CA2530668A1 - Produit comprenant au moins un inhibiteur de phosphatase cdc25 en association avec au moins un autre agent anti-cancereux - Google Patents
Produit comprenant au moins un inhibiteur de phosphatase cdc25 en association avec au moins un autre agent anti-cancereux Download PDFInfo
- Publication number
- CA2530668A1 CA2530668A1 CA002530668A CA2530668A CA2530668A1 CA 2530668 A1 CA2530668 A1 CA 2530668A1 CA 002530668 A CA002530668 A CA 002530668A CA 2530668 A CA2530668 A CA 2530668A CA 2530668 A1 CA2530668 A1 CA 2530668A1
- Authority
- CA
- Canada
- Prior art keywords
- radical
- alkyl
- independently
- radicals
- amino
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 229940127084 other anti-cancer agent Drugs 0.000 title claims abstract description 9
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 title claims description 21
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 title claims description 21
- WFRKJMRGXGWHBM-UHFFFAOYSA-M sodium;octyl sulfate Chemical compound [Na+].CCCCCCCCOS([O-])(=O)=O WFRKJMRGXGWHBM-UHFFFAOYSA-M 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 245
- 150000003839 salts Chemical class 0.000 claims abstract description 62
- 102000007588 cdc25 Phosphatases Human genes 0.000 claims abstract description 56
- 108010046616 cdc25 Phosphatases Proteins 0.000 claims abstract description 56
- 239000003112 inhibitor Substances 0.000 claims abstract description 43
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 41
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims abstract description 24
- 108091007914 CDKs Proteins 0.000 claims abstract description 13
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 12
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 claims abstract description 9
- 201000011510 cancer Diseases 0.000 claims abstract description 9
- 230000001413 cellular effect Effects 0.000 claims abstract description 7
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 claims abstract description 6
- 229940127093 camptothecin Drugs 0.000 claims abstract description 6
- VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 claims abstract description 6
- 230000019491 signal transduction Effects 0.000 claims abstract description 6
- 230000001225 therapeutic effect Effects 0.000 claims abstract description 6
- 101710183280 Topoisomerase Proteins 0.000 claims abstract description 5
- 102000034345 heterotrimeric G proteins Human genes 0.000 claims abstract description 4
- 108091006093 heterotrimeric G proteins Proteins 0.000 claims abstract description 4
- 102000005454 Dimethylallyltranstransferase Human genes 0.000 claims abstract description 3
- 108010006731 Dimethylallyltranstransferase Proteins 0.000 claims abstract description 3
- 239000002168 alkylating agent Substances 0.000 claims abstract description 3
- 229940100198 alkylating agent Drugs 0.000 claims abstract description 3
- 230000032823 cell division Effects 0.000 claims abstract description 3
- 210000004292 cytoskeleton Anatomy 0.000 claims abstract description 3
- -1 alkoxyalkyl radical Chemical group 0.000 claims description 416
- 125000000217 alkyl group Chemical group 0.000 claims description 211
- 150000003254 radicals Chemical class 0.000 claims description 206
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 132
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 114
- 125000005843 halogen group Chemical group 0.000 claims description 98
- 125000000623 heterocyclic group Chemical group 0.000 claims description 93
- 125000003118 aryl group Chemical group 0.000 claims description 75
- 125000003545 alkoxy group Chemical group 0.000 claims description 72
- 125000001424 substituent group Chemical group 0.000 claims description 63
- 229940122907 Phosphatase inhibitor Drugs 0.000 claims description 49
- 229910052757 nitrogen Inorganic materials 0.000 claims description 42
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 38
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 38
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 36
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 36
- 125000004429 atom Chemical group 0.000 claims description 35
- 229910052739 hydrogen Inorganic materials 0.000 claims description 35
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 33
- 239000001257 hydrogen Substances 0.000 claims description 32
- 125000001188 haloalkyl group Chemical group 0.000 claims description 30
- 125000005842 heteroatom Chemical group 0.000 claims description 30
- 238000006243 chemical reaction Methods 0.000 claims description 27
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 26
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 24
- 238000000034 method Methods 0.000 claims description 24
- 229910052736 halogen Inorganic materials 0.000 claims description 22
- 229910052717 sulfur Inorganic materials 0.000 claims description 21
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 20
- 150000005840 aryl radicals Chemical class 0.000 claims description 20
- 229910052760 oxygen Inorganic materials 0.000 claims description 20
- 125000001072 heteroaryl group Chemical group 0.000 claims description 19
- 125000004414 alkyl thio group Chemical group 0.000 claims description 18
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 18
- 125000004432 carbon atom Chemical group C* 0.000 claims description 17
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 17
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 15
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 15
- 125000003282 alkyl amino group Chemical group 0.000 claims description 14
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
- 230000000295 complement effect Effects 0.000 claims description 12
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 12
- 229910052799 carbon Inorganic materials 0.000 claims description 11
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 10
- 239000003795 chemical substances by application Substances 0.000 claims description 10
- JEVCWSUVFOYBFI-UHFFFAOYSA-N cyanyl Chemical compound N#[C] JEVCWSUVFOYBFI-UHFFFAOYSA-N 0.000 claims description 10
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 10
- BLNWTAHYTCHDJH-UHFFFAOYSA-O hydroxy(oxo)azanium Chemical compound O[NH+]=O BLNWTAHYTCHDJH-UHFFFAOYSA-O 0.000 claims description 10
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 9
- 125000003342 alkenyl group Chemical group 0.000 claims description 9
- 230000001093 anti-cancer Effects 0.000 claims description 9
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 9
- MJVAVZPDRWSRRC-UHFFFAOYSA-N vitamin K3 Natural products C1=CC=C2C(=O)C(C)=CC(=O)C2=C1 MJVAVZPDRWSRRC-UHFFFAOYSA-N 0.000 claims description 9
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 claims description 8
- SLRMQYXOBQWXCR-UHFFFAOYSA-N 2154-56-5 Chemical compound [CH2]C1=CC=CC=C1 SLRMQYXOBQWXCR-UHFFFAOYSA-N 0.000 claims description 8
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 8
- 125000000304 alkynyl group Chemical group 0.000 claims description 8
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 8
- 125000002837 carbocyclic group Chemical group 0.000 claims description 8
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 8
- GUJAGMICFDYKNR-UHFFFAOYSA-N 1,4-benzodiazepine Chemical compound N1C=CN=CC2=CC=CC=C12 GUJAGMICFDYKNR-UHFFFAOYSA-N 0.000 claims description 7
- LFQCJSBXBZRMTN-OAQYLSRUSA-N diflomotecan Chemical compound CC[C@@]1(O)CC(=O)OCC(C2=O)=C1C=C1N2CC2=CC3=CC(F)=C(F)C=C3N=C21 LFQCJSBXBZRMTN-OAQYLSRUSA-N 0.000 claims description 7
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 6
- 150000001721 carbon Chemical group 0.000 claims description 6
- 125000002757 morpholinyl group Chemical group 0.000 claims description 6
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 6
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 5
- 108091000080 Phosphotransferase Proteins 0.000 claims description 5
- 230000015572 biosynthetic process Effects 0.000 claims description 5
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 5
- TUJKJAMUKRIRHC-UHFFFAOYSA-N hydroxyl Chemical compound [OH] TUJKJAMUKRIRHC-UHFFFAOYSA-N 0.000 claims description 5
- 102000020233 phosphotransferase Human genes 0.000 claims description 5
- 125000004076 pyridyl group Chemical group 0.000 claims description 5
- 125000001544 thienyl group Chemical group 0.000 claims description 5
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 5
- 125000004953 trihalomethyl group Chemical group 0.000 claims description 5
- 235000012711 vitamin K3 Nutrition 0.000 claims description 5
- 239000011652 vitamin K3 Substances 0.000 claims description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- 102000007317 Farnesyltranstransferase Human genes 0.000 claims description 4
- 108010007508 Farnesyltranstransferase Proteins 0.000 claims description 4
- SVSARCCKBMZNMR-UHFFFAOYSA-N [1-[2-[methyl-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethyl]amino]ethyl]pyridin-4-ylidene]methyl-oxoazanium;dichloride Chemical compound [Cl-].[Cl-].C1=CC(=C[NH+]=O)C=CN1CCN(C)CCN1C=CC(=C[NH+]=O)C=C1 SVSARCCKBMZNMR-UHFFFAOYSA-N 0.000 claims description 4
- 125000000278 alkyl amino alkyl group Chemical group 0.000 claims description 4
- 125000006350 alkyl thio alkyl group Chemical group 0.000 claims description 4
- 125000003368 amide group Chemical group 0.000 claims description 4
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 4
- 125000002883 imidazolyl group Chemical group 0.000 claims description 4
- 125000004628 isothiazolidinyl group Chemical group S1N(CCC1)* 0.000 claims description 4
- 125000004193 piperazinyl group Chemical group 0.000 claims description 4
- 239000002798 polar solvent Substances 0.000 claims description 4
- 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 claims description 4
- 125000003107 substituted aryl group Chemical group 0.000 claims description 4
- 229940041603 vitamin k 3 Drugs 0.000 claims description 4
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 3
- 102000016736 Cyclin Human genes 0.000 claims description 3
- 108050006400 Cyclin Proteins 0.000 claims description 3
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 3
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 3
- 230000001419 dependent effect Effects 0.000 claims description 3
- JYGFTBXVXVMTGB-UHFFFAOYSA-N indolin-2-one Chemical compound C1=CC=C2NC(=O)CC2=C1 JYGFTBXVXVMTGB-UHFFFAOYSA-N 0.000 claims description 3
- 125000001624 naphthyl group Chemical group 0.000 claims description 3
- CFHIDWOYWUOIHU-UHFFFAOYSA-N oxomethyl Chemical compound O=[CH] CFHIDWOYWUOIHU-UHFFFAOYSA-N 0.000 claims description 3
- 238000003786 synthesis reaction Methods 0.000 claims description 3
- 125000000335 thiazolyl group Chemical group 0.000 claims description 3
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 2
- GNYQLPKGXMSQNY-UHFFFAOYSA-N 2-methyl-5-(2-piperidin-1-ylethylamino)-1,3-benzothiazole-4,7-dione Chemical compound S1C(C)=NC(C2=O)=C1C(=O)C=C2NCCN1CCCCC1 GNYQLPKGXMSQNY-UHFFFAOYSA-N 0.000 claims description 2
- LSDWHZYIIRIPCU-UHFFFAOYSA-N 2-methyl-5-(2-pyrrolidin-1-ylethylamino)-1,3-benzothiazole-4,7-dione Chemical compound S1C(C)=NC(C2=O)=C1C(=O)C=C2NCCN1CCCC1 LSDWHZYIIRIPCU-UHFFFAOYSA-N 0.000 claims description 2
- 125000006088 2-oxoazepinyl group Chemical group 0.000 claims description 2
- 125000004638 2-oxopiperazinyl group Chemical group O=C1N(CCNC1)* 0.000 claims description 2
