 1
- CDAWCLOXVUBKRW-UHFFFAOYSA-N 2-aminophenol Chemical compound NC1=CC=CC=C1O CDAWCLOXVUBKRW-UHFFFAOYSA-N 0.000 description 1
- XMFAFBGIXMWQPR-UHFFFAOYSA-N 2-bromo-n-[2-(bromomethyl)-1h-pyrrolo[2,3-b]pyridin-5-yl]benzamide Chemical compound C=1N=C2NC(CBr)=CC2=CC=1NC(=O)C1=CC=CC=C1Br XMFAFBGIXMWQPR-UHFFFAOYSA-N 0.000 description 1
- AHDMPEPNBHGIGD-UHFFFAOYSA-N 2-bromo-n-[2-(hydroxymethyl)-1h-pyrrolo[2,3-b]pyridin-5-yl]benzamide Chemical compound C=1N=C2NC(CO)=CC2=CC=1NC(=O)C1=CC=CC=C1Br AHDMPEPNBHGIGD-UHFFFAOYSA-N 0.000 description 1
- SAVZSNFJYXJRPZ-UHFFFAOYSA-N 2-bromo-n-[2-(morpholin-4-ylmethyl)-1h-pyrrolo[2,3-b]pyridin-5-yl]benzamide Chemical compound BrC1=CC=CC=C1C(=O)NC1=CN=C(NC(CN2CCOCC2)=C2)C2=C1 SAVZSNFJYXJRPZ-UHFFFAOYSA-N 0.000 description 1
- AKYZFIHDZNFGCA-UHFFFAOYSA-N 2-bromo-n-[2-[(3-methoxyanilino)methyl]-1h-pyrrolo[2,3-b]pyridin-5-yl]benzamide Chemical compound COC1=CC=CC(NCC=2NC3=NC=C(NC(=O)C=4C(=CC=CC=4)Br)C=C3C=2)=C1 AKYZFIHDZNFGCA-UHFFFAOYSA-N 0.000 description 1
- NXBJTVNQGGVASP-UHFFFAOYSA-N 2-bromo-n-[2-[(3-nitroanilino)methyl]-1h-pyrrolo[2,3-b]pyridin-5-yl]benzamide Chemical compound [O-][N+](=O)C1=CC=CC(NCC=2NC3=NC=C(NC(=O)C=4C(=CC=CC=4)Br)C=C3C=2)=C1 NXBJTVNQGGVASP-UHFFFAOYSA-N 0.000 description 1
- FTYCWUMDMDTTJH-UHFFFAOYSA-N 2-bromo-n-[2-[[(2-methylcyclohexyl)amino]methyl]-1h-pyrrolo[2,3-b]pyridin-5-yl]benzamide Chemical compound CC1CCCCC1NCC1=CC2=CC(NC(=O)C=3C(=CC=CC=3)Br)=CN=C2N1 FTYCWUMDMDTTJH-UHFFFAOYSA-N 0.000 description 1
- NZCKTGCKFJDGFD-UHFFFAOYSA-N 2-bromobenzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1Br NZCKTGCKFJDGFD-UHFFFAOYSA-N 0.000 description 1
- STNAQENUCOFEKN-UHFFFAOYSA-N 2-cyanobenzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1C#N STNAQENUCOFEKN-UHFFFAOYSA-N 0.000 description 1
- SXJNRYPVXFTJOU-UHFFFAOYSA-N 2-fluoro-5-nitrobenzoyl chloride Chemical compound [O-][N+](=O)C1=CC=C(F)C(C(Cl)=O)=C1 SXJNRYPVXFTJOU-UHFFFAOYSA-N 0.000 description 1
- RAAGZOYMEQDCTD-UHFFFAOYSA-N 2-fluorobenzoyl chloride Chemical compound FC1=CC=CC=C1C(Cl)=O RAAGZOYMEQDCTD-UHFFFAOYSA-N 0.000 description 1
- RRHZXEQDWRUHNB-UHFFFAOYSA-N 2-methyl-5-[[4-[(4-methylpiperazin-1-yl)methyl]benzoyl]amino]benzoic acid Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(C(C)=CC=2)C(O)=O)C=C1 RRHZXEQDWRUHNB-UHFFFAOYSA-N 0.000 description 1
- BMGKQFRMINVVPP-UHFFFAOYSA-N 2-phenoxybenzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1OC1=CC=CC=C1 BMGKQFRMINVVPP-UHFFFAOYSA-N 0.000 description 1
- FTEUTJYYROCUBI-UHFFFAOYSA-N 2-propylsulfanylpyridine-3-carbonyl chloride Chemical compound CCCSC1=NC=CC=C1C(Cl)=O FTEUTJYYROCUBI-UHFFFAOYSA-N 0.000 description 1
- GNFTZDOKVXKIBK-UHFFFAOYSA-N 3-(2-methoxyethoxy)benzohydrazide Chemical compound COCCOC1=CC=CC(C(=O)NN)=C1 GNFTZDOKVXKIBK-UHFFFAOYSA-N 0.000 description 1
- AZKSAVLVSZKNRD-UHFFFAOYSA-M 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide Chemical compound [Br-].S1C(C)=C(C)N=C1[N+]1=NC(C=2C=CC=CC=2)=NN1C1=CC=CC=C1 AZKSAVLVSZKNRD-UHFFFAOYSA-M 0.000 description 1
- OWIRCRREDNEXTA-UHFFFAOYSA-N 3-nitro-1h-indazole Chemical compound C1=CC=C2C([N+](=O)[O-])=NNC2=C1 OWIRCRREDNEXTA-UHFFFAOYSA-N 0.000 description 1
- JQQBMLYOMLPPHQ-UHFFFAOYSA-N 4-[[3-(dimethylamino)pyrrolidin-1-yl]methyl]-3-(trifluoromethyl)benzoic acid Chemical compound C1C(N(C)C)CCN1CC1=CC=C(C(O)=O)C=C1C(F)(F)F JQQBMLYOMLPPHQ-UHFFFAOYSA-N 0.000 description 1
- ZEYHEAKUIGZSGI-UHFFFAOYSA-N 4-methoxybenzoic acid Chemical compound COC1=CC=C(C(O)=O)C=C1 ZEYHEAKUIGZSGI-UHFFFAOYSA-N 0.000 description 1
