ES2221904T3 - Imidazolo-5-il-2-anilino-pirimidinas como agentes para la inhibicion de la proliferacion celular. - Google Patents
Imidazolo-5-il-2-anilino-pirimidinas como agentes para la inhibicion de la proliferacion celular.Info
- Publication number
- ES2221904T3 ES2221904T3 ES01963159T ES01963159T ES2221904T3 ES 2221904 T3 ES2221904 T3 ES 2221904T3 ES 01963159 T ES01963159 T ES 01963159T ES 01963159 T ES01963159 T ES 01963159T ES 2221904 T3 ES2221904 T3 ES 2221904T3
- Authority
- ES
- Spain
- Prior art keywords
- sulfamoyl
- alkyl
- formula
- compound
- pharmaceutically acceptable
- 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.)
- Expired - Lifetime
Links
- 230000004663 cell proliferation Effects 0.000 title description 13
- 230000005764 inhibitory process Effects 0.000 title description 11
- -1 nitro, cyano, hydroxy, amino, carboxy, carbamoyl Chemical group 0.000 claims abstract description 401
- 150000001875 compounds Chemical class 0.000 claims abstract description 230
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 150
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 128
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 63
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 58
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 56
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 55
- 239000001257 hydrogen Substances 0.000 claims abstract description 52
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 52
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims abstract description 51
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 43
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 29
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 26
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 26
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims abstract description 22
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 20
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims abstract description 15
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 15
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 14
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims abstract description 11
- 125000003884 phenylalkyl group Chemical group 0.000 claims abstract description 11
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 10
- 125000001589 carboacyl group Chemical group 0.000 claims abstract description 9
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 9
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims abstract description 8
- 125000004423 acyloxy group Chemical group 0.000 claims abstract description 8
- 125000005236 alkanoylamino group Chemical group 0.000 claims abstract description 8
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 8
- 125000004845 (C1-C6) alkylsulfonylamino group Chemical group 0.000 claims abstract description 7
- 150000002829 nitrogen Chemical group 0.000 claims abstract description 4
- 125000001475 halogen functional group Chemical group 0.000 claims abstract 14
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract 9
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract 2
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims abstract 2
- 238000000034 method Methods 0.000 claims description 183
- 150000003839 salts Chemical class 0.000 claims description 67
- 239000007787 solid Substances 0.000 claims description 65
- 150000002148 esters Chemical class 0.000 claims description 64
- 238000001727 in vivo Methods 0.000 claims description 64
- 238000011282 treatment Methods 0.000 claims description 38
- 206010028980 Neoplasm Diseases 0.000 claims description 28
- 241001465754 Metazoa Species 0.000 claims description 27
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 25
- 238000004519 manufacturing process Methods 0.000 claims description 23
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 20
- 150000002431 hydrogen Chemical class 0.000 claims description 20
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 18
- 239000003814 drug Substances 0.000 claims description 18
- 230000002401 inhibitory effect Effects 0.000 claims description 18
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 17
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 14
- 230000022131 cell cycle Effects 0.000 claims description 13
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 12
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 12
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 11
- 125000003342 alkenyl group Chemical group 0.000 claims description 11
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 11
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 11
- 150000001412 amines Chemical class 0.000 claims description 10
- 239000000460 chlorine Substances 0.000 claims description 10
- 229910052801 chlorine Inorganic materials 0.000 claims description 10
- 208000032839 leukemia Diseases 0.000 claims description 10
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 229910052717 sulfur Inorganic materials 0.000 claims description 9
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 8
- 229910052794 bromium Inorganic materials 0.000 claims description 8
- 239000003085 diluting agent Substances 0.000 claims description 8
- 230000035755 proliferation Effects 0.000 claims description 8
- 210000002307 prostate Anatomy 0.000 claims description 8
- 230000001154 acute effect Effects 0.000 claims description 7
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 7
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 7
- 230000008569 process Effects 0.000 claims description 7
- 206010051113 Arterial restenosis Diseases 0.000 claims description 6
- 206010003210 Arteriosclerosis Diseases 0.000 claims description 6
- 201000001320 Atherosclerosis Diseases 0.000 claims description 6
- 208000037260 Atherosclerotic Plaque Diseases 0.000 claims description 6
- 208000020084 Bone disease Diseases 0.000 claims description 6
- 208000007766 Kaposi sarcoma Diseases 0.000 claims description 6
- 201000004681 Psoriasis Diseases 0.000 claims description 6
- 201000011510 cancer Diseases 0.000 claims description 6
- 210000001072 colon Anatomy 0.000 claims description 6
- 208000035475 disorder Diseases 0.000 claims description 6
- 208000030533 eye disease Diseases 0.000 claims description 6
- 230000000893 fibroproliferative effect Effects 0.000 claims description 6
- 201000011066 hemangioma Diseases 0.000 claims description 6
- 229910052740 iodine Inorganic materials 0.000 claims description 6
- 210000004072 lung Anatomy 0.000 claims description 6
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 210000001210 retinal vessel Anatomy 0.000 claims description 6
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 6
- 208000023275 Autoimmune disease Diseases 0.000 claims description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
- 208000038016 acute inflammation Diseases 0.000 claims description 5
- 230000006022 acute inflammation Effects 0.000 claims description 5
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 5
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 5
- 210000000481 breast Anatomy 0.000 claims description 5
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 5
- 125000006125 ethylsulfonyl group Chemical group 0.000 claims description 5
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 5
- 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims description 4
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 4
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 4
- 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 claims description 4
- 208000030090 Acute Disease Diseases 0.000 claims description 4
- 125000000304 alkynyl group Chemical group 0.000 claims description 4
- 230000001028 anti-proliverative effect Effects 0.000 claims description 4
- 208000037976 chronic inflammation Diseases 0.000 claims description 4
- 230000006020 chronic inflammation Effects 0.000 claims description 4
- 208000020832 chronic kidney disease Diseases 0.000 claims description 4
- 230000012010 growth Effects 0.000 claims description 4
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 4
- 210000000496 pancreas Anatomy 0.000 claims description 4
- 230000000306 recurrent effect Effects 0.000 claims description 4
- 210000003491 skin Anatomy 0.000 claims description 4
- 210000001519 tissue Anatomy 0.000 claims description 4
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 3
- 230000002611 ovarian Effects 0.000 claims description 3
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 3
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 3
- KVJXNCXRESCVKS-UHFFFAOYSA-N 4-[[4-(3-ethyl-2-methylimidazol-4-yl)pyrimidin-2-yl]amino]-n-(2-methoxyethyl)benzenesulfonamide Chemical compound CCN1C(C)=NC=C1C1=CC=NC(NC=2C=CC(=CC=2)S(=O)(=O)NCCOC)=N1 KVJXNCXRESCVKS-UHFFFAOYSA-N 0.000 claims description 2
- 201000009030 Carcinoma Diseases 0.000 claims description 2
- 206010025323 Lymphomas Diseases 0.000 claims description 2
- 206010039491 Sarcoma Diseases 0.000 claims description 2
- 210000000936 intestine Anatomy 0.000 claims description 2
- 210000003734 kidney Anatomy 0.000 claims description 2
- 210000004185 liver Anatomy 0.000 claims description 2
- 230000017066 negative regulation of growth Effects 0.000 claims description 2
- 230000001012 protector Effects 0.000 claims description 2
- 210000002784 stomach Anatomy 0.000 claims description 2
- 210000003905 vulva Anatomy 0.000 claims description 2
- SGMLRJXBDRNXBJ-UHFFFAOYSA-N 4-[[4-(2,3-dimethylimidazol-4-yl)pyrimidin-2-yl]amino]-n-(2,2,2-trifluoroethyl)benzenesulfonamide Chemical compound CN1C(C)=NC=C1C1=CC=NC(NC=2C=CC(=CC=2)S(=O)(=O)NCC(F)(F)F)=N1 SGMLRJXBDRNXBJ-UHFFFAOYSA-N 0.000 claims 1
- 208000026310 Breast neoplasm Diseases 0.000 claims 1
- BUPDQZDNTBNFFR-UHFFFAOYSA-N n-(cyclopropylmethyl)-4-[[4-(2,3-dimethylimidazol-4-yl)pyrimidin-2-yl]amino]benzenesulfonamide Chemical compound CN1C(C)=NC=C1C1=CC=NC(NC=2C=CC(=CC=2)S(=O)(=O)NCC2CC2)=N1 BUPDQZDNTBNFFR-UHFFFAOYSA-N 0.000 claims 1
- ZJDZXCYQBNODMM-UHFFFAOYSA-N n-(cyclopropylmethyl)-4-[[4-(3-ethyl-2-methylimidazol-4-yl)pyrimidin-2-yl]amino]benzenesulfonamide Chemical compound CCN1C(C)=NC=C1C1=CC=NC(NC=2C=CC(=CC=2)S(=O)(=O)NCC2CC2)=N1 ZJDZXCYQBNODMM-UHFFFAOYSA-N 0.000 claims 1
- QSHDCKRJZSDIGZ-UHFFFAOYSA-N n-(cyclopropylmethyl)-4-[[4-(3-methyl-2-propan-2-ylimidazol-4-yl)pyrimidin-2-yl]amino]benzenesulfonamide Chemical compound CN1C(C(C)C)=NC=C1C1=CC=NC(NC=2C=CC(=CC=2)S(=O)(=O)NCC2CC2)=N1 QSHDCKRJZSDIGZ-UHFFFAOYSA-N 0.000 claims 1
- DYOCFCUPENQNPU-UHFFFAOYSA-N n-cyclobutyl-4-[[4-(2,3-dimethylimidazol-4-yl)pyrimidin-2-yl]amino]benzenesulfonamide Chemical compound CN1C(C)=NC=C1C1=CC=NC(NC=2C=CC(=CC=2)S(=O)(=O)NC2CCC2)=N1 DYOCFCUPENQNPU-UHFFFAOYSA-N 0.000 claims 1
