NO322214B1 - Forbindelser som er pyrrolotriazin-inhibitorer for kinaser, farmasoytiske preparater omfattende forbindelsene, samt anvendelser derav for fremstilling av er farmasoytisk preparat. - Google Patents

Info

Publication number

NO322214B1

NO322214B1 NO20015650A NO20015650A NO322214B1 NO 322214 B1 NO322214 B1 NO 322214B1 NO 20015650 A NO20015650 A NO 20015650A NO 20015650 A NO20015650 A NO 20015650A NO 322214 B1 NO322214 B1 NO 322214B1

Authority

NO

Norway

Prior art keywords

triazine

carboxylic acid

amino

methyl ester

methylpyrrolo

Prior art date

1999-05-21

Links

• Espacenet
• Global Dossier
• Discuss

• 150000001875 compounds Chemical class 0.000 title claims description 257
• 238000002360 preparation method Methods 0.000 title claims description 30
• 102000001253 Protein Kinase Human genes 0.000 title claims description 6
• 108060006633 protein kinase Proteins 0.000 title claims description 6
• 239000003112 inhibitor Substances 0.000 title description 11
• SUPXSFXAMJPEPH-UHFFFAOYSA-N 5h-pyrrolo[3,2-d]triazine Chemical compound N1=NC=C2NC=CC2=N1 SUPXSFXAMJPEPH-UHFFFAOYSA-N 0.000 title description 2
• 239000008194 pharmaceutical composition Substances 0.000 title 2
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 152
• -1 3-hydroxy-4-methylphenyl Chemical group 0.000 claims description 112
• 238000011282 treatment Methods 0.000 claims description 53
• 206010028980 Neoplasm Diseases 0.000 claims description 33
• 239000000825 pharmaceutical preparation Substances 0.000 claims description 26
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 24
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 21
• 201000011510 cancer Diseases 0.000 claims description 20
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 17
• 230000000694 effects Effects 0.000 claims description 17
• 238000004519 manufacturing process Methods 0.000 claims description 15
• 201000010099 disease Diseases 0.000 claims description 14
• 239000003937 drug carrier Substances 0.000 claims description 12
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 12
• 102000009465 Growth Factor Receptors Human genes 0.000 claims description 11
• 108010009202 Growth Factor Receptors Proteins 0.000 claims description 11
• 239000002253 acid Substances 0.000 claims description 11
• 239000002246 antineoplastic agent Substances 0.000 claims description 10
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
• 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims description 8
• 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims description 8
• 230000001772 anti-angiogenic effect Effects 0.000 claims description 8
• 239000002254 cytotoxic agent Substances 0.000 claims description 8
• 229940127089 cytotoxic agent Drugs 0.000 claims description 8
• 231100000599 cytotoxic agent Toxicity 0.000 claims description 8
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 8
• 208000023275 Autoimmune disease Diseases 0.000 claims description 7
• LDECUSDQMXVUMP-UHFFFAOYSA-N benzyl 3-[6-[[2-(butylamino)-1-[3-methoxycarbonyl-4-(2-methoxy-2-oxoethoxy)phenyl]-2-oxoethyl]-hexylamino]-6-oxohexyl]-4-methyl-2-oxo-6-(4-phenylphenyl)-1,6-dihydropyrimidine-5-carboxylate Chemical compound O=C1NC(C=2C=CC(=CC=2)C=2C=CC=CC=2)C(C(=O)OCC=2C=CC=CC=2)=C(C)N1CCCCCC(=O)N(CCCCCC)C(C(=O)NCCCC)C1=CC=C(OCC(=O)OC)C(C(=O)OC)=C1 LDECUSDQMXVUMP-UHFFFAOYSA-N 0.000 claims description 7
• 230000002062 proliferating effect Effects 0.000 claims description 7
• 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 claims description 6
• 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 claims description 6
• NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 claims description 6
• RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 claims description 6
• 230000001093 anti-cancer Effects 0.000 claims description 6
• 150000004702 methyl esters Chemical class 0.000 claims description 6
• 230000002401 inhibitory effect Effects 0.000 claims description 5
• 230000037361 pathway Effects 0.000 claims description 5
• 230000008728 vascular permeability Effects 0.000 claims description 5
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 4
• 206010061218 Inflammation Diseases 0.000 claims description 4
• DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims description 4
• 229960004316 cisplatin Drugs 0.000 claims description 4
• 230000004054 inflammatory process Effects 0.000 claims description 4
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 4
• 230000008054 signal transmission Effects 0.000 claims description 4
• LKJPYSCBVHEWIU-KRWDZBQOSA-N (R)-bicalutamide Chemical compound C([C@@](O)(C)C(=O)NC=1C=C(C(C#N)=CC=1)C(F)(F)F)S(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-KRWDZBQOSA-N 0.000 claims description 3
• STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 claims description 3
• BFYIZQONLCFLEV-DAELLWKTSA-N Aromasine Chemical compound O=C1C=C[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC(=C)C2=C1 BFYIZQONLCFLEV-DAELLWKTSA-N 0.000 claims description 3
• COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 claims description 3
• UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 claims description 3
• 108010092160 Dactinomycin Proteins 0.000 claims description 3
• WEAHRLBPCANXCN-UHFFFAOYSA-N Daunomycin Natural products CCC1(O)CC(OC2CC(N)C(O)C(C)O2)c3cc4C(=O)c5c(OC)cccc5C(=O)c4c(O)c3C1 WEAHRLBPCANXCN-UHFFFAOYSA-N 0.000 claims description 3
• ZQZFYGIXNQKOAV-OCEACIFDSA-N Droloxifene Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=C(O)C=CC=1)\C1=CC=C(OCCN(C)C)C=C1 ZQZFYGIXNQKOAV-OCEACIFDSA-N 0.000 claims description 3
• GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 3
• 108010069236 Goserelin Proteins 0.000 claims description 3
• XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XDXDZDZNSLXDNA-TZNDIEGXSA-N 0.000 claims description 3
• XDXDZDZNSLXDNA-UHFFFAOYSA-N Idarubicin Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XDXDZDZNSLXDNA-UHFFFAOYSA-N 0.000 claims description 3
• 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 claims description 3
• 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 claims description 3
• 229930012538 Paclitaxel Natural products 0.000 claims description 3
• RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 claims 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 claims description 3
• 229960001220 amsacrine Drugs 0.000 claims description 3
• 229960002932 anastrozole Drugs 0.000 claims description 3
• YBBLVLTVTVSKRW-UHFFFAOYSA-N anastrozole Chemical compound N#CC(C)(C)C1=CC(C(C)(C#N)C)=CC(CN2N=CN=C2)=C1 YBBLVLTVTVSKRW-UHFFFAOYSA-N 0.000 claims description 3
• 229960000997 bicalutamide Drugs 0.000 claims description 3
• BGECDVWSWDRFSP-UHFFFAOYSA-N borazine Chemical compound B1NBNBN1 BGECDVWSWDRFSP-UHFFFAOYSA-N 0.000 claims description 3
• 229960002092 busulfan Drugs 0.000 claims description 3
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
• 229960004562 carboplatin Drugs 0.000 claims description 3
• JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 claims description 3
• 229960004630 chlorambucil Drugs 0.000 claims description 3
• UWFYSQMTEOIJJG-FDTZYFLXSA-N cyproterone acetate Chemical compound C1=C(Cl)C2=CC(=O)[C@@H]3C[C@@H]3[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)C)[C@@]1(C)CC2 UWFYSQMTEOIJJG-FDTZYFLXSA-N 0.000 claims description 3
• 229960000978 cyproterone acetate Drugs 0.000 claims description 3
• 229960000640 dactinomycin Drugs 0.000 claims description 3
• STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 claims description 3
• 229960004679 doxorubicin Drugs 0.000 claims description 3
• 229950004203 droloxifene Drugs 0.000 claims description 3
• 229930013356 epothilone Natural products 0.000 claims description 3
• 150000003883 epothilone derivatives Chemical class 0.000 claims description 3
• VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 claims description 3
• 229960005420 etoposide Drugs 0.000 claims description 3
• 229960000255 exemestane Drugs 0.000 claims description 3
• DBEPLOCGEIEOCV-WSBQPABSSA-N finasteride Chemical compound N([C@@H]1CC2)C(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](C(=O)NC(C)(C)C)[C@@]2(C)CC1 DBEPLOCGEIEOCV-WSBQPABSSA-N 0.000 claims description 3
• 229960004039 finasteride Drugs 0.000 claims description 3
• 229960002949 fluorouracil Drugs 0.000 claims description 3
• 229960002074 flutamide Drugs 0.000 claims description 3
• MKXKFYHWDHIYRV-UHFFFAOYSA-N flutamide Chemical compound CC(C)C(=O)NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 MKXKFYHWDHIYRV-UHFFFAOYSA-N 0.000 claims description 3
• 229960003690 goserelin acetate Drugs 0.000 claims description 3
• 229960000908 idarubicin Drugs 0.000 claims description 3
• HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 claims description 3
• 229960001101 ifosfamide Drugs 0.000 claims description 3
• 229960003881 letrozole Drugs 0.000 claims description 3
• HPJKCIUCZWXJDR-UHFFFAOYSA-N letrozole Chemical compound C1=CC(C#N)=CC=C1C(N1N=CN=C1)C1=CC=C(C#N)C=C1 HPJKCIUCZWXJDR-UHFFFAOYSA-N 0.000 claims description 3
• RQZAXGRLVPAYTJ-GQFGMJRRSA-N megestrol acetate Chemical compound C1=C(C)C2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)C)[C@@]1(C)CC2 RQZAXGRLVPAYTJ-GQFGMJRRSA-N 0.000 claims description 3
• 229960004296 megestrol acetate Drugs 0.000 claims description 3
• SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 claims description 3
• 229960001924 melphalan Drugs 0.000 claims description 3
• 229960000485 methotrexate Drugs 0.000 claims description 3
• CFCUWKMKBJTWLW-BKHRDMLASA-N mithramycin Chemical compound O([C@@H]1C[C@@H](O[C@H](C)[C@H]1O)OC=1C=C2C=C3C[C@H]([C@@H](C(=O)C3=C(O)C2=C(O)C=1C)O[C@@H]1O[C@H](C)[C@@H](O)[C@H](O[C@@H]2O[C@H](C)[C@H](O)[C@H](O[C@@H]3O[C@H](C)[C@@H](O)[C@@](C)(O)C3)C2)C1)[C@H](OC)C(=O)[C@@H](O)[C@@H](C)O)[C@H]1C[C@@H](O)[C@H](O)[C@@H](C)O1 CFCUWKMKBJTWLW-BKHRDMLASA-N 0.000 claims description 3