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 1
- NOWRIRSAASGKRU-UHFFFAOYSA-N 5-nitro-1h-pyrrolo[2,3-b]pyridine-2-carboxamide Chemical compound [O-][N+](=O)C1=CN=C2NC(C(=O)N)=CC2=C1 NOWRIRSAASGKRU-UHFFFAOYSA-N 0.000 description 1
- WYVYATUJBANZIN-UHFFFAOYSA-N 5-nitro-1h-pyrrolo[2,3-b]pyridine-2-carboxylic acid Chemical compound [O-][N+](=O)C1=CN=C2NC(C(=O)O)=CC2=C1 WYVYATUJBANZIN-UHFFFAOYSA-N 0.000 description 1
- 125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 description 1
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 1
- KLSJWNVTNUYHDU-UHFFFAOYSA-N Amitrole Chemical compound NC1=NC=NN1 KLSJWNVTNUYHDU-UHFFFAOYSA-N 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 102000004000 Aurora Kinase A Human genes 0.000 description 1
- 102000003989 Aurora kinases Human genes 0.000 description 1
- 108090000433 Aurora kinases Proteins 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 101150049556 Bcr gene Proteins 0.000 description 1
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- VIFCSOHSTIPPOS-UHFFFAOYSA-N BrC1=C(C(=O)NC=2C=C3C(=NC=2)NC(=C3)C(=O)O)C=CC=C1 Chemical compound BrC1=C(C(=O)NC=2C=C3C(=NC=2)NC(=C3)C(=O)O)C=CC=C1 VIFCSOHSTIPPOS-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- FGUUSXIOTUKUDN-IBGZPJMESA-N C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 Chemical compound C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 FGUUSXIOTUKUDN-IBGZPJMESA-N 0.000 description 1
- 101150041968 CDC13 gene Proteins 0.000 description 1
- 102000009728 CDC2 Protein Kinase Human genes 0.000 description 1
- 108010034798 CDC2 Protein Kinase Proteins 0.000 description 1
- 102100035861 Cytosolic 5'-nucleotidase 1A Human genes 0.000 description 1
- 101100285402 Danio rerio eng1a gene Proteins 0.000 description 1
- 208000008334 Dermatofibrosarcoma Diseases 0.000 description 1
- 206010057070 Dermatofibrosarcoma protuberans Diseases 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 102100025027 E3 ubiquitin-protein ligase TRIM69 Human genes 0.000 description 1
- 229910052693 Europium Inorganic materials 0.000 description 1
- 206010018364 Glomerulonephritis Diseases 0.000 description 1
- 101000798300 Homo sapiens Aurora kinase A Proteins 0.000 description 1
- 101000802744 Homo sapiens Cytosolic 5'-nucleotidase 1A Proteins 0.000 description 1
- 101000830203 Homo sapiens E3 ubiquitin-protein ligase TRIM69 Proteins 0.000 description 1
- 206010048643 Hypereosinophilic syndrome Diseases 0.000 description 1
- 206010064912 Malignant transformation Diseases 0.000 description 1
- 208000009905 Neurofibromatoses Diseases 0.000 description 1
- 102100026379 Neurofibromin Human genes 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 102000043276 Oncogene Human genes 0.000 description 1
- 241000282320 Panthera leo Species 0.000 description 1
- 208000031481 Pathologic Constriction Diseases 0.000 description 1
- 208000032721 Philadelphia Chromosome Diseases 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- 208000002151 Pleural effusion Diseases 0.000 description 1
- 208000004403 Prostatic Hyperplasia Diseases 0.000 description 1
- 102000003923 Protein Kinase C Human genes 0.000 description 1
- 108090000315 Protein Kinase C Proteins 0.000 description 1
- 108700020978 Proto-Oncogene Proteins 0.000 description 1
- 102000052575 Proto-Oncogene Human genes 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 150000001348 alkyl chlorides Chemical group 0.000 description 1