- YUBLGYSOQYIMIG-UHFFFAOYSA-N n-cyclopropyl-4-[[4-(2,3-dimethylimidazol-4-yl)pyrimidin-2-yl]amino]benzenesulfonamide Chemical compound CN1C(C)=NC=C1C1=CC=NC(NC=2C=CC(=CC=2)S(=O)(=O)NC2CC2)=N1 YUBLGYSOQYIMIG-UHFFFAOYSA-N 0.000 claims 1
- MDUHIEIIDZPVRB-UHFFFAOYSA-N n-cyclopropyl-4-[[4-(3-ethyl-2-methylimidazol-4-yl)pyrimidin-2-yl]amino]benzenesulfonamide Chemical compound CCN1C(C)=NC=C1C1=CC=NC(NC=2C=CC(=CC=2)S(=O)(=O)NC2CC2)=N1 MDUHIEIIDZPVRB-UHFFFAOYSA-N 0.000 claims 1
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 abstract 1
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 abstract 1
- 125000006592 (C2-C3) alkenyl group Chemical group 0.000 abstract 1
- 125000006593 (C2-C3) alkynyl group Chemical group 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 164
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 153
- 239000000203 mixture Substances 0.000 description 94
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 90
- 239000000243 solution Substances 0.000 description 77
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 53
- 238000001704 evaporation Methods 0.000 description 51
- 230000008020 evaporation Effects 0.000 description 51
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 49
- 235000019439 ethyl acetate Nutrition 0.000 description 45
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 38
- 239000002904 solvent Substances 0.000 description 36
- 238000006243 chemical reaction Methods 0.000 description 35
- 239000003039 volatile agent Substances 0.000 description 35
- 210000004027 cell Anatomy 0.000 description 33
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 31
- 125000005843 halogen group Chemical group 0.000 description 31
- CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 30
- 239000000741 silica gel Substances 0.000 description 30
- 229910002027 silica gel Inorganic materials 0.000 description 30
- 238000001914 filtration Methods 0.000 description 29
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- 125000002252 acyl group Chemical group 0.000 description 23
- 239000011541 reaction mixture Substances 0.000 description 23
- 239000012267 brine Substances 0.000 description 22
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 22
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
- 108010024986 Cyclin-Dependent Kinase 2 Proteins 0.000 description 21
- 102100036239 Cyclin-dependent kinase 2 Human genes 0.000 description 21
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
- 239000003921 oil Substances 0.000 description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
- 238000003818 flash chromatography Methods 0.000 description 20
- 238000004587 chromatography analysis Methods 0.000 description 19
- 108091007914 CDKs Proteins 0.000 description 18
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 18
- 238000010992 reflux Methods 0.000 description 17
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 16
- 238000004440 column chromatography Methods 0.000 description 16
- 239000003112 inhibitor Substances 0.000 description 16
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 16
- 241000282414 Homo sapiens Species 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 239000000284 extract Substances 0.000 description 15
- 239000000725 suspension Substances 0.000 description 15
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 14
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 14
- 230000000694 effects Effects 0.000 description 14
- 239000008177 pharmaceutical agent Substances 0.000 description 14
- 235000017557 sodium bicarbonate Nutrition 0.000 description 14
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 14
- 239000007864 aqueous solution Substances 0.000 description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- 125000006239 protecting group Chemical group 0.000 description 11
- 102000003909 Cyclin E Human genes 0.000 description 10
- 108090000257 Cyclin E Proteins 0.000 description 10
- 239000000706 filtrate Substances 0.000 description 10
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 10
- 108090000623 proteins and genes Proteins 0.000 description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 9
- 125000001424 substituent group Chemical group 0.000 description 9
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- 229960000583 acetic acid Drugs 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
- 125000004429 atom Chemical group 0.000 description 8
- 239000000872 buffer Substances 0.000 description 8
- 201000010099 disease Diseases 0.000 description 8
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 8
- 102000004169 proteins and genes Human genes 0.000 description 8
- 239000012265 solid product Substances 0.000 description 8
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 7
- 201000004384 Alopecia Diseases 0.000 description 7
- 108010025464 Cyclin-Dependent Kinase 4 Proteins 0.000 description 7
- 108010025468 Cyclin-Dependent Kinase 6 Proteins 0.000 description 7
- 102100036252 Cyclin-dependent kinase 4 Human genes 0.000 description 7
- 102100026804 Cyclin-dependent kinase 6 Human genes 0.000 description 7
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 125000001309 chloro group Chemical group Cl* 0.000 description 7
- 238000000605 extraction Methods 0.000 description 7
- 125000001153 fluoro group Chemical group F* 0.000 description 7
- 208000024963 hair loss Diseases 0.000 description 7
- 230000003676 hair loss Effects 0.000 description 7
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 7
- 239000002244 precipitate Substances 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 7
- KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 6
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 6
- 239000012044 organic layer Substances 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- 238000010561 standard procedure Methods 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- QAVCQCQQTYJKSO-UHFFFAOYSA-N 2-chloro-11-cyclopropyl-4-methyl-5h-dipyrido[2,3-b:2',3'-f][1,4]diazepin-6-one Chemical compound C12=NC=CC=C2C(=O)NC=2C(C)=CC(Cl)=NC=2N1C1CC1 QAVCQCQQTYJKSO-UHFFFAOYSA-N 0.000 description 5
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 5
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
- 230000018199 S phase Effects 0.000 description 5
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
- 239000007983 Tris buffer Substances 0.000 description 5
- 241000700605 Viruses Species 0.000 description 5
- 235000011114 ammonium hydroxide Nutrition 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 238000004090 dissolution Methods 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- DAZXVJBJRMWXJP-UHFFFAOYSA-N n,n-dimethylethylamine Chemical compound CCN(C)C DAZXVJBJRMWXJP-UHFFFAOYSA-N 0.000 description 5
- 150000003230 pyrimidines Chemical class 0.000 description 5
- 229910052708 sodium Inorganic materials 0.000 description 5
- 239000012312 sodium hydride Substances 0.000 description 5
- 229910000104 sodium hydride Inorganic materials 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 4
- DWLMIHRZURMFAQ-UHFFFAOYSA-N 2-(3-chlorophenyl)guanidine Chemical compound NC(N)=NC1=CC=CC(Cl)=C1 DWLMIHRZURMFAQ-UHFFFAOYSA-N 0.000 description 4
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 4
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 4
- XKPFKMJJVRQAPO-UHFFFAOYSA-N 4-(2,3-dimethylimidazol-4-yl)pyrimidin-2-amine Chemical compound CN1C(C)=NC=C1C1=CC=NC(N)=N1 XKPFKMJJVRQAPO-UHFFFAOYSA-N 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin 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 4
- 239000007995 HEPES buffer Substances 0.000 description 4
- 239000002841 Lewis acid Substances 0.000 description 4
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
- ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 4
- 230000001093 anti-cancer Effects 0.000 description 4
- 125000003435 aroyl group Chemical group 0.000 description 4
- 239000012298 atmosphere Substances 0.000 description 4
- XDSYAIICRRZSJX-UHFFFAOYSA-N carbamimidoyl(phenyl)azanium;hydrogen carbonate Chemical compound OC(O)=O.NC(N)=NC1=CC=CC=C1 XDSYAIICRRZSJX-UHFFFAOYSA-N 0.000 description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 230000001684 chronic effect Effects 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 239000003102 growth factor Substances 0.000 description 4
- 230000007062 hydrolysis Effects 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- 125000000842 isoxazolyl group Chemical group 0.000 description 4
- 150000007517 lewis acids Chemical class 0.000 description 4
- REPVNSJSTLRQEQ-UHFFFAOYSA-N n,n-dimethylacetamide;n,n-dimethylformamide Chemical compound CN(C)C=O.CN(C)C(C)=O REPVNSJSTLRQEQ-UHFFFAOYSA-N 0.000 description 4
- FYGTYCKLWZVDDV-UHFFFAOYSA-N n-(3-chlorophenyl)-4-(1-tritylimidazol-4-yl)pyrimidin-2-amine Chemical compound ClC1=CC=CC(NC=2N=C(C=CN=2)C=2N=CN(C=2)C(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 FYGTYCKLWZVDDV-UHFFFAOYSA-N 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 125000004076 pyridyl group Chemical group 0.000 description 4
- 239000011593 sulfur Substances 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- YISBSCKPBDXRLO-UHFFFAOYSA-N 1-(2-methyl-1-tritylimidazol-4-yl)ethanone Chemical compound CC1=NC(C(=O)C)=CN1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 YISBSCKPBDXRLO-UHFFFAOYSA-N 0.000 description 3
- GVAHJJWRUPHVGW-UHFFFAOYSA-N 3-(dimethylamino)-1-(2,3-dimethylimidazol-4-yl)prop-2-en-1-one Chemical compound CN(C)C=CC(=O)C1=CN=C(C)N1C GVAHJJWRUPHVGW-UHFFFAOYSA-N 0.000 description 3
- DAUUUCULWCEHGZ-UHFFFAOYSA-N 4-(3-ethyl-2-methylimidazol-4-yl)-n-phenylpyrimidin-2-amine Chemical compound CCN1C(C)=NC=C1C1=CC=NC(NC=2C=CC=CC=2)=N1 DAUUUCULWCEHGZ-UHFFFAOYSA-N 0.000 description 3
- UAKCGBGWTHBQPH-UHFFFAOYSA-N 4-(3-methylimidazol-4-yl)-n-phenylpyrimidin-2-amine Chemical compound CN1C=NC=C1C1=CC=NC(NC=2C=CC=CC=2)=N1 UAKCGBGWTHBQPH-UHFFFAOYSA-N 0.000 description 3
- FTBCOQFMQSTCQQ-UHFFFAOYSA-N 4-bromobenzenethiol Chemical compound SC1=CC=C(Br)C=C1 FTBCOQFMQSTCQQ-UHFFFAOYSA-N 0.000 description 3
- MRCSGMSWDXJCPY-UHFFFAOYSA-N 4-iodo-n-(2-methoxyethyl)benzenesulfonamide Chemical compound COCCNS(=O)(=O)C1=CC=C(I)C=C1 MRCSGMSWDXJCPY-UHFFFAOYSA-N 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 108010039627 Aprotinin Proteins 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 241000588724 Escherichia coli Species 0.000 description 3
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 3
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 3
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 3
- 108091000080 Phosphotransferase Proteins 0.000 description 3
- 239000004743 Polypropylene Substances 0.000 description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
- 229960004405 aprotinin Drugs 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 3
- 229910000024 caesium carbonate Inorganic materials 0.000 description 3