- 125000004637 2-oxopiperidinyl group Chemical group O=C1N(CCCC1)* 0.000 claims description 2
- MTUYOFGUEXWKLC-UHFFFAOYSA-N 5-[2-(dimethylamino)ethylamino]-2-methyl-1,3-benzothiazole-4,7-dione Chemical compound O=C1C(NCCN(C)C)=CC(=O)C2=C1N=C(C)S2 MTUYOFGUEXWKLC-UHFFFAOYSA-N 0.000 claims description 2
- 101100509371 Arabidopsis thaliana CHR11 gene Proteins 0.000 claims description 2
- 108091006027 G proteins Proteins 0.000 claims description 2
- 102000030782 GTP binding Human genes 0.000 claims description 2
- 108091000058 GTP-Binding Proteins 0.000 claims description 2
- LFMFPKKYRXFHHZ-UHFFFAOYSA-N R24 Chemical compound C1=C(Cl)C(C)=CC=C1NC1=NC(N)=C(C=CC=C2)C2=N1 LFMFPKKYRXFHHZ-UHFFFAOYSA-N 0.000 claims description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- YUDRVAHLXDBKSR-UHFFFAOYSA-N [CH]1CCCCC1 Chemical compound [CH]1CCCCC1 YUDRVAHLXDBKSR-UHFFFAOYSA-N 0.000 claims description 2
- BQIKRTGTPBOIMK-UHFFFAOYSA-N [O]C[O] Chemical compound [O]C[O] BQIKRTGTPBOIMK-UHFFFAOYSA-N 0.000 claims description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 2
- 125000005099 aryl alkyl carbonyl group Chemical group 0.000 claims description 2
- 125000004659 aryl alkyl thio group Chemical group 0.000 claims description 2
- 125000004104 aryloxy group Chemical group 0.000 claims description 2
- 125000002785 azepinyl group Chemical group 0.000 claims description 2
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 2
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 claims description 2
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
- 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 claims description 2
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 2
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
- 125000004600 benzothiopyranyl group Chemical group S1C(C=CC2=C1C=CC=C2)* 0.000 claims description 2
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 2
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 claims description 2
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 claims description 2
- 229920001577 copolymer Chemical group 0.000 claims description 2
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 2
- 125000005366 cycloalkylthio group Chemical group 0.000 claims description 2
- 125000004598 dihydrobenzofuryl group Chemical group O1C(CC2=C1C=CC=C2)* 0.000 claims description 2
- 125000004582 dihydrobenzothienyl group Chemical group S1C(CC2=C1C=CC=C2)* 0.000 claims description 2
- 125000004597 dihydrobenzothiopyranyl group Chemical group S1C(CCC2=C1C=CC=C2)* 0.000 claims description 2
- 239000000539 dimer Substances 0.000 claims description 2
- 125000004993 haloalkoxycarbonyl group Chemical group 0.000 claims description 2
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical group O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 claims description 2
- 125000002632 imidazolidinyl group Chemical group 0.000 claims description 2
- 125000002636 imidazolinyl group Chemical group 0.000 claims description 2
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 2
- 125000001041 indolyl group Chemical group 0.000 claims description 2
- 125000003384 isochromanyl group Chemical group C1(OCCC2=CC=CC=C12)* 0.000 claims description 2
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 claims description 2
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 2
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 claims description 2
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 2
- 125000005476 oxopyrrolidinyl group Chemical group 0.000 claims description 2
- 125000005936 piperidyl group Chemical group 0.000 claims description 2
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 2
- 239000011593 sulfur Substances 0.000 claims description 2
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 2
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 claims description 2
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 claims description 2
- 125000005329 tetralinyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims description 2
- 125000006089 thiamorpholinyl sulfoxide group Chemical group 0.000 claims description 2
- 125000002769 thiazolinyl group Chemical group 0.000 claims description 2
- 125000004589 thienofuryl group Chemical group O1C(=CC2=C1C=CS2)* 0.000 claims description 2
- 125000004587 thienothienyl group Chemical group S1C(=CC2=C1C=CS2)* 0.000 claims description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims 4
- 102000019337 Prenyltransferases Human genes 0.000 claims 2
- 108050006837 Prenyltransferases Proteins 0.000 claims 2
- WCUXJAHSNPROCI-UHFFFAOYSA-N 2-(2-chloro-6-fluorophenyl)-5-[2-(dimethylamino)ethylamino]-1,3-benzothiazole-4,7-dione Chemical compound N=1C=2C(=O)C(NCCN(C)C)=CC(=O)C=2SC=1C1=C(F)C=CC=C1Cl WCUXJAHSNPROCI-UHFFFAOYSA-N 0.000 claims 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 claims 1
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims 1
- 125000005055 alkyl alkoxy group Chemical group 0.000 claims 1
- RMRFFCXPLWYOOY-UHFFFAOYSA-N allyl radical Chemical compound [CH2]C=C RMRFFCXPLWYOOY-UHFFFAOYSA-N 0.000 claims 1
- 125000004601 benzofurazanyl group Chemical group N1=C2C(=NO1)C(=CC=C2)* 0.000 claims 1
- 150000002019 disulfides Chemical class 0.000 claims 1
- 239000003534 dna topoisomerase inhibitor Substances 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 229940044693 topoisomerase inhibitor Drugs 0.000 claims 1
- 150000003716 vitamin K3 derivatives Chemical group 0.000 claims 1
- 239000002246 antineoplastic agent Substances 0.000 abstract description 44
- 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 abstract description 12
- 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 abstract description 10
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 abstract description 9
- 229960004857 mitomycin Drugs 0.000 abstract description 6
- 229960004316 cisplatin Drugs 0.000 abstract description 5
- 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 abstract description 4
- 229960004679 doxorubicin Drugs 0.000 abstract description 4
- 102000003903 Cyclin-dependent kinases Human genes 0.000 abstract description 3
- 108090000266 Cyclin-dependent kinases Proteins 0.000 abstract description 3
- 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 abstract description 3
- 229960001220 amsacrine Drugs 0.000 abstract description 3
- 229960000485 methotrexate Drugs 0.000 abstract description 3
- 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 abstract description 3
- 230000006820 DNA synthesis Effects 0.000 abstract description 2
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 abstract description 2
- 239000003528 protein farnesyltransferase inhibitor Substances 0.000 abstract description 2
- 229960003048 vinblastine Drugs 0.000 abstract description 2
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 abstract description 2
- 239000004052 folic acid antagonist Substances 0.000 abstract 1
- 239000000203 mixture Substances 0.000 description 164
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 144
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 78
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 76
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 76
- 239000000047 product Substances 0.000 description 66
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 65
- 238000005481 NMR spectroscopy Methods 0.000 description 59
- 238000005160 1H NMR spectroscopy Methods 0.000 description 57
- 239000000243 solution Substances 0.000 description 52
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 50
- 210000004027 cell Anatomy 0.000 description 50
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
- LOQLWFZHXKIBLK-UHFFFAOYSA-N 1,3-benzoxazole-2,4-dione Chemical group C1=CC(=O)C2=NC(=O)OC2=C1 LOQLWFZHXKIBLK-UHFFFAOYSA-N 0.000 description 46
- 238000006073 displacement reaction Methods 0.000 description 46
- 238000002844 melting Methods 0.000 description 45
- 230000008018 melting Effects 0.000 description 45
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 42
- 239000000543 intermediate Substances 0.000 description 40
- 238000012360 testing method Methods 0.000 description 39
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 36
- 230000004663 cell proliferation Effects 0.000 description 32
- 230000002829 reductive effect Effects 0.000 description 32
- AFMPMSCZPVNPEM-UHFFFAOYSA-N 2-bromobenzonitrile Chemical compound BrC1=CC=CC=C1C#N AFMPMSCZPVNPEM-UHFFFAOYSA-N 0.000 description 30
- 239000000377 silicon dioxide Substances 0.000 description 30
- DILRJUIACXKSQE-UHFFFAOYSA-N n',n'-dimethylethane-1,2-diamine Chemical compound CN(C)CCN DILRJUIACXKSQE-UHFFFAOYSA-N 0.000 description 29
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 27
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- 239000002131 composite material Substances 0.000 description 27
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 25
- 239000002904 solvent Substances 0.000 description 25
- 239000011541 reaction mixture Substances 0.000 description 23
- 239000000843 powder Substances 0.000 description 22
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 20
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 20
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 19
- 239000003480 eluent Substances 0.000 description 19
- WRXNJTBODVGDRY-UHFFFAOYSA-N 2-pyrrolidin-1-ylethanamine Chemical compound NCCN1CCCC1 WRXNJTBODVGDRY-UHFFFAOYSA-N 0.000 description 18
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 18
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 18
- 238000004587 chromatography analysis Methods 0.000 description 18
- 239000012074 organic phase Substances 0.000 description 18
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 16
- 239000002253 acid Substances 0.000 description 16
- 239000007787 solid Substances 0.000 description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical group CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 13
- 238000002360 preparation method Methods 0.000 description 12
- 238000001914 filtration Methods 0.000 description 11
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 11
- 238000000746 purification Methods 0.000 description 11
- 239000012429 reaction media Substances 0.000 description 11
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 230000009471 action Effects 0.000 description 10
- 229960000583 acetic acid Drugs 0.000 description 9
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 9
- 235000019341 magnesium sulphate Nutrition 0.000 description 9
- FGWYWKIOMUZSQF-UHFFFAOYSA-N 1,1,1-triethoxypropane Chemical compound CCOC(CC)(OCC)OCC FGWYWKIOMUZSQF-UHFFFAOYSA-N 0.000 description 8
- YRLKKEUFEGYXKE-UHFFFAOYSA-N 2-amino-1,3-benzoxazole-4,7-dione Chemical compound NC=1OC2=C(N=1)C(C=CC2=O)=O YRLKKEUFEGYXKE-UHFFFAOYSA-N 0.000 description 8
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 8
- 229910052681 coesite Inorganic materials 0.000 description 8
- 229910052906 cristobalite Inorganic materials 0.000 description 8
- 235000012239 silicon dioxide Nutrition 0.000 description 8
- 229910052682 stishovite Inorganic materials 0.000 description 8
- 229910052905 tridymite Inorganic materials 0.000 description 8
- BTHOJZRXYXQUTI-UHFFFAOYSA-N 1,3-benzothiazole-4,7-dione Chemical class O=C1C=CC(=O)C2=C1N=CS2 BTHOJZRXYXQUTI-UHFFFAOYSA-N 0.000 description 7
- 102000004190 Enzymes Human genes 0.000 description 7