- 238000005576 amination reaction Methods 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 150000003927 aminopyridines Chemical class 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 229940045686 antimetabolites antineoplastic purine analogs Drugs 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 150000003934 aromatic aldehydes Chemical class 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- KQNZLOUWXSAZGD-UHFFFAOYSA-N benzylperoxymethylbenzene Chemical compound C=1C=CC=CC=1COOCC1=CC=CC=C1 KQNZLOUWXSAZGD-UHFFFAOYSA-N 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 1
- 229910010277 boron hydride Inorganic materials 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- 125000004799 bromophenyl group Chemical group 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 102220347004 c.89G>A Human genes 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 201000010902 chronic myelomonocytic leukemia Diseases 0.000 description 1
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 1
- 238000012866 crystallographic experiment Methods 0.000 description 1
- 125000006165 cyclic alkyl group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 125000006333 difluoro benzoyl group Chemical group 0.000 description 1
- IUNMPGNGSSIWFP-UHFFFAOYSA-N dimethylaminopropylamine Chemical compound CN(C)CCCN IUNMPGNGSSIWFP-UHFFFAOYSA-N 0.000 description 1
- WJJMNDUMQPNECX-UHFFFAOYSA-N dipicolinic acid Chemical compound OC(=O)C1=CC=CC(C(O)=O)=N1 WJJMNDUMQPNECX-UHFFFAOYSA-N 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- IZCSREAMZDZVFW-UHFFFAOYSA-N ethyl 5-amino-1,3-thiazole-2-carboxylate Chemical compound CCOC(=O)C1=NC=C(N)S1 IZCSREAMZDZVFW-UHFFFAOYSA-N 0.000 description 1
- LIWAQLJGPBVORC-UHFFFAOYSA-N ethylmethylamine Chemical compound CCNC LIWAQLJGPBVORC-UHFFFAOYSA-N 0.000 description 1
- OGPBJKLSAFTDLK-UHFFFAOYSA-N europium atom Chemical compound [Eu] OGPBJKLSAFTDLK-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 229940080856 gleevec Drugs 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hcl hcl Chemical compound Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 238000012188 high-throughput screening assay Methods 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- YLMAHDNUQAMNNX-UHFFFAOYSA-N imatinib methanesulfonate Chemical compound CS(O)(=O)=O.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 YLMAHDNUQAMNNX-UHFFFAOYSA-N 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- NCBZRJODKRCREW-UHFFFAOYSA-N m-anisidine Chemical compound COC1=CC=CC(N)=C1 NCBZRJODKRCREW-UHFFFAOYSA-N 0.000 description 1
- 230000036212 malign transformation Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- CKJNUZNMWOVDFN-UHFFFAOYSA-N methanone Chemical compound O=[CH-] CKJNUZNMWOVDFN-UHFFFAOYSA-N 0.000 description 1
- HCLLOQLXKCCWLJ-UHFFFAOYSA-N methyl 2-amino-6-methylbenzoate Chemical compound COC(=O)C1=C(C)C=CC=C1N HCLLOQLXKCCWLJ-UHFFFAOYSA-N 0.000 description 1
- IHGOYDMXENEUOO-UHFFFAOYSA-N methyl 2-aminopyrimidine-4-carboxylate Chemical compound COC(=O)C1=CC=NC(N)=N1 IHGOYDMXENEUOO-UHFFFAOYSA-N 0.000 description 1
- LXXRFFAIWGWJMA-UHFFFAOYSA-N methyl 4-(bromomethyl)-3-(trifluoromethyl)benzoate Chemical compound COC(=O)C1=CC=C(CBr)C(C(F)(F)F)=C1 LXXRFFAIWGWJMA-UHFFFAOYSA-N 0.000 description 1
- PYQRUDYLXHRTQU-UHFFFAOYSA-N methyl 4-aminopyrimidine-2-carboxylate Chemical compound COC(=O)C1=NC=CC(N)=N1 PYQRUDYLXHRTQU-UHFFFAOYSA-N 0.000 description 1