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 3
- 229940088598 enzyme Drugs 0.000 description 3
- 239000006260 foam Substances 0.000 description 3
- 239000012362 glacial acetic acid Substances 0.000 description 3
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 3
- 238000005984 hydrogenation reaction Methods 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 3
- 239000011630 iodine Substances 0.000 description 3
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 3
- 108010052968 leupeptin Proteins 0.000 description 3
- 239000002480 mineral oil Substances 0.000 description 3
- 235000010446 mineral oil Nutrition 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 125000002950 monocyclic group Chemical group 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 150000007530 organic bases Chemical class 0.000 description 3
- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 102000020233 phosphotransferase Human genes 0.000 description 3
- 229920001155 polypropylene Polymers 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 235000011181 potassium carbonates Nutrition 0.000 description 3
- 125000003373 pyrazinyl group Chemical group 0.000 description 3
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000002594 sorbent Substances 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 125000004434 sulfur atom Chemical group 0.000 description 3
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 3
- 230000009885 systemic effect Effects 0.000 description 3
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 3
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 3
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 3
- FUOSTELFLYZQCW-UHFFFAOYSA-N 1,2-oxazol-3-one Chemical compound OC=1C=CON=1 FUOSTELFLYZQCW-UHFFFAOYSA-N 0.000 description 2
- WMKGGPCROCCUDY-UHFFFAOYSA-N 1,5-diphenylpenta-1,4-dien-3-one Chemical compound C=1C=CC=CC=1C=CC(=O)C=CC1=CC=CC=C1 WMKGGPCROCCUDY-UHFFFAOYSA-N 0.000 description 2
- APWRZPQBPCAXFP-UHFFFAOYSA-N 1-(1-oxo-2H-isoquinolin-5-yl)-5-(trifluoromethyl)-N-[2-(trifluoromethyl)pyridin-4-yl]pyrazole-4-carboxamide Chemical compound O=C1NC=CC2=C(C=CC=C12)N1N=CC(=C1C(F)(F)F)C(=O)NC1=CC(=NC=C1)C(F)(F)F APWRZPQBPCAXFP-UHFFFAOYSA-N 0.000 description 2
- CXHBDLBUHRTUCX-UHFFFAOYSA-N 1-(1-tritylimidazol-4-yl)ethanone Chemical compound C1=NC(C(=O)C)=CN1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 CXHBDLBUHRTUCX-UHFFFAOYSA-N 0.000 description 2
- UELKIIFZVNFDDY-UHFFFAOYSA-N 1-bromo-4-(3,3,3-trifluoropropylsulfanyl)benzene Chemical compound FC(F)(F)CCSC1=CC=C(Br)C=C1 UELKIIFZVNFDDY-UHFFFAOYSA-N 0.000 description 2
- SBASXUCJHJRPEV-UHFFFAOYSA-N 2-(2-methoxyethoxy)ethanol Chemical compound COCCOCCO SBASXUCJHJRPEV-UHFFFAOYSA-N 0.000 description 2
- UZPIRAFSNIRTDY-UHFFFAOYSA-N 2-(2-methyl-1-tritylimidazol-4-yl)ethanol Chemical compound CC1=NC(CCO)=CN1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 UZPIRAFSNIRTDY-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 2
- MNKMNMXRPSSOIY-UHFFFAOYSA-N 2-[2-[5-[2-(3-chloroanilino)pyrimidin-4-yl]imidazol-1-yl]ethyl]isoindole-1,3-dione Chemical compound ClC1=CC=CC(NC=2N=C(C=CN=2)C=2N(C=NC=2)CCN2C(C3=CC=CC=C3C2=O)=O)=C1 MNKMNMXRPSSOIY-UHFFFAOYSA-N 0.000 description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 2
- ZPVPPQGNYLYSRQ-UHFFFAOYSA-N 3-(4-bromophenyl)sulfanyl-n,n-dimethylpropan-1-amine Chemical compound CN(C)CCCSC1=CC=C(Br)C=C1 ZPVPPQGNYLYSRQ-UHFFFAOYSA-N 0.000 description 2
- FAXDZWQIWUSWJH-UHFFFAOYSA-N 3-methoxypropan-1-amine Chemical compound COCCCN FAXDZWQIWUSWJH-UHFFFAOYSA-N 0.000 description 2
- QMEHPLCOBIOVAP-UHFFFAOYSA-N 4-(2,3-dimethylimidazol-4-yl)-n-phenylpyrimidin-2-amine Chemical compound CN1C(C)=NC=C1C1=CC=NC(NC=2C=CC=CC=2)=N1 QMEHPLCOBIOVAP-UHFFFAOYSA-N 0.000 description 2
- GEKVGYUULFDKLT-UHFFFAOYSA-N 4-(2-methyl-1h-imidazol-5-yl)-n-phenylpyrimidin-2-amine Chemical compound N1C(C)=NC=C1C1=CC=NC(NC=2C=CC=CC=2)=N1 GEKVGYUULFDKLT-UHFFFAOYSA-N 0.000 description 2
- MUIGUCQQCWKTFW-UHFFFAOYSA-N 4-[3-(2-aminoethyl)imidazol-4-yl]-n-(3-chlorophenyl)pyrimidin-2-amine Chemical compound NCCN1C=NC=C1C1=CC=NC(NC=2C=C(Cl)C=CC=2)=N1 MUIGUCQQCWKTFW-UHFFFAOYSA-N 0.000 description 2
- XYZNJJAFIUQYLC-UHFFFAOYSA-N 4-[[4-(2,3-dimethylimidazol-4-yl)pyrimidin-2-yl]amino]-n-(2-methoxyethyl)benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)NCCOC)=CC=C1NC1=NC=CC(C=2N(C(C)=NC=2)C)=N1 XYZNJJAFIUQYLC-UHFFFAOYSA-N 0.000 description 2
- MDQRGAHTHCBASJ-UHFFFAOYSA-N 4-[[4-(2,3-dimethylimidazol-4-yl)pyrimidin-2-yl]amino]benzenesulfonyl fluoride Chemical compound CN1C(C)=NC=C1C1=CC=NC(NC=2C=CC(=CC=2)S(F)(=O)=O)=N1 MDQRGAHTHCBASJ-UHFFFAOYSA-N 0.000 description 2
- XVGUXFWBYAHLPP-UHFFFAOYSA-N 4-amino-n-[3-(2-oxopyrrolidin-1-yl)propyl]benzenesulfonamide Chemical compound C1=CC(N)=CC=C1S(=O)(=O)NCCCN1C(=O)CCC1 XVGUXFWBYAHLPP-UHFFFAOYSA-N 0.000 description 2
- OISQSDKFWKJEBA-UHFFFAOYSA-N 4-amino-n-methylbenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(N)C=C1 OISQSDKFWKJEBA-UHFFFAOYSA-N 0.000 description 2
- XFAREXHITCIFFQ-UHFFFAOYSA-N 4-n-[4-(2,3-dimethylimidazol-4-yl)pyrimidin-2-yl]benzene-1,4-diamine Chemical compound CN1C(C)=NC=C1C1=CC=NC(NC=2C=CC(N)=CC=2)=N1 XFAREXHITCIFFQ-UHFFFAOYSA-N 0.000 description 2
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 2
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 description 2
- 102000016736 Cyclin Human genes 0.000 description 2
- 108050006400 Cyclin Proteins 0.000 description 2
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 2
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 2
- 108010092160 Dactinomycin Proteins 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 2
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 108010024636 Glutathione Proteins 0.000 description 2
- 241000238631 Hexapoda Species 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 239000005909 Kieselgur Substances 0.000 description 2
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 2
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol 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 2
- AHVYPIQETPWLSZ-UHFFFAOYSA-N N-methyl-pyrrolidine Natural products CN1CC=CC1 AHVYPIQETPWLSZ-UHFFFAOYSA-N 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 229930012538 Paclitaxel Natural products 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 2
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 2
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 2
- 229940100198 alkylating agent Drugs 0.000 description 2
- 239000002168 alkylating agent Substances 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- XYXNTHIYBIDHGM-UHFFFAOYSA-N ammonium thiosulfate Chemical compound [NH4+].[NH4+].[O-]S([O-])(=O)=S XYXNTHIYBIDHGM-UHFFFAOYSA-N 0.000 description 2
- 150000001448 anilines Chemical class 0.000 description 2
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
- 230000000340 anti-metabolite Effects 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 229940100197 antimetabolite Drugs 0.000 description 2
- 239000002256 antimetabolite Substances 0.000 description 2
- 238000007080 aromatic substitution reaction Methods 0.000 description 2
- 125000005101 aryl methoxy carbonyl group Chemical group 0.000 description 2
- 125000005002 aryl methyl group Chemical group 0.000 description 2
- 125000002619 bicyclic group Chemical group 0.000 description 2
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical group 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 2
- 230000000711 cancerogenic effect Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 231100000315 carcinogenic Toxicity 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 239000012230 colorless oil Substances 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 229960004397 cyclophosphamide Drugs 0.000 description 2
- 229960000640 dactinomycin Drugs 0.000 description 2
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin 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(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 229960004679 doxorubicin Drugs 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000009977 dual effect Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 2
- 229960005420 etoposide Drugs 0.000 description 2
- 229960002949 fluorouracil Drugs 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 229960003180 glutathione Drugs 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 229960001101 ifosfamide Drugs 0.000 description 2
- HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 238000005342 ion exchange Methods 0.000 description 2
- 125000001786 isothiazolyl group Chemical group 0.000 description 2
- 208000017169 kidney disease Diseases 0.000 description 2
- 229940043355 kinase inhibitor Drugs 0.000 description 2
- 239000012139 lysis buffer Substances 0.000 description 2
- 229910001629 magnesium chloride Inorganic materials 0.000 description 2
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
- 238000001819 mass spectrum Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 229960000485 methotrexate Drugs 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 229960004857 mitomycin Drugs 0.000 description 2
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- 231100000590 oncogenic Toxicity 0.000 description 2
- 230000002246 oncogenic effect Effects 0.000 description 2
- 125000002971 oxazolyl group Chemical group 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 229960001592 paclitaxel Drugs 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 229950000964 pepstatin Drugs 0.000 description 2
- 108010091212 pepstatin Proteins 0.000 description 2
- FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 2
- 125000005544 phthalimido group Chemical group 0.000 description 2
- 125000004193 piperazinyl group Chemical group 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 2
- 239000012264 purified product Substances 0.000 description 2
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 description 2
- 125000001422 pyrrolinyl group Chemical group 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 2
- 238000001179 sorption measurement Methods 0.000 description 2
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 2
- DBQNXSQYHOYDCO-UHFFFAOYSA-N tert-butyl n-[2-(1,2-oxazol-3-yloxy)ethyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCOC=1C=CON=1 DBQNXSQYHOYDCO-UHFFFAOYSA-N 0.000 description 2
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 125000001984 thiazolidinyl group Chemical group 0.000 description 2
- 125000000335 thiazolyl group Chemical group 0.000 description 2
- 125000003396 thiol group Chemical group [H]S* 0.000 description 2
- 238000011200 topical administration Methods 0.000 description 2
- 229960000303 topotecan Drugs 0.000 description 2
- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 2
- 229960004528 vincristine Drugs 0.000 description 2