- 108090000790 Enzymes Proteins 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- 239000007864 aqueous solution Substances 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 239000002609 medium Substances 0.000 description 7
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- 229910052938 sodium sulfate Inorganic materials 0.000 description 7
- 235000011152 sodium sulphate Nutrition 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- 238000004809 thin layer chromatography Methods 0.000 description 7
- KGCQVCRIAZKTIR-UHFFFAOYSA-N 1,3-benzoxazole-4,7-dione Chemical class O=C1C=CC(=O)C2=C1N=CO2 KGCQVCRIAZKTIR-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 6
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 6
- 238000009833 condensation Methods 0.000 description 6
- 230000005494 condensation Effects 0.000 description 6
- WCYWZMWISLQXQU-UHFFFAOYSA-N methyl Chemical compound [CH3] WCYWZMWISLQXQU-UHFFFAOYSA-N 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 6
- GDHXJNRAJRCGMX-UHFFFAOYSA-N 2-fluorobenzonitrile Chemical compound FC1=CC=CC=C1C#N GDHXJNRAJRCGMX-UHFFFAOYSA-N 0.000 description 5
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 5
- 229930012538 Paclitaxel Natural products 0.000 description 5
- 229910004298 SiO 2 Inorganic materials 0.000 description 5
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 230000004927 fusion Effects 0.000 description 5
- 229960001592 paclitaxel Drugs 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 5
- CCNOLEZFWHPBBC-UHFFFAOYSA-N 2-(2,6-difluorophenyl)-5-methoxy-1,3-benzothiazole-4,7-dione Chemical compound N=1C=2C(=O)C(OC)=CC(=O)C=2SC=1C1=C(F)C=CC=C1F CCNOLEZFWHPBBC-UHFFFAOYSA-N 0.000 description 4
- GDCQVRBAMXJYJC-UHFFFAOYSA-N 2-ethyl-1,3-benzoxazole-4,7-dione Chemical compound O=C1C=CC(=O)C2=C1OC(CC)=N2 GDCQVRBAMXJYJC-UHFFFAOYSA-N 0.000 description 4
- OLYFGLXPXPABOP-XXIQNXCHSA-N 220997-99-9 Chemical compound Cl.C([C@]1(O)CC)C(=O)OCC(C(N2CC3=4)=O)=C1C=C2C3=NC1=CC(Cl)=C(C)C=C1C=4CN1CCC(C)CC1 OLYFGLXPXPABOP-XXIQNXCHSA-N 0.000 description 4
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 description 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 4
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 4
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
- 229910052794 bromium Inorganic materials 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- 238000003379 elimination reaction Methods 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 125000000524 functional group Chemical group 0.000 description 4
- ZQBFAOFFOQMSGJ-UHFFFAOYSA-N hexafluorobenzene Chemical compound FC1=C(F)C(F)=C(F)C(F)=C1F ZQBFAOFFOQMSGJ-UHFFFAOYSA-N 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 125000003386 piperidinyl group Chemical group 0.000 description 4
- 230000035755 proliferation Effects 0.000 description 4
- 235000018102 proteins Nutrition 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 4
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 4
- 239000012047 saturated solution Substances 0.000 description 4
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 4
- 239000003039 volatile agent Substances 0.000 description 4
- SCZNXLWKYFICFV-UHFFFAOYSA-N 1,2,3,4,5,7,8,9-octahydropyrido[1,2-b]diazepine Chemical compound C1CCCNN2CCCC=C21 SCZNXLWKYFICFV-UHFFFAOYSA-N 0.000 description 3
- GKPHNZYMLJPYJJ-UHFFFAOYSA-N 2,3-difluorobenzonitrile Chemical compound FC1=CC=CC(C#N)=C1F GKPHNZYMLJPYJJ-UHFFFAOYSA-N 0.000 description 3
- LCISFYAQKHOWBP-UHFFFAOYSA-N 2-chloro-5-(trifluoromethyl)benzonitrile Chemical compound FC(F)(F)C1=CC=C(Cl)C(C#N)=C1 LCISFYAQKHOWBP-UHFFFAOYSA-N 0.000 description 3
- OGQYJDHTHFAPRN-UHFFFAOYSA-N 2-fluoro-6-(trifluoromethyl)benzonitrile Chemical compound FC1=CC=CC(C(F)(F)F)=C1C#N OGQYJDHTHFAPRN-UHFFFAOYSA-N 0.000 description 3
- IVLRKZIPVIULOL-UHFFFAOYSA-N 2-methyl-1,3-benzothiazole-4,7-dione Chemical compound O=C1C=CC(=O)C2=C1SC(C)=N2 IVLRKZIPVIULOL-UHFFFAOYSA-N 0.000 description 3
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 description 3
- QWBZNOKUBXSLRE-UHFFFAOYSA-N 3-O-methylfluorescein 6-phosphate Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(OP(O)(O)=O)C=C1OC1=CC(OC)=CC=C21 QWBZNOKUBXSLRE-UHFFFAOYSA-N 0.000 description 3
- ZPMBWIBEGMMUSR-UHFFFAOYSA-N 5-anilino-2-ethyl-1,3-benzoxazole-4,7-dione Chemical compound O1C(CC)=NC(C2=O)=C1C(=O)C=C2NC1=CC=CC=C1 ZPMBWIBEGMMUSR-UHFFFAOYSA-N 0.000 description 3
- SBQFGJRZLXSCFL-UHFFFAOYSA-N 8-bromo-2-methylsulfanyl-n-(pyridin-3-ylmethyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine Chemical compound N12N=CC(Br)=C2N=C(SC)N=C1NCC1=CC=CN=C1 SBQFGJRZLXSCFL-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 229940043378 cyclin-dependent kinase inhibitor Drugs 0.000 description 3
- IUNMPGNGSSIWFP-UHFFFAOYSA-N dimethylaminopropylamine Chemical compound CN(C)CCCN IUNMPGNGSSIWFP-UHFFFAOYSA-N 0.000 description 3
- 125000004119 disulfanediyl group Chemical group *SS* 0.000 description 3
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 3
- 230000008030 elimination Effects 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 230000002255 enzymatic effect Effects 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- 239000011630 iodine Substances 0.000 description 3
- 150000002596 lactones Chemical group 0.000 description 3
- CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 3
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical compound [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 3
- LNTQTAKMAZWNSW-UHFFFAOYSA-N n-(2,5-dimethoxyphenyl)cyclohexanecarbothioamide Chemical compound COC1=CC=C(OC)C(NC(=S)C2CCCCC2)=C1 LNTQTAKMAZWNSW-UHFFFAOYSA-N 0.000 description 3
- BVAITUYABNDCPN-UHFFFAOYSA-N n-(2,5-dimethoxyphenyl)cyclohexanecarboxamide Chemical compound COC1=CC=C(OC)C(NC(=O)C2CCCCC2)=C1 BVAITUYABNDCPN-UHFFFAOYSA-N 0.000 description 3
- NTMHWRHEGDRTPD-UHFFFAOYSA-N n-(4-azidosulfonylphenyl)acetamide Chemical compound CC(=O)NC1=CC=C(S(=O)(=O)N=[N+]=[N-])C=C1 NTMHWRHEGDRTPD-UHFFFAOYSA-N 0.000 description 3
- RWIVICVCHVMHMU-UHFFFAOYSA-N n-aminoethylmorpholine Chemical compound NCCN1CCOCC1 RWIVICVCHVMHMU-UHFFFAOYSA-N 0.000 description 3
- 150000002905 orthoesters Chemical class 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 125000002456 taxol group Chemical group 0.000 description 3
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
- IECKAVQTURBPON-UHFFFAOYSA-N trimethoxymethylbenzene Chemical compound COC(OC)(OC)C1=CC=CC=C1 IECKAVQTURBPON-UHFFFAOYSA-N 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- 239000008096 xylene Substances 0.000 description 3
- PEZNEXFPRSOYPL-UHFFFAOYSA-N (bis(trifluoroacetoxy)iodo)benzene Chemical compound FC(F)(F)C(=O)OI(OC(=O)C(F)(F)F)C1=CC=CC=C1 PEZNEXFPRSOYPL-UHFFFAOYSA-N 0.000 description 2
- GLTGXIGJLCSEAM-UHFFFAOYSA-N 2,3,4,5-tetrafluorobenzonitrile Chemical compound FC1=CC(C#N)=C(F)C(F)=C1F GLTGXIGJLCSEAM-UHFFFAOYSA-N 0.000 description 2
- KTPHYLJFAZNALV-UHFFFAOYSA-N 2,3,4-trifluorobenzonitrile Chemical compound FC1=CC=C(C#N)C(F)=C1F KTPHYLJFAZNALV-UHFFFAOYSA-N 0.000 description 2
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 description 2
- OJTMHIMQUQOLJV-UHFFFAOYSA-N 2,5-difluorobenzonitrile Chemical compound FC1=CC=C(F)C(C#N)=C1 OJTMHIMQUQOLJV-UHFFFAOYSA-N 0.000 description 2
- NAZDVUBIEPVUKE-UHFFFAOYSA-N 2,5-dimethoxyaniline Chemical class COC1=CC=C(OC)C(N)=C1 NAZDVUBIEPVUKE-UHFFFAOYSA-N 0.000 description 2
- DEDKKOOGYIMMBC-UHFFFAOYSA-N 2,6-dichloro-5-fluoropyridine-3-carbonitrile Chemical compound FC1=CC(C#N)=C(Cl)N=C1Cl DEDKKOOGYIMMBC-UHFFFAOYSA-N 0.000 description 2
- NRQAKUXSQZZBSB-UHFFFAOYSA-N 2-(2,6-difluorophenyl)-4-nitro-1,3-benzoxazole Chemical compound N=1C=2C([N+](=O)[O-])=CC=CC=2OC=1C1=C(F)C=CC=C1F NRQAKUXSQZZBSB-UHFFFAOYSA-N 0.000 description 2
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 2
- PAWQVTBBRAZDMG-UHFFFAOYSA-N 2-(3-bromo-2-fluorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC(Br)=C1F PAWQVTBBRAZDMG-UHFFFAOYSA-N 0.000 description 2
- HXWPKDLSQVPQNG-UHFFFAOYSA-N 2-(4-fluorophenyl)-5-(2-pyrrolidin-1-ylethylamino)-1,3-benzothiazole-4,7-dione Chemical compound C1=CC(F)=CC=C1C1=NC(C(C(NCCN2CCCC2)=CC2=O)=O)=C2S1 HXWPKDLSQVPQNG-UHFFFAOYSA-N 0.000 description 2
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
- KUCWUAFNGCMZDB-UHFFFAOYSA-N 2-amino-3-nitrophenol Chemical compound NC1=C(O)C=CC=C1[N+]([O-])=O KUCWUAFNGCMZDB-UHFFFAOYSA-N 0.000 description 2
- XPTAYRHLHAFUOS-UHFFFAOYSA-N 2-chloro-6-fluorobenzonitrile Chemical compound FC1=CC=CC(Cl)=C1C#N XPTAYRHLHAFUOS-UHFFFAOYSA-N 0.000 description 2
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 2
- PHFSCOHSDUXPSK-UHFFFAOYSA-N 2-cyclohexyl-4,7-dimethoxy-1,3-benzothiazole Chemical compound N=1C=2C(OC)=CC=C(OC)C=2SC=1C1CCCCC1 PHFSCOHSDUXPSK-UHFFFAOYSA-N 0.000 description 2
- OSRMNRFXLQPQQA-UHFFFAOYSA-N 2-cyclohexyl-5-(2-pyrrolidin-1-ylethylamino)-1,3-benzothiazole-4,7-dione Chemical compound O=C1C=2N=C(C3CCCCC3)SC=2C(=O)C=C1NCCN1CCCC1 OSRMNRFXLQPQQA-UHFFFAOYSA-N 0.000 description 2
- ASWXQMIZDXNTKA-UHFFFAOYSA-N 2-ethyl-1,3-benzoxazol-4-amine Chemical compound C1=CC=C2OC(CC)=NC2=C1N ASWXQMIZDXNTKA-UHFFFAOYSA-N 0.000 description 2
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 2
- KDXNYSZNOWTPLE-UHFFFAOYSA-N 3'-hydroxy-6'-methoxyspiro[2-benzofuran-3,9'-xanthene]-1-one Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(OC)=CC=C21 KDXNYSZNOWTPLE-UHFFFAOYSA-N 0.000 description 2
- XFKYJMGXZXJYBS-UHFFFAOYSA-N 3,4,5-trifluorobenzonitrile Chemical compound FC1=CC(C#N)=CC(F)=C1F XFKYJMGXZXJYBS-UHFFFAOYSA-N 0.000 description 2
- CQXZSEXZQVKCHW-UHFFFAOYSA-N 3,5-difluorobenzonitrile Chemical compound FC1=CC(F)=CC(C#N)=C1 CQXZSEXZQVKCHW-UHFFFAOYSA-N 0.000 description 2
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 description 2
- KUQQONVKIURIQU-UHFFFAOYSA-N 3-fluoro-4-methylbenzonitrile Chemical compound CC1=CC=C(C#N)C=C1F KUQQONVKIURIQU-UHFFFAOYSA-N 0.000 description 2
- ZAFKWADGQSJLBQ-UHFFFAOYSA-N 3-n-methylbutane-2,3-diamine Chemical compound CNC(C)C(C)N ZAFKWADGQSJLBQ-UHFFFAOYSA-N 0.000 description 2
- YEJRWHAVMIAJKC-UHFFFAOYSA-N 4-Butyrolactone Chemical compound O=C1CCCO1 YEJRWHAVMIAJKC-UHFFFAOYSA-N 0.000 description 2
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 2
- WAYQKVSKSDCGSG-UHFFFAOYSA-N 5-methoxy-2-methyl-1,3-benzothiazole-4,7-dione Chemical compound O=C1C(OC)=CC(=O)C2=C1N=C(C)S2 WAYQKVSKSDCGSG-UHFFFAOYSA-N 0.000 description 2
- DMIIMPQQPXUKOO-UHFFFAOYSA-N 5-methylcyclohexane-1,3-dione Chemical compound CC1CC(=O)CC(=O)C1 DMIIMPQQPXUKOO-UHFFFAOYSA-N 0.000 description 2
- RGQCBAKQUWQVCY-UHFFFAOYSA-N 6-anilino-2-ethyl-1,3-benzoxazole-4,7-dione Chemical compound O1C(CC)=NC(C(C=2)=O)=C1C(=O)C=2NC1=CC=CC=C1 RGQCBAKQUWQVCY-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
- 206010006187 Breast cancer Diseases 0.000 description 2
- 208000026310 Breast neoplasm Diseases 0.000 description 2
- FHYQTAPNRRTBFY-UHFFFAOYSA-N CN(CCNC1=CC(C2=C(N=CS2)C1=O)=O)C Chemical compound CN(CCNC1=CC(C2=C(N=CS2)C1=O)=O)C FHYQTAPNRRTBFY-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- 206010009944 Colon cancer Diseases 0.000 description 2
- 108020005199 Dehydrogenases Proteins 0.000 description 2
- WZKSXHQDXQKIQJ-UHFFFAOYSA-N F[C](F)F Chemical compound F[C](F)F WZKSXHQDXQKIQJ-UHFFFAOYSA-N 0.000 description 2
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-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
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 2
- 229930182555 Penicillin Natural products 0.000 description 2