- LXUTXZRWQVCTTR-UHFFFAOYSA-N methyl 4-methyl-3-(trifluoromethyl)benzoate Chemical compound COC(=O)C1=CC=C(C)C(C(F)(F)F)=C1 LXUTXZRWQVCTTR-UHFFFAOYSA-N 0.000 description 1
- KXJQXFXXPCNCQU-UHFFFAOYSA-N methyl 5-(1h-indole-5-carbonylamino)-1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound C1=C2NC=CC2=CC(C(=O)NC=2C=C3C=C(NC3=NC=2)C(=O)OC)=C1 KXJQXFXXPCNCQU-UHFFFAOYSA-N 0.000 description 1
- MMNVTXMHJPCDLZ-UHFFFAOYSA-N methyl 5-(3-methoxyanilino)-1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound C=1N=C2NC(C(=O)OC)=CC2=CC=1NC1=CC=CC(OC)=C1 MMNVTXMHJPCDLZ-UHFFFAOYSA-N 0.000 description 1
- GXDKEOXBKFYQBY-UHFFFAOYSA-N methyl 5-(4-methoxyanilino)-1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound C=1N=C2NC(C(=O)OC)=CC2=CC=1NC1=CC=C(OC)C=C1 GXDKEOXBKFYQBY-UHFFFAOYSA-N 0.000 description 1
- VYMBFNQPILFZQT-UHFFFAOYSA-N methyl 5-(cyclopropanecarbonylamino)-1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound C=1N=C2NC(C(=O)OC)=CC2=CC=1NC(=O)C1CC1 VYMBFNQPILFZQT-UHFFFAOYSA-N 0.000 description 1
- KVVSEHVSCHEWNZ-UHFFFAOYSA-N methyl 5-(pyridin-4-ylamino)-1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound C=1N=C2NC(C(=O)OC)=CC2=CC=1NC1=CC=NC=C1 KVVSEHVSCHEWNZ-UHFFFAOYSA-N 0.000 description 1
- OLZRIODOWJKSQV-UHFFFAOYSA-N methyl 5-(pyridine-3-carbonylamino)-1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound C=1N=C2NC(C(=O)OC)=CC2=CC=1NC(=O)C1=CC=CN=C1 OLZRIODOWJKSQV-UHFFFAOYSA-N 0.000 description 1
- CMUUMIKNQANVSF-UHFFFAOYSA-N methyl 5-(thiophene-2-carbonylamino)-1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound C=1N=C2NC(C(=O)OC)=CC2=CC=1NC(=O)C1=CC=CS1 CMUUMIKNQANVSF-UHFFFAOYSA-N 0.000 description 1
- INHKTKGJEIKALZ-UHFFFAOYSA-N methyl 5-[(2,6-dichlorobenzoyl)amino]-1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound C=1N=C2NC(C(=O)OC)=CC2=CC=1NC(=O)C1=C(Cl)C=CC=C1Cl INHKTKGJEIKALZ-UHFFFAOYSA-N 0.000 description 1
- KNTPBVJWLVSQOV-UHFFFAOYSA-N methyl 5-[(2-chloro-6-methylphenyl)methylamino]-1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound C=1N=C2NC(C(=O)OC)=CC2=CC=1NCC1=C(C)C=CC=C1Cl KNTPBVJWLVSQOV-UHFFFAOYSA-N 0.000 description 1
- MDMLHBBPUVVDII-UHFFFAOYSA-N methyl 5-[(2-methoxybenzoyl)amino]-1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound C=1N=C2NC(C(=O)OC)=CC2=CC=1NC(=O)C1=CC=CC=C1OC MDMLHBBPUVVDII-UHFFFAOYSA-N 0.000 description 1
- XHNJVFQIMAESOO-UHFFFAOYSA-N methyl 5-[(2-methoxyphenyl)methylamino]-1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound C=1N=C2NC(C(=O)OC)=CC2=CC=1NCC1=CC=CC=C1OC XHNJVFQIMAESOO-UHFFFAOYSA-N 0.000 description 1
- ONXVBFWIQSGWAH-UHFFFAOYSA-N methyl 5-[(2-methylphenyl)methylamino]-1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound C=1N=C2NC(C(=O)OC)=CC2=CC=1NCC1=CC=CC=C1C ONXVBFWIQSGWAH-UHFFFAOYSA-N 0.000 description 1
- USCVUGRORRBEPZ-UHFFFAOYSA-N methyl 5-[(2-phenoxybenzoyl)amino]-1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound C=1N=C2NC(C(=O)OC)=CC2=CC=1NC(=O)C1=CC=CC=C1OC1=CC=CC=C1 USCVUGRORRBEPZ-UHFFFAOYSA-N 0.000 description 1
- VVHXNKYRTPCMBO-UHFFFAOYSA-N methyl 5-[(3-bromobenzoyl)amino]-1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound C=1N=C2NC(C(=O)OC)=CC2=CC=1NC(=O)C1=CC=CC(Br)=C1 VVHXNKYRTPCMBO-UHFFFAOYSA-N 0.000 description 1
- ZOVLDGHFLOZXCR-UHFFFAOYSA-N methyl 5-[(3-fluorobenzoyl)amino]-1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound C=1N=C2NC(C(=O)OC)=CC2=CC=1NC(=O)C1=CC=CC(F)=C1 ZOVLDGHFLOZXCR-UHFFFAOYSA-N 0.000 description 1