• 229960004857 mitomycin Drugs 0.000 claims description 3
• BLCLNMBMMGCOAS-UHFFFAOYSA-N n-[1-[[1-[[1-[[1-[[1-[[1-[[1-[2-[(carbamoylamino)carbamoyl]pyrrolidin-1-yl]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-[(2-methylpropan-2-yl)oxy]-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amin Chemical compound C1CCC(C(=O)NNC(N)=O)N1C(=O)C(CCCN=C(N)N)NC(=O)C(CC(C)C)NC(=O)C(COC(C)(C)C)NC(=O)C(NC(=O)C(CO)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C(CC=1NC=NC=1)NC(=O)C1NC(=O)CC1)CC1=CC=C(O)C=C1 BLCLNMBMMGCOAS-UHFFFAOYSA-N 0.000 claims description 3
• 229960002653 nilutamide Drugs 0.000 claims description 3
• XWXYUMMDTVBTOU-UHFFFAOYSA-N nilutamide Chemical compound O=C1C(C)(C)NC(=O)N1C1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 XWXYUMMDTVBTOU-UHFFFAOYSA-N 0.000 claims description 3
• 229960001592 paclitaxel Drugs 0.000 claims description 3
• 229960003171 plicamycin Drugs 0.000 claims description 3
• 229960004622 raloxifene Drugs 0.000 claims description 3
• GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 claims description 3
• 229960001603 tamoxifen Drugs 0.000 claims 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 claims description 3
• 229940063683 taxotere Drugs 0.000 claims description 3
• NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 claims description 3
• 229960001278 teniposide Drugs 0.000 claims description 3
• UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 claims description 3
• 229960000303 topotecan Drugs 0.000 claims description 3
• 229960005026 toremifene Drugs 0.000 claims description 3
• XFCLJVABOIYOMF-QPLCGJKRSA-N toremifene Chemical compound C1=CC(OCCN(C)C)=CC=C1C(\C=1C=CC=CC=1)=C(\CCCl)C1=CC=CC=C1 XFCLJVABOIYOMF-QPLCGJKRSA-N 0.000 claims description 3
• OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 claims description 3
• 229960004528 vincristine Drugs 0.000 claims description 3
• OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 claims description 3
• QWKFRPBJBADCAF-UHFFFAOYSA-N 2-hydroxy-5-[(6-methoxycarbonyl-5-methylpyrrolo[2,1-f][1,2,4]triazin-4-yl)amino]benzoic acid Chemical compound C12=C(C)C(C(=O)OC)=CN2N=CN=C1NC1=CC=C(O)C(C(O)=O)=C1 QWKFRPBJBADCAF-UHFFFAOYSA-N 0.000 claims description 2
• PUQRBNHBRWCBGJ-UHFFFAOYSA-N 4-(4-bromo-2-fluoroanilino)-5-methoxy-n-(2-pyrrolidin-1-ylethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide Chemical compound C12=C(OC)C(C(=O)NCCN3CCCC3)=CN2N=CN=C1NC1=CC=C(Br)C=C1F PUQRBNHBRWCBGJ-UHFFFAOYSA-N 0.000 claims description 2
• NSSREJILCYZENK-UHFFFAOYSA-N 5-[(5,6-dimethylpyrrolo[2,1-f][1,2,4]triazin-4-yl)amino]-2-methylphenol Chemical compound C12=C(C)C(C)=CN2N=CN=C1NC1=CC=C(C)C(O)=C1 NSSREJILCYZENK-UHFFFAOYSA-N 0.000 claims description 2
• FLYWWNDDXORVRE-UHFFFAOYSA-N 5-[(5,7-dimethylpyrrolo[2,1-f][1,2,4]triazin-4-yl)amino]-2-methylphenol Chemical compound C12=C(C)C=C(C)N2N=CN=C1NC1=CC=C(C)C(O)=C1 FLYWWNDDXORVRE-UHFFFAOYSA-N 0.000 claims description 2
• KNVIJRHUKKOQEA-UHFFFAOYSA-N 5-[(5-ethylpyrrolo[2,1-f][1,2,4]triazin-4-yl)amino]-2-methylphenol Chemical compound C12=C(CC)C=CN2N=CN=C1NC1=CC=C(C)C(O)=C1 KNVIJRHUKKOQEA-UHFFFAOYSA-N 0.000 claims description 2
• OYWONCFUNIWAQD-UHFFFAOYSA-N 5-[[2-(dimethylamino)pyrrolo[2,1-f][1,2,4]triazin-4-yl]amino]-2-methylphenol Chemical compound C12=CC=CN2N=C(N(C)C)N=C1NC1=CC=C(C)C(O)=C1 OYWONCFUNIWAQD-UHFFFAOYSA-N 0.000 claims description 2
• SSEICAMCKGJKRN-UHFFFAOYSA-N 5-ethyl-4-[(6-methoxypyridin-3-yl)amino]pyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid Chemical compound C12=C(CC)C(C(O)=O)=CN2N=CN=C1NC1=CC=C(OC)N=C1 SSEICAMCKGJKRN-UHFFFAOYSA-N 0.000 claims description 2
• VHPIKEMJVIXMSH-UHFFFAOYSA-N 5-methyl-4-(2-oxo-1,3-dihydroindol-3-yl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid Chemical compound O=C1NC2=CC=CC=C2C1C1=NC=NN2C=C(C(O)=O)C(C)=C12 VHPIKEMJVIXMSH-UHFFFAOYSA-N 0.000 claims description 2
• SDPZKXVWIGGJLK-UHFFFAOYSA-N benzyl n-[5-ethyl-4-[(6-methoxypyridin-3-yl)amino]pyrrolo[2,1-f][1,2,4]triazin-6-yl]carbamate Chemical compound C=1N2N=CN=C(NC=3C=NC(OC)=CC=3)C2=C(CC)C=1NC(=O)OCC1=CC=CC=C1 SDPZKXVWIGGJLK-UHFFFAOYSA-N 0.000 claims description 2
• SBZWEENTHCBFJG-UHFFFAOYSA-N chembl400486 Chemical compound FC1=CC=C2C(C3=NC=NN4C=C(C(=C43)C)C(=O)OC)=C(O)NC2=C1 SBZWEENTHCBFJG-UHFFFAOYSA-N 0.000 claims description 2
• ZLOWIHLTINOBGA-UHFFFAOYSA-N diethyl 4-(3-hydroxy-4-methylanilino)pyrrolo[2,1-f][1,2,4]triazine-5,6-dicarboxylate Chemical compound C12=C(C(=O)OCC)C(C(=O)OCC)=CN2N=CN=C1NC1=CC=C(C)C(O)=C1 ZLOWIHLTINOBGA-UHFFFAOYSA-N 0.000 claims description 2
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 2
• ZTOVINQRRLDIIS-UHFFFAOYSA-N ethyl 4-[(6-methoxypyridin-3-yl)amino]-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C)C(C(=O)OCC)=CN2N=CN=C1NC1=CC=C(OC)N=C1 ZTOVINQRRLDIIS-UHFFFAOYSA-N 0.000 claims description 2
• MPVVGXKXQOZABD-UHFFFAOYSA-N ethyl 5-ethyl-4-(2-oxo-1,3-dihydroindol-3-yl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound O=C1NC2=CC=CC=C2C1C1=NC=NN2C=C(C(=O)OCC)C(CC)=C21 MPVVGXKXQOZABD-UHFFFAOYSA-N 0.000 claims description 2
• OKYDIKYNMQSXSY-UHFFFAOYSA-N ethyl 5-ethyl-4-[3-(methanesulfonamido)-4-methylanilino]pyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(CC)C(C(=O)OCC)=CN2N=CN=C1NC1=CC=C(C)C(NS(C)(=O)=O)=C1 OKYDIKYNMQSXSY-UHFFFAOYSA-N 0.000 claims description 2
• 229940022353 herceptin Drugs 0.000 claims description 2
• UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 claims description 2
• 229960004768 irinotecan Drugs 0.000 claims description 2
• GZOLPVDOLYQBMB-UHFFFAOYSA-N methyl 4-(1h-indol-6-ylamino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C1=C2C=CNC2=CC(NC2=NC=NN3C=C(C(=C32)C)C(=O)OC)=C1 GZOLPVDOLYQBMB-UHFFFAOYSA-N 0.000 claims description 2
• GKAZEUGTXYNBFY-UHFFFAOYSA-N methyl 4-(2,3-dihydro-1,4-benzodioxin-6-ylamino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound O1CCOC2=CC(NC3=NC=NN4C=C(C(=C43)C)C(=O)OC)=CC=C21 GKAZEUGTXYNBFY-UHFFFAOYSA-N 0.000 claims description 2
• YFGKHNXPJPMCFJ-UHFFFAOYSA-N methyl 4-(3-hydroxy-4-methoxyanilino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C)C(C(=O)OC)=CN2N=CN=C1NC1=CC=C(OC)C(O)=C1 YFGKHNXPJPMCFJ-UHFFFAOYSA-N 0.000 claims description 2
• HDUYYHXMLYTCAI-UHFFFAOYSA-N methyl 4-(3-hydroxyanilino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C)C(C(=O)OC)=CN2N=CN=C1NC1=CC=CC(O)=C1 HDUYYHXMLYTCAI-UHFFFAOYSA-N 0.000 claims description 2
• HGLFWYTYWBQLDW-UHFFFAOYSA-N methyl 4-(3-hydroxyphenoxy)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C)C(C(=O)OC)=CN2N=CN=C1OC1=CC=CC(O)=C1 HGLFWYTYWBQLDW-UHFFFAOYSA-N 0.000 claims description 2
• MNXPSLVOIQHJAN-UHFFFAOYSA-N methyl 4-(4-chloro-3-nitroanilino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C)C(C(=O)OC)=CN2N=CN=C1NC1=CC=C(Cl)C([N+]([O-])=O)=C1 MNXPSLVOIQHJAN-UHFFFAOYSA-N 0.000 claims description 2
• XLAJOHUNILNDLC-UHFFFAOYSA-N methyl 4-(5-carbamoyl-2-oxo-1,3-dihydroindol-3-yl)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound O=C1NC2=CC=C(C(N)=O)C=C2C1C1=NC=NN2C=C(C(=O)OC)C(C)=C21 XLAJOHUNILNDLC-UHFFFAOYSA-N 0.000 claims description 2
• HNFPSZBXRLSFSU-UHFFFAOYSA-N methyl 4-[(1,3-dioxoisoindol-5-yl)amino]-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C1=C2C(=O)NC(=O)C2=CC(NC2=NC=NN3C=C(C(=C32)C)C(=O)OC)=C1 HNFPSZBXRLSFSU-UHFFFAOYSA-N 0.000 claims description 2
• QBXSUGIMUCOYBG-UHFFFAOYSA-N methyl 4-[(1-benzylindazol-5-yl)amino]-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C)C(C(=O)OC)=CN2N=CN=C1NC(C=C1C=N2)=CC=C1N2CC1=CC=CC=C1 QBXSUGIMUCOYBG-UHFFFAOYSA-N 0.000 claims description 2
• DVQZXKDRIWJVMP-UHFFFAOYSA-N methyl 4-[(6-methoxypyridin-3-yl)amino]-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C)C(C(=O)OC)=CN2N=CN=C1NC1=CC=C(OC)N=C1 DVQZXKDRIWJVMP-UHFFFAOYSA-N 0.000 claims description 2
• GYHKNUWTEFVSCN-UHFFFAOYSA-N methyl 4-[3-(hydrazinecarbonyl)anilino]-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C)C(C(=O)OC)=CN2N=CN=C1NC1=CC=CC(C(=O)NN)=C1 GYHKNUWTEFVSCN-UHFFFAOYSA-N 0.000 claims description 2
• FBQMXMWCIZVMNC-UHFFFAOYSA-N methyl 4-[3-(hydroxymethyl)anilino]-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C)C(C(=O)OC)=CN2N=CN=C1NC1=CC=CC(CO)=C1 FBQMXMWCIZVMNC-UHFFFAOYSA-N 0.000 claims description 2
• QQQPACPTNIDJCA-UHFFFAOYSA-N methyl 4-[5-(2-hydroxyethylsulfamoyl)-2-oxo-1,3-dihydroindol-3-yl]-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound O=C1NC2=CC=C(S(=O)(=O)NCCO)C=C2C1C1=NC=NN2C=C(C(=O)OC)C(C)=C21 QQQPACPTNIDJCA-UHFFFAOYSA-N 0.000 claims description 2
• RQLQWLJKCZHOIM-UHFFFAOYSA-N methyl 5-ethyl-4-[(6-methoxypyridin-3-yl)amino]pyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(CC)C(C(=O)OC)=CN2N=CN=C1NC1=CC=C(OC)N=C1 RQLQWLJKCZHOIM-UHFFFAOYSA-N 0.000 claims description 2
• QYEALBQJKRHZQW-UHFFFAOYSA-N methyl 5-methyl-4-(1h-pyrazol-5-ylamino)pyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C)C(C(=O)OC)=CN2N=CN=C1NC=1C=CNN=1 QYEALBQJKRHZQW-UHFFFAOYSA-N 0.000 claims description 2
• CJPKZAUMMYLARG-UHFFFAOYSA-N methyl 5-methyl-4-(3-oxo-1h-indazol-2-yl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound N1C2=CC=CC=C2C(=O)N1C1=NC=NN2C=C(C(=O)OC)C(C)=C21 CJPKZAUMMYLARG-UHFFFAOYSA-N 0.000 claims description 2
• KTNDTJVXEQRHRU-UHFFFAOYSA-N methyl 5-methyl-4-(3-oxo-2,4-dihydroquinoxalin-1-yl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C1C(=O)NC2=CC=CC=C2N1C1=NC=NN2C=C(C(=O)OC)C(C)=C21 KTNDTJVXEQRHRU-UHFFFAOYSA-N 0.000 claims description 2
• WQQASJBTDWIWDV-UHFFFAOYSA-N methyl 5-methyl-4-(3-oxo-2h-indazol-1-yl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound N1C(=O)C2=CC=CC=C2N1C1=NC=NN2C=C(C(=O)OC)C(C)=C21 WQQASJBTDWIWDV-UHFFFAOYSA-N 0.000 claims description 2
• RRFQIXSTCQXRJH-UHFFFAOYSA-N methyl 5-methyl-4-(4-methyl-3-nitroanilino)pyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C)C(C(=O)OC)=CN2N=CN=C1NC1=CC=C(C)C([N+]([O-])=O)=C1 RRFQIXSTCQXRJH-UHFFFAOYSA-N 0.000 claims description 2