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical group N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 206010060862 Prostate cancer Diseases 0.000 description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-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
- ZBIKORITPGTTGI-UHFFFAOYSA-N [acetyloxy(phenyl)-$l^{3}-iodanyl] acetate Chemical compound CC(=O)OI(OC(C)=O)C1=CC=CC=C1 ZBIKORITPGTTGI-UHFFFAOYSA-N 0.000 description 2
- UGAPHEBNTGUMBB-UHFFFAOYSA-N acetic acid;ethyl acetate Chemical compound CC(O)=O.CCOC(C)=O UGAPHEBNTGUMBB-UHFFFAOYSA-N 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 238000005899 aromatization reaction Methods 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 125000002393 azetidinyl group Chemical group 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 2
- 239000004327 boric acid Substances 0.000 description 2
- 238000005893 bromination reaction Methods 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 230000022131 cell cycle Effects 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 208000029742 colonic neoplasm Diseases 0.000 description 2
- 238000004737 colorimetric analysis Methods 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- 239000007822 coupling agent Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- HJSLFCCWAKVHIW-UHFFFAOYSA-N cyclohexane-1,3-dione Chemical compound O=C1CCCC(=O)C1 HJSLFCCWAKVHIW-UHFFFAOYSA-N 0.000 description 2
- UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 238000010586 diagram Methods 0.000 description 2
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 125000001153 fluoro group Chemical group F* 0.000 description 2
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
- 230000026030 halogenation Effects 0.000 description 2
- 238000005658 halogenation reaction Methods 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 2
- QWTDNUCVQCZILF-UHFFFAOYSA-N isopentane Chemical compound CCC(C)C QWTDNUCVQCZILF-UHFFFAOYSA-N 0.000 description 2
- 238000012417 linear regression Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000004811 liquid chromatography Methods 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 230000002438 mitochondrial effect Effects 0.000 description 2
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 2
- RIVIDPPYRINTTH-UHFFFAOYSA-N n-ethylpropan-2-amine Chemical compound CCNC(C)C RIVIDPPYRINTTH-UHFFFAOYSA-N 0.000 description 2
- 150000002923 oximes Chemical class 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229940049954 penicillin Drugs 0.000 description 2
- 238000005897 peptide coupling reaction Methods 0.000 description 2
- 238000010647 peptide synthesis reaction Methods 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- YZTJYBJCZXZGCT-UHFFFAOYSA-N phenylpiperazine Chemical compound C1CNCCN1C1=CC=CC=C1 YZTJYBJCZXZGCT-UHFFFAOYSA-N 0.000 description 2
- 229920000137 polyphosphoric acid Polymers 0.000 description 2
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 2
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 2
- JQRYUMGHOUYJFW-UHFFFAOYSA-N pyridine;trihydrobromide Chemical compound [Br-].[Br-].[Br-].C1=CC=[NH+]C=C1.C1=CC=[NH+]C=C1.C1=CC=[NH+]C=C1 JQRYUMGHOUYJFW-UHFFFAOYSA-N 0.000 description 2
- 125000000168 pyrrolyl group Chemical group 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- SVOOVMQUISJERI-UHFFFAOYSA-K rhodium(3+);triacetate Chemical compound [Rh+3].CC([O-])=O.CC([O-])=O.CC([O-])=O SVOOVMQUISJERI-UHFFFAOYSA-K 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- JUJBNYBVVQSIOU-UHFFFAOYSA-M sodium;4-[2-(4-iodophenyl)-3-(4-nitrophenyl)tetrazol-2-ium-5-yl]benzene-1,3-disulfonate Chemical compound [Na+].C1=CC([N+](=O)[O-])=CC=C1N1[N+](C=2C=CC(I)=CC=2)=NC(C=2C(=CC(=CC=2)S([O-])(=O)=O)S([O-])(=O)=O)=N1 JUJBNYBVVQSIOU-UHFFFAOYSA-M 0.000 description 2
- 229960005322 streptomycin Drugs 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 2
- 125000003831 tetrazolyl group Chemical group 0.000 description 2
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
- VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 1
- JKFFCLLPXXOZNV-AWEZNQCLSA-N (2r)-2-[[8-bromo-4-[(3-fluorophenyl)methylamino]pyrazolo[1,5-a][1,3,5]triazin-2-yl]amino]-3-methylbutan-1-ol Chemical compound N12N=CC(Br)=C2N=C(N[C@@H](CO)C(C)C)N=C1NCC1=CC=CC(F)=C1 JKFFCLLPXXOZNV-AWEZNQCLSA-N 0.000 description 1
- MHDQAZHYHAOTKR-UWVGGRQHSA-N (2r)-3-[[(2r)-2-carboxy-2-[(2-methylpropan-2-yl)oxycarbonylamino]ethyl]disulfanyl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)CSSC[C@@H](C(O)=O)NC(=O)OC(C)(C)C MHDQAZHYHAOTKR-UWVGGRQHSA-N 0.000 description 1
- FXHADQJMIJZCQJ-UHFFFAOYSA-N (3,7-dihydroxynaphthalen-2-yl)-(4-methylsulfonylpiperazin-1-yl)methanone Chemical compound C1CN(S(=O)(=O)C)CCN1C(=O)C1=CC2=CC(O)=CC=C2C=C1O FXHADQJMIJZCQJ-UHFFFAOYSA-N 0.000 description 1
- HVRKWBHTTRXSRK-UHFFFAOYSA-N (3,7-dihydroxynaphthalen-2-yl)-[4-(4-methylphenyl)sulfonylpiperazin-1-yl]methanone Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N1CCN(C(=O)C=2C(=CC3=CC=C(O)C=C3C=2)O)CC1 HVRKWBHTTRXSRK-UHFFFAOYSA-N 0.000 description 1
- AHEQWNGHWSENKP-UHFFFAOYSA-N (4-butylsulfonylpiperazin-1-yl)-(3,7-dihydroxynaphthalen-2-yl)methanone Chemical compound C1CN(S(=O)(=O)CCCC)CCN1C(=O)C1=CC2=CC(O)=CC=C2C=C1O AHEQWNGHWSENKP-UHFFFAOYSA-N 0.000 description 1
- PAEZRCINULFAGO-OAQYLSRUSA-N (R)-homocamptothecin Chemical compound CC[C@@]1(O)CC(=O)OCC(C2=O)=C1C=C1N2CC2=CC3=CC=CC=C3N=C21 PAEZRCINULFAGO-OAQYLSRUSA-N 0.000 description 1
- MOWXJLUYGFNTAL-DEOSSOPVSA-N (s)-[2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(6-methoxypyridazin-3-yl)methanol Chemical compound N1=NC(OC)=CC=C1[C@@H](O)C1=CC(C=2C3=CC=C(C=C3N=CN=2)N2CCOCC2)=C(F)C=C1Cl MOWXJLUYGFNTAL-DEOSSOPVSA-N 0.000 description 1
- FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 description 1
- UDHBJMJETZDHBA-UHFFFAOYSA-N 1,3-benzothiazole 1,1-dioxide Chemical group C1=CC=C2S(=O)(=O)C=NC2=C1 UDHBJMJETZDHBA-UHFFFAOYSA-N 0.000 description 1
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical class C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 1
- ABDDQTDRAHXHOC-QMMMGPOBSA-N 1-[(7s)-5,7-dihydro-4h-thieno[2,3-c]pyran-7-yl]-n-methylmethanamine Chemical compound CNC[C@@H]1OCCC2=C1SC=C2 ABDDQTDRAHXHOC-QMMMGPOBSA-N 0.000 description 1
- AHOIUNCTKJPCIH-UHFFFAOYSA-N 1-[2-[4-(methanesulfonamido)phenyl]ethyl]naphthalene-2-carboxamide Chemical compound CS(=O)(=O)NC1=CC=C(C=C1)CCC1=C(C=CC2=CC=CC=C12)C(=O)N AHOIUNCTKJPCIH-UHFFFAOYSA-N 0.000 description 1
- DUKXTXZYXQCVCZ-UHFFFAOYSA-N 1-[2-[4-(naphthalen-1-ylsulfonylamino)phenyl]ethyl]naphthalene-2-carboxamide Chemical compound C1(=CC=CC2=CC=CC=C12)S(=O)(=O)NC1=CC=C(C=C1)CCC1=C(C=CC2=CC=CC=C12)C(=O)N DUKXTXZYXQCVCZ-UHFFFAOYSA-N 0.000 description 1
- LUPBJRUOCSIUFA-UHFFFAOYSA-N 1-[2-[4-(thiophen-2-ylsulfonylamino)phenyl]ethyl]naphthalene-2-carboxamide Chemical compound S1C(=CC=C1)S(=O)(=O)NC1=CC=C(C=C1)CCC1=C(C=CC2=CC=CC=C12)C(=O)N LUPBJRUOCSIUFA-UHFFFAOYSA-N 0.000 description 1
- PMPPXTMMXKXAJH-UHFFFAOYSA-N 1-[2-[4-[(4-nitrophenyl)sulfonylamino]phenyl]ethyl]naphthalene-2-carboxamide Chemical compound [N+](=O)([O-])C1=CC=C(C=C1)S(=O)(=O)NC1=CC=C(C=C1)CCC1=C(C=CC2=CC=CC=C12)C(=O)N PMPPXTMMXKXAJH-UHFFFAOYSA-N 0.000 description 1
- MDXNKAYXXXOQBO-UHFFFAOYSA-N 1-[2-[4-[[3-(trifluoromethyl)phenyl]sulfonylamino]phenyl]ethyl]naphthalene-2-carboxamide Chemical compound FC(C=1C=C(C=CC=1)S(=O)(=O)NC1=CC=C(C=C1)CCC1=C(C=CC2=CC=CC=C12)C(=O)N)(F)F MDXNKAYXXXOQBO-UHFFFAOYSA-N 0.000 description 1
- YOBXDNYNXDZNQA-UHFFFAOYSA-N 1-[2-[4-[[4-(trifluoromethyl)phenyl]sulfonylamino]phenyl]ethyl]naphthalene-2-carboxamide Chemical compound FC(C1=CC=C(C=C1)S(=O)(=O)NC1=CC=C(C=C1)CCC1=C(C=CC2=CC=CC=C12)C(=O)N)(F)F YOBXDNYNXDZNQA-UHFFFAOYSA-N 0.000 description 1
- FQYVGMWFZXPKFR-UHFFFAOYSA-N 1-[[3-(4-methylpiperidin-1-yl)sulfonylphenyl]methyl]naphthalene-2-carboxamide Chemical compound CC1CCN(CC1)S(=O)(=O)C=1C=C(CC2=C(C=CC3=CC=CC=C23)C(=O)N)C=CC=1 FQYVGMWFZXPKFR-UHFFFAOYSA-N 0.000 description 1
- HBVNLKQGRZPGRP-UHFFFAOYSA-N 1-benzylpyrrolidin-3-amine Chemical compound C1C(N)CCN1CC1=CC=CC=C1 HBVNLKQGRZPGRP-UHFFFAOYSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- HNBXASAJXOOGQD-UHFFFAOYSA-N 2,3,3a,4-tetrahydro-1,3-benzoxazole Chemical class C1C=CC=C2OCNC21 HNBXASAJXOOGQD-UHFFFAOYSA-N 0.000 description 1
- LJFDXXUKKMEQKE-UHFFFAOYSA-N 2,4-difluorobenzonitrile Chemical compound FC1=CC=C(C#N)C(F)=C1 LJFDXXUKKMEQKE-UHFFFAOYSA-N 0.000 description 1
- LSDXJRORXMVOJR-UHFFFAOYSA-N 2,5-dichloro-n-(3,5-dimethoxyphenyl)thiophene-3-carbothioamide Chemical compound COC1=CC(OC)=CC(NC(=S)C2=C(SC(Cl)=C2)Cl)=C1 LSDXJRORXMVOJR-UHFFFAOYSA-N 0.000 description 1
- ONOTYLMNTZNAQZ-UHFFFAOYSA-N 2,6-difluorobenzoic acid Chemical compound OC(=O)C1=C(F)C=CC=C1F ONOTYLMNTZNAQZ-UHFFFAOYSA-N 0.000 description 1
- QRHUZEVERIHEPT-UHFFFAOYSA-N 2,6-difluorobenzoyl chloride Chemical compound FC1=CC=CC(F)=C1C(Cl)=O QRHUZEVERIHEPT-UHFFFAOYSA-N 0.000 description 1
- HTIJYNSSIQXJKF-UHFFFAOYSA-N 2-(2,3-difluorophenyl)-6-(2-pyrrolidin-1-ylethylamino)-1,3-benzoxazole-4,7-dione Chemical compound FC1=CC=CC(C=2OC3=C(C(C=C(NCCN4CCCC4)C3=O)=O)N=2)=C1F HTIJYNSSIQXJKF-UHFFFAOYSA-N 0.000 description 1
- QPUYFHLNRBUBEJ-UHFFFAOYSA-N 2-(2,5-dichlorothiophen-3-yl)-5,7-dimethoxy-1,3-benzothiazole Chemical compound N=1C2=CC(OC)=CC(OC)=C2SC=1C=1C=C(Cl)SC=1Cl QPUYFHLNRBUBEJ-UHFFFAOYSA-N 0.000 description 1
- PZTFVEXPTRLXGC-UHFFFAOYSA-N 2-(2,5-dichlorothiophen-3-yl)-5-(2-pyrrolidin-1-ylethylamino)-1,3-benzothiazole-4,7-dione Chemical compound S1C(Cl)=CC(C=2SC3=C(C(C(NCCN4CCCC4)=CC3=O)=O)N=2)=C1Cl PZTFVEXPTRLXGC-UHFFFAOYSA-N 0.000 description 1
- ZHDLEMZSRBTRSG-UHFFFAOYSA-N 2-(2,5-dichlorothiophen-3-yl)-5-methoxy-1,3-benzothiazole-4,7-dione Chemical compound N=1C=2C(=O)C(OC)=CC(=O)C=2SC=1C=1C=C(Cl)SC=1Cl ZHDLEMZSRBTRSG-UHFFFAOYSA-N 0.000 description 1
- RRRVEXCKUQPPGE-UHFFFAOYSA-N 2-(2,5-dichlorothiophen-3-yl)-6-(2-pyrrolidin-1-ylethylamino)-1,3-benzothiazole-4,7-dione Chemical compound S1C(Cl)=CC(C=2SC3=C(C(C=C(NCCN4CCCC4)C3=O)=O)N=2)=C1Cl RRRVEXCKUQPPGE-UHFFFAOYSA-N 0.000 description 1
- JXIIDAGXFYZTGC-UHFFFAOYSA-N 2-(2,5-difluorophenyl)-6-(2-pyrrolidin-1-ylethylamino)-1,3-benzoxazole-4,7-dione Chemical compound FC1=CC=C(F)C(C=2OC3=C(C(C=C(NCCN4CCCC4)C3=O)=O)N=2)=C1 JXIIDAGXFYZTGC-UHFFFAOYSA-N 0.000 description 1
- FOJHTOMZWUIILB-UHFFFAOYSA-N 2-(2,5-difluorophenyl)-6-[2-(dimethylamino)ethylamino]-1,3-benzoxazole-4,7-dione Chemical compound O1C=2C(=O)C(NCCN(C)C)=CC(=O)C=2N=C1C1=CC(F)=CC=C1F FOJHTOMZWUIILB-UHFFFAOYSA-N 0.000 description 1
- RWDXKAPXMLDJNT-UHFFFAOYSA-N 2-(2,6-dichloro-5-fluoropyridin-3-yl)-5-[2-(dimethylamino)ethylamino]-1,3-benzoxazole-4,7-dione Chemical compound N=1C=2C(=O)C(NCCN(C)C)=CC(=O)C=2OC=1C1=CC(F)=C(Cl)N=C1Cl RWDXKAPXMLDJNT-UHFFFAOYSA-N 0.000 description 1
- DFPQVSNWUMDZKR-UHFFFAOYSA-N 2-(2,6-dichloro-5-fluoropyridin-3-yl)-6-(2-pyrrolidin-1-ylethylamino)-1,3-benzoxazole-4,7-dione Chemical compound N1=C(Cl)C(F)=CC(C=2OC3=C(C(C=C(NCCN4CCCC4)C3=O)=O)N=2)=C1Cl DFPQVSNWUMDZKR-UHFFFAOYSA-N 0.000 description 1
- GGZFUWRBKWFYKX-UHFFFAOYSA-N 2-(2,6-difluorophenyl)-1,3-benzoxazol-4-amine Chemical compound N=1C=2C(N)=CC=CC=2OC=1C1=C(F)C=CC=C1F GGZFUWRBKWFYKX-UHFFFAOYSA-N 0.000 description 1
- STRIQEOWWDUADX-UHFFFAOYSA-N 2-(2,6-difluorophenyl)-5,7-dimethoxy-1,3-benzothiazol-4-amine Chemical compound N=1C2=C(N)C(OC)=CC(OC)=C2SC=1C1=C(F)C=CC=C1F STRIQEOWWDUADX-UHFFFAOYSA-N 0.000 description 1
- DSXPWIQRMSTROM-UHFFFAOYSA-N 2-(2,6-difluorophenyl)-5,7-dimethoxy-1,3-benzothiazole Chemical compound N=1C2=CC(OC)=CC(OC)=C2SC=1C1=C(F)C=CC=C1F DSXPWIQRMSTROM-UHFFFAOYSA-N 0.000 description 1