- PRGAKQWPQRXYMK-UHFFFAOYSA-N methyl 5-[4-(methylcarbamoyl)anilino]-1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound C1=CC(C(=O)NC)=CC=C1NC1=CN=C(NC(=C2)C(=O)OC)C2=C1 PRGAKQWPQRXYMK-UHFFFAOYSA-N 0.000 description 1
- MFAPLYWBOUSVJJ-UHFFFAOYSA-N methyl 5-[[2-(trifluoromethyl)phenyl]methylamino]-1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound C=1N=C2NC(C(=O)OC)=CC2=CC=1NCC1=CC=CC=C1C(F)(F)F MFAPLYWBOUSVJJ-UHFFFAOYSA-N 0.000 description 1
- XMWIFLVZWPUCKV-UHFFFAOYSA-N methyl 5-[[3-(furan-2-ylmethylsulfamoyl)benzoyl]amino]-1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound C=1N=C2NC(C(=O)OC)=CC2=CC=1NC(=O)C(C=1)=CC=CC=1S(=O)(=O)NCC1=CC=CO1 XMWIFLVZWPUCKV-UHFFFAOYSA-N 0.000 description 1
- CRVZXFNTTPPUBA-UHFFFAOYSA-N methyl 5-[[4-(2-methyl-1,3-thiazol-4-yl)benzoyl]amino]-1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound C=1N=C2NC(C(=O)OC)=CC2=CC=1NC(=O)C(C=C1)=CC=C1C1=CSC(C)=N1 CRVZXFNTTPPUBA-UHFFFAOYSA-N 0.000 description 1
- OBWMULCASPZKTP-UHFFFAOYSA-N methyl 5-[[4-(chloromethyl)benzoyl]amino]-2-methylbenzoate Chemical compound C1=C(C)C(C(=O)OC)=CC(NC(=O)C=2C=CC(CCl)=CC=2)=C1 OBWMULCASPZKTP-UHFFFAOYSA-N 0.000 description 1
- VVZPNTKFLOUJNQ-UHFFFAOYSA-N methyl 5-[[4-[[3-(dimethylamino)pyrrolidin-1-yl]methyl]-3-(trifluoromethyl)benzoyl]amino]-2-methylbenzoate Chemical compound C1=C(C)C(C(=O)OC)=CC(NC(=O)C=2C=C(C(CN3CC(CC3)N(C)C)=CC=2)C(F)(F)F)=C1 VVZPNTKFLOUJNQ-UHFFFAOYSA-N 0.000 description 1
- NXIWKVKEGODGND-UHFFFAOYSA-N methyl 5-[[5-[[4-[[3-(dimethylamino)pyrrolidin-1-yl]methyl]-3-(trifluoromethyl)benzoyl]amino]-2-methylbenzoyl]amino]-1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound C=1N=C2NC(C(=O)OC)=CC2=CC=1NC(=O)C(C(=CC=1)C)=CC=1NC(=O)C(C=C1C(F)(F)F)=CC=C1CN1CCC(N(C)C)C1 NXIWKVKEGODGND-UHFFFAOYSA-N 0.000 description 1
- OHIHEJTUXNQOPM-UHFFFAOYSA-N methyl 6-aminopyridine-2-carboxylate Chemical compound COC(=O)C1=CC=CC(N)=N1 OHIHEJTUXNQOPM-UHFFFAOYSA-N 0.000 description 1
- 229940095102 methyl benzoate Drugs 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 230000004001 molecular interaction Effects 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- SNHPRBGZISTEER-UHFFFAOYSA-N morpholin-4-yl-(5-nitro-1h-pyrrolo[2,3-b]pyridin-2-yl)methanone Chemical compound C=1C2=CC([N+](=O)[O-])=CN=C2NC=1C(=O)N1CCOCC1 SNHPRBGZISTEER-UHFFFAOYSA-N 0.000 description 1
- LCEDQNDDFOCWGG-UHFFFAOYSA-N morpholine-4-carbaldehyde Chemical compound O=CN1CCOCC1 LCEDQNDDFOCWGG-UHFFFAOYSA-N 0.000 description 1
- 230000004899 motility Effects 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- YRWYLPAVVWDGGS-UHFFFAOYSA-N n,n-dimethoxypropan-1-amine Chemical compound CCCN(OC)OC YRWYLPAVVWDGGS-UHFFFAOYSA-N 0.000 description 1
- ZUHZZVMEUAUWHY-UHFFFAOYSA-N n,n-dimethylpropan-1-amine Chemical compound CCCN(C)C ZUHZZVMEUAUWHY-UHFFFAOYSA-N 0.000 description 1
- AVAWMINJNRAQFS-UHFFFAOYSA-N n,n-dimethylpyrrolidin-3-amine Chemical compound CN(C)C1CCNC1 AVAWMINJNRAQFS-UHFFFAOYSA-N 0.000 description 1
- IXTUUGMNSAQPHI-UHFFFAOYSA-N n-[2-(anilinomethyl)-1h-pyrrolo[2,3-b]pyridin-5-yl]-2-bromobenzamide Chemical compound BrC1=CC=CC=C1C(=O)NC1=CN=C(NC(CNC=2C=CC=CC=2)=C2)C2=C1 IXTUUGMNSAQPHI-UHFFFAOYSA-N 0.000 description 1
- PNEJDIFQKCQXPM-UHFFFAOYSA-N n-[2-[[bis(2-methoxyethyl)amino]methyl]-1h-pyrrolo[2,3-b]pyridin-5-yl]-2-bromobenzamide Chemical compound C=1N=C2NC(CN(CCOC)CCOC)=CC2=CC=1NC(=O)C1=CC=CC=C1Br PNEJDIFQKCQXPM-UHFFFAOYSA-N 0.000 description 1
