BG105974A - Индигоидни бисиндолови производни - Google Patents
Индигоидни бисиндолови производни Download PDFInfo
- Publication number
- BG105974A BG105974A BG105974A BG10597401A BG105974A BG 105974 A BG105974 A BG 105974A BG 105974 A BG105974 A BG 105974A BG 10597401 A BG10597401 A BG 10597401A BG 105974 A BG105974 A BG 105974A
- Authority
- BG
- Bulgaria
- Prior art keywords
- indol
- group
- ylidene
- indole
- amino
- Prior art date
Links
- 239000003814 drug Substances 0.000 claims abstract description 5
- 239000007787 solid Substances 0.000 claims abstract description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 153
- 229910052757 nitrogen Inorganic materials 0.000 claims description 144
- JXDYKVIHCLTXOP-UHFFFAOYSA-N isatin Chemical compound C1=CC=C2C(=O)C(=O)NC2=C1 JXDYKVIHCLTXOP-UHFFFAOYSA-N 0.000 claims description 98
- -1 phosphoryl groups Chemical group 0.000 claims description 78
- QNLOWBMKUIXCOW-UHFFFAOYSA-N indol-2-one Chemical compound C1=CC=CC2=NC(=O)C=C21 QNLOWBMKUIXCOW-UHFFFAOYSA-N 0.000 claims description 75
- 125000004432 carbon atom Chemical group C* 0.000 claims description 29
- 125000005842 heteroatom Chemical group 0.000 claims description 28
- 125000000217 alkyl group Chemical group 0.000 claims description 24
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 24
- 125000003118 aryl group Chemical group 0.000 claims description 18
- 150000001875 compounds Chemical class 0.000 claims description 17
- 125000003277 amino group Chemical group 0.000 claims description 16
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 13
- 159000000000 sodium salts Chemical class 0.000 claims description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 11
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 11
- 150000001413 amino acids Chemical class 0.000 claims description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 9
- 229930182470 glycoside Natural products 0.000 claims description 9
- 150000002338 glycosides Chemical class 0.000 claims description 9
- 150000002772 monosaccharides Chemical class 0.000 claims description 9
- 229920001542 oligosaccharide Polymers 0.000 claims description 9
- 150000002482 oligosaccharides Chemical class 0.000 claims description 9
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 9
- 235000000346 sugar Nutrition 0.000 claims description 9
- 150000008163 sugars Chemical class 0.000 claims description 9
- 125000002252 acyl group Chemical group 0.000 claims description 8
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 8
- 150000002016 disaccharides Chemical class 0.000 claims description 8
- 125000005843 halogen group Chemical group 0.000 claims description 8
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 8
- 239000003270 steroid hormone Substances 0.000 claims description 8
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
- 201000011510 cancer Diseases 0.000 claims description 5
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- 229930182474 N-glycoside Natural products 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- VRYALKFFQXWPIH-PBXRRBTRSA-N (3r,4s,5r)-3,4,5,6-tetrahydroxyhexanal Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)CC=O VRYALKFFQXWPIH-PBXRRBTRSA-N 0.000 claims description 3
- VRYALKFFQXWPIH-HSUXUTPPSA-N 2-deoxy-D-galactose Chemical compound OC[C@@H](O)[C@H](O)[C@H](O)CC=O VRYALKFFQXWPIH-HSUXUTPPSA-N 0.000 claims description 3
- 229930182473 O-glycoside Natural products 0.000 claims description 3
- 150000008444 O-glycosides Chemical class 0.000 claims description 3
- 239000002202 Polyethylene glycol Substances 0.000 claims description 3
- PMMURAAUARKVCB-UHFFFAOYSA-N alpha-D-ara-dHexp Natural products OCC1OC(O)CC(O)C1O PMMURAAUARKVCB-UHFFFAOYSA-N 0.000 claims description 3
- 229920001223 polyethylene glycol Polymers 0.000 claims description 3
- 125000001273 sulfonato group Chemical group [O-]S(*)(=O)=O 0.000 claims description 3
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 claims description 2
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical group OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 claims description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 2