• CMHKTCZJLHLZPT-UHFFFAOYSA-N methyl 5-methyl-4-(4-methyl-3-sulfamoylanilino)pyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C)C(C(=O)OC)=CN2N=CN=C1NC1=CC=C(C)C(S(N)(=O)=O)=C1 CMHKTCZJLHLZPT-UHFFFAOYSA-N 0.000 claims description 2
• JOHFSMPXICYLLT-UHFFFAOYSA-N methyl 5-methyl-4-(4-phenoxyanilino)pyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C)C(C(=O)OC)=CN2N=CN=C1NC(C=C1)=CC=C1OC1=CC=CC=C1 JOHFSMPXICYLLT-UHFFFAOYSA-N 0.000 claims description 2
• ZTHCOUWUGAEMFY-UHFFFAOYSA-N methyl 5-methyl-4-(6-methylsulfonyl-2-oxo-1,3-dihydroindol-3-yl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound O=C1NC2=CC(S(C)(=O)=O)=CC=C2C1C1=NC=NN2C=C(C(=O)OC)C(C)=C21 ZTHCOUWUGAEMFY-UHFFFAOYSA-N 0.000 claims description 2
• LRFKLXQCKKTUKG-UHFFFAOYSA-N methyl 5-methyl-4-(quinolin-5-ylamino)pyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C1=CC=C2C(NC3=NC=NN4C=C(C(=C43)C)C(=O)OC)=CC=CC2=N1 LRFKLXQCKKTUKG-UHFFFAOYSA-N 0.000 claims description 2
• UQWPABVGTSYMKX-UHFFFAOYSA-N methyl 5-methyl-4-[(5-methylpyridin-2-yl)amino]pyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C)C(C(=O)OC)=CN2N=CN=C1NC1=CC=C(C)C=N1 UQWPABVGTSYMKX-UHFFFAOYSA-N 0.000 claims description 2
• JVEDGNVJCQGYSS-UHFFFAOYSA-N n-(4-chloro-2-fluorophenyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine Chemical compound FC1=CC(Cl)=CC=C1NC1=NC=NN2C1=CC=C2 JVEDGNVJCQGYSS-UHFFFAOYSA-N 0.000 claims description 2
• OSTGTTZJOCZWJG-UHFFFAOYSA-N nitrosourea Chemical class NC(=O)N=NO OSTGTTZJOCZWJG-UHFFFAOYSA-N 0.000 claims description 2
• 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 2
• RLNCTIUJEJXMBZ-UHFFFAOYSA-N pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide Chemical compound C1=NC=NN2C=C(C(=O)N)C=C21 RLNCTIUJEJXMBZ-UHFFFAOYSA-N 0.000 claims description 2
• 230000001603 reducing effect Effects 0.000 claims description 2
• NPIISCWCOBHJGF-UHFFFAOYSA-N 1-[6-(pyrrolo[2,1-f][1,2,4]triazin-4-ylamino)-2,3-dihydroindol-1-yl]ethanone Chemical compound C1=NN2C=CC=C2C(NC2=CC=C3CCN(C3=C2)C(=O)C)=N1 NPIISCWCOBHJGF-UHFFFAOYSA-N 0.000 claims 1
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
• QVHFAUADDZADAN-UHFFFAOYSA-N 2-methyl-5-(pyrrolo[2,1-f][1,2,4]triazin-4-ylamino)phenol Chemical compound C1=C(O)C(C)=CC=C1NC1=NC=NN2C1=CC=C2 QVHFAUADDZADAN-UHFFFAOYSA-N 0.000 claims 1
• ATRMGRIXDIZXRO-UHFFFAOYSA-N 2-methyl-5-[(5-methylpyrrolo[2,1-f][1,2,4]triazin-4-yl)amino]phenol Chemical compound C12=C(C)C=CN2N=CN=C1NC1=CC=C(C)C(O)=C1 ATRMGRIXDIZXRO-UHFFFAOYSA-N 0.000 claims 1
• BNJHLXRPLVJJDL-UHFFFAOYSA-N 2-methyl-5-[(6-methylpyrrolo[2,1-f][1,2,4]triazin-4-yl)amino]phenol Chemical compound N=1C=NN2C=C(C)C=C2C=1NC1=CC=C(C)C(O)=C1 BNJHLXRPLVJJDL-UHFFFAOYSA-N 0.000 claims 1
• QFAYCQKPUDKQJB-UHFFFAOYSA-N 2-methyl-5-[(7-methylpyrrolo[2,1-f][1,2,4]triazin-4-yl)amino]phenol Chemical compound N=1C=NN2C(C)=CC=C2C=1NC1=CC=C(C)C(O)=C1 QFAYCQKPUDKQJB-UHFFFAOYSA-N 0.000 claims 1
• 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims 1
• MZDDOGMKTHYLKJ-UHFFFAOYSA-N 4-(3-hydroxy-4-methylanilino)-5-methyl-n-(2-pyrrolidin-1-ylethyl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide Chemical compound C12=C(C)C(C(=O)NCCN3CCCC3)=CN2N=CN=C1NC1=CC=C(C)C(O)=C1 MZDDOGMKTHYLKJ-UHFFFAOYSA-N 0.000 claims 1
• WQLIOGMNMDBAAX-UHFFFAOYSA-N 5-[(6-ethyl-5,7-dimethylpyrrolo[2,1-f][1,2,4]triazin-4-yl)amino]-2-methylphenol Chemical compound N=1C=NN2C(C)=C(CC)C(C)=C2C=1NC1=CC=C(C)C(O)=C1 WQLIOGMNMDBAAX-UHFFFAOYSA-N 0.000 claims 1
• FTGMAZNZVBHTAD-UHFFFAOYSA-N 5-[[6-(hydroxymethyl)-5-methylpyrrolo[2,1-f][1,2,4]triazin-4-yl]amino]-2-methylphenol Chemical compound C12=C(C)C(CO)=CN2N=CN=C1NC1=CC=C(C)C(O)=C1 FTGMAZNZVBHTAD-UHFFFAOYSA-N 0.000 claims 1
• QEQRJVUCJACZTO-UHFFFAOYSA-N 5-methyl-n-(3-morpholin-4-ylpropyl)-4-(2-oxo-1,3-dihydroindol-3-yl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide Chemical compound C=1N2N=CN=C(C3C4=CC=CC=C4NC3=O)C2=C(C)C=1C(=O)NCCCN1CCOCC1 QEQRJVUCJACZTO-UHFFFAOYSA-N 0.000 claims 1
• NEUKZNKEOJUFJS-UHFFFAOYSA-N 7-bromo-n-(4-chlorophenyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine Chemical compound C1=CC(Cl)=CC=C1NC1=NC=NN2C1=CC=C2Br NEUKZNKEOJUFJS-UHFFFAOYSA-N 0.000 claims 1
• RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims 1
• DVQHYTBCTGYNNN-UHFFFAOYSA-N azane;cyclobutane-1,1-dicarboxylic acid;platinum Chemical compound N.N.[Pt].OC(=O)C1(C(O)=O)CCC1 DVQHYTBCTGYNNN-UHFFFAOYSA-N 0.000 claims 1
• UUQGIFBMQJPEQA-UHFFFAOYSA-N ethyl 4-(4-bromo-2-fluoroanilino)-5-methoxypyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(OC)C(C(=O)OCC)=CN2N=CN=C1NC1=CC=C(Br)C=C1F UUQGIFBMQJPEQA-UHFFFAOYSA-N 0.000 claims 1
• RHBOWHNVBCWQNE-UHFFFAOYSA-N ethyl 4-[(6-chloropyridin-3-yl)amino]-5-ethylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(CC)C(C(=O)OCC)=CN2N=CN=C1NC1=CC=C(Cl)N=C1 RHBOWHNVBCWQNE-UHFFFAOYSA-N 0.000 claims 1
• CRIXUQMXXYMARY-UHFFFAOYSA-N methyl 4-(2,3-dihydro-1h-indol-6-ylamino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C1=C2CCNC2=CC(NC2=NC=NN3C=C(C(=C32)C)C(=O)OC)=C1 CRIXUQMXXYMARY-UHFFFAOYSA-N 0.000 claims 1
• UEMMUOLAXAGUOE-UHFFFAOYSA-N methyl 4-(3,4-dimethoxyanilino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C)C(C(=O)OC)=CN2N=CN=C1NC1=CC=C(OC)C(OC)=C1 UEMMUOLAXAGUOE-UHFFFAOYSA-N 0.000 claims 1
• QNYCTGJEBPXCTG-UHFFFAOYSA-N methyl 4-(3-hydroxy-2-methylanilino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C)C(C(=O)OC)=CN2N=CN=C1NC1=CC=CC(O)=C1C QNYCTGJEBPXCTG-UHFFFAOYSA-N 0.000 claims 1
• UUJOHQIBEVTNOG-UHFFFAOYSA-N methyl 4-(3-methoxy-4-methylanilino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C)C(C(=O)OC)=CN2N=CN=C1NC1=CC=C(C)C(OC)=C1 UUJOHQIBEVTNOG-UHFFFAOYSA-N 0.000 claims 1
• MNNKPBFQXFETNB-UHFFFAOYSA-N methyl 4-(4-bromo-3-methylanilino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C)C(C(=O)OC)=CN2N=CN=C1NC1=CC=C(Br)C(C)=C1 MNNKPBFQXFETNB-UHFFFAOYSA-N 0.000 claims 1
• GVERDVRZRGMLFU-UHFFFAOYSA-N methyl 4-(4-methoxyanilino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C)C(C(=O)OC)=CN2N=CN=C1NC1=CC=C(OC)C=C1 GVERDVRZRGMLFU-UHFFFAOYSA-N 0.000 claims 1
• GCEQGTGMPGWITJ-UHFFFAOYSA-N methyl 4-[(1,4-dioxo-2,3-dihydrophthalazin-6-yl)amino]-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound O=C1NNC(=O)C=2C1=CC(NC1=NC=NN3C=C(C(=C31)C)C(=O)OC)=CC=2 GCEQGTGMPGWITJ-UHFFFAOYSA-N 0.000 claims 1
• MXCCSODVRVBQDW-UHFFFAOYSA-N methyl 4-[(6-acetamidopyridin-3-yl)amino]-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C)C(C(=O)OC)=CN2N=CN=C1NC1=CC=C(NC(C)=O)N=C1 MXCCSODVRVBQDW-UHFFFAOYSA-N 0.000 claims 1
• IWFGSLJPHSRHBZ-UHFFFAOYSA-N methyl 4-[5-(hydroxymethyl)-2-methylanilino]-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C)C(C(=O)OC)=CN2N=CN=C1NC1=CC(CO)=CC=C1C IWFGSLJPHSRHBZ-UHFFFAOYSA-N 0.000 claims 1
• ACBLGNYVHXMIRT-UHFFFAOYSA-N methyl 4-[5-(methanesulfonamido)-2-methylanilino]-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C)C(C(=O)OC)=CN2N=CN=C1NC1=CC(NS(C)(=O)=O)=CC=C1C ACBLGNYVHXMIRT-UHFFFAOYSA-N 0.000 claims 1
• XETYQQCOCNFGNU-UHFFFAOYSA-N methyl 5-methyl-4-(2-oxo-5-sulfamoyl-1,3-dihydroindol-3-yl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound O=C1NC2=CC=C(S(N)(=O)=O)C=C2C1C1=NC=NN2C=C(C(=O)OC)C(C)=C21 XETYQQCOCNFGNU-UHFFFAOYSA-N 0.000 claims 1
• FULKGEZKAZEMGJ-UHFFFAOYSA-N methyl 5-methyl-4-(2-sulfamoylanilino)pyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C)C(C(=O)OC)=CN2N=CN=C1NC1=CC=CC=C1S(N)(=O)=O FULKGEZKAZEMGJ-UHFFFAOYSA-N 0.000 claims 1
• CKYTZCXEVIEESK-UHFFFAOYSA-N methyl 5-methyl-4-[(4-methyl-2-oxo-1h-quinolin-7-yl)amino]pyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound CC1=CC(=O)NC2=CC(NC3=NC=NN4C=C(C(=C43)C)C(=O)OC)=CC=C21 CKYTZCXEVIEESK-UHFFFAOYSA-N 0.000 claims 1
• VOUNLYITVOORCX-UHFFFAOYSA-N methyl 5-methyl-4-[2-oxo-5-(2-pyrrolidin-1-ylethylsulfamoyl)-1,3-dihydroindol-3-yl]pyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C)C(C(=O)OC)=CN2N=CN=C1C(C1=C2)C(=O)NC1=CC=C2S(=O)(=O)NCCN1CCCC1 VOUNLYITVOORCX-UHFFFAOYSA-N 0.000 claims 1
• XIMGLZFQDMXMFJ-UHFFFAOYSA-N n-(4-bromo-2-fluorophenyl)-5-methylpyrrolo[2,1-f][1,2,4]triazin-4-amine Chemical compound C12=C(C)C=CN2N=CN=C1NC1=CC=C(Br)C=C1F XIMGLZFQDMXMFJ-UHFFFAOYSA-N 0.000 claims 1
• IFXVRDKZKKJSNV-UHFFFAOYSA-N n-(4-bromo-2-fluorophenyl)-6-methylpyrrolo[2,1-f][1,2,4]triazin-4-amine Chemical compound N=1C=NN2C=C(C)C=C2C=1NC1=CC=C(Br)C=C1F IFXVRDKZKKJSNV-UHFFFAOYSA-N 0.000 claims 1
• IXAJVUSXXSIQIH-UHFFFAOYSA-N n-(4-bromo-2-fluorophenyl)-7-methylpyrrolo[2,1-f][1,2,4]triazin-4-amine Chemical compound N=1C=NN2C(C)=CC=C2C=1NC1=CC=C(Br)C=C1F IXAJVUSXXSIQIH-UHFFFAOYSA-N 0.000 claims 1
• KYIQAYJZDHANBH-UHFFFAOYSA-N n-(4-bromo-2-fluorophenyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine Chemical compound FC1=CC(Br)=CC=C1NC1=NC=NN2C1=CC=C2 KYIQAYJZDHANBH-UHFFFAOYSA-N 0.000 claims 1
• BCJSNVMCIXCJRZ-UHFFFAOYSA-N n-(4-chlorophenyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine Chemical compound C1=CC(Cl)=CC=C1NC1=NC=NN2C1=CC=C2 BCJSNVMCIXCJRZ-UHFFFAOYSA-N 0.000 claims 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 252
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 153
• OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 144
• 239000007787 solid Substances 0.000 description 137
• 239000000203 mixture Substances 0.000 description 130
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 121
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 118
• 238000005160 1H NMR spectroscopy Methods 0.000 description 111
• 239000000243 solution Substances 0.000 description 92
• 238000000034 method Methods 0.000 description 91
• 235000019439 ethyl acetate Nutrition 0.000 description 87
• 239000011541 reaction mixture Substances 0.000 description 78
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 76
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 62
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 62
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 62
• 229940126062 Compound A Drugs 0.000 description 51
• NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 51