- VSSWZOOAQIXYDI-UHFFFAOYSA-N n-[3-(hydroxymethyl)-4-methylphenyl]-4-[(4-methylpiperazin-1-yl)methyl]benzamide Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(CO)C(C)=CC=2)C=C1 VSSWZOOAQIXYDI-UHFFFAOYSA-N 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- RWIVICVCHVMHMU-UHFFFAOYSA-N n-aminoethylmorpholine Chemical compound NCCN1CCOCC1 RWIVICVCHVMHMU-UHFFFAOYSA-N 0.000 description 1
- JCSQXEINQFERDM-UHFFFAOYSA-N n-benzyl-1h-indazol-3-amine Chemical compound N=1NC2=CC=CC=C2C=1NCC1=CC=CC=C1 JCSQXEINQFERDM-UHFFFAOYSA-N 0.000 description 1
- ILCQYORZHHFLNL-UHFFFAOYSA-N n-bromoaniline Chemical compound BrNC1=CC=CC=C1 ILCQYORZHHFLNL-UHFFFAOYSA-N 0.000 description 1
- VBEGHXKAFSLLGE-UHFFFAOYSA-N n-phenylnitramide Chemical compound [O-][N+](=O)NC1=CC=CC=C1 VBEGHXKAFSLLGE-UHFFFAOYSA-N 0.000 description 1
- XGXNTJHZPBRBHJ-UHFFFAOYSA-N n-phenylpyrimidin-2-amine Chemical compound N=1C=CC=NC=1NC1=CC=CC=C1 XGXNTJHZPBRBHJ-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 201000004931 neurofibromatosis Diseases 0.000 description 1
- 230000036963 noncompetitive effect Effects 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- NWVVVBRKAWDGAB-UHFFFAOYSA-N p-methoxyphenol Chemical compound COC1=CC=C(O)C=C1 NWVVVBRKAWDGAB-UHFFFAOYSA-N 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 238000009521 phase II clinical trial Methods 0.000 description 1
- 210000004214 philadelphia chromosome Anatomy 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 208000015768 polyposis Diseases 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 208000005069 pulmonary fibrosis Diseases 0.000 description 1
- 159000000018 pyrido[2,3-d]pyrimidines Chemical class 0.000 description 1
- 229910052761 rare earth metal Inorganic materials 0.000 description 1
- 150000002910 rare earth metals Chemical class 0.000 description 1
- QEVHRUUCFGRFIF-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C(C5=CC=C(OC)C=C5N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 QEVHRUUCFGRFIF-MDEJGZGSSA-N 0.000 description 1
- 238000002821 scintillation proximity assay Methods 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- FDDDEECHVMSUSB-UHFFFAOYSA-N sulfanilamide Chemical compound NC1=CC=C(S(N)(=O)=O)C=C1 FDDDEECHVMSUSB-UHFFFAOYSA-N 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- 150000003668 tyrosines Chemical class 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US20227909P | 2009-02-12 | 2009-02-12 | |
| US61/202,279 | 2009-02-12 | ||
| FR0900631A FR2941948B1 (fr) | 2009-02-12 | 2009-02-12 | Derives d'azaindoles en tant qu'inhibiteur des proteines kinases abl et src |
| FR0900631 | 2009-02-12 | ||
| PCT/IB2010/000593 WO2010092489A1 (en) | 2009-02-12 | 2010-02-12 | Derivatives of azaindoles as inhibitors of protein kinases abl and src |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2751478A1 true CA2751478A1 (en) | 2010-08-19 |
Family
ID=40886859
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2751478A Abandoned CA2751478A1 (en) | 2009-02-12 | 2010-02-12 | Derivatives of azaindoles as inhibitors of protein kinases abl and src |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US8580815B2 (enExample) |
| EP (1) | EP2396325B1 (enExample) |
| JP (1) | JP5583698B2 (enExample) |
| AU (1) | AU2010212560B2 (enExample) |
| CA (1) | CA2751478A1 (enExample) |
| DK (1) | DK2396325T3 (enExample) |
| ES (1) | ES2540962T3 (enExample) |