- LVLMZHQUFJCZDE-UHFFFAOYSA-N 2-(2,6-difluorophenyl)-5,7-dimethoxy-4-nitro-1,3-benzothiazole Chemical compound N=1C2=C([N+]([O-])=O)C(OC)=CC(OC)=C2SC=1C1=C(F)C=CC=C1F LVLMZHQUFJCZDE-UHFFFAOYSA-N 0.000 description 1
- HWZJDHBOCLRYAD-UHFFFAOYSA-N 2-(2,6-difluorophenyl)-6-(2-pyrrolidin-1-ylethylamino)-1,3-benzothiazole-4,7-dione Chemical compound FC1=CC=CC(F)=C1C1=NC(C(C=C(NCCN2CCCC2)C2=O)=O)=C2S1 HWZJDHBOCLRYAD-UHFFFAOYSA-N 0.000 description 1
- RKHJGEQSYCJBIC-UHFFFAOYSA-N 2-(2,6-difluorophenyl)-6-(2-pyrrolidin-1-ylethylamino)-1,3-benzoxazole-4,7-dione Chemical compound FC1=CC=CC(F)=C1C1=NC(C(C=C(NCCN2CCCC2)C2=O)=O)=C2O1 RKHJGEQSYCJBIC-UHFFFAOYSA-N 0.000 description 1
- JXESSMNOTWQBIL-UHFFFAOYSA-N 2-(2-bromophenyl)-5-(2-pyrrolidin-1-ylethylamino)-1,3-benzoxazole-4,7-dione Chemical compound BrC1=CC=CC=C1C1=NC(C(C(NCCN2CCCC2)=CC2=O)=O)=C2O1 JXESSMNOTWQBIL-UHFFFAOYSA-N 0.000 description 1
- ZJZBPXOQDWEKTP-UHFFFAOYSA-N 2-(2-chloro-6-fluorophenyl)-5,7-dimethoxy-1,3-benzothiazole Chemical compound N=1C2=CC(OC)=CC(OC)=C2SC=1C1=C(F)C=CC=C1Cl ZJZBPXOQDWEKTP-UHFFFAOYSA-N 0.000 description 1
- ZWMLEEZTZFHBSL-UHFFFAOYSA-N 2-(2-chloro-6-fluorophenyl)-5-[3-(dimethylamino)propylamino]-1,3-benzoxazole-4,7-dione Chemical compound N=1C=2C(=O)C(NCCCN(C)C)=CC(=O)C=2OC=1C1=C(F)C=CC=C1Cl ZWMLEEZTZFHBSL-UHFFFAOYSA-N 0.000 description 1
- LISVSEFXUWMCHB-UHFFFAOYSA-N 2-(2-chloro-6-fluorophenyl)-6-(2-pyrrolidin-1-ylethylamino)-1,3-benzoxazole-4,7-dione Chemical compound FC1=CC=CC(Cl)=C1C1=NC(C(C=C(NCCN2CCCC2)C2=O)=O)=C2O1 LISVSEFXUWMCHB-UHFFFAOYSA-N 0.000 description 1
- FIHULUVPAVJDNE-UHFFFAOYSA-N 2-(2-chlorophenyl)-5-(2-pyrrolidin-1-ylethylamino)-1,3-benzoxazole-4,7-dione Chemical compound ClC1=CC=CC=C1C1=NC(C(C(NCCN2CCCC2)=CC2=O)=O)=C2O1 FIHULUVPAVJDNE-UHFFFAOYSA-N 0.000 description 1
- MSANPKATBOTZKD-UHFFFAOYSA-N 2-(2-fluorophenyl)-5-(2-pyrrolidin-1-ylethylamino)-1,3-benzoxazole-4,7-dione Chemical compound FC1=CC=CC=C1C1=NC(C(C(NCCN2CCCC2)=CC2=O)=O)=C2O1 MSANPKATBOTZKD-UHFFFAOYSA-N 0.000 description 1
- KTQJFPUZZOHGLN-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-6-[2-(dimethylamino)ethylamino]-1,3-benzoxazole-4,7-dione Chemical compound C1=C(OC)C(OC)=CC=C1C1=NC(C(C=C(NCCN(C)C)C2=O)=O)=C2O1 KTQJFPUZZOHGLN-UHFFFAOYSA-N 0.000 description 1
- GKLDSXVHMRSCPR-UHFFFAOYSA-N 2-(3,5-difluorophenyl)-6-(2-pyrrolidin-1-ylethylamino)-1,3-benzoxazole-4,7-dione Chemical compound FC1=CC(F)=CC(C=2OC3=C(C(C=C(NCCN4CCCC4)C3=O)=O)N=2)=C1 GKLDSXVHMRSCPR-UHFFFAOYSA-N 0.000 description 1
- LGRWMKFQYZWMLF-UHFFFAOYSA-N 2-(3-fluoro-4-methylphenyl)-6-(2-pyrrolidin-1-ylethylamino)-1,3-benzoxazole-4,7-dione Chemical compound C1=C(F)C(C)=CC=C1C1=NC(C(C=C(NCCN2CCCC2)C2=O)=O)=C2O1 LGRWMKFQYZWMLF-UHFFFAOYSA-N 0.000 description 1
- TZDIXPYIXRJKHK-UHFFFAOYSA-N 2-(4-bromophenyl)-5-(2-pyrrolidin-1-ylethylamino)-1,3-benzoxazole-4,7-dione Chemical compound C1=CC(Br)=CC=C1C1=NC(C(C(NCCN2CCCC2)=CC2=O)=O)=C2O1 TZDIXPYIXRJKHK-UHFFFAOYSA-N 0.000 description 1
- ZFDIRIRYJUNZPD-UHFFFAOYSA-N 2-(4-bromophenyl)-6-[2-(dimethylamino)ethylamino]-1,3-benzoxazole-4,7-dione Chemical compound O1C=2C(=O)C(NCCN(C)C)=CC(=O)C=2N=C1C1=CC=C(Br)C=C1 ZFDIRIRYJUNZPD-UHFFFAOYSA-N 0.000 description 1
- LVCVCCHWEKBOCR-UHFFFAOYSA-N 2-(4-chlorophenyl)-5-[2-(dimethylamino)ethylamino]-1,3-benzothiazole-4,7-dione Chemical compound N=1C=2C(=O)C(NCCN(C)C)=CC(=O)C=2SC=1C1=CC=C(Cl)C=C1 LVCVCCHWEKBOCR-UHFFFAOYSA-N 0.000 description 1
- TXDMLSSNYPAHEW-UHFFFAOYSA-N 2-(4-chlorophenyl)-5-[2-(dimethylamino)ethylamino]-1,3-benzoxazole-4,7-dione Chemical compound N=1C=2C(=O)C(NCCN(C)C)=CC(=O)C=2OC=1C1=CC=C(Cl)C=C1 TXDMLSSNYPAHEW-UHFFFAOYSA-N 0.000 description 1
- ITCSSBVTGKGLOT-UHFFFAOYSA-N 2-(4-chlorophenyl)-6-[2-(dimethylamino)ethylamino]-1,3-benzoxazole-4,7-dione Chemical compound O1C=2C(=O)C(NCCN(C)C)=CC(=O)C=2N=C1C1=CC=C(Cl)C=C1 ITCSSBVTGKGLOT-UHFFFAOYSA-N 0.000 description 1
- GNVGWFVMIIMFDB-UHFFFAOYSA-N 2-(4-ethylphenyl)-5-(2-pyrrolidin-1-ylethylamino)-1,3-benzoxazole-4,7-dione Chemical compound C1=CC(CC)=CC=C1C1=NC(C(C(NCCN2CCCC2)=CC2=O)=O)=C2O1 GNVGWFVMIIMFDB-UHFFFAOYSA-N 0.000 description 1
- JSTUBYSJHGUPMI-UHFFFAOYSA-N 2-(4-fluorophenyl)-1,3-benzoxazole-4,7-dione Chemical compound C1=CC(F)=CC=C1C1=NC(C(C=CC2=O)=O)=C2O1 JSTUBYSJHGUPMI-UHFFFAOYSA-N 0.000 description 1
- FQUKHOWWEDWMLZ-UHFFFAOYSA-N 2-(4-fluorophenyl)-5,7-dimethoxy-1,3-benzothiazole Chemical compound N=1C2=CC(OC)=CC(OC)=C2SC=1C1=CC=C(F)C=C1 FQUKHOWWEDWMLZ-UHFFFAOYSA-N 0.000 description 1
- RZUBSDPCXMRFRR-UHFFFAOYSA-N 2-(4-fluorophenyl)-5-(2-pyrrolidin-1-ylethylamino)-1,3-benzoxazole-4,7-dione Chemical compound C1=CC(F)=CC=C1C1=NC(C(C(NCCN2CCCC2)=CC2=O)=O)=C2O1 RZUBSDPCXMRFRR-UHFFFAOYSA-N 0.000 description 1
- OQZGYMRYZAKXAF-UHFFFAOYSA-N 2-(4-methylcyclohexyl)acetic acid Chemical compound CC1CCC(CC(O)=O)CC1 OQZGYMRYZAKXAF-UHFFFAOYSA-N 0.000 description 1
- CVAFJSPTOVRIHQ-UHFFFAOYSA-N 2-(bromomethyl)-5-methoxy-1,3-benzothiazole Chemical compound COC1=CC=C2SC(CBr)=NC2=C1 CVAFJSPTOVRIHQ-UHFFFAOYSA-N 0.000 description 1
- ISUVACHTWJLRNF-UHFFFAOYSA-N 2-(furan-2-yl)-5-(2-pyrrolidin-1-ylethylamino)-1,3-benzothiazole-4,7-dione Chemical compound O=C1C=2N=C(C=3OC=CC=3)SC=2C(=O)C=C1NCCN1CCCC1 ISUVACHTWJLRNF-UHFFFAOYSA-N 0.000 description 1
- CBRZTRLYKPBSRR-UHFFFAOYSA-N 2-(furan-2-yl)-6-(2-pyrrolidin-1-ylethylamino)-1,3-benzothiazole-4,7-dione Chemical compound O=C1C=2SC(C=3OC=CC=3)=NC=2C(=O)C=C1NCCN1CCCC1 CBRZTRLYKPBSRR-UHFFFAOYSA-N 0.000 description 1
- QINOWIDNVMAQCI-UHFFFAOYSA-N 2-[2-chloro-5-(trifluoromethyl)phenyl]-5-(2-pyrrolidin-1-ylethylamino)-1,3-benzoxazole-4,7-dione Chemical compound FC(F)(F)C1=CC=C(Cl)C(C=2OC3=C(C(C(NCCN4CCCC4)=CC3=O)=O)N=2)=C1 QINOWIDNVMAQCI-UHFFFAOYSA-N 0.000 description 1
- VJSVBOJJANEPJU-UHFFFAOYSA-N 2-[2-chloro-5-(trifluoromethyl)phenyl]-5-[3-(dimethylamino)propylamino]-1,3-benzoxazole-4,7-dione Chemical compound N=1C=2C(=O)C(NCCCN(C)C)=CC(=O)C=2OC=1C1=CC(C(F)(F)F)=CC=C1Cl VJSVBOJJANEPJU-UHFFFAOYSA-N 0.000 description 1
- QFDNBOIIWIDMEM-UHFFFAOYSA-N 2-[2-fluoro-6-(trifluoromethyl)phenyl]-5-(2-pyrrolidin-1-ylethylamino)-1,3-benzoxazole-4,7-dione Chemical compound FC1=CC=CC(C(F)(F)F)=C1C1=NC(C(C(NCCN2CCCC2)=CC2=O)=O)=C2O1 QFDNBOIIWIDMEM-UHFFFAOYSA-N 0.000 description 1
- NQVIIUBWMBHLOZ-UHFFFAOYSA-N 2-[2-hydroxyethyl-[6-[(4-methoxyphenyl)methylamino]-9-propan-2-ylpurin-2-yl]amino]ethanol Chemical compound C1=CC(OC)=CC=C1CNC1=NC(N(CCO)CCO)=NC2=C1N=CN2C(C)C NQVIIUBWMBHLOZ-UHFFFAOYSA-N 0.000 description 1
- SSMRWGMPNOXAAQ-UHFFFAOYSA-N 2-[4-(diethylamino)phenyl]-6-(2-pyrrolidin-1-ylethylamino)-1,3-benzoxazole-4,7-dione Chemical compound C1=CC(N(CC)CC)=CC=C1C1=NC(C(C=C(NCCN2CCCC2)C2=O)=O)=C2O1 SSMRWGMPNOXAAQ-UHFFFAOYSA-N 0.000 description 1
- QFCAQHGLHXOPGP-UHFFFAOYSA-N 2-[4-(diethylamino)phenyl]-6-[2-(dimethylamino)ethylamino]-1,3-benzoxazole-4,7-dione Chemical compound C1=CC(N(CC)CC)=CC=C1C1=NC(C(C=C(NCCN(C)C)C2=O)=O)=C2O1 QFCAQHGLHXOPGP-UHFFFAOYSA-N 0.000 description 1
- FLRPUKIZUAJKOH-UHFFFAOYSA-N 2-amino-1,3-benzothiazole-4,7-dione Chemical compound NC=1SC2=C(N=1)C(C=CC2=O)=O FLRPUKIZUAJKOH-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 1
- CDAWCLOXVUBKRW-UHFFFAOYSA-N 2-aminophenol Chemical compound NC1=CC=CC=C1O CDAWCLOXVUBKRW-UHFFFAOYSA-N 0.000 description 1
- QIPXEPRGYVAQFI-UHFFFAOYSA-N 2-bromopyridine-3-carbonitrile Chemical compound BrC1=NC=CC=C1C#N QIPXEPRGYVAQFI-UHFFFAOYSA-N 0.000 description 1
- NHWQMJMIYICNBP-UHFFFAOYSA-N 2-chlorobenzonitrile Chemical compound ClC1=CC=CC=C1C#N NHWQMJMIYICNBP-UHFFFAOYSA-N 0.000 description 1
- ALIYHEUZXRTBSR-UHFFFAOYSA-N 2-cyclohexyl-1,3-benzothiazole-4,7-dione Chemical compound N=1C=2C(=O)C=CC(=O)C=2SC=1C1CCCCC1 ALIYHEUZXRTBSR-UHFFFAOYSA-N 0.000 description 1
- OVBVSZIKMCKRFP-UHFFFAOYSA-N 2-cyclohexyl-5-[2-(dimethylamino)ethylamino]-1,3-benzothiazole-4,7-dione Chemical compound N=1C=2C(=O)C(NCCN(C)C)=CC(=O)C=2SC=1C1CCCCC1 OVBVSZIKMCKRFP-UHFFFAOYSA-N 0.000 description 1
- SPFDJKAFYPIXTA-UHFFFAOYSA-N 2-cyclohexyl-6-(2-pyrrolidin-1-ylethylamino)-1,3-benzothiazole-4,7-dione Chemical compound O=C1C=2SC(C3CCCCC3)=NC=2C(=O)C=C1NCCN1CCCC1 SPFDJKAFYPIXTA-UHFFFAOYSA-N 0.000 description 1
- OFEBRXOADLZYFH-UHFFFAOYSA-N 2-cyclopropyl-6-[2-(dimethylamino)ethylamino]-1,3-benzoxazole-4,7-dione Chemical compound O1C=2C(=O)C(NCCN(C)C)=CC(=O)C=2N=C1C1CC1 OFEBRXOADLZYFH-UHFFFAOYSA-N 0.000 description 1
- ZAPBTXJLDAKYDU-UHFFFAOYSA-N 2-diazonio-6-oxocyclohexen-1-olate Chemical compound [N-]=[N+]=C1CCCC(=O)C1=O ZAPBTXJLDAKYDU-UHFFFAOYSA-N 0.000 description 1
- GFFUECODASEGJP-UHFFFAOYSA-N 2-ethyl-5-(4-fluoroanilino)-1,3-benzoxazole-4,7-dione Chemical compound O1C(CC)=NC(C2=O)=C1C(=O)C=C2NC1=CC=C(F)C=C1 GFFUECODASEGJP-UHFFFAOYSA-N 0.000 description 1
- CEMFCOGDDBLXGY-UHFFFAOYSA-N 2-ethyl-5-(4-methylpiperazin-1-yl)-1,3-benzoxazole-4,7-dione Chemical compound O1C(CC)=NC(C2=O)=C1C(=O)C=C2N1CCN(C)CC1 CEMFCOGDDBLXGY-UHFFFAOYSA-N 0.000 description 1
- VZLYXYJYRGLIHY-UHFFFAOYSA-N 2-ethyl-5-(4-pyrrolidin-1-ylbutylamino)-1,3-benzoxazole-4,7-dione Chemical compound O1C(CC)=NC(C2=O)=C1C(=O)C=C2NCCCCN1CCCC1 VZLYXYJYRGLIHY-UHFFFAOYSA-N 0.000 description 1
- QOANXGMFGBBCQW-UHFFFAOYSA-N 2-ethyl-5-(octan-3-ylamino)-1,3-benzoxazole-4,7-dione Chemical compound O=C1C(NC(CC)CCCCC)=CC(=O)C2=C1N=C(CC)O2 QOANXGMFGBBCQW-UHFFFAOYSA-N 0.000 description 1
- ADFKQOWVYWDFAJ-UHFFFAOYSA-N 2-ethyl-5-morpholin-4-yl-1,3-benzoxazole-4,7-dione Chemical compound O1C(CC)=NC(C2=O)=C1C(=O)C=C2N1CCOCC1 ADFKQOWVYWDFAJ-UHFFFAOYSA-N 0.000 description 1
- SNSFOENBFCGLBA-UHFFFAOYSA-N 2-ethyl-6-(4-fluoroanilino)-1,3-benzoxazole-4,7-dione Chemical compound O1C(CC)=NC(C(C=2)=O)=C1C(=O)C=2NC1=CC=C(F)C=C1 SNSFOENBFCGLBA-UHFFFAOYSA-N 0.000 description 1
- ZNGZRWCPQFLFAB-UHFFFAOYSA-N 2-ethyl-6-(4-methylpiperazin-1-yl)-1,3-benzoxazole-4,7-dione Chemical compound O1C(CC)=NC(C(C=2)=O)=C1C(=O)C=2N1CCN(C)CC1 ZNGZRWCPQFLFAB-UHFFFAOYSA-N 0.000 description 1
- RNSFUNQHKPZJHB-UHFFFAOYSA-N 2-ethyl-6-(4-pyrrolidin-1-ylbutylamino)-1,3-benzoxazole-4,7-dione Chemical compound O1C(CC)=NC(C(C=2)=O)=C1C(=O)C=2NCCCCN1CCCC1 RNSFUNQHKPZJHB-UHFFFAOYSA-N 0.000 description 1
- FLABTPOXLGBOOZ-UHFFFAOYSA-N 2-ethyl-6-(octan-3-ylamino)-1,3-benzoxazole-4,7-dione Chemical compound O=C1C(NC(CC)CCCCC)=CC(=O)C2=C1OC(CC)=N2 FLABTPOXLGBOOZ-UHFFFAOYSA-N 0.000 description 1
- NLHYUUOYJOCKAN-UHFFFAOYSA-N 2-ethyl-6-methyl-1,3-benzoxazol-4-amine Chemical compound C1=C(C)C=C2OC(CC)=NC2=C1N NLHYUUOYJOCKAN-UHFFFAOYSA-N 0.000 description 1
- HQFPLPJPFXRYML-UHFFFAOYSA-N 2-ethyl-6-morpholin-4-yl-1,3-benzoxazole-4,7-dione Chemical compound O1C(CC)=NC(C(C=2)=O)=C1C(=O)C=2N1CCOCC1 HQFPLPJPFXRYML-UHFFFAOYSA-N 0.000 description 1
- NMBWXBWFDHVLGS-UHFFFAOYSA-N 2-ethylbenzenesulfonamide Chemical compound CCC1=CC=CC=C1S(N)(=O)=O NMBWXBWFDHVLGS-UHFFFAOYSA-N 0.000 description 1
- LTHNHFOGQMKPOV-UHFFFAOYSA-N 2-ethylhexan-1-amine Chemical compound CCCCC(CC)CN LTHNHFOGQMKPOV-UHFFFAOYSA-N 0.000 description 1
- ZLGCCOMHHHCYJU-UHFFFAOYSA-N 2-methyl-5-(octan-3-ylamino)-1,3-benzothiazole-4,7-dione Chemical compound O=C1C(NC(CC)CCCCC)=CC(=O)C2=C1N=C(C)S2 ZLGCCOMHHHCYJU-UHFFFAOYSA-N 0.000 description 1
- VDKLTPHRSXFGEA-UHFFFAOYSA-N 2-methyl-5-(propylamino)-1,3-benzothiazole-4,7-dione Chemical compound O=C1C(NCCC)=CC(=O)C2=C1N=C(C)S2 VDKLTPHRSXFGEA-UHFFFAOYSA-N 0.000 description 1
- QULGJKTVLDBBRD-UHFFFAOYSA-N 2-methyl-5-(pyridin-4-ylmethylamino)-1,3-benzothiazole-4,7-dione Chemical compound S1C(C)=NC(C2=O)=C1C(=O)C=C2NCC1=CC=NC=C1 QULGJKTVLDBBRD-UHFFFAOYSA-N 0.000 description 1