• 239000000741 silica gel Substances 0.000 description 50
• 229910002027 silica gel Inorganic materials 0.000 description 50
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 43
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 39
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 38
• 229910052786 argon Inorganic materials 0.000 description 31
• 238000004587 chromatography analysis Methods 0.000 description 31
• 239000002904 solvent Substances 0.000 description 31
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 31
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 28
• 239000000284 extract Substances 0.000 description 28
• 239000003921 oil Substances 0.000 description 28
• 235000019198 oils Nutrition 0.000 description 28
• 239000011734 sodium Substances 0.000 description 27
• FYADHXFMURLYQI-UHFFFAOYSA-N 1,2,4-triazine Chemical compound C1=CN=NC=N1 FYADHXFMURLYQI-UHFFFAOYSA-N 0.000 description 26
• 229910000104 sodium hydride Inorganic materials 0.000 description 26
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 24
• 239000000463 material Substances 0.000 description 24
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 23
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 23
• LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 22
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 20
• 238000002953 preparative HPLC Methods 0.000 description 20
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 19
• 238000006243 chemical reaction Methods 0.000 description 19
• 238000003818 flash chromatography Methods 0.000 description 19
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
• 125000000217 alkyl group Chemical group 0.000 description 17
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 17
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 17
• 229920006395 saturated elastomer Polymers 0.000 description 17
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 16
• 125000003118 aryl group Chemical group 0.000 description 16
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 16
• 238000000746 purification Methods 0.000 description 15
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 14
• 239000002585 base Substances 0.000 description 14
• 239000012267 brine Substances 0.000 description 14
• 239000000047 product Substances 0.000 description 14
• 150000003839 salts Chemical class 0.000 description 14
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 14
• 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 13
• 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 description 13
• 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 13
• 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 13
• 239000000460 chlorine Substances 0.000 description 13
• 239000003960 organic solvent Substances 0.000 description 13
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 13
• 238000003756 stirring Methods 0.000 description 13
• 239000000725 suspension Substances 0.000 description 13
• 239000001257 hydrogen Substances 0.000 description 12
• 229910052739 hydrogen Inorganic materials 0.000 description 12
• 238000010992 reflux Methods 0.000 description 12
• 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 11
• 125000004432 carbon atom Chemical group C* 0.000 description 11
• 229940125898 compound 5 Drugs 0.000 description 11
• 229910052736 halogen Inorganic materials 0.000 description 11
• 102000005962 receptors Human genes 0.000 description 11
• 108020003175 receptors Proteins 0.000 description 11
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 10
• 125000003710 aryl alkyl group Chemical group 0.000 description 10
• 239000013058 crude material Substances 0.000 description 10
• 150000002367 halogens Chemical class 0.000 description 10
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 10
• BJHCYTJNPVGSBZ-YXSASFKJSA-N 1-[4-[6-amino-5-[(Z)-methoxyiminomethyl]pyrimidin-4-yl]oxy-2-chlorophenyl]-3-ethylurea Chemical compound CCNC(=O)Nc1ccc(Oc2ncnc(N)c2\C=N/OC)cc1Cl BJHCYTJNPVGSBZ-YXSASFKJSA-N 0.000 description 9
• DBFYESDCPWWCHN-UHFFFAOYSA-N 5-amino-2-methylphenol Chemical compound CC1=CC=C(N)C=C1O DBFYESDCPWWCHN-UHFFFAOYSA-N 0.000 description 9
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
• 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 9
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 9
• 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 9
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
• 150000001412 amines Chemical class 0.000 description 9
• JNGZXGGOCLZBFB-IVCQMTBJSA-N compound E Chemical compound N([C@@H](C)C(=O)N[C@@H]1C(N(C)C2=CC=CC=C2C(C=2C=CC=CC=2)=N1)=O)C(=O)CC1=CC(F)=CC(F)=C1 JNGZXGGOCLZBFB-IVCQMTBJSA-N 0.000 description 9
• 238000001816 cooling Methods 0.000 description 9
• 239000012074 organic phase Substances 0.000 description 9
• 125000001424 substituent group Chemical group 0.000 description 9
• 125000000547 substituted alkyl group Chemical group 0.000 description 9
• GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 8
• FEKWWZCCJDUWLY-UHFFFAOYSA-N 3-methyl-1h-pyrrole Chemical compound CC=1C=CNC=1 FEKWWZCCJDUWLY-UHFFFAOYSA-N 0.000 description 8
• 102000001301 EGF receptor Human genes 0.000 description 8
• ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 8
• PCKPVGOLPKLUHR-UHFFFAOYSA-N OH-Indolxyl Natural products C1=CC=C2C(O)=CNC2=C1 PCKPVGOLPKLUHR-UHFFFAOYSA-N 0.000 description 8
• 201000004681 Psoriasis Diseases 0.000 description 8
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
• 229940126214 compound 3 Drugs 0.000 description 8
• 210000002889 endothelial cell Anatomy 0.000 description 8
• 229910052757 nitrogen Inorganic materials 0.000 description 8
• 125000003107 substituted aryl group Chemical group 0.000 description 8
• ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-UHFFFAOYSA-N 0.000 description 8
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 7
• 101100067974 Arabidopsis thaliana POP2 gene Proteins 0.000 description 7
• 101100118549 Homo sapiens EGFR gene Proteins 0.000 description 7
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 7
• 108091000080 Phosphotransferase Proteins 0.000 description 7
• 101100123851 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) HER1 gene Proteins 0.000 description 7
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 7
• 239000008346 aqueous phase Substances 0.000 description 7
• 239000003795 chemical substances by application Substances 0.000 description 7
• 229940125782 compound 2 Drugs 0.000 description 7
• 239000000706 filtrate Substances 0.000 description 7
• 125000000623 heterocyclic group Chemical group 0.000 description 7
• JYGFTBXVXVMTGB-UHFFFAOYSA-N indolin-2-one Chemical compound C1=CC=C2NC(=O)CC2=C1 JYGFTBXVXVMTGB-UHFFFAOYSA-N 0.000 description 7
• 239000008363 phosphate buffer Substances 0.000 description 7
• 102000020233 phosphotransferase Human genes 0.000 description 7
• 239000002994 raw material Substances 0.000 description 7
• 239000012312 sodium hydride Substances 0.000 description 7
• 238000005406 washing Methods 0.000 description 7
• GZRMNMGWNKSANY-UHFFFAOYSA-N 4-bromo-2-fluoroaniline Chemical compound NC1=CC=C(Br)C=C1F GZRMNMGWNKSANY-UHFFFAOYSA-N 0.000 description 6
• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
• 102100023593 Fibroblast growth factor receptor 1 Human genes 0.000 description 6
• 101710182386 Fibroblast growth factor receptor 1 Proteins 0.000 description 6
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
• 125000003545 alkoxy group Chemical group 0.000 description 6
• VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 6
• 230000015572 biosynthetic process Effects 0.000 description 6
• 230000004663 cell proliferation Effects 0.000 description 6
• 125000005842 heteroatom Chemical group 0.000 description 6
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
• RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 6
• 239000002244 precipitate Substances 0.000 description 6
• 229940002612 prodrug Drugs 0.000 description 6
• 239000000651 prodrug Substances 0.000 description 6
• 108091008598 receptor tyrosine kinases Proteins 0.000 description 6
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 6
• 239000003039 volatile agent Substances 0.000 description 6
• SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 5
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 5
• 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 5
• 125000005236 alkanoylamino group Chemical group 0.000 description 5
• SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 5
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 5
• 229910052799 carbon Inorganic materials 0.000 description 5
• 210000004027 cell Anatomy 0.000 description 5
• 238000001914 filtration Methods 0.000 description 5
• 235000019253 formic acid Nutrition 0.000 description 5
• 239000003102 growth factor Substances 0.000 description 5
• 150000002431 hydrogen Chemical class 0.000 description 5
• 239000005457 ice water Substances 0.000 description 5
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 5
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 5
• UXCDUFKZSUBXGM-UHFFFAOYSA-N phosphoric tribromide Chemical compound BrP(Br)(Br)=O UXCDUFKZSUBXGM-UHFFFAOYSA-N 0.000 description 5
• 102000004169 proteins and genes Human genes 0.000 description 5
• 108090000623 proteins and genes Proteins 0.000 description 5
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
• 102000027426 receptor tyrosine kinases Human genes 0.000 description 5
• 239000000377 silicon dioxide Substances 0.000 description 5
• 229940124530 sulfonamide Drugs 0.000 description 5
• 150000003456 sulfonamides Chemical class 0.000 description 5
• 230000004614 tumor growth Effects 0.000 description 5
• MFFMQGGZCLEMCI-UHFFFAOYSA-N 2,4-dimethyl-1h-pyrrole Chemical compound CC1=CNC(C)=C1 MFFMQGGZCLEMCI-UHFFFAOYSA-N 0.000 description 4
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