- 150000001408 amides Chemical class 0.000 claims description 2
- 125000000539 amino acid group Chemical group 0.000 claims description 2
- 125000004104 aryloxy group Chemical group 0.000 claims description 2
- 125000004429 atom Chemical group 0.000 claims description 2
- 125000000751 azo group Chemical group [*]N=N[*] 0.000 claims description 2
- AVXURJPOCDRRFD-UHFFFAOYSA-N hydroxylamine group Chemical group NO AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 125000000018 nitroso group Chemical group N(=O)* 0.000 claims description 2
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L sulfate group Chemical group S(=O)(=O)([O-])[O-] QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 2
- 125000000565 sulfonamide group Chemical group 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 125000004665 trialkylsilyl group Chemical group 0.000 claims description 2
- 125000005106 triarylsilyl group Chemical group 0.000 claims description 2
- XVPZRKIQCKKYNE-UHFFFAOYSA-N Arborine Chemical compound N=1C(=O)C2=CC=CC=C2N(C)C=1CC1=CC=CC=C1 XVPZRKIQCKKYNE-UHFFFAOYSA-N 0.000 claims 1
- ALEXXDVDDISNDU-JZYPGELDSA-N cortisol 21-acetate Chemical group C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)COC(=O)C)(O)[C@@]1(C)C[C@@H]2O ALEXXDVDDISNDU-JZYPGELDSA-N 0.000 claims 1
- 239000005556 hormone Substances 0.000 claims 1
- 229940088597 hormone Drugs 0.000 claims 1
- 229910052760 oxygen Inorganic materials 0.000 claims 1
- 150000003431 steroids Chemical class 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 abstract description 10
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- 229910052799 carbon Inorganic materials 0.000 description 148
- 238000000160 carbon, hydrogen and nitrogen elemental analysis Methods 0.000 description 76
- 239000000843 powder Substances 0.000 description 36
- 239000013078 crystal Substances 0.000 description 35
- CRDNMYFJWFXOCH-YPKPFQOOSA-N (3z)-3-(3-oxo-1h-indol-2-ylidene)-1h-indol-2-one Chemical compound N/1C2=CC=CC=C2C(=O)C\1=C1/C2=CC=CC=C2NC1=O CRDNMYFJWFXOCH-YPKPFQOOSA-N 0.000 description 28
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
- 238000000034 method Methods 0.000 description 20
- 241001062009 Indigofera Species 0.000 description 12
- 235000000177 Indigofera tinctoria Nutrition 0.000 description 12
- 230000000259 anti-tumor effect Effects 0.000 description 12
- 229940097275 indigo Drugs 0.000 description 12
- COHYTHOBJLSHDF-UHFFFAOYSA-N indigo powder Natural products N1C2=CC=CC=C2C(=O)C1=C1C(=O)C2=CC=CC=C2N1 COHYTHOBJLSHDF-UHFFFAOYSA-N 0.000 description 12
- CRDNMYFJWFXOCH-BUHFOSPRSA-N Couroupitine B Natural products N\1C2=CC=CC=C2C(=O)C/1=C1/C2=CC=CC=C2NC1=O CRDNMYFJWFXOCH-BUHFOSPRSA-N 0.000 description 10
- CRDNMYFJWFXOCH-UHFFFAOYSA-N isoindigotin Natural products N1C2=CC=CC=C2C(=O)C1=C1C2=CC=CC=C2NC1=O CRDNMYFJWFXOCH-UHFFFAOYSA-N 0.000 description 10
- 239000013543 active substance Substances 0.000 description 8
- 125000002344 aminooxy group Chemical group [H]N([H])O[*] 0.000 description 8
- 210000000170 cell membrane Anatomy 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 7
- 210000004027 cell Anatomy 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 6
- 201000009030 Carcinoma Diseases 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 210000004881 tumor cell Anatomy 0.000 description 5
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- PCKPVGOLPKLUHR-UHFFFAOYSA-N indoxyl Chemical compound C1=CC=C2C(O)=CNC2=C1 PCKPVGOLPKLUHR-UHFFFAOYSA-N 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- MLCPSWPIYHDOKG-BUHFOSPRSA-N (3e)-3-(2-oxo-1h-indol-3-ylidene)-1h-indol-2-one Chemical compound O=C\1NC2=CC=CC=C2C/1=C1/C2=CC=CC=C2NC1=O MLCPSWPIYHDOKG-BUHFOSPRSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000000719 anti-leukaemic effect Effects 0.000 description 3
- 239000000428 dust Substances 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 230000004565 tumor cell growth Effects 0.000 description 3
- SZIFAVKTNFCBPC-UHFFFAOYSA-N 2-chloroethanol Chemical compound OCCCl SZIFAVKTNFCBPC-UHFFFAOYSA-N 0.000 description 2
- 241000409707 Brassiceae Species 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 241000334154 Isatis tinctoria Species 0.000 description 2