- JGMBWHOPRFHZND-UHFFFAOYSA-N 2-methyl-5-(thiophen-2-ylmethylamino)-1,3-benzothiazole-4,7-dione Chemical compound S1C(C)=NC(C2=O)=C1C(=O)C=C2NCC1=CC=CS1 JGMBWHOPRFHZND-UHFFFAOYSA-N 0.000 description 1
- SVAIJSCVSHMINZ-UHFFFAOYSA-N 2-methyl-5-[2-(1-methylpyrrolidin-2-yl)ethylamino]-1,3-benzothiazole-4,7-dione Chemical compound CN1CCCC1CCNC(C1=O)=CC(=O)C2=C1N=C(C)S2 SVAIJSCVSHMINZ-UHFFFAOYSA-N 0.000 description 1
- DFYXUKXLHGGUEC-UHFFFAOYSA-N 2-phenylpentanamide Chemical compound CCCC(C(N)=O)C1=CC=CC=C1 DFYXUKXLHGGUEC-UHFFFAOYSA-N 0.000 description 1
- COHQCOIIBYMTJT-UHFFFAOYSA-N 2h-benzotriazole;1,1,3,3-tetramethylurea Chemical compound CN(C)C(=O)N(C)C.C1=CC=C2NN=NC2=C1 COHQCOIIBYMTJT-UHFFFAOYSA-N 0.000 description 1
- OSEQIDSFSBWXRE-UHFFFAOYSA-N 3,4-dimethoxybenzonitrile Chemical compound COC1=CC=C(C#N)C=C1OC OSEQIDSFSBWXRE-UHFFFAOYSA-N 0.000 description 1
- WNRGWPVJGDABME-UHFFFAOYSA-N 3,5-Dimethoxyaniline Chemical compound COC1=CC(N)=CC(OC)=C1 WNRGWPVJGDABME-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
- WNEODWDFDXWOLU-QHCPKHFHSA-N 3-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2s)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl]amino]-6-oxopyridin-3-yl]pyridin-2-yl]-7,7-dimethyl-1,2,6,8-tetrahydrocyclopenta[3,4]pyrrolo[3,5-b]pyrazin-4-one Chemical compound C([C@@H](N(CC1)C=2C=NC(NC=3C(N(C)C=C(C=3)C=3C(=C(N4C(C5=CC=6CC(C)(C)CC=6N5CC4)=O)N=CC=3)CO)=O)=CC=2)C)N1C1COC1 WNEODWDFDXWOLU-QHCPKHFHSA-N 0.000 description 1
- STXAVEHFKAXGOX-UHFFFAOYSA-N 3-bromobenzonitrile Chemical compound BrC1=CC=CC(C#N)=C1 STXAVEHFKAXGOX-UHFFFAOYSA-N 0.000 description 1
- QYLJAQYCWCNDAI-UHFFFAOYSA-N 4-(dimethylamino)-2-[[2-(4-nitrophenyl)ethylamino]methyl]phenol Chemical compound CN(C)C1=CC=C(O)C(CNCCC=2C=CC(=CC=2)[N+]([O-])=O)=C1 QYLJAQYCWCNDAI-UHFFFAOYSA-N 0.000 description 1
- VTZZFHYCFVDZRI-UHFFFAOYSA-N 4-(dimethylamino)-2-[[methyl-[2-(4-nitrophenyl)ethyl]amino]methyl]phenol Chemical compound CN(C)C1=CC=C(O)C(CN(C)CCC=2C=CC(=CC=2)[N+]([O-])=O)=C1 VTZZFHYCFVDZRI-UHFFFAOYSA-N 0.000 description 1
- PBKWFQXZOSIIAD-UHFFFAOYSA-N 4-(dimethylamino)-2-methoxy-6-[[2-(4-nitrophenyl)ethylamino]methyl]phenol Chemical compound COC1=CC(N(C)C)=CC(CNCCC=2C=CC(=CC=2)[N+]([O-])=O)=C1O PBKWFQXZOSIIAD-UHFFFAOYSA-N 0.000 description 1
- GOKYHQGRIIXMNE-UHFFFAOYSA-N 4-(dimethylamino)-2-methoxy-6-[[methyl-[2-(4-nitrophenyl)ethyl]amino]methyl]phenol Chemical compound COC1=CC(N(C)C)=CC(CN(C)CCC=2C=CC(=CC=2)[N+]([O-])=O)=C1O GOKYHQGRIIXMNE-UHFFFAOYSA-N 0.000 description 1
- KVCQTKNUUQOELD-UHFFFAOYSA-N 4-amino-n-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide Chemical compound N=1C=CC2=C(NC(=O)C=3C4=NC=NC(N)=C4SC=3)C(C)=CC=C2C=1NC1=CC=CC(Cl)=C1F KVCQTKNUUQOELD-UHFFFAOYSA-N 0.000 description 1
- HQSCPPCMBMFJJN-UHFFFAOYSA-N 4-bromobenzonitrile Chemical compound BrC1=CC=C(C#N)C=C1 HQSCPPCMBMFJJN-UHFFFAOYSA-N 0.000 description 1
- WNWVKZTYMQWFHE-UHFFFAOYSA-N 4-ethylmorpholine Chemical group [CH2]CN1CCOCC1 WNWVKZTYMQWFHE-UHFFFAOYSA-N 0.000 description 1
- 125000004860 4-ethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])C([H])([H])[H] 0.000 description 1
- KRZCOLNOCZKSDF-UHFFFAOYSA-N 4-fluoroaniline Chemical compound NC1=CC=C(F)C=C1 KRZCOLNOCZKSDF-UHFFFAOYSA-N 0.000 description 1
- AEKVBBNGWBBYLL-UHFFFAOYSA-N 4-fluorobenzonitrile Chemical compound FC1=CC=C(C#N)C=C1 AEKVBBNGWBBYLL-UHFFFAOYSA-N 0.000 description 1
- FHOBRROJCIHYJK-UHFFFAOYSA-N 5-(1-adamantylmethylamino)-2-methyl-1,3-benzothiazole-4,7-dione Chemical compound C1C(C2)CC(C3)CC2CC13CNC(C1=O)=CC(=O)C2=C1N=C(C)S2 FHOBRROJCIHYJK-UHFFFAOYSA-N 0.000 description 1
- LIUPFBIGVISQMZ-UHFFFAOYSA-N 5-(2,3-dihydro-1h-inden-1-ylamino)-2-methyl-1,3-benzothiazole-4,7-dione Chemical compound C1CC2=CC=CC=C2C1NC(C1=O)=CC(=O)C2=C1N=C(C)S2 LIUPFBIGVISQMZ-UHFFFAOYSA-N 0.000 description 1
- YPXPIADGQLWKJV-UHFFFAOYSA-N 5-(2-methoxyethylamino)-2-methyl-1,3-benzothiazole-4,7-dione Chemical compound O=C1C(NCCOC)=CC(=O)C2=C1N=C(C)S2 YPXPIADGQLWKJV-UHFFFAOYSA-N 0.000 description 1
- VJFSPXMFGZIBNB-UHFFFAOYSA-N 5-(2-pyrrolidin-1-ylethylamino)-2-(2,3,4,5-tetrafluorophenyl)-1,3-benzoxazole-4,7-dione Chemical compound FC1=C(F)C(F)=CC(C=2OC3=C(C(C(NCCN4CCCC4)=CC3=O)=O)N=2)=C1F VJFSPXMFGZIBNB-UHFFFAOYSA-N 0.000 description 1
- QVFSIKIBGQWZSC-UHFFFAOYSA-N 5-(2-pyrrolidin-1-ylethylamino)-2-(2,3,4-trifluorophenyl)-1,3-benzoxazole-4,7-dione Chemical compound FC1=C(F)C(F)=CC=C1C1=NC(C(C(NCCN2CCCC2)=CC2=O)=O)=C2O1 QVFSIKIBGQWZSC-UHFFFAOYSA-N 0.000 description 1
- LOGWVNAZQPYDKD-UHFFFAOYSA-N 5-(2-pyrrolidin-1-ylethylamino)-2-(2,4,6-trifluorophenyl)-1,3-benzothiazole-4,7-dione Chemical compound FC1=CC(F)=CC(F)=C1C1=NC(C(C(NCCN2CCCC2)=CC2=O)=O)=C2S1 LOGWVNAZQPYDKD-UHFFFAOYSA-N 0.000 description 1
- TYMFWTFOGORBKI-UHFFFAOYSA-N 5-(2-pyrrolidin-1-ylethylamino)-2-(3,4,5-trifluorophenyl)-1,3-benzoxazole-4,7-dione Chemical compound FC1=C(F)C(F)=CC(C=2OC3=C(C(C(NCCN4CCCC4)=CC3=O)=O)N=2)=C1 TYMFWTFOGORBKI-UHFFFAOYSA-N 0.000 description 1
- UQHLADFHHZTRSL-UHFFFAOYSA-N 5-(2-pyrrolidin-1-ylethylamino)-2-thiophen-2-yl-1,3-benzothiazole-4,7-dione Chemical compound O=C1C=2N=C(C=3SC=CC=3)SC=2C(=O)C=C1NCCN1CCCC1 UQHLADFHHZTRSL-UHFFFAOYSA-N 0.000 description 1
- YGUWBSFLMCSQNR-UHFFFAOYSA-N 5-(3-aminopropylamino)-2-methyl-1,3-benzothiazole-4,7-dione Chemical compound O=C1C=C(NCCCN)C(=O)C2=C1SC(C)=N2 YGUWBSFLMCSQNR-UHFFFAOYSA-N 0.000 description 1
- VOYLHXXVGRIKGT-UHFFFAOYSA-N 5-(4-benzylpiperazin-1-yl)-2-methyl-1,3-benzothiazole-4,7-dione Chemical compound S1C(C)=NC(C2=O)=C1C(=O)C=C2N(CC1)CCN1CC1=CC=CC=C1 VOYLHXXVGRIKGT-UHFFFAOYSA-N 0.000 description 1
- XCANYGAUZSXXTJ-UHFFFAOYSA-N 5-(azocan-1-yl)-2-ethyl-1,3-benzoxazole-4,7-dione Chemical compound O1C(CC)=NC(C2=O)=C1C(=O)C=C2N1CCCCCCC1 XCANYGAUZSXXTJ-UHFFFAOYSA-N 0.000 description 1
- QNHZBFLZTSGCIV-UHFFFAOYSA-N 5-(octan-3-ylamino)-2-phenyl-1,3-benzoxazole-4,7-dione Chemical compound N=1C=2C(=O)C(NC(CC)CCCCC)=CC(=O)C=2OC=1C1=CC=CC=C1 QNHZBFLZTSGCIV-UHFFFAOYSA-N 0.000 description 1
- UYAOYVVWBLEPDU-UHFFFAOYSA-N 5-[(1-benzylpyrrolidin-3-yl)amino]-2-(4-fluorophenyl)-1,3-benzoxazole-4,7-dione Chemical compound C1=CC(F)=CC=C1C1=NC(C(C(NC2CN(CC=3C=CC=CC=3)CC2)=CC2=O)=O)=C2O1 UYAOYVVWBLEPDU-UHFFFAOYSA-N 0.000 description 1
- ULWVXPYGWGHEAY-UHFFFAOYSA-N 5-[(1-benzylpyrrolidin-3-yl)amino]-2-methyl-1,3-benzothiazole-4,7-dione Chemical compound S1C(C)=NC(C2=O)=C1C(=O)C=C2NC(C1)CCN1CC1=CC=CC=C1 ULWVXPYGWGHEAY-UHFFFAOYSA-N 0.000 description 1
- SEJJJLDNVSSSGN-UHFFFAOYSA-N 5-[(3-chlorophenyl)methylamino]-2-methyl-1,3-benzothiazole-4,7-dione Chemical compound S1C(C)=NC(C2=O)=C1C(=O)C=C2NCC1=CC=CC(Cl)=C1 SEJJJLDNVSSSGN-UHFFFAOYSA-N 0.000 description 1
- AVHRTEMOUDCSPZ-UHFFFAOYSA-N 5-[2-(dimethylamino)ethylamino]-2-(2-methoxyphenyl)-1,3-benzothiazole-4,7-dione Chemical compound COC1=CC=CC=C1C1=NC(C(C(NCCN(C)C)=CC2=O)=O)=C2S1 AVHRTEMOUDCSPZ-UHFFFAOYSA-N 0.000 description 1
- BVRHJJFTESVWQK-UHFFFAOYSA-N 5-[2-(dimethylamino)ethylamino]-2-(3,4,5-trifluorophenyl)-1,3-benzothiazole-4,7-dione Chemical compound N=1C=2C(=O)C(NCCN(C)C)=CC(=O)C=2SC=1C1=CC(F)=C(F)C(F)=C1 BVRHJJFTESVWQK-UHFFFAOYSA-N 0.000 description 1
- RBYMHDGTUBZAJN-UHFFFAOYSA-N 5-[2-(dimethylamino)ethylamino]-2-(3-fluoro-4-methylphenyl)-1,3-benzoxazole-4,7-dione Chemical compound N=1C=2C(=O)C(NCCN(C)C)=CC(=O)C=2OC=1C1=CC=C(C)C(F)=C1 RBYMHDGTUBZAJN-UHFFFAOYSA-N 0.000 description 1
- LPEHETKTJYHXOD-UHFFFAOYSA-N 5-[2-(dimethylamino)ethylamino]-2-(4-fluorophenyl)-1,3-benzothiazole-4,7-dione Chemical compound N=1C=2C(=O)C(NCCN(C)C)=CC(=O)C=2SC=1C1=CC=C(F)C=C1 LPEHETKTJYHXOD-UHFFFAOYSA-N 0.000 description 1
- LRRCBIXIHGZWPB-UHFFFAOYSA-N 5-[2-(dimethylamino)ethylamino]-2-(morpholin-4-ylmethyl)-1,3-benzothiazole-4,7-dione Chemical compound N=1C=2C(=O)C(NCCN(C)C)=CC(=O)C=2SC=1CN1CCOCC1 LRRCBIXIHGZWPB-UHFFFAOYSA-N 0.000 description 1
- WIMDBDXRRSPPFQ-UHFFFAOYSA-N 5-[2-(dimethylamino)ethylamino]-2-phenyl-1,3-benzoxazole-4,7-dione Chemical compound N=1C=2C(=O)C(NCCN(C)C)=CC(=O)C=2OC=1C1=CC=CC=C1 WIMDBDXRRSPPFQ-UHFFFAOYSA-N 0.000 description 1
- VESSJVRKQWHDJW-UHFFFAOYSA-N 5-amino-2-(3,4,5-trifluorophenyl)-1,3-benzoxazole-4,7-dione Chemical compound NC1=CC(C2=C(N=C(O2)C2=CC(=C(C(=C2)F)F)F)C1=O)=O VESSJVRKQWHDJW-UHFFFAOYSA-N 0.000 description 1
- FALDRDKLBJMOKD-UHFFFAOYSA-N 5-amino-6-[2-(dimethylamino)ethyl]-2-(4-fluorophenyl)-1,3-benzoxazole-4,7-dione Chemical compound CN(CCC=1C(C2=C(N=C(O2)C2=CC=C(C=C2)F)C(C=1N)=O)=O)C FALDRDKLBJMOKD-UHFFFAOYSA-N 0.000 description 1
- YKPNXTNAGDEAKQ-UHFFFAOYSA-N 5-anilino-6-chloro-2-ethyl-1,3-benzoxazole-4,7-dione Chemical compound O1C(CC)=NC(C2=O)=C1C(=O)C(Cl)=C2NC1=CC=CC=C1 YKPNXTNAGDEAKQ-UHFFFAOYSA-N 0.000 description 1
- KUBUJZQXINOXSL-UHFFFAOYSA-N 5-methoxy-2-(morpholin-4-ylmethyl)-1,3-benzothiazol-4-amine Chemical compound N=1C2=C(N)C(OC)=CC=C2SC=1CN1CCOCC1 KUBUJZQXINOXSL-UHFFFAOYSA-N 0.000 description 1
- ITGWJBARKAJORR-UHFFFAOYSA-N 5-methoxy-2-(morpholin-4-ylmethyl)-1,3-benzothiazole-4,7-dione Chemical compound N=1C=2C(=O)C(OC)=CC(=O)C=2SC=1CN1CCOCC1 ITGWJBARKAJORR-UHFFFAOYSA-N 0.000 description 1
- SAQMNBWVOKYKPZ-UHFFFAOYSA-N 5-methoxy-2-methyl-1,3-benzothiazole Chemical compound COC1=CC=C2SC(C)=NC2=C1 SAQMNBWVOKYKPZ-UHFFFAOYSA-N 0.000 description 1
- FRHTYGQKBDVXJW-UHFFFAOYSA-N 6,7-dihydro-5h-1,3-benzoxazol-4-one Chemical class O=C1CCCC2=C1N=CO2 FRHTYGQKBDVXJW-UHFFFAOYSA-N 0.000 description 1
- UNAGKNCELVXOCM-UHFFFAOYSA-N 6-(2-pyrrolidin-1-ylethylamino)-2-thiophen-2-yl-1,3-benzothiazole-4,7-dione Chemical compound O=C1C=2SC(C=3SC=CC=3)=NC=2C(=O)C=C1NCCN1CCCC1 UNAGKNCELVXOCM-UHFFFAOYSA-N 0.000 description 1
- GQQPHFMVVUHYLB-UHFFFAOYSA-N 6-(azocan-1-yl)-2-ethyl-1,3-benzoxazole-4,7-dione Chemical compound O1C(CC)=NC(C(C=2)=O)=C1C(=O)C=2N1CCCCCCC1 GQQPHFMVVUHYLB-UHFFFAOYSA-N 0.000 description 1
- VXSJEXCJHCGDCW-UHFFFAOYSA-N 6-(octan-3-ylamino)-2-phenyl-1,3-benzoxazole-4,7-dione Chemical compound O1C=2C(=O)C(NC(CC)CCCCC)=CC(=O)C=2N=C1C1=CC=CC=C1 VXSJEXCJHCGDCW-UHFFFAOYSA-N 0.000 description 1
- HHPMZOUVQKNJSK-UHFFFAOYSA-N 6-[(1-benzylpyrrolidin-3-yl)amino]-2-(4-fluorophenyl)-1,3-benzoxazole-4,7-dione Chemical compound C1=CC(F)=CC=C1C1=NC(C(C=C(NC2CN(CC=3C=CC=CC=3)CC2)C2=O)=O)=C2O1 HHPMZOUVQKNJSK-UHFFFAOYSA-N 0.000 description 1
- RSWLRYKLNMENRY-UHFFFAOYSA-N 6-[2-(dimethylamino)ethylamino]-2-(2,3,4,5-tetrafluorophenyl)-1,3-benzoxazole-4,7-dione Chemical compound O1C=2C(=O)C(NCCN(C)C)=CC(=O)C=2N=C1C1=CC(F)=C(F)C(F)=C1F RSWLRYKLNMENRY-UHFFFAOYSA-N 0.000 description 1
- XUORMNZTMUOTQO-UHFFFAOYSA-N 6-[2-(dimethylamino)ethylamino]-2-(2-fluorophenyl)-1,3-benzothiazole-4,7-dione Chemical compound S1C=2C(=O)C(NCCN(C)C)=CC(=O)C=2N=C1C1=CC=CC=C1F XUORMNZTMUOTQO-UHFFFAOYSA-N 0.000 description 1
- ZNRYJRLEDKLKDH-UHFFFAOYSA-N 6-[2-(dimethylamino)ethylamino]-2-(2-methoxyphenyl)-1,3-benzothiazole-4,7-dione Chemical compound COC1=CC=CC=C1C1=NC(C(C=C(NCCN(C)C)C2=O)=O)=C2S1 ZNRYJRLEDKLKDH-UHFFFAOYSA-N 0.000 description 1
- CBFWHBJWHLQTHH-UHFFFAOYSA-N 6-[2-(dimethylamino)ethylamino]-2-(3,4,5-trifluorophenyl)-1,3-benzothiazole-4,7-dione Chemical compound S1C=2C(=O)C(NCCN(C)C)=CC(=O)C=2N=C1C1=CC(F)=C(F)C(F)=C1 CBFWHBJWHLQTHH-UHFFFAOYSA-N 0.000 description 1
- RDVQKKDZVPAXCM-UHFFFAOYSA-N 6-[3-(dimethylamino)propylamino]-2-[2-fluoro-6-(trifluoromethyl)phenyl]-1,3-benzoxazole-4,7-dione Chemical compound O1C=2C(=O)C(NCCCN(C)C)=CC(=O)C=2N=C1C1=C(F)C=CC=C1C(F)(F)F RDVQKKDZVPAXCM-UHFFFAOYSA-N 0.000 description 1
- BAPQLAKMMJJRDB-UHFFFAOYSA-N 6-[3-(dimethylamino)propylamino]-2-ethyl-1,3-benzoxazole-4,7-dione Chemical compound O=C1C(NCCCN(C)C)=CC(=O)C2=C1OC(CC)=N2 BAPQLAKMMJJRDB-UHFFFAOYSA-N 0.000 description 1