• 201000001320 Atherosclerosis Diseases 0.000 description 4
• 206010012689 Diabetic retinopathy Diseases 0.000 description 4
• 102000004190 Enzymes Human genes 0.000 description 4
• 108090000790 Enzymes Proteins 0.000 description 4
• 102100024785 Fibroblast growth factor 2 Human genes 0.000 description 4
• 208000007766 Kaposi sarcoma Diseases 0.000 description 4
• OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 4
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
• 125000004423 acyloxy group Chemical group 0.000 description 4
• 125000003282 alkyl amino group Chemical group 0.000 description 4
• 125000004390 alkyl sulfonyl group Chemical group 0.000 description 4
• 125000004414 alkyl thio group Chemical group 0.000 description 4
• 230000033115 angiogenesis Effects 0.000 description 4
• 230000001028 anti-proliverative effect Effects 0.000 description 4
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
• 125000002619 bicyclic group Chemical group 0.000 description 4
• 210000000481 breast Anatomy 0.000 description 4
• 125000001589 carboacyl group Chemical group 0.000 description 4
• 239000003153 chemical reaction reagent Substances 0.000 description 4
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Natural products OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 4
• 125000004093 cyano group Chemical group *C#N 0.000 description 4
• 229940088598 enzyme Drugs 0.000 description 4
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 4
• 238000001704 evaporation Methods 0.000 description 4
• 230000008020 evaporation Effects 0.000 description 4
• 125000002541 furyl group Chemical group 0.000 description 4
• 238000010438 heat treatment Methods 0.000 description 4
• 201000011066 hemangioma Diseases 0.000 description 4
• 150000003840 hydrochlorides Chemical class 0.000 description 4
• 230000007062 hydrolysis Effects 0.000 description 4
• 238000006460 hydrolysis reaction Methods 0.000 description 4
• 125000002883 imidazolyl group Chemical group 0.000 description 4
• 208000017169 kidney disease Diseases 0.000 description 4
• 210000004072 lung Anatomy 0.000 description 4
• 125000002950 monocyclic group Chemical group 0.000 description 4
• 239000012071 phase Substances 0.000 description 4
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
• 125000006239 protecting group Chemical group 0.000 description 4
• 125000004076 pyridyl group Chemical group 0.000 description 4
• 125000000714 pyrimidinyl group Chemical group 0.000 description 4
• 150000003233 pyrroles Chemical class 0.000 description 4
• 206010039073 rheumatoid arthritis Diseases 0.000 description 4
• 230000011664 signaling Effects 0.000 description 4
• 125000000335 thiazolyl group Chemical group 0.000 description 4
• 125000001544 thienyl group Chemical group 0.000 description 4
• 150000003573 thiols Chemical class 0.000 description 4
• CFOAUYCPAUGDFF-UHFFFAOYSA-N tosmic Chemical compound CC1=CC=C(S(=O)(=O)C[N+]#[C-])C=C1 CFOAUYCPAUGDFF-UHFFFAOYSA-N 0.000 description 4
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
• OXHNLMTVIGZXSG-UHFFFAOYSA-N 1-Methylpyrrole Chemical compound CN1C=CC=C1 OXHNLMTVIGZXSG-UHFFFAOYSA-N 0.000 description 3
• QKCSJWQVCNJXDZ-UHFFFAOYSA-N 1-amino-3-methylpyrrole-2-carbonitrile Chemical compound CC=1C=CN(N)C=1C#N QKCSJWQVCNJXDZ-UHFFFAOYSA-N 0.000 description 3
• BQUSMTPKYUILPD-UHFFFAOYSA-N 1-benzylindazol-5-amine Chemical compound N1=CC2=CC(N)=CC=C2N1CC1=CC=CC=C1 BQUSMTPKYUILPD-UHFFFAOYSA-N 0.000 description 3
• 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 3
• BYHQTRFJOGIQAO-GOSISDBHSA-N 3-(4-bromophenyl)-8-[(2R)-2-hydroxypropyl]-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C[C@H](CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)Br)O BYHQTRFJOGIQAO-GOSISDBHSA-N 0.000 description 3
• 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 3
• NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 3
• PXRKCOCTEMYUEG-UHFFFAOYSA-N 5-aminoisoindole-1,3-dione Chemical compound NC1=CC=C2C(=O)NC(=O)C2=C1 PXRKCOCTEMYUEG-UHFFFAOYSA-N 0.000 description 3
• UUVDJIWRSIJEBS-UHFFFAOYSA-N 6-methoxypyridin-3-amine Chemical compound COC1=CC=C(N)C=N1 UUVDJIWRSIJEBS-UHFFFAOYSA-N 0.000 description 3
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
• 206010003210 Arteriosclerosis Diseases 0.000 description 3
• 208000037260 Atherosclerotic Plaque Diseases 0.000 description 3
• 206010006187 Breast cancer Diseases 0.000 description 3
• 208000026310 Breast neoplasm Diseases 0.000 description 3
• KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical group NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 3
• 102100034724 Lipocalin-1 Human genes 0.000 description 3
• 241000124008 Mammalia Species 0.000 description 3
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
• 239000007832 Na2SO4 Substances 0.000 description 3
• 208000008589 Obesity Diseases 0.000 description 3
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 3
• OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 3
• 102000016548 Vascular Endothelial Growth Factor Receptor-1 Human genes 0.000 description 3
• 108010053096 Vascular Endothelial Growth Factor Receptor-1 Proteins 0.000 description 3
• 230000004913 activation Effects 0.000 description 3
• 230000001154 acute effect Effects 0.000 description 3
• 125000003342 alkenyl group Chemical group 0.000 description 3
• 229940100198 alkylating agent Drugs 0.000 description 3
• 239000002168 alkylating agent Substances 0.000 description 3
• 125000000304 alkynyl group Chemical group 0.000 description 3
• CHKQALUEEULCPZ-UHFFFAOYSA-N amino 2,4,6-trimethylbenzenesulfonate Chemical compound CC1=CC(C)=C(S(=O)(=O)ON)C(C)=C1 CHKQALUEEULCPZ-UHFFFAOYSA-N 0.000 description 3
• 150000001450 anions Chemical class 0.000 description 3
• 239000007864 aqueous solution Substances 0.000 description 3
• 206010003246 arthritis Diseases 0.000 description 3
• 125000002837 carbocyclic group Chemical group 0.000 description 3
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
• 239000003054 catalyst Substances 0.000 description 3
• 238000002512 chemotherapy Methods 0.000 description 3
• 229940125904 compound 1 Drugs 0.000 description 3
• 239000007822 coupling agent Substances 0.000 description 3
• 125000004122 cyclic group Chemical group 0.000 description 3
• 230000001086 cytosolic effect Effects 0.000 description 3
• 230000018109 developmental process Effects 0.000 description 3
• 206010012601 diabetes mellitus Diseases 0.000 description 3
• 125000004663 dialkyl amino group Chemical group 0.000 description 3
• MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 3
• 208000035475 disorder Diseases 0.000 description 3
• 239000003814 drug Substances 0.000 description 3
• 230000002255 enzymatic effect Effects 0.000 description 3
• 238000000605 extraction Methods 0.000 description 3
• 239000012065 filter cake Substances 0.000 description 3
• 150000002430 hydrocarbons Chemical group 0.000 description 3
• 238000005984 hydrogenation reaction Methods 0.000 description 3
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
• 125000001041 indolyl group Chemical group 0.000 description 3
• 239000003446 ligand Substances 0.000 description 3
• 239000012280 lithium aluminium hydride Substances 0.000 description 3
• NJKRDPIHNOWVJI-UHFFFAOYSA-N n-diphenylphosphorylhydroxylamine Chemical compound C=1C=CC=CC=1P(=O)(NO)C1=CC=CC=C1 NJKRDPIHNOWVJI-UHFFFAOYSA-N 0.000 description 3
• 235000020824 obesity Nutrition 0.000 description 3
• 230000002611 ovarian Effects 0.000 description 3
• 229910052760 oxygen Inorganic materials 0.000 description 3
• 229910052763 palladium Inorganic materials 0.000 description 3
• 238000012746 preparative thin layer chromatography Methods 0.000 description 3
• 230000008569 process Effects 0.000 description 3
• 230000035755 proliferation Effects 0.000 description 3
• 239000001632 sodium acetate Substances 0.000 description 3
• 235000017281 sodium acetate Nutrition 0.000 description 3
• 229910052938 sodium sulfate Inorganic materials 0.000 description 3
• 235000011152 sodium sulphate Nutrition 0.000 description 3
• 229910052717 sulfur Inorganic materials 0.000 description 3
• 210000001685 thyroid gland Anatomy 0.000 description 3
• QQOWHRYOXYEMTL-UHFFFAOYSA-N triazin-4-amine Chemical compound N=C1C=CN=NN1 QQOWHRYOXYEMTL-UHFFFAOYSA-N 0.000 description 3
• PVFOMCVHYWHZJE-UHFFFAOYSA-N trichloroacetyl chloride Chemical compound ClC(=O)C(Cl)(Cl)Cl PVFOMCVHYWHZJE-UHFFFAOYSA-N 0.000 description 3
• SWEICGMKXPNXNU-UHFFFAOYSA-N 1,2-dihydroindazol-3-one Chemical compound C1=CC=C2C(O)=NNC2=C1 SWEICGMKXPNXNU-UHFFFAOYSA-N 0.000 description 2
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 2
• KEJFADGISRFLFO-UHFFFAOYSA-N 1H-indazol-6-amine Chemical compound NC1=CC=C2C=NNC2=C1 KEJFADGISRFLFO-UHFFFAOYSA-N 0.000 description 2
• VOZKAJLKRJDJLL-UHFFFAOYSA-N 2,4-diaminotoluene Chemical compound CC1=CC=C(N)C=C1N VOZKAJLKRJDJLL-UHFFFAOYSA-N 0.000 description 2
• FRUNDADHVMDNAW-UHFFFAOYSA-N 2-methyl-5,7-dihydropyrrolo[2,3-d]pyrimidin-6-one Chemical compound CC1=NC=C2CC(=O)NC2=N1 FRUNDADHVMDNAW-UHFFFAOYSA-N 0.000 description 2
• OJFOWGWQOFZNNJ-UHFFFAOYSA-N 3,4-dimethyl-1h-pyrrole Chemical compound CC1=CNC=C1C OJFOWGWQOFZNNJ-UHFFFAOYSA-N 0.000 description 2
• DOLQYFPDPKPQSS-UHFFFAOYSA-N 3,4-dimethylaniline Chemical compound CC1=CC=C(N)C=C1C DOLQYFPDPKPQSS-UHFFFAOYSA-N 0.000 description 2
• RDFZYUOHJBXMJA-UHFFFAOYSA-N 3,5-dimethyl-1h-pyrrole-2-carbaldehyde Chemical compound CC1=CC(C)=C(C=O)N1 RDFZYUOHJBXMJA-UHFFFAOYSA-N 0.000 description 2
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
• JPVKCHIPRSQDKL-UHFFFAOYSA-N 3-aminobenzenesulfonamide Chemical compound NC1=CC=CC(S(N)(=O)=O)=C1 JPVKCHIPRSQDKL-UHFFFAOYSA-N 0.000 description 2
• MCSXGCZMEPXKIW-UHFFFAOYSA-N 3-hydroxy-4-[(4-methyl-2-nitrophenyl)diazenyl]-N-(3-nitrophenyl)naphthalene-2-carboxamide Chemical compound Cc1ccc(N=Nc2c(O)c(cc3ccccc23)C(=O)Nc2cccc(c2)[N+]([O-])=O)c(c1)[N+]([O-])=O MCSXGCZMEPXKIW-UHFFFAOYSA-N 0.000 description 2