- 206010027476 Metastases Diseases 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 238000005273 aeration Methods 0.000 description 2
- 150000001335 aliphatic alkanes Chemical class 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- FQCPPVRJPILDIK-UHFFFAOYSA-N chembl126077 Chemical compound N1C2=CC=CC=C2C(N=O)=C1C1=C(O)NC2=CC=CC=C21 FQCPPVRJPILDIK-UHFFFAOYSA-N 0.000 description 2
- NRQCVZPNBUOBQY-UHFFFAOYSA-N chembl174343 Chemical compound C1=CC=C2C(=O)C(C=3C4=CC=C(I)C=C4NC=3O)=NC2=C1 NRQCVZPNBUOBQY-UHFFFAOYSA-N 0.000 description 2
- 210000000172 cytosol Anatomy 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- HBDSHCUSXQATPO-BGBJRWHRSA-N indirubin-3'-monoxime Chemical compound O=C/1NC2=CC=CC=C2C\1=C\1/C(=N/O)/C2=CC=CC=C2N/1 HBDSHCUSXQATPO-BGBJRWHRSA-N 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- MKQLBNJQQZRQJU-UHFFFAOYSA-N morpholin-4-amine Chemical compound NN1CCOCC1 MKQLBNJQQZRQJU-UHFFFAOYSA-N 0.000 description 2
- 230000035515 penetration Effects 0.000 description 2
- IYPZRUYMFDWKSS-UHFFFAOYSA-N piperazin-1-amine Chemical compound NN1CCNCC1 IYPZRUYMFDWKSS-UHFFFAOYSA-N 0.000 description 2
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 229940080818 propionamide Drugs 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- JNUZADQZHYFJGW-JOCHJYFZSA-N (2R)-N-[3-[5-fluoro-2-(2-fluoro-3-methylsulfonylanilino)pyrimidin-4-yl]-1H-indol-7-yl]-3-methoxy-2-(4-methylpiperazin-1-yl)propanamide Chemical compound FC=1C(=NC(=NC=1)NC1=C(C(=CC=C1)S(=O)(=O)C)F)C1=CNC2=C(C=CC=C12)NC([C@@H](COC)N1CCN(CC1)C)=O JNUZADQZHYFJGW-JOCHJYFZSA-N 0.000 description 1
- KEEKMOIRJUWKNK-CABZTGNLSA-N (2S)-2-[[2-[(4R)-4-(difluoromethyl)-2-oxo-1,3-thiazolidin-3-yl]-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepin-9-yl]amino]propanamide Chemical compound FC([C@H]1N(C(SC1)=O)C=1N=C2N(CCOC3=C2C=CC(=C3)N[C@H](C(=O)N)C)C=1)F KEEKMOIRJUWKNK-CABZTGNLSA-N 0.000 description 1
- MPCAJMNYNOGXPB-KCDKBNATSA-N (2r,3r,4r,5s)-2-(hydroxymethyl)oxane-3,4,5-triol Chemical compound OC[C@H]1OC[C@H](O)[C@@H](O)[C@H]1O MPCAJMNYNOGXPB-KCDKBNATSA-N 0.000 description 1
- XFJAMQQAAMJFGB-ZQGJOIPISA-N (2s,3r,4r,5s,6r)-2-[3-(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)-4-ethylphenyl]-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound C1=C(CC=2C=C3OCCOC3=CC=2)C(CC)=CC=C1[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O XFJAMQQAAMJFGB-ZQGJOIPISA-N 0.000 description 1
- NYNZQNWKBKUAII-KBXCAEBGSA-N (3s)-n-[5-[(2r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-3-hydroxypyrrolidine-1-carboxamide Chemical compound C1[C@@H](O)CCN1C(=O)NC1=C2N=C(N3[C@H](CCC3)C=3C(=CC=C(F)C=3)F)C=CN2N=C1 NYNZQNWKBKUAII-KBXCAEBGSA-N 0.000 description 1
- LCFFREMLXLZNHE-GBOLQPHISA-N (e)-2-[(3r)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile Chemical compound C12=C(N)N=CN=C2N([C@@H]2CCCN(C2)C(=O)C(/C#N)=C/C(C)(C)N2CCN(CC2)C2COC2)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 LCFFREMLXLZNHE-GBOLQPHISA-N 0.000 description 1
- KYVBNYUBXIEUFW-UHFFFAOYSA-N 1,1,3,3-tetramethylguanidine Chemical compound CN(C)C(=N)N(C)C KYVBNYUBXIEUFW-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- MWKYMZXCGYXLPL-ZDUSSCGKSA-N 1-[(3s)-3-[[6-[6-methoxy-5-(trifluoromethyl)pyridin-3-yl]-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-yl]amino]pyrrolidin-1-yl]propan-1-one Chemical compound C1N(C(=O)CC)CC[C@@H]1NC1=NC=NC2=C1CN(C=1C=C(C(OC)=NC=1)C(F)(F)F)CC2 MWKYMZXCGYXLPL-ZDUSSCGKSA-N 0.000 description 1
- MXHZAYVEIKSPIA-ZHACJKMWSA-N 1-[(E)-4-[5-carbamoyl-7-[3-(dimethylamino)propoxy]-2-[(2-ethyl-5-methylpyrazole-3-carbonyl)amino]benzimidazol-1-yl]but-2-enyl]-2-[(2-ethyl-5-methylpyrazole-3-carbonyl)amino]-7-methoxybenzimidazole-5-carboxamide Chemical compound CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN(C)C)=C12)C(N)=O)C(N)=O MXHZAYVEIKSPIA-ZHACJKMWSA-N 0.000 description 1
- OCNBSSLDAIWTKS-UHFFFAOYSA-N 3-[[[3,5-bis(trifluoromethyl)phenyl]methyl-(2-methyltetrazol-5-yl)amino]methyl]-n,n-bis(cyclopropylmethyl)-8-methylquinolin-2-amine Chemical compound C1CC1CN(CC1CC1)C=1N=C2C(C)=CC=CC2=CC=1CN(C1=NN(C)N=N1)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 OCNBSSLDAIWTKS-UHFFFAOYSA-N 0.000 description 1