- IYJYAKJDIUFKAC-UHFFFAOYSA-N 6-chloro-5-[2-(dimethylamino)ethylamino]-2-ethyl-1,3-benzoxazole-4,7-dione Chemical compound O=C1C(Cl)=C(NCCN(C)C)C(=O)C2=C1OC(CC)=N2 IYJYAKJDIUFKAC-UHFFFAOYSA-N 0.000 description 1
- CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 1
- OZAIFHULBGXAKX-VAWYXSNFSA-N AIBN Substances N#CC(C)(C)\N=N\C(C)(C)C#N OZAIFHULBGXAKX-VAWYXSNFSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- 108010087765 Antipain Proteins 0.000 description 1
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- HPYWYWKOYXJLGC-UHFFFAOYSA-N C=1C=C2SC(C)=NC2=CC=1NCCN1CCCCC1 Chemical compound C=1C=C2SC(C)=NC2=CC=1NCCN1CCCCC1 HPYWYWKOYXJLGC-UHFFFAOYSA-N 0.000 description 1
- PRQKAFMZAXEFGJ-UHFFFAOYSA-N CN(C)CCCC1=C(C(=O)C2=C(C1=O)OC(=N2)C3=CC=C(C=C3)F)N Chemical compound CN(C)CCCC1=C(C(=O)C2=C(C1=O)OC(=N2)C3=CC=C(C=C3)F)N PRQKAFMZAXEFGJ-UHFFFAOYSA-N 0.000 description 1
- 101100281516 Caenorhabditis elegans fox-1 gene Proteins 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 229910052684 Cerium Inorganic materials 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 1
- 229910021592 Copper(II) chloride Inorganic materials 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical class S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 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 1
- 241000196324 Embryophyta Species 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- 206010027603 Migraine headaches Diseases 0.000 description 1
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 1
- AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 1
- YIAZMRPRAMQJBS-UHFFFAOYSA-N N-[2-[4-[(4-methylphenyl)sulfonylamino]phenyl]ethyl]naphthalene-2-carboxamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(C=C1)=CC=C1CCNC(=O)C1=CC=C(C=CC=C2)C2=C1 YIAZMRPRAMQJBS-UHFFFAOYSA-N 0.000 description 1
- AAKDPDFZMNYDLR-UHFFFAOYSA-N N-methyl deoxynojirimycin Natural products CN1CC(O)C(O)C(O)C1CO AAKDPDFZMNYDLR-UHFFFAOYSA-N 0.000 description 1
- AAKDPDFZMNYDLR-XZBKPIIZSA-N N-methyl-1-deoxynojirimycin Chemical compound CN1C[C@H](O)[C@@H](O)[C@H](O)[C@H]1CO AAKDPDFZMNYDLR-XZBKPIIZSA-N 0.000 description 1
- DQMQYOFEYFVLEG-UHFFFAOYSA-N NC1=CC(C2=C(N=C(S2)C2=C(C=CC=C2)F)C1=O)=O Chemical compound NC1=CC(C2=C(N=C(S2)C2=C(C=CC=C2)F)C1=O)=O DQMQYOFEYFVLEG-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 102000001424 Ryanodine receptors Human genes 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 239000002262 Schiff base Substances 0.000 description 1
- 150000004753 Schiff bases Chemical class 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- LXRZVMYMQHNYJB-UNXOBOICSA-N [(1R,2S,4R)-4-[[5-[4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate Chemical compound CC1=C(C=C(S1)C(=O)C1=C(N[C@H]2C[C@H](O)[C@@H](COS(N)(=O)=O)C2)N=CN=C1)[C@@H]1NCCC2=C1C=C(Cl)C=C2 LXRZVMYMQHNYJB-UNXOBOICSA-N 0.000 description 1
- BFKVXNPJXXJUGQ-UHFFFAOYSA-N [CH2]CCCC Chemical compound [CH2]CCCC BFKVXNPJXXJUGQ-UHFFFAOYSA-N 0.000 description 1
- 206010000210 abortion Diseases 0.000 description 1
- 231100000176 abortion Toxicity 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 1
- 125000002877 alkyl aryl group Chemical group 0.000 description 1
- 125000005189 alkyl hydroxy group Chemical group 0.000 description 1
- BIIVYFLTOXDAOV-YVEFUNNKSA-N alvocidib Chemical compound O[C@@H]1CN(C)CC[C@@H]1C1=C(O)C=C(O)C2=C1OC(C=1C(=CC=CC=1)Cl)=CC2=O BIIVYFLTOXDAOV-YVEFUNNKSA-N 0.000 description 1
- 229950010817 alvocidib Drugs 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- SDNYTAYICBFYFH-TUFLPTIASA-N antipain Chemical compound NC(N)=NCCC[C@@H](C=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 SDNYTAYICBFYFH-TUFLPTIASA-N 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical class C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 1
- 235000019400 benzoyl peroxide Nutrition 0.000 description 1
- PPDJNZTUDFPAHX-UHFFFAOYSA-N benzyltrimethylammonium dichloroiodate Chemical compound Cl[I-]Cl.C[N+](C)(C)CC1=CC=CC=C1 PPDJNZTUDFPAHX-UHFFFAOYSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 239000007844 bleaching agent Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- WQAQPCDUOCURKW-UHFFFAOYSA-N butanethiol Chemical compound CCCCS WQAQPCDUOCURKW-UHFFFAOYSA-N 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- XMPZTFVPEKAKFH-UHFFFAOYSA-P ceric ammonium nitrate Chemical compound [NH4+].[NH4+].[Ce+4].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O XMPZTFVPEKAKFH-UHFFFAOYSA-P 0.000 description 1
- ZMIGMASIKSOYAM-UHFFFAOYSA-N cerium Chemical compound [Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce] ZMIGMASIKSOYAM-UHFFFAOYSA-N 0.000 description 1
- ITZXULOAYIAYNU-UHFFFAOYSA-N cerium(4+) Chemical compound [Ce+4] ITZXULOAYIAYNU-UHFFFAOYSA-N 0.000 description 1
- LQCIDLXXSFUYSA-UHFFFAOYSA-N cerium(4+);tetranitrate Chemical compound [Ce+4].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O LQCIDLXXSFUYSA-UHFFFAOYSA-N 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 1
- QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 238000006352 cycloaddition reaction Methods 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- AUQDITHEDVOTCU-UHFFFAOYSA-N cyclopropyl cyanide Chemical compound N#CC1CC1 AUQDITHEDVOTCU-UHFFFAOYSA-N 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 230000030609 dephosphorylation Effects 0.000 description 1
- 238000006209 dephosphorylation reaction Methods 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- AFABGHUZZDYHJO-UHFFFAOYSA-N dimethyl butane Natural products CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 1
- 239000001177 diphosphate Substances 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- AXZAYXJCENRGIM-UHFFFAOYSA-J dipotassium;tetrabromoplatinum(2-) Chemical compound [K+].[K+].[Br-].[Br-].[Br-].[Br-].[Pt+2] AXZAYXJCENRGIM-UHFFFAOYSA-J 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 229910000397 disodium phosphate Inorganic materials 0.000 description 1
- 235000019800 disodium phosphate Nutrition 0.000 description 1
- XNFVGEUMTFIVHQ-UHFFFAOYSA-N disodium;sulfide;hydrate Chemical compound O.[Na+].[Na+].[S-2] XNFVGEUMTFIVHQ-UHFFFAOYSA-N 0.000 description 1
- 229960003668 docetaxel Drugs 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 238000007345 electrophilic aromatic substitution reaction Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- HKSZLNNOFSGOKW-UHFFFAOYSA-N ent-staurosporine Natural products C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1C1CC(NC)C(OC)C4(C)O1 HKSZLNNOFSGOKW-UHFFFAOYSA-N 0.000 description 1
- 150000002148 esters Chemical group 0.000 description 1
- QUPDWYMUPZLYJZ-UHFFFAOYSA-N ethyl Chemical compound C[CH2] QUPDWYMUPZLYJZ-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- YAGKRVSRTSUGEY-UHFFFAOYSA-N ferricyanide Chemical compound [Fe+3].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-] YAGKRVSRTSUGEY-UHFFFAOYSA-N 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 229960000304 folic acid Drugs 0.000 description 1
- 235000019152 folic acid Nutrition 0.000 description 1
- 239000011724 folic acid Substances 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 208000014829 head and neck neoplasm Diseases 0.000 description 1
- 239000004009 herbicide Substances 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 229960004337 hydroquinone Drugs 0.000 description 1
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 229910052738 indium Inorganic materials 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- RDPLOLUNEKBWBR-UHFFFAOYSA-L magnesium;sodium;sulfate Chemical compound [Na+].[Mg+2].[O-]S([O-])(=O)=O RDPLOLUNEKBWBR-UHFFFAOYSA-L 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000021121 meiosis Effects 0.000 description 1
- LWJROJCJINYWOX-UHFFFAOYSA-L mercury dichloride Chemical compound Cl[Hg]Cl LWJROJCJINYWOX-UHFFFAOYSA-L 0.000 description 1
- HZVOZRGWRWCICA-UHFFFAOYSA-N methanediyl Chemical compound [CH2] HZVOZRGWRWCICA-UHFFFAOYSA-N 0.000 description 1
- XELZGAJCZANUQH-UHFFFAOYSA-N methyl 1-acetylthieno[3,2-c]pyrazole-5-carboxylate Chemical compound CC(=O)N1N=CC2=C1C=C(C(=O)OC)S2 XELZGAJCZANUQH-UHFFFAOYSA-N 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 230000011278 mitosis Effects 0.000 description 1
- ZUXUNWLVIWKEHB-UHFFFAOYSA-N n',n'-dimethylhexane-1,6-diamine Chemical compound CN(C)CCCCCCN ZUXUNWLVIWKEHB-UHFFFAOYSA-N 0.000 description 1
- HVOYZOQVDYHUPF-UHFFFAOYSA-N n,n',n'-trimethylethane-1,2-diamine Chemical compound CNCCN(C)C HVOYZOQVDYHUPF-UHFFFAOYSA-N 0.000 description 1
- ULHKEHDMXOVKII-UHFFFAOYSA-N n-(3,5-dimethoxyphenyl)-2,6-difluorobenzamide Chemical compound COC1=CC(OC)=CC(NC(=O)C=2C(=CC=CC=2F)F)=C1 ULHKEHDMXOVKII-UHFFFAOYSA-N 0.000 description 1
- DHTBTFWCUGGRIS-UHFFFAOYSA-N n-(3,5-dimethoxyphenyl)-2,6-difluorobenzenecarbothioamide Chemical compound COC1=CC(OC)=CC(NC(=S)C=2C(=CC=CC=2F)F)=C1 DHTBTFWCUGGRIS-UHFFFAOYSA-N 0.000 description 1
- JVQSEYMTPJHQFF-UHFFFAOYSA-N n-(3,5-dimethoxyphenyl)-4-fluorobenzamide Chemical compound COC1=CC(OC)=CC(NC(=O)C=2C=CC(F)=CC=2)=C1 JVQSEYMTPJHQFF-UHFFFAOYSA-N 0.000 description 1
- ZTFNUHLBVWEXSM-UHFFFAOYSA-N n-(3,5-dimethoxyphenyl)-4-fluorobenzenecarbothioamide Chemical compound COC1=CC(OC)=CC(NC(=S)C=2C=CC(F)=CC=2)=C1 ZTFNUHLBVWEXSM-UHFFFAOYSA-N 0.000 description 1
- YNTOKMNHRPSGFU-UHFFFAOYSA-N n-Propyl carbamate Chemical compound CCCOC(N)=O YNTOKMNHRPSGFU-UHFFFAOYSA-N 0.000 description 1
- CQTDVDBFPSMFRR-UHFFFAOYSA-N n-[2-[4-[(4-fluorophenyl)sulfonylamino]phenyl]ethyl]-3,7-dihydroxynaphthalene-2-carboxamide Chemical compound C=1C2=CC(O)=CC=C2C=C(O)C=1C(=O)NCCC(C=C1)=CC=C1NS(=O)(=O)C1=CC=C(F)C=C1 CQTDVDBFPSMFRR-UHFFFAOYSA-N 0.000 description 1
- WYOOPENEUHDZIT-UHFFFAOYSA-N n-[4-(4-methylpiperazin-1-yl)phenyl]butanamide Chemical compound C1=CC(NC(=O)CCC)=CC=C1N1CCN(C)CC1 WYOOPENEUHDZIT-UHFFFAOYSA-N 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
- 101150115538 nero gene Proteins 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 238000006396 nitration reaction Methods 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 150000002828 nitro derivatives Chemical class 0.000 description 1
- 125000006501 nitrophenyl group Chemical group 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- GTVPOLSIJWJJNY-UHFFFAOYSA-N olomoucine Chemical compound N1=C(NCCO)N=C2N(C)C=NC2=C1NCC1=CC=CC=C1 GTVPOLSIJWJJNY-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 230000000865 phosphorylative effect Effects 0.000 description 1
- 108091008695 photoreceptors Proteins 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920006316 polyvinylpyrrolidine Polymers 0.000 description 1
- 239000004323 potassium nitrate Substances 0.000 description 1
- 235000010333 potassium nitrate Nutrition 0.000 description 1
- IHSLHAZEJBXKMN-UHFFFAOYSA-L potassium nitrosodisulfonate Chemical compound [K+].[K+].[O-]S(=O)(=O)N([O])S([O-])(=O)=O IHSLHAZEJBXKMN-UHFFFAOYSA-L 0.000 description 1
- 229910001487 potassium perchlorate Inorganic materials 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000011535 reaction buffer Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000008521 reorganization Effects 0.000 description 1
- YNWSXIWHOSSPCO-UHFFFAOYSA-N rhodium(2+) Chemical compound [Rh+2] YNWSXIWHOSSPCO-UHFFFAOYSA-N 0.000 description 1
- 239000010979 ruby Substances 0.000 description 1
- 229910001750 ruby Inorganic materials 0.000 description 1
- 108091052345 ryanodine receptor (TC 1.A.3.1) family Proteins 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 235000004400 serine Nutrition 0.000 description 1