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 2
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- 125000006621 (C3-C8) cycloalkyl-(C1-C6) alkyl group Chemical group 0.000 description 1
- LKJPYSCBVHEWIU-KRWDZBQOSA-N (R)-bicalutamide Chemical compound C([C@@](O)(C)C(=O)NC=1C=C(C(C#N)=CC=1)C(F)(F)F)S(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-KRWDZBQOSA-N 0.000 description 1
- MUHCEAIVGKVBHE-UHFFFAOYSA-N 1,2,5-thiadiazol-3-one Chemical compound OC=1C=NSN=1 MUHCEAIVGKVBHE-UHFFFAOYSA-N 0.000 description 1
- 125000004517 1,2,5-thiadiazolyl group Chemical group 0.000 description 1
- GIWQSPITLQVMSG-UHFFFAOYSA-N 1,2-dimethylimidazole Chemical compound CC1=NC=CN1C GIWQSPITLQVMSG-UHFFFAOYSA-N 0.000 description 1
- 125000005871 1,3-benzodioxolyl group Chemical group 0.000 description 1
- JPRPJUMQRZTTED-UHFFFAOYSA-N 1,3-dioxolanyl Chemical group [CH]1OCCO1 JPRPJUMQRZTTED-UHFFFAOYSA-N 0.000 description 1
- NOLHRFLIXVQPSZ-UHFFFAOYSA-N 1,3-thiazolidin-4-one Chemical compound O=C1CSCN1 NOLHRFLIXVQPSZ-UHFFFAOYSA-N 0.000 description 1
- 125000005940 1,4-dioxanyl group Chemical group 0.000 description 1
- AMCBMIZVYBLKQA-UHFFFAOYSA-N 1-(1-tritylimidazol-4-yl)ethanol Chemical compound C1=NC(C(O)C)=CN1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 AMCBMIZVYBLKQA-UHFFFAOYSA-N 0.000 description 1
- MZJZNADJWQEIIG-UHFFFAOYSA-N 1-(2-methyl-1h-imidazol-5-yl)ethanone Chemical compound CC(=O)C1=CN=C(C)N1 MZJZNADJWQEIIG-UHFFFAOYSA-N 0.000 description 1
- HJORCZCMNWLHMB-UHFFFAOYSA-N 1-(3-aminopropyl)pyrrolidin-2-one Chemical compound NCCCN1CCCC1=O HJORCZCMNWLHMB-UHFFFAOYSA-N 0.000 description 1
- LGCYNMXZSRVKIH-UHFFFAOYSA-N 1-(3-but-3-enyl-2-methylimidazol-4-yl)ethanone Chemical compound CC(=O)C1=CN=C(C)N1CCC=C LGCYNMXZSRVKIH-UHFFFAOYSA-N 0.000 description 1
- FMHKREROEFVVOL-UHFFFAOYSA-N 1-(3-ethyl-2-methylimidazol-4-yl)ethanone Chemical compound CCN1C(C)=NC=C1C(C)=O FMHKREROEFVVOL-UHFFFAOYSA-N 0.000 description 1
- DBBKCUGGTZSDJD-UHFFFAOYSA-N 1-(3-methylimidazol-4-yl)ethanol Chemical compound CC(O)C1=CN=CN1C DBBKCUGGTZSDJD-UHFFFAOYSA-N 0.000 description 1
- BYEDDTKLQQQEQP-UHFFFAOYSA-N 1-[3-(2-methoxyethyl)-2-methylimidazol-4-yl]ethanone Chemical compound COCCN1C(C)=NC=C1C(C)=O BYEDDTKLQQQEQP-UHFFFAOYSA-N 0.000 description 1
- NVZZKSUKAQCUDG-UHFFFAOYSA-N 1-bromo-4-(3,3,3-trifluoropropylsulfonyl)benzene Chemical compound FC(F)(F)CCS(=O)(=O)C1=CC=C(Br)C=C1 NVZZKSUKAQCUDG-UHFFFAOYSA-N 0.000 description 1
- SFRFMJYOARYANS-UHFFFAOYSA-N 1-bromo-4-(3-methoxypropylsulfonyl)benzene Chemical compound COCCCS(=O)(=O)C1=CC=C(Br)C=C1 SFRFMJYOARYANS-UHFFFAOYSA-N 0.000 description 1
- BRGVKVZXDWGJBX-UHFFFAOYSA-N 1-bromo-4-butylbenzene Chemical compound CCCCC1=CC=C(Br)C=C1 BRGVKVZXDWGJBX-UHFFFAOYSA-N 0.000 description 1
- JFOOLODLNJPCDW-UHFFFAOYSA-N 1-bromo-4-butylsulfonylbenzene Chemical compound CCCCS(=O)(=O)C1=CC=C(Br)C=C1 JFOOLODLNJPCDW-UHFFFAOYSA-N 0.000 description 1
- YEUYZNNBXLMFCW-UHFFFAOYSA-N 1-bromo-4-methylsulfanylbenzene Chemical compound CSC1=CC=C(Br)C=C1 YEUYZNNBXLMFCW-UHFFFAOYSA-N 0.000 description 1
- FJLFSYRGFJDJMQ-UHFFFAOYSA-N 1-bromo-4-methylsulfonylbenzene Chemical compound CS(=O)(=O)C1=CC=C(Br)C=C1 FJLFSYRGFJDJMQ-UHFFFAOYSA-N 0.000 description 1
- AVFZOVWCLRSYKC-UHFFFAOYSA-N 1-methylpyrrolidine Chemical compound CN1CCCC1 AVFZOVWCLRSYKC-UHFFFAOYSA-N 0.000 description 1
- 125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000006017 1-propenyl group Chemical group 0.000 description 1
- 125000000530 1-propynyl group Chemical group [H]C([H])([H])C#C* 0.000 description 1
- XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 description 1
- TWRUAOUDLJOMMI-UHFFFAOYSA-N 2-(1,2-oxazol-3-yloxy)ethanamine;hydrochloride Chemical compound Cl.NCCOC=1C=CON=1 TWRUAOUDLJOMMI-UHFFFAOYSA-N 0.000 description 1
- GPMQSZDCZSXGCH-UHFFFAOYSA-N 2-(2-methyl-1h-imidazol-5-yl)ethanol Chemical compound CC1=NC(CCO)=CN1 GPMQSZDCZSXGCH-UHFFFAOYSA-N 0.000 description 1
- WOXFMYVTSLAQMO-UHFFFAOYSA-N 2-Pyridinemethanamine Chemical compound NCC1=CC=CC=N1 WOXFMYVTSLAQMO-UHFFFAOYSA-N 0.000 description 1
- WKNMKGVLOWGGOU-UHFFFAOYSA-N 2-aminoacetamide;hydron;chloride Chemical compound Cl.NCC(N)=O WKNMKGVLOWGGOU-UHFFFAOYSA-N 0.000 description 1
- AXAVXPMQTGXXJZ-UHFFFAOYSA-N 2-aminoacetic acid;2-amino-2-(hydroxymethyl)propane-1,3-diol Chemical compound NCC(O)=O.OCC(N)(CO)CO AXAVXPMQTGXXJZ-UHFFFAOYSA-N 0.000 description 1
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- ASUDFOJKTJLAIK-UHFFFAOYSA-N 2-methoxyethanamine Chemical compound COCCN ASUDFOJKTJLAIK-UHFFFAOYSA-N 0.000 description 1
- XCVDRKJGVQKLMR-UHFFFAOYSA-N 2-methoxyethyl trifluoromethanesulfonate Chemical compound COCCOS(=O)(=O)C(F)(F)F XCVDRKJGVQKLMR-UHFFFAOYSA-N 0.000 description 1
- ZWULFIBGPXWGFG-UHFFFAOYSA-N 2-methyl-1h-imidazole-5-carbaldehyde Chemical compound CC1=NC=C(C=O)N1 ZWULFIBGPXWGFG-UHFFFAOYSA-N 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- QRJZGVVKGFIGLI-UHFFFAOYSA-N 2-phenylguanidine Chemical compound NC(=N)NC1=CC=CC=C1 QRJZGVVKGFIGLI-UHFFFAOYSA-N 0.000 description 1
- NDMPLJNOPCLANR-UHFFFAOYSA-N 3,4-dihydroxy-15-(4-hydroxy-18-methoxycarbonyl-5,18-seco-ibogamin-18-yl)-16-methoxy-1-methyl-6,7-didehydro-aspidospermidine-3-carboxylic acid methyl ester Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 NDMPLJNOPCLANR-UHFFFAOYSA-N 0.000 description 1
- HCDMJFOHIXMBOV-UHFFFAOYSA-N 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one Chemical compound C=1C2=C3N(CC)C(=O)N(C=4C(=C(OC)C=C(OC)C=4F)F)CC3=CN=C2NC=1CN1CCOCC1 HCDMJFOHIXMBOV-UHFFFAOYSA-N 0.000 description 1
- YGRACZUPGBWHJA-UHFFFAOYSA-N 3-(4-bromophenyl)sulfonyl-n,n-dimethylpropan-1-amine Chemical compound CN(C)CCCS(=O)(=O)C1=CC=C(Br)C=C1 YGRACZUPGBWHJA-UHFFFAOYSA-N 0.000 description 1
- IZBKLEBLCPWCQI-UHFFFAOYSA-N 3-(dimethylamino)-1-(2-methyl-1h-imidazol-5-yl)prop-2-en-1-one Chemical compound CN(C)C=CC(=O)C1=CN=C(C)N1 IZBKLEBLCPWCQI-UHFFFAOYSA-N 0.000 description 1
- SRVXSISGYBMIHR-UHFFFAOYSA-N 3-[3-[3-(2-amino-2-oxoethyl)phenyl]-5-chlorophenyl]-3-(5-methyl-1,3-thiazol-2-yl)propanoic acid Chemical compound S1C(C)=CN=C1C(CC(O)=O)C1=CC(Cl)=CC(C=2C=C(CC(N)=O)C=CC=2)=C1 SRVXSISGYBMIHR-UHFFFAOYSA-N 0.000 description 1
- OYWXYRRKTGPYJB-UHFFFAOYSA-N 3-benzyl-2-methylimidazole-4-carbaldehyde Chemical compound CC1=NC=C(C=O)N1CC1=CC=CC=C1 OYWXYRRKTGPYJB-UHFFFAOYSA-N 0.000 description 1
- SAUGMJLWYLQPEM-UHFFFAOYSA-N 3-bromo-1,1,1-trifluoropropane Chemical compound FC(F)(F)CCBr SAUGMJLWYLQPEM-UHFFFAOYSA-N 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- JDFDHBSESGTDAL-UHFFFAOYSA-N 3-methoxypropan-1-ol Chemical compound COCCCO JDFDHBSESGTDAL-UHFFFAOYSA-N 0.000 description 1
- BNYKZFOZWZMEJD-UHFFFAOYSA-N 3-methylimidazole-4-carbaldehyde Chemical compound CN1C=NC=C1C=O BNYKZFOZWZMEJD-UHFFFAOYSA-N 0.000 description 1
- UIKUBYKUYUSRSM-UHFFFAOYSA-N 3-morpholinopropylamine Chemical compound NCCCN1CCOCC1 UIKUBYKUYUSRSM-UHFFFAOYSA-N 0.000 description 1
- AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin 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-VTZDEGQISA-N 0.000 description 1
- TZNBHFIWOSIMED-UHFFFAOYSA-N 4-(3-benzyl-2-methylimidazol-4-yl)-n-(3-chlorophenyl)pyrimidin-2-amine Chemical compound C=1C=CC=CC=1CN1C(C)=NC=C1C(N=1)=CC=NC=1NC1=CC=CC(Cl)=C1 TZNBHFIWOSIMED-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- COSQYHQHMYBDLB-UHFFFAOYSA-N 4-[[4-(2,3-dimethylimidazol-4-yl)pyrimidin-2-yl]amino]-n-(2-methylsulfonylethyl)benzenesulfonamide Chemical compound CN1C(C)=NC=C1C1=CC=NC(NC=2C=CC(=CC=2)S(=O)(=O)NCCS(C)(=O)=O)=N1 COSQYHQHMYBDLB-UHFFFAOYSA-N 0.000 description 1
- WZTZNANCAAYIJE-UHFFFAOYSA-N 4-[[4-(2,3-dimethylimidazol-4-yl)pyrimidin-2-yl]amino]-n-[2-(2-methoxyethoxy)ethyl]benzenesulfonamide;hydrochloride Chemical compound Cl.C1=CC(S(=O)(=O)NCCOCCOC)=CC=C1NC1=NC=CC(C=2N(C(C)=NC=2)C)=N1 WZTZNANCAAYIJE-UHFFFAOYSA-N 0.000 description 1
- GSUPOCRGRUJTTN-UHFFFAOYSA-N 4-[[4-(2,3-dimethylimidazol-4-yl)pyrimidin-2-yl]amino]-n-[3-(2-oxopyrrolidin-1-yl)propyl]benzenesulfonamide Chemical compound CN1C(C)=NC=C1C1=CC=NC(NC=2C=CC(=CC=2)S(=O)(=O)NCCCN2C(CCC2)=O)=N1 GSUPOCRGRUJTTN-UHFFFAOYSA-N 0.000 description 1
- MYLOKGPRUSRDBK-UHFFFAOYSA-N 4-[[4-(2,3-dimethylimidazol-4-yl)pyrimidin-2-yl]amino]-n-methylbenzenesulfonamide Chemical compound C1=CC(S(=O)(=O)NC)=CC=C1NC1=NC=CC(C=2N(C(C)=NC=2)C)=N1 MYLOKGPRUSRDBK-UHFFFAOYSA-N 0.000 description 1
- UQEPZHPATDPKPO-UHFFFAOYSA-N 4-[[4-(2,3-dimethylimidazol-4-yl)pyrimidin-2-yl]amino]benzenesulfonamide Chemical compound CN1C(C)=NC=C1C1=CC=NC(NC=2C=CC(=CC=2)S(N)(=O)=O)=N1 UQEPZHPATDPKPO-UHFFFAOYSA-N 0.000 description 1
- IQSFAMSAFMMKSL-UHFFFAOYSA-N 4-[[4-(2-methyl-1h-imidazol-5-yl)pyrimidin-2-yl]amino]benzenesulfonamide Chemical compound N1C(C)=NC=C1C1=CC=NC(NC=2C=CC(=CC=2)S(N)(=O)=O)=N1 IQSFAMSAFMMKSL-UHFFFAOYSA-N 0.000 description 1
- WQWSTOXCTQPWKG-UHFFFAOYSA-N 4-[[4-(3-ethyl-2-methylimidazol-4-yl)pyrimidin-2-yl]amino]-n-(2-hydroxyethyl)benzenesulfonamide Chemical compound CCN1C(C)=NC=C1C1=CC=NC(NC=2C=CC(=CC=2)S(=O)(=O)NCCO)=N1 WQWSTOXCTQPWKG-UHFFFAOYSA-N 0.000 description 1
- BNKGWLVOGWKWGS-UHFFFAOYSA-N 4-[[4-(3-ethyl-2-methylimidazol-4-yl)pyrimidin-2-yl]amino]-n-[2-(2-hydroxyethoxy)ethyl]benzenesulfonamide Chemical compound CCN1C(C)=NC=C1C1=CC=NC(NC=2C=CC(=CC=2)S(=O)(=O)NCCOCCO)=N1 BNKGWLVOGWKWGS-UHFFFAOYSA-N 0.000 description 1
- ICIBYHFYXSNHTA-UHFFFAOYSA-N 4-[[4-(3-methylimidazol-4-yl)pyrimidin-2-yl]amino]benzenesulfonamide Chemical compound CN1C=NC=C1C1=CC=NC(NC=2C=CC(=CC=2)S(N)(=O)=O)=N1 ICIBYHFYXSNHTA-UHFFFAOYSA-N 0.000 description 1
- MKVPNBXOJZSBRW-UHFFFAOYSA-N 4-[[4-[3-(2-methoxyethyl)-2-methylimidazol-4-yl]pyrimidin-2-yl]amino]-n-(oxolan-2-ylmethyl)benzenesulfonamide Chemical compound COCCN1C(C)=NC=C1C1=CC=NC(NC=2C=CC(=CC=2)S(=O)(=O)NCC2OCCC2)=N1 MKVPNBXOJZSBRW-UHFFFAOYSA-N 0.000 description 1
- CXOIRUKCQXCKPR-UHFFFAOYSA-N 4-[[5-bromo-4-(2,3-dimethylimidazol-4-yl)pyrimidin-2-yl]amino]-n-(2-methoxyethyl)benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)NCCOC)=CC=C1NC1=NC=C(Br)C(C=2N(C(C)=NC=2)C)=N1 CXOIRUKCQXCKPR-UHFFFAOYSA-N 0.000 description 1
- QHXRYOSNKJOSGW-UHFFFAOYSA-N 4-[[5-bromo-4-(3-methylimidazol-4-yl)pyrimidin-2-yl]amino]benzenesulfonamide Chemical compound CN1C=NC=C1C1=NC(NC=2C=CC(=CC=2)S(N)(=O)=O)=NC=C1Br QHXRYOSNKJOSGW-UHFFFAOYSA-N 0.000 description 1
- ZVFHXORCDVURDC-UHFFFAOYSA-N 4-[[5-chloro-4-(2,3-dimethylimidazol-4-yl)pyrimidin-2-yl]amino]benzenesulfonamide Chemical compound CN1C(C)=NC=C1C1=NC(NC=2C=CC(=CC=2)S(N)(=O)=O)=NC=C1Cl ZVFHXORCDVURDC-UHFFFAOYSA-N 0.000 description 1
- RLHGHGNMIHBMIM-UHFFFAOYSA-N 4-[[5-chloro-4-(3-ethyl-2-methylimidazol-4-yl)pyrimidin-2-yl]amino]-n-(2-methoxyethyl)benzenesulfonamide Chemical compound CCN1C(C)=NC=C1C1=NC(NC=2C=CC(=CC=2)S(=O)(=O)NCCOC)=NC=C1Cl RLHGHGNMIHBMIM-UHFFFAOYSA-N 0.000 description 1
- BLFRQYKZFKYQLO-UHFFFAOYSA-N 4-aminobutan-1-ol Chemical compound NCCCCO BLFRQYKZFKYQLO-UHFFFAOYSA-N 0.000 description 1