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-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
- WPFUFWIHMYZXSF-UHFFFAOYSA-N 4-[2-(difluoromethyl)benzimidazol-1-yl]-n-[2-methyl-1-[2-(1-methylpiperidin-4-yl)phenyl]propan-2-yl]-6-morpholin-4-yl-1,3,5-triazin-2-amine Chemical compound C1CN(C)CCC1C1=CC=CC=C1CC(C)(C)NC1=NC(N2CCOCC2)=NC(N2C3=CC=CC=C3N=C2C(F)F)=N1 WPFUFWIHMYZXSF-UHFFFAOYSA-N 0.000 description 1
- YZSCPLGKKMSBMV-UHFFFAOYSA-N 5-fluoro-4-(8-fluoro-4-propan-2-yl-2,3-dihydro-1,4-benzoxazin-6-yl)-N-[5-(1-methylpiperidin-4-yl)pyridin-2-yl]pyrimidin-2-amine Chemical compound FC=1C(=NC(=NC=1)NC1=NC=C(C=C1)C1CCN(CC1)C)C1=CC2=C(OCCN2C(C)C)C(=C1)F YZSCPLGKKMSBMV-UHFFFAOYSA-N 0.000 description 1
- KOAWAWHSMVKCON-UHFFFAOYSA-N 6-[difluoro-(6-pyridin-4-yl-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methyl]quinoline Chemical compound C=1C=C2N=CC=CC2=CC=1C(F)(F)C(N1N=2)=NN=C1C=CC=2C1=CC=NC=C1 KOAWAWHSMVKCON-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 208000003200 Adenoma Diseases 0.000 description 1
- 206010003571 Astrocytoma Diseases 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 102000005600 Cathepsins Human genes 0.000 description 1
- 108010084457 Cathepsins Proteins 0.000 description 1
- 102000029816 Collagenase Human genes 0.000 description 1
- 108060005980 Collagenase Proteins 0.000 description 1
- 241000220485 Fabaceae Species 0.000 description 1
- 108010088842 Fibrinolysin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- QQILFGKZUJYXGS-UHFFFAOYSA-N Indigo dye Chemical compound C1=CC=C2C(=O)C(C3=C(C4=CC=CC=C4N3)O)=NC2=C1 QQILFGKZUJYXGS-UHFFFAOYSA-N 0.000 description 1
- 240000004343 Indigofera suffruticosa Species 0.000 description 1
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 1
- 241000334160 Isatis Species 0.000 description 1
- SRBFZHDQGSBBOR-HWQSCIPKSA-N L-arabinopyranose Chemical compound O[C@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-HWQSCIPKSA-N 0.000 description 1
- 206010023774 Large cell lung cancer Diseases 0.000 description 1
- 206010023825 Laryngeal cancer Diseases 0.000 description 1
- 238000005684 Liebig rearrangement reaction Methods 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- BTMKEDDEMKKSEF-QGZVFWFLSA-N N-[5-[[4-[5-chloro-4-fluoro-2-(2-hydroxypropan-2-yl)anilino]pyrimidin-2-yl]amino]-2-[(3R)-3-(dimethylamino)pyrrolidin-1-yl]-4-methoxyphenyl]prop-2-enamide Chemical compound C(C=C)(=O)NC1=C(C=C(C(=C1)NC1=NC=CC(=N1)NC1=C(C=C(C(=C1)Cl)F)C(C)(C)O)OC)N1C[C@@H](CC1)N(C)C BTMKEDDEMKKSEF-QGZVFWFLSA-N 0.000 description 1
- 229930182559 Natural dye Natural products 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 102000015636 Oligopeptides Human genes 0.000 description 1
- 108010038807 Oligopeptides Proteins 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical group [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 206010041067 Small cell lung cancer Diseases 0.000 description 1
- 206010043276 Teratoma Diseases 0.000 description 1
- UMPVMAYCLYMYGA-ONGXEEELSA-N Val-Leu-Gly Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O UMPVMAYCLYMYGA-ONGXEEELSA-N 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- MCRWZBYTLVCCJJ-DKALBXGISA-N [(1s,3r)-3-[[(3s,4s)-3-methoxyoxan-4-yl]amino]-1-propan-2-ylcyclopentyl]-[(1s,4s)-5-[6-(trifluoromethyl)pyrimidin-4-yl]-2,5-diazabicyclo[2.2.1]heptan-2-yl]methanone Chemical compound C([C@]1(N(C[C@]2([H])C1)C(=O)[C@@]1(C[C@@H](CC1)N[C@@H]1[C@@H](COCC1)OC)C(C)C)[H])N2C1=CC(C(F)(F)F)=NC=N1 MCRWZBYTLVCCJJ-DKALBXGISA-N 0.000 description 1
- FXXACINHVKSMDR-UHFFFAOYSA-N acetyl bromide Chemical compound CC(Br)=O FXXACINHVKSMDR-UHFFFAOYSA-N 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- 208000009956 adenocarcinoma Diseases 0.000 description 1
- 229920000180 alkyd Polymers 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229940126575 aminoglycoside Drugs 0.000 description 1
- 239000003098 androgen Substances 0.000 description 1
- 229940030486 androgens Drugs 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000001754 anti-pyretic effect Effects 0.000 description 1
- 229940030225 antihemorrhagics Drugs 0.000 description 1
- 239000002221 antipyretic Substances 0.000 description 1