- 150000003355 serines Chemical class 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
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- LDTLADDKFLAYJA-UHFFFAOYSA-L sodium metabisulphite Chemical compound [Na+].[Na+].[O-]S(=O)OS([O-])=O LDTLADDKFLAYJA-UHFFFAOYSA-L 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- HKSZLNNOFSGOKW-FYTWVXJKSA-N staurosporine Chemical compound C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1[C@H]1C[C@@H](NC)[C@@H](OC)[C@]4(C)O1 HKSZLNNOFSGOKW-FYTWVXJKSA-N 0.000 description 1
- CGPUWJWCVCFERF-UHFFFAOYSA-N staurosporine Natural products C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1C1CC(NC)C(OC)C4(OC)O1 CGPUWJWCVCFERF-UHFFFAOYSA-N 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 229940063683 taxotere Drugs 0.000 description 1
- YJBKVPRVZAQTPY-UHFFFAOYSA-J tetrachlorostannane;dihydrate Chemical compound O.O.Cl[Sn](Cl)(Cl)Cl YJBKVPRVZAQTPY-UHFFFAOYSA-J 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000010409 thin film Substances 0.000 description 1
- 150000003556 thioamides Chemical class 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 235000008521 threonine Nutrition 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- NDLIRBZKZSDGSO-UHFFFAOYSA-N tosyl azide Chemical compound CC1=CC=C(S(=O)(=O)[N-][N+]#N)C=C1 NDLIRBZKZSDGSO-UHFFFAOYSA-N 0.000 description 1
- 231100000048 toxicity data Toxicity 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- 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
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pulmonology (AREA)
- Urology & Nephrology (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR0307649A FR2856688B1 (fr) | 2003-06-25 | 2003-06-25 | PRODUIT COMPRENANT AU MOINS UN INHIBITEUR DE PHOSPHATASE CDc25 EN ASSOCIATION AVEC AU MOINS UN AUTRE AGENT ANTI-CANCEREUX |
| FR03/07649 | 2003-06-25 | ||
| PCT/FR2004/001586 WO2005000852A2 (fr) | 2003-06-25 | 2004-06-24 | Produit comprenant au moins un inhibiteur de phosphates cdc25 en association avec au moins un autre agent anti-cancereux |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2530668A1 true CA2530668A1 (fr) | 2005-01-06 |
Family
ID=33515382
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002530668A Abandoned CA2530668A1 (fr) | 2003-06-25 | 2004-06-24 | Produit comprenant au moins un inhibiteur de phosphatase cdc25 en association avec au moins un autre agent anti-cancereux |
Country Status (14)
| Country | Link |
|---|---|
| US (3) | US20060281736A1 (https=) |
| EP (3) | EP1792905A1 (https=) |
| JP (2) | JP2007514639A (https=) |
| AR (2) | AR044930A1 (https=) |
| AT (1) | ATE439836T1 (https=) |
| CA (1) | CA2530668A1 (https=) |
| DE (1) | DE602004022674D1 (https=) |
| DK (1) | DK1641453T3 (https=) |
| ES (1) | ES2332137T3 (https=) |
| FR (1) | FR2856688B1 (https=) |
| MX (1) | MXPA06000216A (https=) |
| MY (1) | MY141725A (https=) |
| PL (1) | PL1641453T3 (https=) |
| WO (1) | WO2005000852A2 (https=) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2834289B1 (fr) * | 2001-12-27 | 2004-03-19 | Sod Conseils Rech Applic | Derives de benzothiazole-4,7-diones et benzooxazole-4,7- diones, leur preparation et leurs applications therapeutiques |
| CN100425600C (zh) * | 2001-12-27 | 2008-10-15 | 科学研究和应用咨询公司 | 苯并噻唑－和苯并唑－4,7－二酮衍生物及其作为cdc25磷酸酯酶抑制剂的用途 |
| FR2856688B1 (fr) * | 2003-06-25 | 2008-05-30 | Sod Conseils Rech Applic | PRODUIT COMPRENANT AU MOINS UN INHIBITEUR DE PHOSPHATASE CDc25 EN ASSOCIATION AVEC AU MOINS UN AUTRE AGENT ANTI-CANCEREUX |
| DE10353792A1 (de) | 2003-11-13 | 2005-06-23 | Exner, Heinrich, Dr.med.vet. | Heil- und Wundsalbe auf der Basis einer wässrigen Emulsion |
| FR2877667B1 (fr) * | 2004-11-05 | 2007-03-23 | Sod Conseils Rech Applic | Derives de 4,7-dioxobenzothiazole-2-carboxamides, leur preparation et leurs applications therapeutiques |
| FR2879598B1 (fr) * | 2004-12-17 | 2007-03-30 | Sod Conseils Rech Applic | Inhibiteurs de phosphatases cdc25 |
| FR2879460B1 (fr) * | 2004-12-17 | 2007-02-23 | Sod Conseils Rech Applic | Associations anti-douleur comprenant un derive de dihydroimidazopyrazine |
| US7723336B2 (en) | 2005-09-22 | 2010-05-25 | Bristol-Myers Squibb Company | Fused heterocyclic compounds useful as kinase modulators |
| ES2366874T3 (es) * | 2007-09-06 | 2011-10-26 | Basf Se | Mezclas de poliariléteres ramificados y polímeros hidrófilos. |
| WO2009100375A1 (en) | 2008-02-06 | 2009-08-13 | Bristol-Myers Squibb Company | Substituted imidazopyridazines useful as kinase inhibitors |
| AR077463A1 (es) | 2009-07-09 | 2011-08-31 | Irm Llc | Derivados de imidazo[1, 2 - a]pirazina y su uso en medicamentos para el tratamiento de enfermedades parasitarias |
| RS54648B1 (sr) * | 2010-11-12 | 2016-08-31 | Pharma Mar S.A. | Kombinovana terapija sa antitumorskim alkaloidom |
| CN110691597A (zh) | 2017-04-24 | 2020-01-14 | 诺华股份有限公司 | 2-氨基-1-(2-(4-氟苯基)-3-(4-氟苯基氨基)-8,8-二甲基-5,6-二氢咪唑并[1,2-a]吡嗪-7(8H)-基)乙酮及其组合的治疗方案 |
| US20210106567A1 (en) * | 2019-10-01 | 2021-04-15 | United States Government As Represented By The Department Of Veterans Affairs | Compositions and methods for inhibiting carp-1 binding to nemo |
| PE20252386A1 (es) | 2019-11-21 | 2025-10-10 | Pharma Mar Sa | Metodo de tratamiento del cancer de pulmon de celulas pequenas con formulaciones de lurbinectedina |
| US11981645B1 (en) | 2023-10-10 | 2024-05-14 | King Faisal University | N′-(2-naphthoyloxy)-2-(benzo[d]oxazol-2-yl)acetimidamide as antimicrobial compound |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US735674A (en) * | 1902-01-29 | 1903-08-04 | William C Matthias | Sparking igniter for explosive-engines. |
| FR50000E (fr) | 1938-11-29 | 1939-09-29 | Moulin à café | |
| US5523430A (en) * | 1994-04-14 | 1996-06-04 | Bristol-Myers Squibb Company | Protein farnesyl transferase inhibitors |
| US6673927B2 (en) | 1996-02-16 | 2004-01-06 | Societe De Conseils De Recherches Et D'applications Scientifiques, S.A.S. | Farnesyl transferase inhibitors |
| US6383871B1 (en) * | 1999-08-31 | 2002-05-07 | Micron Technology, Inc. | Method of forming multiple oxide thicknesses for merged memory and logic applications |
| CZ20021550A3 (cs) * | 1999-11-09 | 2003-02-12 | Societe De Conseils De Recherches Et D'application | Produkt zahrnující inhibitor transdukce signálů heterotrimerického G proteinu kombinovaný s jiným protirakovinným činidlem pro terapeutické použití v léčbě rakoviny |
| FR2812198B1 (fr) * | 2000-07-28 | 2008-07-18 | Sod Conseils Rech Applic | DERIVES D'AMIDINES INHIBITEURS DE PHOSPHATASES cdc25 |
| EP1345941A1 (fr) * | 2000-12-20 | 2003-09-24 | Societe De Conseils De Recherches Et D'applications Scientifiques (S.C.R.A.S.) | Inhibiteurs de kinases dependantes des cylines (cdk) et de la glycogene synthase kinase-3 (gsk-3) |
| FR2825278A1 (fr) * | 2001-05-30 | 2002-12-06 | Sod Conseils Rech Applic | Produit comprenant du mikanolide, du dihydromikanolide ou un analogue de ceux-ci en association avec un autre agent anti-cancereux pour une utilisation therapeutique dans le traitement du cancer |
| AR037714A1 (es) * | 2001-12-06 | 2004-12-01 | Maxia Pharmaceuticals Inc | Derivados de tiazolidinona y oxazolidinona 2-sustituidos para la inhibicion de fosfatasas y el tratamiento de cancer |
| FR2834289B1 (fr) * | 2001-12-27 | 2004-03-19 | Sod Conseils Rech Applic | Derives de benzothiazole-4,7-diones et benzooxazole-4,7- diones, leur preparation et leurs applications therapeutiques |
| CN100425600C (zh) * | 2001-12-27 | 2008-10-15 | 科学研究和应用咨询公司 | 苯并噻唑－和苯并唑－4,7－二酮衍生物及其作为cdc25磷酸酯酶抑制剂的用途 |
| FR2856688B1 (fr) * | 2003-06-25 | 2008-05-30 | Sod Conseils Rech Applic | PRODUIT COMPRENANT AU MOINS UN INHIBITEUR DE PHOSPHATASE CDc25 EN ASSOCIATION AVEC AU MOINS UN AUTRE AGENT ANTI-CANCEREUX |
| FR2856686A1 (fr) * | 2003-06-25 | 2004-12-31 | Sod Conseils Rech Applic | Benzothiazole-4,7-diones et benzooxazole-4,7-diones substituees en position 5 ou 6 et leurs procedes de preparation |
| JP4273056B2 (ja) * | 2004-08-12 | 2009-06-03 | 不二越機械工業株式会社 | 研磨装置 |
-
2003
- 2003-06-25 FR FR0307649A patent/FR2856688B1/fr not_active Expired - Fee Related
-
2004
- 2004-06-17 MY MYPI20042361A patent/MY141725A/en unknown
- 2004-06-24 WO PCT/FR2004/001586 patent/WO2005000852A2/fr not_active Ceased
- 2004-06-24 DE DE602004022674T patent/DE602004022674D1/de not_active Expired - Lifetime
- 2004-06-24 US US10/562,625 patent/US20060281736A1/en not_active Abandoned
- 2004-06-24 JP JP2006516322A patent/JP2007514639A/ja active Pending
- 2004-06-24 PL PL04767442T patent/PL1641453T3/pl unknown
- 2004-06-24 CA CA002530668A patent/CA2530668A1/fr not_active Abandoned
- 2004-06-24 ES ES04767442T patent/ES2332137T3/es not_active Expired - Lifetime
- 2004-06-24 EP EP07006144A patent/EP1792905A1/fr not_active Withdrawn
- 2004-06-24 EP EP08020152A patent/EP2335702A1/fr not_active Withdrawn
- 2004-06-24 MX MXPA06000216A patent/MXPA06000216A/es active IP Right Grant
- 2004-06-24 EP EP04767442A patent/EP1641453B1/fr not_active Expired - Lifetime
- 2004-06-24 AT AT04767442T patent/ATE439836T1/de not_active IP Right Cessation
- 2004-06-24 DK DK04767442T patent/DK1641453T3/da active
- 2004-06-25 AR ARP040102257A patent/AR044930A1/es not_active Application Discontinuation
-
2008
- 2008-05-22 US US12/154,319 patent/US20090253685A1/en not_active Abandoned
- 2008-10-07 US US12/247,072 patent/US20090137596A1/en not_active Abandoned
-
2009
- 2009-03-09 AR ARP090100837A patent/AR070977A2/es unknown
- 2009-04-03 JP JP2009091214A patent/JP2009149694A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| PL1641453T3 (pl) | 2010-01-29 |
| US20060281736A1 (en) | 2006-12-14 |
| WO2005000852A3 (fr) | 2005-06-30 |
| US20090253685A1 (en) | 2009-10-08 |
| DE602004022674D1 (de) | 2009-10-01 |
| EP2335702A1 (fr) | 2011-06-22 |
| MY141725A (en) | 2010-06-15 |
| ES2332137T3 (es) | 2010-01-27 |
| ATE439836T1 (de) | 2009-09-15 |
| FR2856688B1 (fr) | 2008-05-30 |
| DK1641453T3 (da) | 2009-12-14 |
| MXPA06000216A (es) | 2006-04-11 |
| FR2856688A1 (fr) | 2004-12-31 |
| AR070977A2 (es) | 2010-05-19 |
| EP1792905A1 (fr) | 2007-06-06 |
| US20090137596A1 (en) | 2009-05-28 |
| JP2009149694A (ja) | 2009-07-09 |
| EP1641453A2 (fr) | 2006-04-05 |
| EP1641453B1 (fr) | 2009-08-19 |
| WO2005000852A2 (fr) | 2005-01-06 |
| AR044930A1 (es) | 2005-10-12 |
| JP2007514639A (ja) | 2007-06-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20090137596A1 (en) | G-protein inhibitor | |
| US20090131428A1 (en) | Benzooxazole-4,7-dione, derivatives and their use as cdc25 phosphate inhibitors | |
| CA2448528A1 (fr) | Produit comprenant du mikanolide, du dihydromikanolide ou un analogue de ceux-ci en association avec un autre agent anti-cancereux pour une utilisation therapeutique dans le traitement du cancer | |
| WO2008049994A1 (fr) | Nouveaux derives du fluorene, compositions les contenant et utilisation comme inhibiteurs de la proteine chpaerone hsp90 | |
| EP1831209B1 (fr) | Inhibiteurs de phosphatases cdc25 | |
| CA2727626A1 (fr) | Nouveaux derives de pyrroloindole inhibiteurs d'hsp90, compositions les contenant et utilisation | |
| US7495021B2 (en) | Benzothiazole- and benzooxazole-4,7-dione, derivatives and their use as cdc25 phosphate inhibitors | |
| EP1641789A2 (fr) | Benzothiazole-4,7-diones et benzoxazole-4,7-diones substituees en position 5 ou 6 et leurs procedes de preparation | |
| EP1814879B1 (fr) | Derives de 4,7-dioxobenzothiazole-2-carboxamides, leur preparation et leurs applications therapeutiques |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |
Effective date: 20121105 |