| FR (1) | FR2941948B1 (enExample) |
| HR (1) | HRP20150697T8 (enExample) |
| HU (1) | HUE024989T2 (enExample) |
| PL (1) | PL2396325T3 (enExample) |
| PT (1) | PT2396325E (enExample) |
| SI (1) | SI2396325T1 (enExample) |
| SM (1) | SMT201500175B (enExample) |
| WO (1) | WO2010092489A1 (enExample) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR112015014752B1 (pt) * | 2012-12-21 | 2022-07-05 | Plexxikon, Inc | Compostos e seus uso para modulação de cinase |
| FR3000494B1 (fr) * | 2012-12-28 | 2015-08-21 | Oribase Pharma | Nouveaux derives d'azaindoles en tant qu'inhibiteurs de proteines kinases |
| FR3000492B1 (fr) * | 2012-12-28 | 2015-09-11 | Oribase Pharma | Nouveaux derives azaindole en tant qu'inhibiteurs multikinases |
| FR3000493A1 (fr) | 2012-12-28 | 2014-07-04 | Oribase Pharma | Nouveaux inhibiteurs de proteines kinases |
| US10722484B2 (en) | 2016-03-09 | 2020-07-28 | K-Gen, Inc. | Methods of cancer treatment |
| EP3601216B1 (en) | 2017-03-21 | 2023-10-25 | Arbutus Biopharma Corporation | Substituted dihydroindene-4-carboxamides and analogs thereof, and methods using same for the treatment of hepatitis b virus infection |
| AU2021263383A1 (en) | 2020-04-29 | 2022-11-24 | Plexxikon Inc. | Synthesis of heterocyclic compounds |
| CN111943947B (zh) * | 2020-07-24 | 2021-04-30 | 重庆文理学院 | 1H-吡咯[2,3-b]吡啶衍生物及其合成方法与应用 |
| AU2021358123A1 (en) * | 2020-10-05 | 2023-06-08 | Enliven Inc. | 5- and 6-azaindole compounds for inhibition of bcr-abl tyrosine kinases |
| JP2023545219A (ja) * | 2020-10-05 | 2023-10-26 | エンライブン インコーポレイテッド | Ｂｃｒ－ａｂｌチロシンキナーゼの阻害のための７－アザインドール化合物 |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0330043D0 (en) * | 2003-12-24 | 2004-01-28 | Pharmacia Italia Spa | Pyrrolo [2,3-b] pyridine derivatives active as kinase inhibitors process for their preparation and pharmaceutical compositions comprising them |
| GB0330042D0 (en) | 2003-12-24 | 2004-01-28 | Pharmacia Italia Spa | Pyrrolo [2,3-b] pyridine derivatives active as kinase inhibitors process for their preparation and pharmaceutical compositions them |
| WO2006009797A1 (en) * | 2004-06-17 | 2006-01-26 | Plexxikon, Inc. | Azaindoles modulating c-kit activity and uses therefor |
| US7361764B2 (en) | 2004-07-27 | 2008-04-22 | Sgx Pharmaceuticals, Inc. | Pyrrolo-pyridine kinase modulators |
| JP2008508303A (ja) | 2004-07-27 | 2008-03-21 | エスジーエックス ファーマシューティカルズ、インコーポレイテッド | ピロロ−ピリジンキナーゼモジュレーター |
| US7709645B2 (en) * | 2004-07-27 | 2010-05-04 | Sgx Pharmaceuticals, Inc. | Pyrrolo-pyridine kinase modulators |
| ES2319462T3 (es) * | 2005-03-28 | 2009-05-07 | Bristol-Myers Squibb Company | Inhibidores competitivos de atp cinasas. |
| CN101511828A (zh) | 2006-09-06 | 2009-08-19 | 霍夫曼-拉罗奇有限公司 | 作为蛋白激酶抑制剂的杂芳基衍生物 |
| US8148361B2 (en) * | 2006-11-10 | 2012-04-03 | Bristol-Myers Squibb Company | Kinase inhibitors |
| WO2008144253A1 (en) * | 2007-05-14 | 2008-11-27 | Irm Llc | Protein kinase inhibitors and methods for using thereof |
| KR20100122505A (ko) * | 2008-02-29 | 2010-11-22 | 어레이 바이오파마 인크. | Ｒａｆ 저해물질 화합물 및 이들의 이용 방법 |
| AU2009320481C1 (en) | 2008-11-03 | 2016-12-08 | Syntarga B.V. | Novel CC-1065 analogs and their conjugates |
-
2009
- 2009-02-12 FR FR0900631A patent/FR2941948B1/fr not_active Expired - Fee Related
-
2010
- 2010-02-12 AU AU2010212560A patent/AU2010212560B2/en not_active Ceased
- 2010-02-12 PT PT107104390T patent/PT2396325E/pt unknown
- 2010-02-12 DK DK10710439.0T patent/DK2396325T3/en active