- 229940125716 antipyretic agent Drugs 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 150000001555 benzenes Chemical class 0.000 description 1
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000027455 binding Effects 0.000 description 1
- 238000009739 binding Methods 0.000 description 1
- 239000001045 blue dye Substances 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 125000004744 butyloxycarbonyl group Chemical group 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 238000000006 cell growth inhibition assay Methods 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- XUZICJHIIJCKQQ-ZDUSSCGKSA-N eclitasertib Chemical compound C(C1=CC=CC=C1)C=1NC(=NN=1)C(=O)N[C@@H]1C(N(C2=C(OC1)C=CC=N2)C)=O XUZICJHIIJCKQQ-ZDUSSCGKSA-N 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 230000007071 enzymatic hydrolysis Effects 0.000 description 1
- 238000006047 enzymatic hydrolysis reaction Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- ZUMNJDGBYXHASJ-UHFFFAOYSA-N ethyl 2-[5-[4-(3-methylsulfonylphenyl)phenyl]-3-(trifluoromethyl)pyrazol-1-yl]acetate Chemical compound CCOC(=O)CN1N=C(C(F)(F)F)C=C1C1=CC=C(C=2C=C(C=CC=2)S(C)(=O)=O)C=C1 ZUMNJDGBYXHASJ-UHFFFAOYSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 229960002442 glucosamine Drugs 0.000 description 1
- 239000003163 gonadal steroid hormone Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 239000002874 hemostatic agent Substances 0.000 description 1
- 230000002439 hemostatic effect Effects 0.000 description 1
- 125000005597 hydrazone group Chemical group 0.000 description 1
- 238000005462 in vivo assay Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 206010023841 laryngeal neoplasm Diseases 0.000 description 1
- 235000021374 legumes Nutrition 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 201000009546 lung large cell carcinoma Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 210000005075 mammary gland Anatomy 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- GSYSFVSGPABNNL-UHFFFAOYSA-N methyl 2-dimethoxyphosphoryl-2-(phenylmethoxycarbonylamino)acetate Chemical group COC(=O)C(P(=O)(OC)OC)NC(=O)OCC1=CC=CC=C1 GSYSFVSGPABNNL-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical compound CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 description 1
- 210000004877 mucosa Anatomy 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
- GUOONOJYWQOJJP-DCMFLLSESA-N n-[(2s,3r)-3-hydroxy-1-phenyl-4-[[3-(trifluoromethoxy)phenyl]methylamino]butan-2-yl]-3-[methyl(methylsulfonyl)amino]-5-[(2r)-2-(4-methyl-1,3-thiazol-2-yl)pyrrolidine-1-carbonyl]benzamide Chemical compound C1([C@H]2CCCN2C(=O)C=2C=C(C=C(C=2)N(C)S(C)(=O)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)[C@H](O)CNCC=2C=C(OC(F)(F)F)C=CC=2)=NC(C)=CS1 GUOONOJYWQOJJP-DCMFLLSESA-N 0.000 description 1
- YBXBWBBVLXZQBJ-UHFFFAOYSA-N n-[2-(5-hydroxy-2-methyl-1h-indol-3-yl)ethyl]-2-methoxyacetamide Chemical compound C1=C(O)C=C2C(CCNC(=O)COC)=C(C)NC2=C1 YBXBWBBVLXZQBJ-UHFFFAOYSA-N 0.000 description 1
- VOVZXURTCKPRDQ-CQSZACIVSA-N n-[4-[chloro(difluoro)methoxy]phenyl]-6-[(3r)-3-hydroxypyrrolidin-1-yl]-5-(1h-pyrazol-5-yl)pyridine-3-carboxamide Chemical compound C1[C@H](O)CCN1C1=NC=C(C(=O)NC=2C=CC(OC(F)(F)Cl)=CC=2)C=C1C1=CC=NN1 VOVZXURTCKPRDQ-CQSZACIVSA-N 0.000 description 1
- 239000000978 natural dye Substances 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 210000003463 organelle Anatomy 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 229940012957 plasmin Drugs 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 239000000583 progesterone congener Substances 0.000 description 1
- 229940095055 progestogen systemic hormonal contraceptives Drugs 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 229940125723 sedative agent Drugs 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 229910052711 selenium Inorganic materials 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 208000000587 small cell lung carcinoma Diseases 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- JDVPQXZIJDEHAN-UHFFFAOYSA-N succinamic acid Chemical compound NC(=O)CCC(O)=O JDVPQXZIJDEHAN-UHFFFAOYSA-N 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 229940037128 systemic glucocorticoids Drugs 0.000 description 1