- GCNTZFIIOFTKIY-UHFFFAOYSA-N 4-hydroxypyridine Chemical compound OC1=CC=NC=C1 GCNTZFIIOFTKIY-UHFFFAOYSA-N 0.000 description 1
- WEFGQYOIWCQPST-UHFFFAOYSA-N 4-iodo-n-(3-morpholin-4-ylpropyl)benzenesulfonamide Chemical compound C1=CC(I)=CC=C1S(=O)(=O)NCCCN1CCOCC1 WEFGQYOIWCQPST-UHFFFAOYSA-N 0.000 description 1
- HIHXBQSAMAPHMI-UHFFFAOYSA-N 4-iodo-n-[2-(methoxymethoxy)ethyl]benzenesulfonamide Chemical compound COCOCCNS(=O)(=O)C1=CC=C(I)C=C1 HIHXBQSAMAPHMI-UHFFFAOYSA-N 0.000 description 1
- KQZFABSTXSNEQH-UHFFFAOYSA-N 4-iodobenzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=C(I)C=C1 KQZFABSTXSNEQH-UHFFFAOYSA-N 0.000 description 1
- POXFXTSTVWDWIR-UHFFFAOYSA-N 4-iodobenzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=C(I)C=C1 POXFXTSTVWDWIR-UHFFFAOYSA-N 0.000 description 1
- ATWMMWPERDAQSC-UHFFFAOYSA-N 4-iodobenzenesulfonyl fluoride Chemical compound FS(=O)(=O)C1=CC=C(I)C=C1 ATWMMWPERDAQSC-UHFFFAOYSA-N 0.000 description 1
- QSNLDUOQYSMBMI-UHFFFAOYSA-N 5-bromo-4-(2,3-dimethylimidazol-4-yl)pyrimidin-2-amine Chemical compound CN1C(C)=NC=C1C1=NC(N)=NC=C1Br QSNLDUOQYSMBMI-UHFFFAOYSA-N 0.000 description 1
- SBQNLTUOJQMPKQ-UHFFFAOYSA-N 5-chloro-4-(2,3-dimethylimidazol-4-yl)pyrimidin-2-amine Chemical compound CN1C(C)=NC=C1C1=NC(N)=NC=C1Cl SBQNLTUOJQMPKQ-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 101000606657 Arabidopsis thaliana Peroxidase 56 Proteins 0.000 description 1
- BFYIZQONLCFLEV-DAELLWKTSA-N Aromasine Chemical compound O=C1C=C[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC(=C)C2=C1 BFYIZQONLCFLEV-DAELLWKTSA-N 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- XJUZRXYOEPSWMB-UHFFFAOYSA-N Chloromethyl methyl ether Chemical compound COCCl XJUZRXYOEPSWMB-UHFFFAOYSA-N 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 208000003322 Coinfection Diseases 0.000 description 1
- 102000002554 Cyclin A Human genes 0.000 description 1
- 108010068192 Cyclin A Proteins 0.000 description 1
- 102100032857 Cyclin-dependent kinase 1 Human genes 0.000 description 1
- 101710106279 Cyclin-dependent kinase 1 Proteins 0.000 description 1
- HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 229940123780 DNA topoisomerase I inhibitor Drugs 0.000 description 1
- WEAHRLBPCANXCN-UHFFFAOYSA-N Daunomycin Natural products CCC1(O)CC(OC2CC(N)C(O)C(C)O2)c3cc4C(=O)c5c(OC)cccc5C(=O)c4c(O)c3C1 WEAHRLBPCANXCN-UHFFFAOYSA-N 0.000 description 1
- ZQZFYGIXNQKOAV-OCEACIFDSA-N Droloxifene Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=C(O)C=CC=1)\C1=CC=C(OCCN(C)C)C=C1 ZQZFYGIXNQKOAV-OCEACIFDSA-N 0.000 description 1
- HTIJFSOGRVMCQR-UHFFFAOYSA-N Epirubicin Natural products COc1cccc2C(=O)c3c(O)c4CC(O)(CC(OC5CC(N)C(=O)C(C)O5)c4c(O)c3C(=O)c12)C(=O)CO HTIJFSOGRVMCQR-UHFFFAOYSA-N 0.000 description 1
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 230000010337 G2 phase Effects 0.000 description 1
- BLCLNMBMMGCOAS-URPVMXJPSA-N Goserelin Chemical compound C([C@@H](C(=O)N[C@H](COC(C)(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1[C@@H](CCC1)C(=O)NNC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 BLCLNMBMMGCOAS-URPVMXJPSA-N 0.000 description 1
- 108010069236 Goserelin Proteins 0.000 description 1
- 102000009465 Growth Factor Receptors Human genes 0.000 description 1
- 108010009202 Growth Factor Receptors Proteins 0.000 description 1
- 108090000100 Hepatocyte Growth Factor Proteins 0.000 description 1
- 102100021866 Hepatocyte growth factor Human genes 0.000 description 1
- 101000904173 Homo sapiens Progonadoliberin-1 Proteins 0.000 description 1
- XDXDZDZNSLXDNA-UHFFFAOYSA-N Idarubicin Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XDXDZDZNSLXDNA-UHFFFAOYSA-N 0.000 description 1
- XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XDXDZDZNSLXDNA-TZNDIEGXSA-N 0.000 description 1
- JJKOTMDDZAJTGQ-DQSJHHFOSA-N Idoxifene Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN2CCCC2)=CC=1)/C1=CC=C(I)C=C1 JJKOTMDDZAJTGQ-DQSJHHFOSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 101150111320 KS gene Proteins 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229910021380 Manganese Chloride Inorganic materials 0.000 description 1
- GLFNIEUTAYBVOC-UHFFFAOYSA-L Manganese chloride Chemical compound Cl[Mn]Cl GLFNIEUTAYBVOC-UHFFFAOYSA-L 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 229930192392 Mitomycin Natural products 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 239000007832 Na2SO4 Substances 0.000 description 1
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 102100024028 Progonadoliberin-1 Human genes 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
- GIIWGCBLYNDKBO-UHFFFAOYSA-N Quinoline 1-oxide Chemical compound C1=CC=C2[N+]([O-])=CC=CC2=C1 GIIWGCBLYNDKBO-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 229910006024 SO2Cl2 Inorganic materials 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 241000256251 Spodoptera frugiperda Species 0.000 description 1
- 101000996723 Sus scrofa Gonadotropin-releasing hormone receptor Proteins 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 229940123237 Taxane Drugs 0.000 description 1
- FOCVUCIESVLUNU-UHFFFAOYSA-N Thiotepa Chemical compound C1CN1P(N1CC1)(=S)N1CC1 FOCVUCIESVLUNU-UHFFFAOYSA-N 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- 239000000365 Topoisomerase I Inhibitor Substances 0.000 description 1
- 102000004357 Transferases Human genes 0.000 description 1
- 108090000992 Transferases Proteins 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- 102000044209 Tumor Suppressor Genes Human genes 0.000 description 1
- 108700025716 Tumor Suppressor Genes Proteins 0.000 description 1
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 1
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 1
- 241000863480 Vinca Species 0.000 description 1
- 229940122803 Vinca alkaloid Drugs 0.000 description 1
- GOPYZMJAIPBUGX-UHFFFAOYSA-N [O-2].[O-2].[Mn+4] Chemical class [O-2].[O-2].[Mn+4] GOPYZMJAIPBUGX-UHFFFAOYSA-N 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 1
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 150000001266 acyl halides Chemical class 0.000 description 1
- 229960005305 adenosine Drugs 0.000 description 1
- 150000003838 adenosines Chemical class 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 125000004849 alkoxymethyl group Chemical group 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 125000004644 alkyl sulfinyl group Chemical group 0.000 description 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- DFNYGALUNNFWKJ-UHFFFAOYSA-N aminoacetonitrile Chemical compound NCC#N DFNYGALUNNFWKJ-UHFFFAOYSA-N 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- XCPGHVQEEXUHNC-UHFFFAOYSA-N amsacrine Chemical compound COC1=CC(NS(C)(=O)=O)=CC=C1NC1=C(C=CC=C2)C2=NC2=CC=CC=C12 XCPGHVQEEXUHNC-UHFFFAOYSA-N 0.000 description 1
- 229960001220 amsacrine Drugs 0.000 description 1
- 229960002932 anastrozole Drugs 0.000 description 1
- YBBLVLTVTVSKRW-UHFFFAOYSA-N anastrozole Chemical compound N#CC(C)(C)C1=CC(C(C)(C#N)C)=CC(CN2N=CN=C2)=C1 YBBLVLTVTVSKRW-UHFFFAOYSA-N 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 238000005349 anion exchange Methods 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 229940045799 anthracyclines and related substance Drugs 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000002280 anti-androgenic effect Effects 0.000 description 1
- 229940046836 anti-estrogen Drugs 0.000 description 1
- 230000001833 anti-estrogenic effect Effects 0.000 description 1
- 230000003432 anti-folate effect Effects 0.000 description 1
- 230000001740 anti-invasion Effects 0.000 description 1
- 230000000118 anti-neoplastic effect Effects 0.000 description 1
- 239000000051 antiandrogen Substances 0.000 description 1
- 229940030495 antiandrogen sex hormone and modulator of the genital system Drugs 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 229940127074 antifolate Drugs 0.000 description 1
- 239000003080 antimitotic agent Substances 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940045719 antineoplastic alkylating agent nitrosoureas Drugs 0.000 description 1
- 239000003972 antineoplastic antibiotic Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 239000006286 aqueous extract Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000003886 aromatase inhibitor Substances 0.000 description 1
- 229940046844 aromatase inhibitors Drugs 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 239000003849 aromatic solvent Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- 229960000997 bicalutamide Drugs 0.000 description 1
- 238000012925 biological evaluation Methods 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- CWBHKBKGKCDGDM-UHFFFAOYSA-N bis[(2,2,2-trifluoroacetyl)oxy]boranyl 2,2,2-trifluoroacetate Chemical compound FC(F)(F)C(=O)OB(OC(=O)C(F)(F)F)OC(=O)C(F)(F)F CWBHKBKGKCDGDM-UHFFFAOYSA-N 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 229960002092 busulfan Drugs 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 230000009702 cancer cell proliferation Effects 0.000 description 1
- 230000005907 cancer growth Effects 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- 125000001721 carboxyacetyl group Chemical group 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 101150073031 cdk2 gene Proteins 0.000 description 1
- 230000006369 cell cycle progression Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000000451 chemical ionisation Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229960004630 chlorambucil Drugs 0.000 description 1
- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 1
- 229940061627 chloromethyl methyl ether Drugs 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000003245 coal Substances 0.000 description 1
- 238000011284 combination treatment Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000026374 cyclin catabolic process Effects 0.000 description 1
- 125000000000 cycloalkoxy group Chemical group 0.000 description 1
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 1
- KZZKOVLJUKWSKX-UHFFFAOYSA-N cyclobutanamine Chemical compound NC1CCC1 KZZKOVLJUKWSKX-UHFFFAOYSA-N 0.000 description 1
- 125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([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
- IGSKHXTUVXSOMB-UHFFFAOYSA-N cyclopropylmethanamine Chemical compound NCC1CC1 IGSKHXTUVXSOMB-UHFFFAOYSA-N 0.000 description 1
- DUSHUSLJJMDGTE-ZJPMUUANSA-N cyproterone Chemical compound C1=C(Cl)C2=CC(=O)[C@@H]3C[C@@H]3[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)C)(O)[C@@]1(C)CC2 DUSHUSLJJMDGTE-ZJPMUUANSA-N 0.000 description 1
- 229960003843 cyproterone Drugs 0.000 description 1
- 229960000684 cytarabine Drugs 0.000 description 1
- 239000000824 cytostatic agent Substances 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 229960000975 daunorubicin Drugs 0.000 description 1
- DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 230000003831 deregulation Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 125000005117 dialkylcarbamoyl group Chemical group 0.000 description 1
- 239000002027 dichloromethane extract Substances 0.000 description 1
- IUNMPGNGSSIWFP-UHFFFAOYSA-N dimethylaminopropylamine Chemical compound CN(C)CCCN IUNMPGNGSSIWFP-UHFFFAOYSA-N 0.000 description 1
- UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical group SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
- CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
- 239000003534 dna topoisomerase inhibitor Substances 0.000 description 1
- 229960003668 docetaxel Drugs 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229950004203 droloxifene Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 229960001904 epirubicin Drugs 0.000 description 1
- 239000000328 estrogen antagonist Substances 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-N ethanesulfonic acid Chemical compound CCS(O)(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-N 0.000 description 1
- OCLXJTCGWSSVOE-UHFFFAOYSA-N ethanol etoh Chemical compound CCO.CCO OCLXJTCGWSSVOE-UHFFFAOYSA-N 0.000 description 1
- 239000002024 ethyl acetate extract Substances 0.000 description 1
- FMVJYQGSRWVMQV-UHFFFAOYSA-N ethyl propiolate Chemical compound CCOC(=O)C#C FMVJYQGSRWVMQV-UHFFFAOYSA-N 0.000 description 1
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 1
- 125000006260 ethylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 229960000255 exemestane Drugs 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- DBEPLOCGEIEOCV-WSBQPABSSA-N finasteride Chemical compound N([C@@H]1CC2)C(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](C(=O)NC(C)(C)C)[C@@]2(C)CC1 DBEPLOCGEIEOCV-WSBQPABSSA-N 0.000 description 1
- 229960004039 finasteride Drugs 0.000 description 1
- 150000005699 fluoropyrimidines Chemical class 0.000 description 1
- 229960002074 flutamide Drugs 0.000 description 1
- MKXKFYHWDHIYRV-UHFFFAOYSA-N flutamide Chemical compound CC(C)C(=O)NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 MKXKFYHWDHIYRV-UHFFFAOYSA-N 0.000 description 1
- 239000004052 folic acid antagonist Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 238000005227 gel permeation chromatography Methods 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
- 229960005277 gemcitabine Drugs 0.000 description 1
- XLXSAKCOAKORKW-UHFFFAOYSA-N gonadorelin Chemical compound C1CCC(C(=O)NCC(N)=O)N1C(=O)C(CCCN=C(N)N)NC(=O)C(CC(C)C)NC(=O)CNC(=O)C(NC(=O)C(CO)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C(CC=1NC=NC=1)NC(=O)C1NC(=O)CC1)CC1=CC=C(O)C=C1 XLXSAKCOAKORKW-UHFFFAOYSA-N 0.000 description 1
- 229960002913 goserelin Drugs 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- 229960000789 guanidine hydrochloride Drugs 0.000 description 1
- PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 229960000908 idarubicin Drugs 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 150000002485 inorganic esters Chemical class 0.000 description 1
- 229910003480 inorganic solid Inorganic materials 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- VDBNYAPERZTOOF-UHFFFAOYSA-N isoquinolin-1(2H)-one Chemical compound C1=CC=C2C(=O)NC=CC2=C1 VDBNYAPERZTOOF-UHFFFAOYSA-N 0.000 description 1
- MGIYRDNGCNKGJU-UHFFFAOYSA-N isothiazolinone Chemical compound O=C1C=CSN1 MGIYRDNGCNKGJU-UHFFFAOYSA-N 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 238000000021 kinase assay Methods 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 1
- 239000011565 manganese chloride Substances 0.000 description 1
- 235000002867 manganese chloride Nutrition 0.000 description 1
- OCSMOTCMPXTDND-OUAUKWLOSA-N marimastat Chemical compound CNC(=O)[C@H](C(C)(C)C)NC(=O)[C@H](CC(C)C)[C@H](O)C(=O)NO OCSMOTCMPXTDND-OUAUKWLOSA-N 0.000 description 1
- 229950008959 marimastat Drugs 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229960004961 mechlorethamine Drugs 0.000 description 1
- HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical class ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 description 1
- 229960001786 megestrol Drugs 0.000 description 1
- RQZAXGRLVPAYTJ-GQFGMJRRSA-N megestrol acetate Chemical compound C1=C(C)C2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)C)[C@@]1(C)CC2 RQZAXGRLVPAYTJ-GQFGMJRRSA-N 0.000 description 1
- SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 description 1
- 229960001924 melphalan Drugs 0.000 description 1
- COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 239000003475 metalloproteinase inhibitor Substances 0.000 description 1
- SSWUZPOBSSQQAN-UHFFFAOYSA-N methanesulfonic acid;3-methoxypropan-1-ol Chemical compound CS(O)(=O)=O.COCCCO SSWUZPOBSSQQAN-UHFFFAOYSA-N 0.000 description 1
- 125000005948 methanesulfonyloxy group Chemical group 0.000 description 1
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 description 1
- CFCUWKMKBJTWLW-BKHRDMLASA-N mithramycin Chemical compound O([C@@H]1C[C@@H](O[C@H](C)[C@H]1O)OC=1C=C2C=C3C[C@H]([C@@H](C(=O)C3=C(O)C2=C(O)C=1C)O[C@@H]1O[C@H](C)[C@@H](O)[C@H](O[C@@H]2O[C@H](C)[C@H](O)[C@H](O[C@@H]3O[C@H](C)[C@@H](O)[C@@](C)(O)C3)C2)C1)[C@H](OC)C(=O)[C@@H](O)[C@@H](C)O)[C@H]1C[C@@H](O)[C@H](O)[C@@H](C)O1 CFCUWKMKBJTWLW-BKHRDMLASA-N 0.000 description 1
- 230000002297 mitogenic effect Effects 0.000 description 1
- 230000035773 mitosis phase Effects 0.000 description 1
- 229960001156 mitoxantrone Drugs 0.000 description 1
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- JRHMCAJLKYKKHE-UHFFFAOYSA-N n-(2,3-dihydroxypropyl)-4-[[4-(2,3-dimethylimidazol-4-yl)pyrimidin-2-yl]amino]benzenesulfonamide Chemical compound CN1C(C)=NC=C1C1=CC=NC(NC=2C=CC(=CC=2)S(=O)(=O)NCC(O)CO)=N1 JRHMCAJLKYKKHE-UHFFFAOYSA-N 0.000 description 1
- BRDBVUKNJZDJFN-UHFFFAOYSA-N n-(3-chlorophenyl)-4-(1h-imidazol-5-yl)pyrimidin-2-amine Chemical compound ClC1=CC=CC(NC=2N=C(C=CN=2)C=2NC=NC=2)=C1 BRDBVUKNJZDJFN-UHFFFAOYSA-N 0.000 description 1
- SHBOKXDRGFPAET-UHFFFAOYSA-N n-(3-chlorophenyl)-4-(2,3-dimethylimidazol-4-yl)pyrimidin-2-amine Chemical compound CN1C(C)=NC=C1C1=CC=NC(NC=2C=C(Cl)C=CC=2)=N1 SHBOKXDRGFPAET-UHFFFAOYSA-N 0.000 description 1
- RDHIHTLXZSEYFY-UHFFFAOYSA-N n-(3-chlorophenyl)-4-(2-methyl-1h-imidazol-5-yl)pyrimidin-2-amine Chemical compound N1C(C)=NC=C1C1=CC=NC(NC=2C=C(Cl)C=CC=2)=N1 RDHIHTLXZSEYFY-UHFFFAOYSA-N 0.000 description 1
- RXZGFJSYAYSWRL-UHFFFAOYSA-N n-(3-chlorophenyl)-4-[3-(2-methoxyethyl)imidazol-4-yl]pyrimidin-2-amine Chemical compound COCCN1C=NC=C1C1=CC=NC(NC=2C=C(Cl)C=CC=2)=N1 RXZGFJSYAYSWRL-UHFFFAOYSA-N 0.000 description 1
- PEVWQXWQEPYRMK-UHFFFAOYSA-N n-(3-methoxypropyl)-4-[[4-(3-methylimidazol-4-yl)pyrimidin-2-yl]amino]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)NCCCOC)=CC=C1NC1=NC=CC(C=2N(C=NC=2)C)=N1 PEVWQXWQEPYRMK-UHFFFAOYSA-N 0.000 description 1
- DTDCMPMHTIVVBN-UHFFFAOYSA-N n-[2-[5-[2-(3-chloroanilino)pyrimidin-4-yl]imidazol-1-yl]ethyl]acetamide Chemical compound CC(=O)NCCN1C=NC=C1C1=CC=NC(NC=2C=C(Cl)C=CC=2)=N1 DTDCMPMHTIVVBN-UHFFFAOYSA-N 0.000 description 1
- FYDMOUSBLGOESH-UHFFFAOYSA-N n-[4-[[4-(2,3-dimethylimidazol-4-yl)pyrimidin-2-yl]amino]phenyl]methanesulfonamide Chemical compound CN1C(C)=NC=C1C1=CC=NC(NC=2C=CC(NS(C)(=O)=O)=CC=2)=N1 FYDMOUSBLGOESH-UHFFFAOYSA-N 0.000 description 1
- GNVRJGIVDSQCOP-UHFFFAOYSA-N n-ethyl-n-methylethanamine Chemical compound CCN(C)CC GNVRJGIVDSQCOP-UHFFFAOYSA-N 0.000 description 1
- 230000017095 negative regulation of cell growth Effects 0.000 description 1
- 230000035407 negative regulation of cell proliferation Effects 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- YNOGYQAEJGADFJ-UHFFFAOYSA-N oxolan-2-ylmethanamine Chemical compound NCC1CCCO1 YNOGYQAEJGADFJ-UHFFFAOYSA-N 0.000 description 1
- 125000005476 oxopyrrolidinyl group Chemical group 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- 150000003014 phosphoric acid esters Chemical class 0.000 description 1
- 125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 description 1
- 125000001557 phthalyl group Chemical group C(=O)(O)C1=C(C(=O)*)C=CC=C1 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229960003171 plicamycin Drugs 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229960003975 potassium Drugs 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000000583 progesterone congener Substances 0.000 description 1
- 229940095055 progestogen systemic hormonal contraceptives Drugs 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 239000003223 protective agent Substances 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- ILVXOBCQQYKLDS-UHFFFAOYSA-N pyridine N-oxide Chemical compound [O-][N+]1=CC=CC=C1 ILVXOBCQQYKLDS-UHFFFAOYSA-N 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 229960004622 raloxifene Drugs 0.000 description 1
- GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 238000012340 reverse transcriptase PCR Methods 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 239000000565 sealant Substances 0.000 description 1
- BTIHMVBBUGXLCJ-OAHLLOKOSA-N seliciclib Chemical compound C=12N=CN(C(C)C)C2=NC(N[C@@H](CO)CC)=NC=1NCC1=CC=CC=C1 BTIHMVBBUGXLCJ-OAHLLOKOSA-N 0.000 description 1
- FZHAPNGMFPVSLP-UHFFFAOYSA-N silanamine Chemical compound [SiH3]N FZHAPNGMFPVSLP-UHFFFAOYSA-N 0.000 description 1
- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 229960002901 sodium glycerophosphate Drugs 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- REULQIKBNNDNDX-UHFFFAOYSA-M sodium;2,3-dihydroxypropyl hydrogen phosphate Chemical compound [Na+].OCC(O)COP(O)([O-])=O REULQIKBNNDNDX-UHFFFAOYSA-M 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000012089 stop solution Substances 0.000 description 1
- 238000012799 strong cation exchange Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 231100000338 sulforhodamine B assay Toxicity 0.000 description 1
- 238000003210 sulforhodamine B staining Methods 0.000 description 1
- 150000003463 sulfur Chemical class 0.000 description 1
- QTJXVIKNLHZIKL-UHFFFAOYSA-N sulfur difluoride Chemical compound FSF QTJXVIKNLHZIKL-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 229960001603 tamoxifen Drugs 0.000 description 1
- 239000008399 tap water Substances 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
- 229940063683 taxotere Drugs 0.000 description 1
- NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 description 1
- 229960001278 teniposide Drugs 0.000 description 1
- SAQUDYJOOPIKFF-UHFFFAOYSA-N tert-butyl n-(4-iodophenyl)sulfonylcarbamate Chemical compound CC(C)(C)OC(=O)NS(=O)(=O)C1=CC=C(I)C=C1 SAQUDYJOOPIKFF-UHFFFAOYSA-N 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229960003604 testosterone Drugs 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 125000004192 tetrahydrofuran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000005505 thiomorpholino group Chemical group 0.000 description 1
- 229960001196 thiotepa Drugs 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 229940044693 topoisomerase inhibitor Drugs 0.000 description 1