• WBMRBLKBBVYQSD-UHFFFAOYSA-N 3-methyl-1h-pyrrole-2-carbaldehyde Chemical compound CC=1C=CNC=1C=O WBMRBLKBBVYQSD-UHFFFAOYSA-N 0.000 description 2
• UIKUBYKUYUSRSM-UHFFFAOYSA-N 3-morpholinopropylamine Chemical compound NCCCN1CCOCC1 UIKUBYKUYUSRSM-UHFFFAOYSA-N 0.000 description 2
• AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 description 2
• PLIKAWJENQZMHA-UHFFFAOYSA-N 4-aminophenol Chemical compound NC1=CC=C(O)C=C1 PLIKAWJENQZMHA-UHFFFAOYSA-N 0.000 description 2
• HUDPLKWXRLNSPC-UHFFFAOYSA-N 4-aminophthalhydrazide Chemical compound O=C1NNC(=O)C=2C1=CC(N)=CC=2 HUDPLKWXRLNSPC-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
• GQIUKYUNGBBIEQ-UHFFFAOYSA-N 4-methyl-1h-pyrrole-2-carbaldehyde Chemical compound CC1=CNC(C=O)=C1 GQIUKYUNGBBIEQ-UHFFFAOYSA-N 0.000 description 2
• BLQFHJKRTDIZLX-UHFFFAOYSA-N 5-amino-2-methoxyphenol Chemical compound COC1=CC=C(N)C=C1O BLQFHJKRTDIZLX-UHFFFAOYSA-N 0.000 description 2
• DDIIYGHHUMKDGI-UHFFFAOYSA-N 5-fluoro-1,3-dihydroindol-2-one Chemical compound FC1=CC=C2NC(=O)CC2=C1 DDIIYGHHUMKDGI-UHFFFAOYSA-N 0.000 description 2
• KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
• 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 2
• 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 2
• 208000032467 Aplastic anaemia Diseases 0.000 description 2
• 206010051113 Arterial restenosis Diseases 0.000 description 2
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
• ZTQSAGDEMFDKMZ-UHFFFAOYSA-N Butyraldehyde Chemical compound CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 2
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
• CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 2
• PAPNRQCYSFBWDI-UHFFFAOYSA-N DMP Natural products CC1=CC=C(C)N1 PAPNRQCYSFBWDI-UHFFFAOYSA-N 0.000 description 2
• 201000004624 Dermatitis Diseases 0.000 description 2
• HTIJFSOGRVMCQR-UHFFFAOYSA-N Epirubicin Natural products COc1cccc2C(=O)c3c(O)c4CC(O)(CC(OC5CC(N)C(=O)C(C)O5)c4c(O)c3C(=O)c12)C(=O)CO HTIJFSOGRVMCQR-UHFFFAOYSA-N 0.000 description 2
• QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
• 101150021185 FGF gene Proteins 0.000 description 2
• 108090000386 Fibroblast Growth Factor 1 Proteins 0.000 description 2
• 206010018364 Glomerulonephritis Diseases 0.000 description 2
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
• ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
• 241000238631 Hexapoda Species 0.000 description 2
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
• WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
• 208000022559 Inflammatory bowel disease Diseases 0.000 description 2
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
• 125000000899 L-alpha-glutamyl group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C([H])([H])C([H])([H])C(O[H])=O 0.000 description 2
• 108010057281 Lipocalin 1 Proteins 0.000 description 2
• 206010058467 Lung neoplasm malignant Diseases 0.000 description 2
• 206010025323 Lymphomas Diseases 0.000 description 2
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
• 239000012359 Methanesulfonyl chloride Substances 0.000 description 2
• 201000003793 Myelodysplastic syndrome Diseases 0.000 description 2
• ZMXDDKWLCZADIW-YYWVXINBSA-N N,N-dimethylformamide-d7 Chemical compound [2H]C(=O)N(C([2H])([2H])[2H])C([2H])([2H])[2H] ZMXDDKWLCZADIW-YYWVXINBSA-N 0.000 description 2
• 208000022873 Ocular disease Diseases 0.000 description 2
• 208000034038 Pathologic Neovascularization Diseases 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 2
• 108091005682 Receptor kinases Proteins 0.000 description 2
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
• 208000005718 Stomach Neoplasms Diseases 0.000 description 2
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 2
• 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 2
• QQIRAVWVGBTHMJ-UHFFFAOYSA-N [dimethyl-(trimethylsilylamino)silyl]methane;lithium Chemical compound [Li].C[Si](C)(C)N[Si](C)(C)C QQIRAVWVGBTHMJ-UHFFFAOYSA-N 0.000 description 2
• 208000038016 acute inflammation Diseases 0.000 description 2
• 230000006022 acute inflammation Effects 0.000 description 2
• 150000001299 aldehydes Chemical class 0.000 description 2
• 238000005576 amination reaction Methods 0.000 description 2
• 150000001413 amino acids Chemical group 0.000 description 2
• 125000003277 amino group Chemical group 0.000 description 2
• VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 2
• 238000004458 analytical method Methods 0.000 description 2
• 239000004037 angiogenesis inhibitor Substances 0.000 description 2
• 230000000259 anti-tumor effect Effects 0.000 description 2
• 230000006907 apoptotic process Effects 0.000 description 2
• 239000003125 aqueous solvent Substances 0.000 description 2
• 125000001691 aryl alkyl amino group Chemical group 0.000 description 2
• 125000001769 aryl amino group Chemical group 0.000 description 2
• 125000004104 aryloxy group Chemical group 0.000 description 2
• 208000010668 atopic eczema Diseases 0.000 description 2
• VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 2
• 235000019445 benzyl alcohol Nutrition 0.000 description 2
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
• 229910052794 bromium Inorganic materials 0.000 description 2
• 239000000872 buffer Substances 0.000 description 2
• 239000011575 calcium Substances 0.000 description 2
• 229910052791 calcium Inorganic materials 0.000 description 2
• 150000001721 carbon Chemical group 0.000 description 2
• 150000003857 carboxamides Chemical class 0.000 description 2
• 210000000170 cell membrane Anatomy 0.000 description 2
• 239000003638 chemical reducing agent Substances 0.000 description 2
• 230000001684 chronic effect Effects 0.000 description 2
• 210000001072 colon Anatomy 0.000 description 2
• 238000005859 coupling reaction Methods 0.000 description 2
• 239000012043 crude product Substances 0.000 description 2
• 238000002425 crystallisation Methods 0.000 description 2
• 230000008025 crystallization Effects 0.000 description 2
• 229960004397 cyclophosphamide Drugs 0.000 description 2
• 239000000824 cytostatic agent Substances 0.000 description 2
• CFCUWKMKBJTWLW-UHFFFAOYSA-N deoliosyl-3C-alpha-L-digitoxosyl-MTM Natural products CC=1C(O)=C2C(O)=C3C(=O)C(OC4OC(C)C(O)C(OC5OC(C)C(O)C(OC6OC(C)C(O)C(C)(O)C6)C5)C4)C(C(OC)C(=O)C(O)C(C)O)CC3=CC2=CC=1OC(OC(C)C1O)CC1OC1CC(O)C(O)C(C)O1 CFCUWKMKBJTWLW-UHFFFAOYSA-N 0.000 description 2
• 230000001419 dependent effect Effects 0.000 description 2
• 238000013461 design Methods 0.000 description 2
• 238000011161 development Methods 0.000 description 2
• QKXBVVVYILIRDO-UHFFFAOYSA-N diethyl 1h-pyrrole-3,4-dicarboxylate Chemical compound CCOC(=O)C1=CNC=C1C(=O)OCC QKXBVVVYILIRDO-UHFFFAOYSA-N 0.000 description 2
• 239000003085 diluting agent Substances 0.000 description 2
• VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 2
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
• 238000010828 elution Methods 0.000 description 2
• 229960001904 epirubicin Drugs 0.000 description 2
• 150000002148 esters Chemical class 0.000 description 2
• VNZGRYAVCWGZCT-UHFFFAOYSA-N ethyl 4-phenyl-1h-pyrrole-3-carboxylate Chemical compound CCOC(=O)C1=CNC=C1C1=CC=CC=C1 VNZGRYAVCWGZCT-UHFFFAOYSA-N 0.000 description 2
• 206010017758 gastric cancer Diseases 0.000 description 2
• 239000000499 gel Substances 0.000 description 2
• 230000012010 growth Effects 0.000 description 2
• 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 description 2
• 230000002140 halogenating effect Effects 0.000 description 2
• 201000005787 hematologic cancer Diseases 0.000 description 2
• 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 2
• 125000001072 heteroaryl group Chemical group 0.000 description 2
• 125000000592 heterocycloalkyl group Chemical group 0.000 description 2
• 238000004128 high performance liquid chromatography Methods 0.000 description 2
• 238000001727 in vivo Methods 0.000 description 2
• 230000005764 inhibitory process Effects 0.000 description 2
• 230000003834 intracellular effect Effects 0.000 description 2
• 125000004628 isothiazolidinyl group Chemical group S1N(CCC1)* 0.000 description 2
• 238000000021 kinase assay Methods 0.000 description 2
• 239000007788 liquid Substances 0.000 description 2
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
• 201000005202 lung cancer Diseases 0.000 description 2
• 208000020816 lung neoplasm Diseases 0.000 description 2
• 239000011777 magnesium Substances 0.000 description 2
• NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
• 239000000155 melt Substances 0.000 description 2
• KBOPZPXVLCULAV-UHFFFAOYSA-N mesalamine Chemical compound NC1=CC=C(O)C(C(O)=O)=C1 KBOPZPXVLCULAV-UHFFFAOYSA-N 0.000 description 2
• 229960004963 mesalazine Drugs 0.000 description 2
• 206010061289 metastatic neoplasm Diseases 0.000 description 2
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
• CTSAXXHOGZNKJR-UHFFFAOYSA-N methyl 2-diethoxyphosphorylacetate Chemical compound CCOP(=O)(OCC)CC(=O)OC CTSAXXHOGZNKJR-UHFFFAOYSA-N 0.000 description 2
• 239000002808 molecular sieve Substances 0.000 description 2
• 208000015122 neurodegenerative disease Diseases 0.000 description 2
• 230000003287 optical effect Effects 0.000 description 2
• AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 2
• BHAAPTBBJKJZER-UHFFFAOYSA-N p-anisidine Chemical compound COC1=CC=C(N)C=C1 BHAAPTBBJKJZER-UHFFFAOYSA-N 0.000 description 2
• 230000026731 phosphorylation Effects 0.000 description 2
• 238000006366 phosphorylation reaction Methods 0.000 description 2
• 229910000027 potassium carbonate Inorganic materials 0.000 description 2
• 235000011181 potassium carbonates Nutrition 0.000 description 2
• LJCNRYVRMXRIQR-OLXYHTOASA-L potassium sodium L-tartrate Chemical compound [Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O LJCNRYVRMXRIQR-OLXYHTOASA-L 0.000 description 2