- 229910052714 tellurium Inorganic materials 0.000 description 1
- PORWMNRCUJJQNO-UHFFFAOYSA-N tellurium atom Chemical group [Te] PORWMNRCUJJQNO-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/32—Oxygen atoms
- C07D209/36—Oxygen atoms in position 3, e.g. adrenochrome
-
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- 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
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/572—Five-membered rings
- C07F9/5728—Five-membered rings condensed with carbocyclic rings or carbocyclic ring systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Oncology (AREA)
- Biochemistry (AREA)
- Communicable Diseases (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Virology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Saccharide Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP99106207 | 1999-04-12 | ||
EP99107429 | 1999-04-27 | ||
PCT/EP2000/003285 WO2000061555A1 (en) | 1999-04-12 | 2000-04-12 | Indigoid bisindole derivatives |
Publications (1)
Publication Number | Publication Date |
---|---|
BG105974A true BG105974A (bg) | 2002-06-28 |
Family
ID=26152940
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
BG105974A BG105974A (bg) | 1999-04-12 | 2001-10-03 | Индигоидни бисиндолови производни |
Country Status (21)
Country | Link |
---|---|
US (1) | US6987092B1 (xx) |
EP (1) | EP1169305A1 (xx) |
JP (1) | JP2002541244A (xx) |
KR (1) | KR20010112424A (xx) |
CN (1) | CN1355789A (xx) |
AU (1) | AU4117800A (xx) |
BG (1) | BG105974A (xx) |
BR (1) | BR0009770A (xx) |
CA (1) | CA2369670A1 (xx) |
CZ (1) | CZ20013555A3 (xx) |
EA (1) | EA200101046A1 (xx) |
HK (1) | HK1041256A1 (xx) |
HR (1) | HRP20010735A2 (xx) |
HU (1) | HUP0200724A3 (xx) |
IL (1) | IL145743A0 (xx) |
MX (1) | MXPA01010214A (xx) |
NO (1) | NO20014948D0 (xx) |
NZ (1) | NZ514663A (xx) |
PL (1) | PL351261A1 (xx) |
SK (1) | SK14272001A3 (xx) |
WO (1) | WO2000061555A1 (xx) |
Families Citing this family (38)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
MXPA01010436A (es) | 1999-04-12 | 2002-09-18 | Eisenbrand Gerhard | El uso de una membrana celular para la penetracion de derivados bisindol indigoides. |
DE10053474A1 (de) * | 2000-10-24 | 2002-05-02 | Schering Ag | Schwefelhaltige Indirubinderivate, deren Herstellung und Verwendung |
DE10061162A1 (de) * | 2000-11-30 | 2002-07-11 | Schering Ag | Aryl-substituierte Indirubinderivate, deren Herstellung und Verwendung |
DE10114138C2 (de) * | 2001-03-16 | 2003-03-27 | Schering Ag | Cdk-inhibitorische Indirubinderivate mit erhöhter Löslichkeit |
DE10125763A1 (de) * | 2001-05-17 | 2002-11-28 | Schering Ag | Verwendung selektiver Indirubinderivate als VEGF-R Inhibitoren |
DE10129028A1 (de) * | 2001-06-11 | 2003-01-02 | Schering Ag | Lösliche Cdk-inhibitorische Indirubinderivate |
US7582670B2 (en) | 2001-12-13 | 2009-09-01 | Natrogen Therapeutics, Inc. | Methods of treating an inflammatory-related disease |
CA2469649C (en) * | 2001-12-13 | 2011-05-03 | Natrogen Therapeutics, Inc. | Derivatives of isoindigo, indigo and indirubin and use in treating cancer |
US6566341B1 (en) * | 2001-12-13 | 2003-05-20 | Natrogen Therapeutics, Inc. | Derivative of isoindigo, indigo and indirubin for the treatment of cancer |
US20050154046A1 (en) | 2004-01-12 | 2005-07-14 | Longgui Wang | Methods of treating an inflammatory-related disease |
US8563525B2 (en) | 2004-01-12 | 2013-10-22 | Natrogen Therapeutics International, Inc. | Methods of treating an inflammatory-related disease |
EP1340745A1 (en) * | 2002-02-20 | 2003-09-03 | Gerhard Prof. Dr. Eisenbrand | Indirubin derivatives and their use for the treatment of cancer |
CN1199946C (zh) * | 2002-10-29 | 2005-05-04 | 无锡杰西医药科技有限公司 | 一种特异性吲哚类化合物及制备方法与其在治疗和预防癌症等疾病中的应用 |
US20120070518A1 (en) * | 2004-01-12 | 2012-03-22 | Natrogen Therapeutics International, Inc. | Methods and compositions for treating psoriasis |
KR100588803B1 (ko) * | 2004-01-27 | 2006-06-12 | 학교법인조선대학교 | 암세포주에 항암활성을 지닌 인디루빈 유도체 |
AU2005239814B2 (en) * | 2004-05-12 | 2010-06-17 | Bayer Cropscience Ag | Plant growth regulation |
CA2633069A1 (en) * | 2005-12-23 | 2007-09-07 | Centre National De La Recherche Scientifique (Cnrs) | New 3'-, 7-substituted indirubins and their applications |