- 229960005026 toremifene Drugs 0.000 description 1
- XFCLJVABOIYOMF-QPLCGJKRSA-N toremifene Chemical compound C1=CC(OCCN(C)C)=CC=C1C(\C=1C=CC=CC=1)=C(\CCCl)C1=CC=CC=C1 XFCLJVABOIYOMF-QPLCGJKRSA-N 0.000 description 1
- 229960001727 tretinoin Drugs 0.000 description 1
- 125000005951 trifluoromethanesulfonyloxy group Chemical group 0.000 description 1
- 239000001226 triphosphate Substances 0.000 description 1
- 235000011178 triphosphate Nutrition 0.000 description 1
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
- UGGWPQSBPIFKDZ-KOTLKJBCSA-N vindesine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(N)=O)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1N=C1[C]2C=CC=C1 UGGWPQSBPIFKDZ-KOTLKJBCSA-N 0.000 description 1
- 229960004355 vindesine Drugs 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 229910000166 zirconium phosphate Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Ophthalmology & Optometry (AREA)
- Vascular Medicine (AREA)
- Oncology (AREA)
- Pain & Pain Management (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Compositions Of Macromolecular Compounds (AREA)
- Adhesives Or Adhesive Processes (AREA)
- Inks, Pencil-Leads, Or Crayons (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0021726.5A GB0021726D0 (en) | 2000-09-05 | 2000-09-05 | Chemical compounds |
| GB0021726 | 2000-09-05 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2221904T3 true ES2221904T3 (es) | 2005-01-16 |
Family
ID=9898838
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES01963159T Expired - Lifetime ES2221904T3 (es) | 2000-09-05 | 2001-08-30 | Imidazolo-5-il-2-anilino-pirimidinas como agentes para la inhibicion de la proliferacion celular. |
Country Status (32)
| Country | Link |
|---|---|
| US (2) | US6969714B2 (OSRAM) |
| EP (1) | EP1351958B1 (OSRAM) |
| JP (1) | JP3523641B2 (OSRAM) |
| KR (1) | KR100802368B1 (OSRAM) |
| CN (1) | CN1269813C (OSRAM) |
| AR (1) | AR033836A1 (OSRAM) |
| AT (1) | ATE269327T1 (OSRAM) |
| AU (2) | AU2001284192B2 (OSRAM) |
| BG (1) | BG107579A (OSRAM) |
| BR (1) | BR0113496A (OSRAM) |
| CA (1) | CA2417148C (OSRAM) |
| CZ (1) | CZ2003617A3 (OSRAM) |
| DE (1) | DE60103935T2 (OSRAM) |
| DK (1) | DK1351958T3 (OSRAM) |
| EE (1) | EE05430B1 (OSRAM) |
| ES (1) | ES2221904T3 (OSRAM) |
| GB (1) | GB0021726D0 (OSRAM) |
| HU (1) | HUP0302922A3 (OSRAM) |
| IL (1) | IL154292A0 (OSRAM) |
| IS (1) | IS2055B (OSRAM) |
| MX (1) | MXPA03001511A (OSRAM) |
| MY (1) | MY127126A (OSRAM) |
| NO (1) | NO324059B1 (OSRAM) |
| NZ (1) | NZ523787A (OSRAM) |
| PL (1) | PL360627A1 (OSRAM) |
| PT (1) | PT1351958E (OSRAM) |
| RU (1) | RU2284327C2 (OSRAM) |
| SK (1) | SK287277B6 (OSRAM) |
| TW (1) | TWI242559B (OSRAM) |
| UA (1) | UA74206C2 (OSRAM) |
| WO (1) | WO2002020512A1 (OSRAM) |
| ZA (1) | ZA200300612B (OSRAM) |
Families Citing this family (59)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9828511D0 (en) | 1998-12-24 | 1999-02-17 | Zeneca Ltd | Chemical compounds |
| GB9919778D0 (en) | 1999-08-21 | 1999-10-27 | Zeneca Ltd | Chemical compounds |
| GB0004890D0 (en) | 2000-03-01 | 2000-04-19 | Astrazeneca Uk Ltd | Chemical compounds |
| GB0004888D0 (en) | 2000-03-01 | 2000-04-19 | Astrazeneca Uk Ltd | Chemical compounds |
| GB0004886D0 (en) | 2000-03-01 | 2000-04-19 | Astrazeneca Uk Ltd | Chemical compounds |
| GB0004887D0 (en) | 2000-03-01 | 2000-04-19 | Astrazeneca Uk Ltd | Chemical compounds |
| GB0007371D0 (en) | 2000-03-28 | 2000-05-17 | Astrazeneca Uk Ltd | Chemical compounds |
| GB0016877D0 (en) | 2000-07-11 | 2000-08-30 | Astrazeneca Ab | Chemical compounds |
| US7129242B2 (en) | 2000-12-06 | 2006-10-31 | Signal Pharmaceuticals, Llc | Anilinopyrimidine derivatives as JNK pathway inhibitors and compositions and methods related thereto |
| US7122544B2 (en) * | 2000-12-06 | 2006-10-17 | Signal Pharmaceuticals, Llc | Anilinopyrimidine derivatives as IKK inhibitors and compositions and methods related thereto |
| GB0103926D0 (en) | 2001-02-17 | 2001-04-04 | Astrazeneca Ab | Chemical compounds |
| GB0113041D0 (en) | 2001-05-30 | 2001-07-18 | Astrazeneca Ab | Chemical compounds |
| JP2005524672A (ja) | 2002-03-09 | 2005-08-18 | アストラゼネカ アクチボラグ | Ｃｄｋ阻害活性を有するイミダゾリル置換ピリミジン誘導体 |
| GB0205690D0 (en) * | 2002-03-09 | 2002-04-24 | Astrazeneca Ab | Chemical compounds |
| GB0205688D0 (en) * | 2002-03-09 | 2002-04-24 | Astrazeneca Ab | Chemical compounds |
| GB0205693D0 (en) * | 2002-03-09 | 2002-04-24 | Astrazeneca Ab | Chemical compounds |
| AR039241A1 (es) * | 2002-04-04 | 2005-02-16 | Biogen Inc | Heteroarilos trisustituidos y metodos para su produccion y uso de los mismos |
| DE10239042A1 (de) * | 2002-08-21 | 2004-03-04 | Schering Ag | Makrozyclische Pyrimidine, deren Herstellung und Verwendung als Arzneimittel |
| UA80295C2 (en) * | 2002-09-06 | 2007-09-10 | Biogen Inc | Pyrazolopyridines and using the same |
| GB0226583D0 (en) * | 2002-11-14 | 2002-12-18 | Cyclacel Ltd | Compounds |
| GB0311276D0 (en) * | 2003-05-16 | 2003-06-18 | Astrazeneca Ab | Chemical compounds |
| GB0311274D0 (en) * | 2003-05-16 | 2003-06-18 | Astrazeneca Ab | Chemical compounds |
| TW200528101A (en) * | 2004-02-03 | 2005-09-01 | Astrazeneca Ab | Chemical compounds |
| MX2007004488A (es) | 2004-10-13 | 2007-09-11 | Wyeth Corp | Analogos de anilino-pirimidina n-bencenosulfonilo sustituidos. |
| CN101083996A (zh) * | 2004-10-28 | 2007-12-05 | Irm责任有限公司 | 作为hedgehog途径调节剂的化合物和组合物 |
| WO2006064251A1 (en) * | 2004-12-17 | 2006-06-22 | Astrazeneca Ab | 4- (4- (imidazol-4-yl) pyrimidin-2-ylamino) benzamides as cdk inhibitors |
| CN1939910A (zh) * | 2004-12-31 | 2007-04-04 | 孙飘扬 | 氨基嘧啶类化合物及其盐和其制备方法与药物用途 |
| GB0504753D0 (en) * | 2005-03-08 | 2005-04-13 | Astrazeneca Ab | Chemical compounds |
| CA2617170A1 (en) | 2005-07-30 | 2007-02-08 | Astrazeneca Ab | Imidazolyl-pyrimidine compounds for use in the treatment of proliferative disorders |
| KR100674813B1 (ko) * | 2005-08-05 | 2007-01-29 | 일양약품주식회사 | Ｎ-페닐-2-피리미딘-아민 유도체 및 그의 제조방법 |
| US7745428B2 (en) * | 2005-09-30 | 2010-06-29 | Astrazeneca Ab | Imidazo[1,2-A]pyridine having anti-cell-proliferation activity |
| UY29827A1 (es) * | 2005-10-03 | 2007-05-31 | Astrazeneca Ab | 2-amina-pirimidina-4-(2-metil-1-(tetrahidro-2h-piran-4-il)-1-imidazol-5-y1) sustituidas y sus derivados, composiciones farmacéuticas que las contienen, procesos para su preparación y aplicaciones |
| EP1942897A1 (en) * | 2005-10-03 | 2008-07-16 | AstraZeneca AB | Use of pyrimidine derivatives in the manufacture of a medicament for prevention and/or treatment of alzheimer's disease |
| WO2007129019A1 (en) * | 2006-04-21 | 2007-11-15 | Astrazeneca Ab | Sulfonamide compounds useful as edg receptor modulators |
| TW200811169A (en) * | 2006-05-26 | 2008-03-01 | Astrazeneca Ab | Chemical compounds |
| US20100240686A1 (en) | 2006-06-21 | 2010-09-23 | Clifford Jones | Chemical compounds |
| TW200815418A (en) * | 2006-06-27 | 2008-04-01 | Astrazeneca Ab | New compounds I |
| TW200815417A (en) * | 2006-06-27 | 2008-04-01 | Astrazeneca Ab | New compounds II |
| US20110003691A1 (en) * | 2008-03-14 | 2011-01-06 | Basf Se | Substituted Pyrazinylmethyl Sulfonamides For Use As Fungicides |
| WO2010009139A2 (en) * | 2008-07-14 | 2010-01-21 | Gilead Colorado, Inc. | Imidazolyl pyrimidine inhibitor compounds |
| CN101503402B (zh) * | 2009-03-10 | 2014-06-25 | 沈阳药科大学 | 2-苯胺嘧啶衍生物及其制备和用途 |
| CA2761064A1 (en) | 2009-04-15 | 2010-10-21 | Astrazeneca Ab | Imidazole substituted pyrimidines useful in the treatment of glycogen synthase kinase 3 related disorders such as alzheimer's disease |
| MX2012014158A (es) | 2010-06-04 | 2013-02-07 | Hoffmann La Roche | Derivados de aminopirimidina como moduladores de proteina cinasa rica repeticiones leucina 2 (lrrk2). |
| ES2653967T3 (es) | 2010-11-10 | 2018-02-09 | Genentech, Inc. | Derivados de pirazol aminopirimidina como moduladores de LRRK2 |
| CN106928192B (zh) * | 2015-12-29 | 2020-11-13 | 中国科学院广州生物医药与健康研究院 | 一种嘧啶类化合物及其制备方法和应用 |
| US11066404B2 (en) | 2018-10-11 | 2021-07-20 | Incyte Corporation | Dihydropyrido[2,3-d]pyrimidinone compounds as CDK2 inhibitors |
| WO2020168197A1 (en) | 2019-02-15 | 2020-08-20 | Incyte Corporation | Pyrrolo[2,3-d]pyrimidinone compounds as cdk2 inhibitors |
| WO2020180959A1 (en) | 2019-03-05 | 2020-09-10 | Incyte Corporation | Pyrazolyl pyrimidinylamine compounds as cdk2 inhibitors |
| WO2020205560A1 (en) | 2019-03-29 | 2020-10-08 | Incyte Corporation | Sulfonylamide compounds as cdk2 inhibitors |
| US11447494B2 (en) | 2019-05-01 | 2022-09-20 | Incyte Corporation | Tricyclic amine compounds as CDK2 inhibitors |
| WO2020223469A1 (en) | 2019-05-01 | 2020-11-05 | Incyte Corporation | N-(1-(methylsulfonyl)piperidin-4-yl)-4,5-di hydro-1h-imidazo[4,5-h]quinazolin-8-amine derivatives and related compounds as cyclin-dependent kinase 2 (cdk2) inhibitors for treating cancer |
| PH12022550361A1 (en) | 2019-08-14 | 2023-02-27 | Incyte Corp | Imidazolyl pyrimidinylamine compounds as cdk2 inhibitors |
| PE20221905A1 (es) | 2019-10-11 | 2022-12-23 | Incyte Corp | Aminas biciclicas como inhibidoras de la cdk2 |
| WO2021138391A1 (en) | 2019-12-30 | 2021-07-08 | Tyra Biosciences, Inc. | Indazole compounds |
| IL303237A (en) * | 2020-11-27 | 2023-07-01 | Anrui Biomedical Tech Guangzhou Co Ltd | Aminoheteroaryl kinase inhibitors |
| US11981671B2 (en) | 2021-06-21 | 2024-05-14 | Incyte Corporation | Bicyclic pyrazolyl amines as CDK2 inhibitors |
| CN113999210B (zh) * | 2021-12-03 | 2023-05-23 | 郑州大学第一附属医院 | 一组2-苯氨基-4-三氮唑基嘧啶类衍生物及其应用 |
| US11976073B2 (en) | 2021-12-10 | 2024-05-07 | Incyte Corporation | Bicyclic amines as CDK2 inhibitors |
| CN116751167B (zh) * | 2023-07-03 | 2025-09-23 | 苏州诚和医药化学有限公司 | 一种(e)-4-(1-苄基-2-甲基-1h-咪唑-5-基)-3-(乙氧基酰基)丁-3-烯酸的制备方法 |
Family Cites Families (66)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4659363A (en) | 1983-07-25 | 1987-04-21 | Ciba-Geigy Corporation | N-(2-nitrophenyl)-2-aminopyrimidine derivatives, the preparation and use thereof |
| US4946956A (en) | 1988-09-21 | 1990-08-07 | Uniroyal Chemical Company, Inc. | Arylenediamine substituted pyrimidines |
| HU206337B (en) | 1988-12-29 | 1992-10-28 | Mitsui Petrochemical Ind | Process for producing pyrimidine derivatives and pharmaceutical compositions |
| US4983608A (en) * | 1989-09-05 | 1991-01-08 | Hoechst-Roussell Pharmaceuticals, Inc. | N-substituted-4-pyrimidinamines and pyrimidinediamines |
| GB9012592D0 (en) | 1990-06-06 | 1990-07-25 | Smithkline Beecham Intercredit | Compounds |
| AU658646B2 (en) | 1991-05-10 | 1995-04-27 | Rhone-Poulenc Rorer International (Holdings) Inc. | Bis mono-and bicyclic aryl and heteroaryl compounds which inhibit EGF and/or PDGF receptor tyrosine kinase |
| US5521184A (en) * | 1992-04-03 | 1996-05-28 | Ciba-Geigy Corporation | Pyrimidine derivatives and processes for the preparation thereof |