• 229940074439 potassium sodium tartrate Drugs 0.000 description 2
• 230000002265 prevention Effects 0.000 description 2
• 210000002307 prostate Anatomy 0.000 description 2
• 238000010926 purge Methods 0.000 description 2
• ZSKGQVFRTSEPJT-UHFFFAOYSA-N pyrrole-2-carboxaldehyde Chemical class O=CC1=CC=CN1 ZSKGQVFRTSEPJT-UHFFFAOYSA-N 0.000 description 2
• VONGYFFEWFJHNP-UHFFFAOYSA-N pyrrolecarboxylic acid methyl ester Natural products COC(=O)C1=CC=CN1 VONGYFFEWFJHNP-UHFFFAOYSA-N 0.000 description 2
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 2
• 238000010791 quenching Methods 0.000 description 2
• 230000009467 reduction Effects 0.000 description 2
• 238000006722 reduction reaction Methods 0.000 description 2
• 230000001850 reproductive effect Effects 0.000 description 2
• GHMLBKRAJCXXBS-UHFFFAOYSA-N resorcinol Chemical compound OC1=CC=CC(O)=C1 GHMLBKRAJCXXBS-UHFFFAOYSA-N 0.000 description 2
• 210000001210 retinal vessel Anatomy 0.000 description 2
• 238000004007 reversed phase HPLC Methods 0.000 description 2
• 238000012552 review Methods 0.000 description 2
• 238000007363 ring formation reaction Methods 0.000 description 2
• 238000000926 separation method Methods 0.000 description 2
• 238000010898 silica gel chromatography Methods 0.000 description 2
• 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 2
• 210000003491 skin Anatomy 0.000 description 2
• URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 2
• 235000011006 sodium potassium tartrate Nutrition 0.000 description 2
• 210000002784 stomach Anatomy 0.000 description 2
• 201000011549 stomach cancer Diseases 0.000 description 2
• 239000000126 substance Substances 0.000 description 2
• 125000005017 substituted alkenyl group Chemical group 0.000 description 2
• 125000004426 substituted alkynyl group Chemical group 0.000 description 2
• 239000000758 substrate Substances 0.000 description 2
• 238000003786 synthesis reaction Methods 0.000 description 2
• 238000004809 thin layer chromatography Methods 0.000 description 2
• KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 description 2
• 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 2
• 230000002792 vascular Effects 0.000 description 2
• 230000029663 wound healing Effects 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
• WNWRJUGCSLZTSG-UHFFFAOYSA-N (3,5-diamino-4-methylphenyl)methanol Chemical compound CC1=C(N)C=C(CO)C=C1N WNWRJUGCSLZTSG-UHFFFAOYSA-N 0.000 description 1
• OJZQOQNSUZLSMV-UHFFFAOYSA-N (3-aminophenyl)methanol Chemical compound NC1=CC=CC(CO)=C1 OJZQOQNSUZLSMV-UHFFFAOYSA-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
• RDJUHLUBPADHNP-UHFFFAOYSA-N 1,2,3,5-tetrahydroxybenzene Chemical compound OC1=CC(O)=C(O)C(O)=C1 RDJUHLUBPADHNP-UHFFFAOYSA-N 0.000 description 1
• SILNNFMWIMZVEQ-UHFFFAOYSA-N 1,3-dihydrobenzimidazol-2-one Chemical compound C1=CC=C2NC(O)=NC2=C1 SILNNFMWIMZVEQ-UHFFFAOYSA-N 0.000 description 1
• ZXSQEZNORDWBGZ-UHFFFAOYSA-N 1,3-dihydropyrrolo[2,3-b]pyridin-2-one Chemical compound C1=CN=C2NC(=O)CC2=C1 ZXSQEZNORDWBGZ-UHFFFAOYSA-N 0.000 description 1
• WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 1
• LTOQUFIOYDCJFJ-UHFFFAOYSA-N 1-(4-chlorophenyl)pyrrole Chemical compound C1=CC(Cl)=CC=C1N1C=CC=C1 LTOQUFIOYDCJFJ-UHFFFAOYSA-N 0.000 description 1
• LOZKZWIQDVEDCQ-UHFFFAOYSA-N 1-(6-amino-2,3-dihydroindol-1-yl)ethanone Chemical compound C1=C(N)C=C2N(C(=O)C)CCC2=C1 LOZKZWIQDVEDCQ-UHFFFAOYSA-N 0.000 description 1
• PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-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
• FAYRYNBQRLFBMN-UHFFFAOYSA-N 1-amino-3-methylpyrrole-2-carboxamide Chemical compound CC=1C=CN(N)C=1C(N)=O FAYRYNBQRLFBMN-UHFFFAOYSA-N 0.000 description 1
• UKYIJKYIUWIFIZ-UHFFFAOYSA-N 1-amino-4-methylpyrrole-2-carbonitrile Chemical compound CC=1C=C(C#N)N(N)C=1 UKYIJKYIUWIFIZ-UHFFFAOYSA-N 0.000 description 1
• XYRBFVJDVOXNLF-UHFFFAOYSA-N 1-amino-4-methylpyrrole-2-carboxamide Chemical compound CC=1C=C(C(N)=O)N(N)C=1 XYRBFVJDVOXNLF-UHFFFAOYSA-N 0.000 description 1
• ZRSGOYBQUGARBK-UHFFFAOYSA-N 1-amino-5-methylpyrrole-2-carbonitrile Chemical compound CC1=CC=C(C#N)N1N ZRSGOYBQUGARBK-UHFFFAOYSA-N 0.000 description 1
• PQPMDTRGVFDJKR-UHFFFAOYSA-N 1-amino-5-methylpyrrole-2-carboxamide Chemical compound CC1=CC=C(C(N)=O)N1N PQPMDTRGVFDJKR-UHFFFAOYSA-N 0.000 description 1
• RSQUAQMIGSMNNE-UHFFFAOYSA-N 1-methyl-3h-indol-2-one Chemical compound C1=CC=C2N(C)C(=O)CC2=C1 RSQUAQMIGSMNNE-UHFFFAOYSA-N 0.000 description 1
• BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 1
• MIMYTSWNVBMNRH-UHFFFAOYSA-N 1h-indol-6-amine Chemical compound NC1=CC=C2C=CNC2=C1 MIMYTSWNVBMNRH-UHFFFAOYSA-N 0.000 description 1
• JVVRJMXHNUAPHW-UHFFFAOYSA-N 1h-pyrazol-5-amine Chemical compound NC=1C=CNN=1 JVVRJMXHNUAPHW-UHFFFAOYSA-N 0.000 description 1
• BZKOZYWGZKRTIB-UHFFFAOYSA-N 2,3-dihydro-1,4-benzodioxin-6-amine Chemical compound O1CCOC2=CC(N)=CC=C21 BZKOZYWGZKRTIB-UHFFFAOYSA-N 0.000 description 1
• SATOBHVAZUERBJ-UHFFFAOYSA-N 2,3-dihydro-1h-indole-5-carboxamide Chemical compound NC(=O)C1=CC=C2NCCC2=C1 SATOBHVAZUERBJ-UHFFFAOYSA-N 0.000 description 1
• LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
• TVCXVUHHCUYLGX-UHFFFAOYSA-N 2-Methylpyrrole Chemical compound CC1=CC=CN1 TVCXVUHHCUYLGX-UHFFFAOYSA-N 0.000 description 1
• 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 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
• UHGULLIUJBCTEF-UHFFFAOYSA-N 2-aminobenzothiazole Chemical compound C1=CC=C2SC(N)=NC2=C1 UHGULLIUJBCTEF-UHFFFAOYSA-N 0.000 description 1
• FZZMTSNZRBFGGU-UHFFFAOYSA-N 2-chloro-7-fluoroquinazolin-4-amine Chemical compound FC1=CC=C2C(N)=NC(Cl)=NC2=C1 FZZMTSNZRBFGGU-UHFFFAOYSA-N 0.000 description 1
• ULQQGOGMQRGFFR-UHFFFAOYSA-N 2-chlorobenzenecarboperoxoic acid Chemical compound OOC(=O)C1=CC=CC=C1Cl ULQQGOGMQRGFFR-UHFFFAOYSA-N 0.000 description 1
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
• CVZREHYXQNAPKJ-UHFFFAOYSA-N 2-methyl-5-methylsulfonylaniline Chemical compound CC1=CC=C(S(C)(=O)=O)C=C1N CVZREHYXQNAPKJ-UHFFFAOYSA-N 0.000 description 1
• 125000004635 2-oxazepinyl group Chemical group O1N(CC=CC=C1)* 0.000 description 1
• NZOSLRYUVHMXTQ-UHFFFAOYSA-N 2-oxo-1,3-dihydroindole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(=O)CC2=C1 NZOSLRYUVHMXTQ-UHFFFAOYSA-N 0.000 description 1
• PJRWVQFEVVSTKZ-UHFFFAOYSA-N 2-oxo-1,3-dihydroindole-5-sulfonamide Chemical compound NS(=O)(=O)C1=CC=C2NC(=O)CC2=C1 PJRWVQFEVVSTKZ-UHFFFAOYSA-N 0.000 description 1
• BDVLJDNTJAMYLR-UHFFFAOYSA-N 2-oxo-n-(2-pyrrolidin-1-ylethyl)-1,3-dihydroindole-5-sulfonamide Chemical compound C=1C=C2NC(=O)CC2=CC=1S(=O)(=O)NCCN1CCCC1 BDVLJDNTJAMYLR-UHFFFAOYSA-N 0.000 description 1
• 125000004638 2-oxopiperazinyl group Chemical group O=C1N(CCNC1)* 0.000 description 1
• 125000004637 2-oxopiperidinyl group Chemical group O=C1N(CCCC1)* 0.000 description 1
• WRXNJTBODVGDRY-UHFFFAOYSA-N 2-pyrrolidin-1-ylethanamine Chemical compound NCCN1CCCC1 WRXNJTBODVGDRY-UHFFFAOYSA-N 0.000 description 1
• XSFHICWNEBCMNN-UHFFFAOYSA-N 2h-benzotriazol-5-amine Chemical compound NC1=CC=C2NN=NC2=C1 XSFHICWNEBCMNN-UHFFFAOYSA-N 0.000 description 1
• HYTIPJFUWHYQON-UHFFFAOYSA-N 3,4-dihydro-1h-quinoxalin-2-one Chemical compound C1=CC=C2NC(=O)CNC2=C1 HYTIPJFUWHYQON-UHFFFAOYSA-N 0.000 description 1
• 125000004610 3,4-dihydro-4-oxo-quinazolinyl group Chemical group O=C1NC(=NC2=CC=CC=C12)* 0.000 description 1
• LGDHZCLREKIGKJ-UHFFFAOYSA-N 3,4-dimethoxyaniline Chemical compound COC1=CC=C(N)C=C1OC LGDHZCLREKIGKJ-UHFFFAOYSA-N 0.000 description 1
• 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 1
• IXXJEYNOJZNYBD-UHFFFAOYSA-N 3-(1,2,4-triazol-1-yl)propan-1-amine Chemical compound NCCCN1C=NC=N1 IXXJEYNOJZNYBD-UHFFFAOYSA-N 0.000 description 1
• AJHPGXZOIAYYDW-UHFFFAOYSA-N 3-(2-cyanophenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)NC(C(O)=O)CC1=CC=CC=C1C#N AJHPGXZOIAYYDW-UHFFFAOYSA-N 0.000 description 1
• SSFNNFZQSCHTQA-UHFFFAOYSA-N 3-[(6-methoxycarbonyl-5-methylpyrrolo[2,1-f][1,2,4]triazin-4-yl)amino]benzoic acid Chemical compound C12=C(C)C(C(=O)OC)=CN2N=CN=C1NC1=CC=CC(C(O)=O)=C1 SSFNNFZQSCHTQA-UHFFFAOYSA-N 0.000 description 1
• VTRKJVRJTVKUIA-UHFFFAOYSA-N 3-amino-2-methoxyphenol Chemical compound COC1=C(N)C=CC=C1O VTRKJVRJTVKUIA-UHFFFAOYSA-N 0.000 description 1
• WGOUCTJBESOZIL-UHFFFAOYSA-N 3-amino-n-butylbenzenesulfonamide Chemical compound CCCCNS(=O)(=O)C1=CC=CC(N)=C1 WGOUCTJBESOZIL-UHFFFAOYSA-N 0.000 description 1
• ZAJAQTYSTDTMCU-UHFFFAOYSA-N 3-aminobenzenesulfonic acid Chemical compound NC1=CC=CC(S(O)(=O)=O)=C1 ZAJAQTYSTDTMCU-UHFFFAOYSA-N 0.000 description 1
• JSIVTKBYJLGBPY-UHFFFAOYSA-N 3-aminobenzohydrazide Chemical compound NNC(=O)C1=CC=CC(N)=C1 JSIVTKBYJLGBPY-UHFFFAOYSA-N 0.000 description 1
• NJXPYZHXZZCTNI-UHFFFAOYSA-N 3-aminobenzonitrile Chemical compound NC1=CC=CC(C#N)=C1 NJXPYZHXZZCTNI-UHFFFAOYSA-N 0.000 description 1
• CWLKGDAVCFYWJK-UHFFFAOYSA-N 3-aminophenol Chemical compound NC1=CC=CC(O)=C1 CWLKGDAVCFYWJK-UHFFFAOYSA-N 0.000 description 1
• RLLBWIDEGAIFPI-UHFFFAOYSA-N 3-ethyl-1h-pyrrole Chemical compound CCC=1C=CNC=1 RLLBWIDEGAIFPI-UHFFFAOYSA-N 0.000 description 1
• XYMXEIDEBKNGTB-UHFFFAOYSA-N 3-ethyl-1h-pyrrole-2-carbaldehyde Chemical compound CCC=1C=CNC=1C=O XYMXEIDEBKNGTB-UHFFFAOYSA-N 0.000 description 1
• ZEBBLOXDLGIMEG-UHFFFAOYSA-N 3-ethyl-2,4-dimethyl-1h-pyrrole Chemical compound CCC=1C(C)=CNC=1C ZEBBLOXDLGIMEG-UHFFFAOYSA-N 0.000 description 1
• MGRHBBRSAFPBIN-UHFFFAOYSA-N 3-fluoro-4-methylaniline Chemical compound CC1=CC=C(N)C=C1F MGRHBBRSAFPBIN-UHFFFAOYSA-N 0.000 description 1
• 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 description 1
• VPBWZBGZWHDNKL-UHFFFAOYSA-N 3-pyrrolidin-1-ylpropan-1-amine Chemical compound NCCCN1CCCC1 VPBWZBGZWHDNKL-UHFFFAOYSA-N 0.000 description 1
• KNBCTKMWYMAHKB-UHFFFAOYSA-N 4-(3-hydroxy-4-methylanilino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid Chemical compound C12=C(C)C(C(O)=O)=CN2N=CN=C1NC1=CC=C(C)C(O)=C1 KNBCTKMWYMAHKB-UHFFFAOYSA-N 0.000 description 1