US8518903B2 (en) | 2007-04-19 | 2013-08-27 | University of Pittsburgh—of the Commonwealth System of Higher Education | Use of toll-like receptor-9 agonists |
CN101074229B (zh) * | 2007-06-08 | 2010-09-01 | 无锡杰西医药科技有限公司 | 7-氮杂靛玉红和7-氮杂异靛蓝衍生物制备及其药学用途 |
ATE529402T1 (de) | 2008-08-01 | 2011-11-15 | Centre Nat Rech Scient | 3',6-substituierte indirubine und ihre biologischen anwendungen |
EP2199292A1 (en) | 2008-12-22 | 2010-06-23 | Technische Universität Kaiserlautern | 7-azaindirubins, 7'-azaindirubins, 7-7'-diazaindirubin and the corresponding 3'-oxime ether derivates: production thereof, their production and use as a medicament |
WO2010072399A1 (en) | 2008-12-22 | 2010-07-01 | Gerhard Eisenbrand | 7-azaindirubins, 7'azaindirubins, 7,7'-diazaindirubins and the corresponding 3'-oxime ether derivatives thereof, their production and use as a medicament |
US9072760B2 (en) | 2010-09-24 | 2015-07-07 | University of Pittsburgh—of the Commonwealth System of Higher Education | TLR4 inhibitors for the treatment of human infectious and inflammatory disorders |
WO2012040719A2 (en) * | 2010-09-24 | 2012-03-29 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Novel tlr4 inhibitors for the treatment of human infectious and inflammatory disorders |
US10668092B2 (en) | 2010-09-24 | 2020-06-02 | The John Hopkins University | Compositions and methods for treatment of inflammatory disorders |
WO2012088425A2 (en) | 2010-12-22 | 2012-06-28 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Gap junction-enhancing agents for treatment of necrotizing enterocolitis and inflammatory bowel disease |
JP6019412B2 (ja) * | 2011-07-15 | 2016-11-02 | 学校法人日本大学 | 悪性腫瘍に対する高選択的細胞毒性を有するインディルビン誘導体 |
US8524121B2 (en) * | 2012-01-27 | 2013-09-03 | Xerox Corporation | Bi-indoline-dithione polymers |
AU2013234955A1 (en) | 2012-03-23 | 2014-11-13 | Dennis Brown | Compositions and methods to improve the therapeutic benefit of indirubin and analogs thereof, including meisoindigo |
WO2014052453A1 (en) | 2012-09-25 | 2014-04-03 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Oral therapy of necrotizing enterocolitis |
CN103333161B (zh) * | 2013-05-28 | 2015-09-30 | 滁州市洛达生物科技有限公司 | 1’-氧代靛玉红的制备和用途 |
KR101855423B1 (ko) * | 2017-04-18 | 2018-05-09 | 주식회사 씨케이바이오텍 | 인디루빈 유도체를 유효성분으로 포함하는 약학 조성물 |
CA3080900C (en) * | 2017-10-31 | 2022-10-25 | Pelemed Co., Ltd. | Pharmaceutical composition for preventing or treating acute myeloid leukemia or metastatic breast cancer |
KR102326617B1 (ko) | 2019-06-20 | 2021-11-15 | 서울대학교산학협력단 | 인돌렌인온의 제조 방법 및 인돌렌인온 합성을 통한 인디루빈 유도체의 제조 방법 |
CN110590640B (zh) * | 2019-06-28 | 2020-12-15 | 贵州医科大学 | 一种靛玉红衍生物及其作为cdk/hdac双靶标抑制剂的应用 |
WO2021090172A1 (en) * | 2019-11-04 | 2021-05-14 | Ck Biotechnology Co. | Compositions and methods for suppressing and/or treating neurodegenerative diseases and/or a clinical condition thereof |
WO2021112626A1 (ko) * | 2019-12-06 | 2021-06-10 | 주식회사 펠레메드 | 신규한 인디루빈 유도체 및 이의 용도 |
EP4329748A1 (en) * | 2021-04-29 | 2024-03-06 | Jawaharlal Nehru Centre For Advanced Scientific Research | Indirubin compounds and methods thereof |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS609022B2 (ja) * | 1981-06-19 | 1985-03-07 | イスクラ産業株式会社 | インジルビン誘導体およびそれを含有する抗腫瘍剤 |
JPS609023B2 (ja) * | 1981-06-19 | 1985-03-07 | イスクラ産業株式会社 | インジルビン誘導体およびそれを含有する抗腫瘍剤 |
JPS617254A (ja) * | 1984-06-20 | 1986-01-13 | Isukura Sangyo Kk | ビスインドリノンおよびそれを主成分とする制癌剤 |
HU198946B (en) | 1985-06-12 | 1989-12-28 | Richter Gedeon Vegyeszet | Process for producing new bisindole derivatives with antitumour action and pharmaceutical compositions comprising same |
JPH03223363A (ja) * | 1989-12-06 | 1991-10-02 | Mitsui Toatsu Chem Inc | ロープ染色用染料および染料組成物、これらを用いる染色法、ならびに染色物 |
AU762830B2 (en) | 1998-05-29 | 2003-07-03 | Cnrs (Centre National De Recherche Scientifique) France Innovation Scientifique Et Transfert | Use of indigoid bisindole derivatives for the manufacture of a medicament to inhibit cyclin dependent kinases |
EP0966963A1 (en) * | 1998-05-29 | 1999-12-29 | Gerhard Prof. Dr. Eisenbrand | Use of indigoid bisindole derivatives as CDK1 inhibitors |
-
2000
- 2000-04-12 EA EA200101046A patent/EA200101046A1/ru unknown