- 2010-02-12 SI SI201030964T patent/SI2396325T1/sl unknown
- 2010-02-12 ES ES10710439.0T patent/ES2540962T3/es active Active
- 2010-02-12 EP EP10710439.0A patent/EP2396325B1/en not_active Not-in-force
- 2010-02-12 HU HUE10710439A patent/HUE024989T2/en unknown
- 2010-02-12 HR HRP20150697TT patent/HRP20150697T8/hr unknown
- 2010-02-12 WO PCT/IB2010/000593 patent/WO2010092489A1/en not_active Ceased
- 2010-02-12 PL PL10710439T patent/PL2396325T3/pl unknown
- 2010-02-12 CA CA2751478A patent/CA2751478A1/en not_active Abandoned
- 2010-02-12 JP JP2011549698A patent/JP5583698B2/ja not_active Expired - Fee Related
- 2010-02-12 US US13/148,988 patent/US8580815B2/en not_active Expired - Fee Related
-
2015
- 2015-07-22 SM SM201500175T patent/SMT201500175B/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| WO2010092489A1 (en) | 2010-08-19 |
| EP2396325A1 (en) | 2011-12-21 |
| HRP20150697T1 (hr) | 2015-08-14 |
| PT2396325E (pt) | 2015-08-21 |
| AU2010212560A1 (en) | 2011-08-11 |
| JP2012517465A (ja) | 2012-08-02 |
| SMT201500175B (it) | 2015-09-07 |
| PL2396325T3 (pl) | 2015-10-30 |
| US20110312959A1 (en) | 2011-12-22 |
| AU2010212560B2 (en) | 2016-01-21 |
| HUE024989T2 (en) | 2016-01-28 |
| DK2396325T3 (en) | 2015-06-29 |
| JP5583698B2 (ja) | 2014-09-03 |
| SI2396325T1 (sl) | 2015-08-31 |
| US8580815B2 (en) | 2013-11-12 |
| FR2941948A1 (fr) | 2010-08-13 |
| FR2941948B1 (fr) | 2013-04-05 |
| HRP20150697T8 (xx) | 2015-11-06 |
| EP2396325B1 (en) | 2015-04-01 |
| ES2540962T3 (es) | 2015-07-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2751478A1 (en) | Derivatives of azaindoles as inhibitors of protein kinases abl and src | |
| ES2426096T3 (es) | Derivados de isoindolona como inhibidores de la quinasa MEK y métodos de utilización | |
| AU2013341186B2 (en) | Amide-substituted heterocyclic compounds useful as modulators of IL-12, IL-23 and/or IFN alpha responses | |
| JP2022506887A (ja) | 窒素含有縮合複素環系ｓｈｐ２阻害剤化合物、製造方法及び使用 | |
| CN103588792B (zh) | 吡啶并嘧啶或嘧啶并嘧啶类化合物、其制备方法、药物组合物及其用途 | |
| CN101475571B (zh) | β-咔啉类细胞周期蛋白依赖性激酶2抑制剂及其用途 | |
| EP2137158A1 (en) | Small molecule inhibitors of protein arginine methyltransferases (prmts) | |
| WO2013134298A1 (en) | Raf inhibitor compounds | |
| CN105732614B (zh) | 磺酰胺基芳基炔类化合物及其用途 | |
| CA2693904A1 (en) | Heterocyclic compounds useful as mk2 inhibitors | |
| WO2015007249A1 (zh) | N-烷基色胺酮衍生物及其制备方法和应用 | |
| KR20110105792A (ko) | 페닐피리미돈을 함유하는 화합물, 그 약물 조성물 및 그 제조방법과 용도 | |
| CN118955505A (zh) | 布鲁顿酪氨酸激酶抑制剂 | |
| WO2016100166A1 (en) | SUBSTITUTED DIHYDRO-1H-PYRROLO[3,2-c]PYRIDIN-4(5H)-ONES AS RIPK3 INHIBITORS | |
| JP2023520595A (ja) | ピラゾロピリダジノン化合物、その医薬組成物及びその用途 | |
| EP1919910B1 (en) | Azabenzimidazole derivatives, their manufacture and use as anti-cancer agents | |
| CN117645598A (zh) | 氮杂二并多元稠环化合物及其药物组合物和应用 | |
| CN113166148B (zh) | 作为cdk-hdac双通路抑制剂的杂环化合物 | |
| WO2025077896A1 (zh) | 一种DNA聚合酶theta抑制剂及其应用 | |
| Wang et al. | Design, synthesis, and anticancer evaluation of arylurea derivatives as potent and selective type II irreversible covalent FGFR4 inhibitors | |
| CN111704610A (zh) | 一类吡咯酰胺并吡啶酮类化合物、制备方法和用途 | |
| EP2825166A1 (en) | Method of treating ophthalmic conditions with kinase inhibitors | |
| CN115124534A (zh) | 非核苷酸类prmt5小分子抑制剂、制备方法及用途 | |
| CN105693744A (zh) | 一种取代的噻吩并嘧啶化合物及其制备方法 | |
| CN112079836B (zh) | 三唑并嘧啶类化合物及其盐、组合物和应用 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20150112 |
|
| FZDE | Discontinued |
Effective date: 20181227 |