| US5516775A (en) * | 1992-08-31 | 1996-05-14 | Ciba-Geigy Corporation | Further use of pyrimidine derivatives |
| DK0664291T3 (da) * | 1992-10-05 | 2000-10-30 | Ube Industries | Pyrimidinforbindelse |
| IL110296A (en) * | 1993-07-16 | 1999-12-31 | Smithkline Beecham Corp | Imidazole compounds process for their preparation and pharmaceutical compositions containing them |
| ATE325113T1 (de) | 1993-10-01 | 2006-06-15 | Novartis Pharma Gmbh | Pharmacologisch wirksame pyrimidinderivate und verfahren zu deren herstellung |
| US5543520A (en) | 1993-10-01 | 1996-08-06 | Ciba-Geigy Corporation | Pyrimidine derivatives |
| DK0672041T3 (da) | 1993-10-01 | 2002-02-25 | Novartis Ag | Farmakologisk aktive pyridinderivater og fremgangsmåder til fremstilling deraf |
| WO1995009847A1 (en) | 1993-10-01 | 1995-04-13 | Ciba-Geigy Ag | Pyrimidineamine derivatives and processes for the preparation thereof |
| GB9325217D0 (en) | 1993-12-09 | 1994-02-09 | Zeneca Ltd | Pyrimidine derivatives |
| US5494998A (en) | 1994-11-14 | 1996-02-27 | Akzo Nobel N.V. | Polymerization of carbon monoxide and ethylene using catalyst containing non-coordinating, non-acidic anion |
| DK0813525T3 (da) | 1995-03-10 | 2004-02-16 | Berlex Lab | Benzamidinderivater, deres fremstilling og anvendelse som antikoagulanter |
| US5658903A (en) | 1995-06-07 | 1997-08-19 | Smithkline Beecham Corporation | Imidazole compounds, compositions and use |
| US5739143A (en) * | 1995-06-07 | 1998-04-14 | Smithkline Beecham Corporation | Imidazole compounds and compositions |
| GB9523675D0 (en) | 1995-11-20 | 1996-01-24 | Celltech Therapeutics Ltd | Chemical compounds |
| JP2000507558A (ja) | 1996-03-25 | 2000-06-20 | スミスクライン・ビーチャム・コーポレイション | Ｃｎｓ損傷についての新規な治療 |
| JP2000511883A (ja) | 1996-04-19 | 2000-09-12 | ノボ ノルディスク アクティーゼルスカブ | ホスホチロシン認識ユニットを有する分子のモジュレーター |
| TW440563B (en) | 1996-05-23 | 2001-06-16 | Hoffmann La Roche | Aryl pyrimidine derivatives and a pharmaceutical composition thereof |
| ES2239357T3 (es) * | 1996-06-10 | 2005-09-16 | MERCK & CO., INC. | Imidazoles sustituidos que tienen actividad inhibidora de citoquinas. |
| GB9619284D0 (en) | 1996-09-16 | 1996-10-30 | Celltech Therapeutics Ltd | Chemical compounds |
| AU5147598A (en) | 1996-10-17 | 1998-05-11 | Smithkline Beecham Corporation | Methods for reversibly inhibiting myelopoiesis in mammalian tissue |
| GB9622363D0 (en) | 1996-10-28 | 1997-01-08 | Celltech Therapeutics Ltd | Chemical compounds |
| ZA9711092B (en) | 1996-12-11 | 1999-07-22 | Smithkline Beecham Corp | Novel compounds. |
| ES2301194T3 (es) | 1997-02-05 | 2008-06-16 | Warner-Lambert Company Llc | Pirido 2,3-d pirimidinas y 4-aminopirimidinas como inhibidores de la proliferacion celular. |
| DE19710435A1 (de) | 1997-03-13 | 1998-09-17 | Hoechst Ag | Verwendung von Pyrimidinderivaten zur Prävention von Krebs allein oder in Kombination mit anderen therapeutischen Maßnahmen |
| GB9705361D0 (en) | 1997-03-14 | 1997-04-30 | Celltech Therapeutics Ltd | Chemical compounds |
| AU734009B2 (en) | 1997-05-30 | 2001-05-31 | Merck & Co., Inc. | Novel angiogenesis inhibitors |
| SK286940B6 (sk) | 1997-06-12 | 2009-07-06 | Aventis Pharma Limited | Spôsob prípravy imidazolového derivátu |
| TW517055B (en) | 1997-07-02 | 2003-01-11 | Smithkline Beecham Corp | Novel substituted imidazole compounds |
| WO1999018096A1 (en) | 1997-10-02 | 1999-04-15 | Merck & Co., Inc. | Inhibitors of prenyl-protein transferase |
| EP1021173A1 (en) | 1997-10-10 | 2000-07-26 | Imperial College Innovations Limited | Use of csaid?tm compounds for the management of uterine contractions |
| JP4135318B2 (ja) | 1997-12-15 | 2008-08-20 | アステラス製薬株式会社 | 新規なピリミジン−５−カルボキサミド誘導体 |
| US6335340B1 (en) * | 1997-12-19 | 2002-01-01 | Smithkline Beecham Corporation | compounds of heteroaryl substituted imidazole, their pharmaceutical compositons and uses |
| CA2321153A1 (en) | 1998-02-17 | 1999-08-19 | Timothy D. Cushing | Anti-viral pyrimidine derivatives |
| DK0945443T3 (da) | 1998-03-27 | 2003-06-02 | Janssen Pharmaceutica Nv | HIV-hæmmende pyrimidinderivater |
| GB9806739D0 (en) | 1998-03-28 | 1998-05-27 | Univ Newcastle Ventures Ltd | Cyclin dependent kinase inhibitors |
| ES2270612T3 (es) | 1998-08-29 | 2007-04-01 | Astrazeneca Ab | Compuestos de pirimidina. |
| AU5438299A (en) | 1998-08-29 | 2000-03-21 | Astrazeneca Ab | Pyrimidine compounds |
| SK3852001A3 (en) | 1998-09-18 | 2003-03-04 | Basf Ag | 4-Aminopyrrolopyrimidines as kinase inhibitors |
| AU6476599A (en) * | 1998-11-03 | 2000-05-22 | Novartis Ag | Anti-inflammatory 4-phenyl-5-pyrimidinyl-imidazoles |
| GB9828511D0 (en) * | 1998-12-24 | 1999-02-17 | Zeneca Ltd | Chemical compounds |
| GB9903762D0 (en) | 1999-02-18 | 1999-04-14 | Novartis Ag | Organic compounds |
| GB9905075D0 (en) | 1999-03-06 | 1999-04-28 | Zeneca Ltd | Chemical compounds |
| US6627633B2 (en) | 1999-03-17 | 2003-09-30 | Albany Molecular Research, Inc. | 6-substituted biaryl purine derivatives as potent cyclin/CDK inhibitors and antiproliferative agents |
| GB9907658D0 (en) | 1999-04-06 | 1999-05-26 | Zeneca Ltd | Chemical compounds |
| GB9914258D0 (en) | 1999-06-18 | 1999-08-18 | Celltech Therapeutics Ltd | Chemical compounds |
| GB9919778D0 (en) | 1999-08-21 | 1999-10-27 | Zeneca Ltd | Chemical compounds |
| GB9924862D0 (en) | 1999-10-20 | 1999-12-22 | Celltech Therapeutics Ltd | Chemical compounds |
| EP1224185B1 (en) | 1999-10-27 | 2005-11-30 | Novartis AG | Thiazole and imidazo[4,5-b]pyridine compounds and their pharmaceutical use |
| IL149150A0 (en) * | 1999-11-22 | 2002-12-01 | Smithkline Beecham Plc | 2-(4-(6-methoxy-naphthalene-2-yl)-5-pyridin-4-yl-1h-imidazole-2-yl)-2-methyl-derivatives, pharmaceutical compositions comprising them and use thereof as tie2 receptor kinase inhibitors |
| DE60043397D1 (de) | 1999-12-28 | 2010-01-07 | Pharmacopeia Inc | Cytokine, insbesondere tnf-alpha, hemmer |
| AU2001237041B9 (en) | 2000-02-17 | 2005-07-28 | Amgen Inc. | Kinase inhibitors |
| GB0004886D0 (en) | 2000-03-01 | 2000-04-19 | Astrazeneca Uk Ltd | Chemical compounds |
| GB0004890D0 (en) | 2000-03-01 | 2000-04-19 | Astrazeneca Uk Ltd | Chemical compounds |
| GB0004888D0 (en) | 2000-03-01 | 2000-04-19 | Astrazeneca Uk Ltd | Chemical compounds |
| GB0004887D0 (en) | 2000-03-01 | 2000-04-19 | Astrazeneca Uk Ltd | Chemical compounds |
| GB0007371D0 (en) | 2000-03-28 | 2000-05-17 | Astrazeneca Uk Ltd | Chemical compounds |
| GB0016877D0 (en) | 2000-07-11 | 2000-08-30 | Astrazeneca Ab | Chemical compounds |
| GB0103926D0 (en) | 2001-02-17 | 2001-04-04 | Astrazeneca Ab | Chemical compounds |
| GB0113041D0 (en) | 2001-05-30 | 2001-07-18 | Astrazeneca Ab | Chemical compounds |
| JP2005511608A (ja) * | 2001-11-07 | 2005-04-28 | エフ．ホフマン−ラ ロシュ アーゲー | アミノピリミジン類及び−ピリジン類 |
-
2000
- 2000-09-05 GB GBGB0021726.5A patent/GB0021726D0/en not_active Ceased
-
2001
- 2001-08-30 IL IL15429201A patent/IL154292A0/xx not_active IP Right Cessation
- 2001-08-30 AT AT01963159T patent/ATE269327T1/de active
- 2001-08-30 UA UA2003042977A patent/UA74206C2/uk unknown
- 2001-08-30 SK SK241-2003A patent/SK287277B6/sk not_active IP Right Cessation
- 2001-08-30 CZ CZ2003617A patent/CZ2003617A3/cs unknown
- 2001-08-30 PT PT01963159T patent/PT1351958E/pt unknown
- 2001-08-30 JP JP2002525133A patent/JP3523641B2/ja not_active Expired - Fee Related
- 2001-08-30 CA CA2417148A patent/CA2417148C/en not_active Expired - Fee Related
- 2001-08-30 NZ NZ523787A patent/NZ523787A/en unknown
- 2001-08-30 AU AU2001284192A patent/AU2001284192B2/en not_active Ceased
- 2001-08-30 HU HU0302922A patent/HUP0302922A3/hu unknown
- 2001-08-30 ES ES01963159T patent/ES2221904T3/es not_active Expired - Lifetime
- 2001-08-30 MX MXPA03001511A patent/MXPA03001511A/es active IP Right Grant
- 2001-08-30 AU AU8419201A patent/AU8419201A/xx active Pending
- 2001-08-30 WO PCT/GB2001/003864 patent/WO2002020512A1/en not_active Ceased
- 2001-08-30 EP EP01963159A patent/EP1351958B1/en not_active Expired - Lifetime
- 2001-08-30 DE DE60103935T patent/DE60103935T2/de not_active Expired - Lifetime
- 2001-08-30 DK DK01963159T patent/DK1351958T3/da active
- 2001-08-30 CN CNB018151744A patent/CN1269813C/zh not_active Expired - Fee Related
- 2001-08-30 EE EEP200300088A patent/EE05430B1/xx not_active IP Right Cessation
- 2001-08-30 BR BR0113496-5A patent/BR0113496A/pt not_active Application Discontinuation
- 2001-08-30 KR KR1020037003215A patent/KR100802368B1/ko not_active Expired - Fee Related
- 2001-08-30 US US10/363,655 patent/US6969714B2/en not_active Expired - Fee Related
- 2001-08-30 PL PL36062701A patent/PL360627A1/xx not_active Application Discontinuation
- 2001-08-30 RU RU2003109612/04A patent/RU2284327C2/ru not_active IP Right Cessation
- 2001-09-03 MY MYPI20014136 patent/MY127126A/en unknown
- 2001-09-05 AR ARP010104228A patent/AR033836A1/es unknown
- 2001-09-11 TW TW090122494A patent/TWI242559B/zh not_active IP Right Cessation
-
2003
- 2003-01-22 ZA ZA200300612A patent/ZA200300612B/en unknown
- 2003-02-12 IS IS6715A patent/IS2055B/is unknown
- 2003-02-21 BG BG107579A patent/BG107579A/bg unknown
- 2003-03-04 NO NO20031006A patent/NO324059B1/no not_active IP Right Cessation
-
2005
- 2005-06-29 US US11/169,197 patent/US20060004033A1/en not_active Abandoned
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2221904T3 (es) | Imidazolo-5-il-2-anilino-pirimidinas como agentes para la inhibicion de la proliferacion celular. | |
| ES2278720T3 (es) | Pirimidinas 2,4-di(hetero-)arilamino(-oxi)-5-sustituidas como agentes antineoplasicos. | |
| ES2292599T3 (es) | Derivados de pirimidina. | |
| ES2236494T3 (es) | Derivados de pirimidina para la inhibicion de la proliferacion celular. | |
| ES2346288T3 (es) | 2,4-di(hetero-)arilamino(-oxi)-5-pirimidinas sustituidas como agentes antineoplasicos. | |
| ES2247078T3 (es) | Derivados 4-amino-5-ciano-2-anilino-pirimidinicos y su uso como inhibidores de quinasas del ciclo celular. | |
| ES2200824T3 (es) | Compuestos de pirimidina. | |
| ES2284617T3 (es) | Compuestos de pirimidina. | |
| ES2274634T3 (es) | Compuestos de pirimidina. | |
| ES2228145T3 (es) | Compuestos de pirimidina. | |
| ES2208397T3 (es) | Derivados de imidazo (1,2-a) piridina y de pirazolo (2,3-a) piridina. | |
| ES2278023T3 (es) | Derivados 2-anilino-pirimidinicos como inhibidores de quinasas dependientes de ciclinas. | |
| ES2328042T3 (es) | Derivados de pirazol como unhibidores de los receptores tirosina cinasa. | |
| EP1487823A1 (en) | Derivatives of 4-(imidazol-5-yl)-2-(4-sulfoanilino)pyrimidine with cdk inhibitory activity | |
| AU2005315392A1 (en) | 4- (4- (imidazol-4-yl) pyrimidin-2-ylamino) benzamides as CDK inhibitors | |
| ES2326636T3 (es) | Compuestos de pirimidina. | |
| ES2317079T3 (es) | Pirimidinas con actividad tie2 (tek). | |
| KR20060129040A (ko) | 세포 증식 억제제로서의이미다졸로-5-일-2-아닐리노피리미딘 | |
| ES2305548T3 (es) | Agentes terapeuticos anti-angiogenicos. | |
| ES2351370T3 (es) | Compuestos químicos. |