- 2000-04-12 WO PCT/EP2000/003285 patent/WO2000061555A1/en not_active Application Discontinuation
- 2000-04-12 CN CN00808852A patent/CN1355789A/zh active Pending
- 2000-04-12 CZ CZ20013555A patent/CZ20013555A3/cs unknown
- 2000-04-12 IL IL14574300A patent/IL145743A0/xx unknown
- 2000-04-12 US US09/958,476 patent/US6987092B1/en not_active Expired - Fee Related
- 2000-04-12 KR KR1020017013056A patent/KR20010112424A/ko not_active Application Discontinuation
- 2000-04-12 CA CA002369670A patent/CA2369670A1/en not_active Abandoned
- 2000-04-12 SK SK1427-2001A patent/SK14272001A3/sk unknown
- 2000-04-12 PL PL00351261A patent/PL351261A1/xx not_active Application Discontinuation
- 2000-04-12 BR BR0009770-5A patent/BR0009770A/pt not_active Application Discontinuation
- 2000-04-12 NZ NZ514663A patent/NZ514663A/xx unknown
- 2000-04-12 MX MXPA01010214A patent/MXPA01010214A/es unknown
- 2000-04-12 AU AU41178/00A patent/AU4117800A/en not_active Abandoned
- 2000-04-12 JP JP2000610830A patent/JP2002541244A/ja active Pending
- 2000-04-12 HU HU0200724A patent/HUP0200724A3/hu unknown
- 2000-04-12 EP EP00920695A patent/EP1169305A1/en not_active Withdrawn
-
2001
- 2001-10-03 BG BG105974A patent/BG105974A/bg unknown
- 2001-10-11 NO NO20014948A patent/NO20014948D0/no not_active Application Discontinuation
- 2001-10-11 HR HR20010735A patent/HRP20010735A2/hr not_active Application Discontinuation
-
2002
- 2002-01-14 HK HK02100234.4A patent/HK1041256A1/zh unknown
Also Published As
Publication number | Publication date |
---|---|
NO20014948L (no) | 2001-10-11 |
NZ514663A (en) | 2002-09-27 |
HRP20010735A2 (en) | 2002-12-31 |
CZ20013555A3 (cs) | 2002-05-15 |
NO20014948D0 (no) | 2001-10-11 |
HK1041256A1 (zh) | 2002-07-05 |
WO2000061555A1 (en) | 2000-10-19 |
JP2002541244A (ja) | 2002-12-03 |
IL145743A0 (en) | 2002-07-25 |
CA2369670A1 (en) | 2000-10-19 |
AU4117800A (en) | 2000-11-14 |
KR20010112424A (ko) | 2001-12-20 |
CN1355789A (zh) | 2002-06-26 |
EP1169305A1 (en) | 2002-01-09 |
PL351261A1 (en) | 2003-04-07 |
US6987092B1 (en) | 2006-01-17 |
MXPA01010214A (es) | 2002-03-27 |
HUP0200724A3 (en) | 2002-10-28 |
SK14272001A3 (sk) | 2002-05-09 |
BR0009770A (pt) | 2002-01-08 |
EA200101046A1 (ru) | 2002-04-25 |
HUP0200724A2 (hu) | 2002-07-29 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
BG105974A (bg) | Индигоидни бисиндолови производни | |
RU2489423C2 (ru) | Водорастворимые аналоги сс-1065 и их конъюгаты | |
BRPI0619331A2 (pt) | método para fazer um composto para preparar um análogo de cbi cc-1065, método para preparar um análogo de cbi cc-1065 e composto | |
RU2584682C2 (ru) | Индолил или индолинилгидроксаматные соединения, их содержащая фармацевтическая композиция (варианты) и способ лечения рака (варианты) с их помощью | |
BRPI0708654A2 (pt) | pró-fármacos melhorados de análogos de cc-1065 | |
CA2229264A1 (en) | Cyclopropylindoles and their seco precursors, and their use as prodrugs | |
US20140206992A1 (en) | Method for diagnosing cancer | |
RU2632206C2 (ru) | Новые алкилирующие средства | |
EP1218004B1 (en) | 5-methyl indirubin for use in the treatment of human solid tumors | |
KR20220008802A (ko) | 변형된 시아닌 염료 및 그것의 콘쥬게이트 | |
NO324594B1 (no) | Nye indolderivater, fremgangsmate for fremstilling derav og deres anvendelse og medikamenter inneholdende derivatene. | |
CN116209722A (zh) | 近红外花青染料及其缀合物 | |
KR20030090712A (ko) | 6 위치에서 치환된 인돌리논 및 키나아제 억제제로서의이의 용도 | |
CN113663067A (zh) | 免疫激活型抗体及其应用 | |
US20040067540A1 (en) | Rapid method for screening compounds for in vivo activity | |
KR20240056582A (ko) | 피리미딘 헤테로사이클릭 화합물의 결정형 및 이의 제조 방법 | |
KR100615345B1 (ko) | 의약으로서 사용되는 포스핀산 및 포스폰산 유도체, 및 이를 포함하는 약제학적 조성물 | |
BR112020004495A2 (pt) | composto, composição, e, método para preparar uma composição. | |
CA2272952A1 (en) | Seco precursors of cyclopropylindolines and their use as prodrugs | |
ZA200108377B (en) | Indigoid bisindole derivatives. | |
BR112021004317A2 (pt) | processos alternativos para a preparação de tubulisinas e intermediários das mesmas | |
NL8205038A (nl) | Esters van 4-hydroxymethyl-1-ftalazonderivaten en zouten daarvan. | |
WO2022178701A1 (zh) | 二茂铁衍生物及其制备方法和用途 | |
CN116601238A (zh) | Ph响应性花青染料及其缀合物 | |
GB2241950A (en) | Heterocyclic oligopeptides endowed with antitumour activity |