• GDIIPKWHAQGCJF-UHFFFAOYSA-N 4-Amino-2-nitrotoluene Chemical compound CC1=CC=C(N)C=C1[N+]([O-])=O GDIIPKWHAQGCJF-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
• MMEGELSFOYDPQW-UHFFFAOYSA-N 4-bromo-3-methylaniline Chemical compound CC1=CC(N)=CC=C1Br MMEGELSFOYDPQW-UHFFFAOYSA-N 0.000 description 1
• WDFQBORIUYODSI-UHFFFAOYSA-N 4-bromoaniline Chemical compound NC1=CC=C(Br)C=C1 WDFQBORIUYODSI-UHFFFAOYSA-N 0.000 description 1
• CSFDTBRRIBJILD-UHFFFAOYSA-N 4-chloro-2-fluoroaniline Chemical compound NC1=CC=C(Cl)C=C1F CSFDTBRRIBJILD-UHFFFAOYSA-N 0.000 description 1
• FOHHWGVAOVDVLP-UHFFFAOYSA-N 4-chloro-3-nitroaniline Chemical compound NC1=CC=C(Cl)C([N+]([O-])=O)=C1 FOHHWGVAOVDVLP-UHFFFAOYSA-N 0.000 description 1
• QSNSCYSYFYORTR-UHFFFAOYSA-N 4-chloroaniline Chemical compound NC1=CC=C(Cl)C=C1 QSNSCYSYFYORTR-UHFFFAOYSA-N 0.000 description 1
• MDFRGUIAJMMLHO-UHFFFAOYSA-N 4-ethyl-1h-pyrrole-2-carbaldehyde Chemical compound CCC1=CNC(C=O)=C1 MDFRGUIAJMMLHO-UHFFFAOYSA-N 0.000 description 1
• 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
• 125000005986 4-piperidonyl group Chemical group 0.000 description 1
• NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 1
• FYTLHYRDGXRYEY-UHFFFAOYSA-N 5-Methyl-3-pyrazolamine Chemical compound CC=1C=C(N)NN=1 FYTLHYRDGXRYEY-UHFFFAOYSA-N 0.000 description 1
• MCXWPQYRAHIVPS-UHFFFAOYSA-N 5-[2-[tert-butyl(dimethyl)silyl]oxyethylsulfonyl]-1,3-dihydroindol-2-one Chemical compound CC(C)(C)[Si](C)(C)OCCS(=O)(=O)C1=CC=C2NC(=O)CC2=C1 MCXWPQYRAHIVPS-UHFFFAOYSA-N 0.000 description 1
• KTPBKMYOIFHJMI-UHFFFAOYSA-N 5-amino-2-methylbenzenesulfonamide Chemical compound CC1=CC=C(N)C=C1S(N)(=O)=O KTPBKMYOIFHJMI-UHFFFAOYSA-N 0.000 description 1
• YDZVQWCVKXYGIU-UHFFFAOYSA-N 5-amino-2-methylbenzonitrile Chemical compound CC1=CC=C(N)C=C1C#N YDZVQWCVKXYGIU-UHFFFAOYSA-N 0.000 description 1
• DTVYNUOOZIKEEX-UHFFFAOYSA-N 5-aminoisoquinoline Chemical compound N1=CC=C2C(N)=CC=CC2=C1 DTVYNUOOZIKEEX-UHFFFAOYSA-N 0.000 description 1
• LFWLUDLUCDRDAF-UHFFFAOYSA-N 5-methyl-1h-pyrrole-2-carbaldehyde Chemical compound CC1=CC=C(C=O)N1 LFWLUDLUCDRDAF-UHFFFAOYSA-N 0.000 description 1
• CMBSSVKZOPZBKW-UHFFFAOYSA-N 5-methylpyridin-2-amine Chemical compound CC1=CC=C(N)N=C1 CMBSSVKZOPZBKW-UHFFFAOYSA-N 0.000 description 1
• SESKLCQTEFAMPM-UHFFFAOYSA-N 5-morpholin-4-ylsulfonyl-1,3-dihydroindol-2-one Chemical compound C=1C=C2NC(=O)CC2=CC=1S(=O)(=O)N1CCOCC1 SESKLCQTEFAMPM-UHFFFAOYSA-N 0.000 description 1
• QAJYCQZQLVENRZ-UHFFFAOYSA-N 6-chloropyridin-3-amine Chemical compound NC1=CC=C(Cl)N=C1 QAJYCQZQLVENRZ-UHFFFAOYSA-N 0.000 description 1
• MJXYFLJHTUSJGU-UHFFFAOYSA-N 7-amino-4-methyl-1h-quinolin-2-one Chemical compound NC1=CC=C2C(C)=CC(=O)NC2=C1 MJXYFLJHTUSJGU-UHFFFAOYSA-N 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-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
• 208000030507 AIDS Diseases 0.000 description 1
• 206010065040 AIDS dementia complex Diseases 0.000 description 1
• IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 1
• 208000031261 Acute myeloid leukaemia Diseases 0.000 description 1
• 208000036762 Acute promyelocytic leukaemia Diseases 0.000 description 1
• 208000024827 Alzheimer disease Diseases 0.000 description 1
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
• 102000012936 Angiostatins Human genes 0.000 description 1
• 108010079709 Angiostatins Proteins 0.000 description 1
• 239000004475 Arginine Substances 0.000 description 1
• BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
• 206010003571 Astrocytoma Diseases 0.000 description 1
• 208000003950 B-cell lymphoma Diseases 0.000 description 1
• 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 1
• 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 1
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
• DNUFLZKDSLBWDP-UHFFFAOYSA-N CC1=CC(NC2=CC(=CC=C12)NC=1C=CNC1C)=O Chemical compound CC1=CC(NC2=CC(=CC=C12)NC=1C=CNC1C)=O DNUFLZKDSLBWDP-UHFFFAOYSA-N 0.000 description 1
• 101100123850 Caenorhabditis elegans her-1 gene Proteins 0.000 description 1
• 206010058019 Cancer Pain Diseases 0.000 description 1
• 201000009030 Carcinoma Diseases 0.000 description 1
• 229940123587 Cell cycle inhibitor Drugs 0.000 description 1
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
• 206010009944 Colon cancer Diseases 0.000 description 1
• 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
• 238000006969 Curtius rearrangement reaction Methods 0.000 description 1
• 201000003883 Cystic fibrosis Diseases 0.000 description 1
• XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
• AADVCYNFEREWOS-OBRABYBLSA-N Discodermolide Chemical class C=C\C=C/[C@H](C)[C@H](OC(N)=O)[C@@H](C)[C@H](O)[C@@H](C)C\C(C)=C/[C@H](C)[C@@H](O)[C@@H](C)\C=C/[C@@H](O)C[C@@H]1OC(=O)[C@H](C)[C@@H](O)[C@H]1C AADVCYNFEREWOS-OBRABYBLSA-N 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
• 201000009273 Endometriosis Diseases 0.000 description 1
• 206010014824 Endotoxic shock Diseases 0.000 description 1
• KBEBGUQPQBELIU-CMDGGOBGSA-N Ethyl cinnamate Chemical compound CCOC(=O)\C=C\C1=CC=CC=C1 KBEBGUQPQBELIU-CMDGGOBGSA-N 0.000 description 1
• ZFDIRQKJPRINOQ-HWKANZROSA-N Ethyl crotonate Chemical compound CCOC(=O)\C=C\C ZFDIRQKJPRINOQ-HWKANZROSA-N 0.000 description 1
• 101150009958 FLT4 gene Proteins 0.000 description 1
• 102000003971 Fibroblast Growth Factor 1 Human genes 0.000 description 1
• 102100031706 Fibroblast growth factor 1 Human genes 0.000 description 1
• 102000003974 Fibroblast growth factor 2 Human genes 0.000 description 1
• 102100023600 Fibroblast growth factor receptor 2 Human genes 0.000 description 1
• 101710182389 Fibroblast growth factor receptor 2 Proteins 0.000 description 1
• 201000008808 Fibrosarcoma Diseases 0.000 description 1
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
• 206010017533 Fungal infection Diseases 0.000 description 1
• 101000993347 Gallus gallus Ciliary neurotrophic factor Proteins 0.000 description 1
• 208000032612 Glial tumor Diseases 0.000 description 1
• 206010018338 Glioma Diseases 0.000 description 1
• 239000004471 Glycine Substances 0.000 description 1
• 108090000100 Hepatocyte Growth Factor Proteins 0.000 description 1
• 102100021866 Hepatocyte growth factor Human genes 0.000 description 1
• 208000017604 Hodgkin disease Diseases 0.000 description 1
• 208000021519 Hodgkin lymphoma Diseases 0.000 description 1
• 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
• 101000946124 Homo sapiens Lipocalin-1 Proteins 0.000 description 1
• 101000692455 Homo sapiens Platelet-derived growth factor receptor beta Proteins 0.000 description 1
• 101000904173 Homo sapiens Progonadoliberin-1 Proteins 0.000 description 1
• 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 1
• 241000701044 Human gammaherpesvirus 4 Species 0.000 description 1
• 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 1
• SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 1
• 206010023825 Laryngeal cancer Diseases 0.000 description 1
• 239000002841 Lewis acid Substances 0.000 description 1
• 229910010084 LiAlH4 Inorganic materials 0.000 description 1
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
• 241001233242 Lontra Species 0.000 description 1
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
• 239000004472 Lysine Substances 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
• 229910021380 Manganese Chloride Inorganic materials 0.000 description 1
• GLFNIEUTAYBVOC-UHFFFAOYSA-L Manganese chloride Chemical compound Cl[Mn]Cl GLFNIEUTAYBVOC-UHFFFAOYSA-L 0.000 description 1
• 206010027476 Metastases Diseases 0.000 description 1
• 241001465754 Metazoa Species 0.000 description 1
• 102000029749 Microtubule Human genes 0.000 description 1
• 108091022875 Microtubule Proteins 0.000 description 1
• 101001043818 Mus musculus Interleukin-31 receptor subunit alpha Proteins 0.000 description 1
• 208000031888 Mycoses Diseases 0.000 description 1
• 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 1
• 208000033776 Myeloid Acute Leukemia Diseases 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
• CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 1
• 125000004633 N-oxo-pyridyl group Chemical group 0.000 description 1
• 238000005481 NMR spectroscopy Methods 0.000 description 1
• 229910020284 Na2SO4.10H2O Inorganic materials 0.000 description 1
• 206010029260 Neuroblastoma Diseases 0.000 description 1
• 208000009905 Neurofibromatoses Diseases 0.000 description 1
• 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
• 235000019502 Orange oil Nutrition 0.000 description 1
• 208000001132 Osteoporosis Diseases 0.000 description 1
• 102000016979 Other receptors Human genes 0.000 description 1
• 206010033128 Ovarian cancer Diseases 0.000 description 1
• 206010061535 Ovarian neoplasm Diseases 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
• 208000018737 Parkinson disease Diseases 0.000 description 1
• ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical class OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 1
• 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 1
• 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 1
• 102100026547 Platelet-derived growth factor receptor beta Human genes 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• 101710098940 Pro-epidermal growth factor Proteins 0.000 description 1
• 102100024028 Progonadoliberin-1 Human genes 0.000 description 1
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
• 208000004403 Prostatic Hyperplasia Diseases 0.000 description 1
• 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
• 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
• 206010063837 Reperfusion injury Diseases 0.000 description 1
• 208000007014 Retinitis pigmentosa Diseases 0.000 description 1
• 206010038923 Retinopathy Diseases 0.000 description 1
• 206010038933 Retinopathy of prematurity Diseases 0.000 description 1
• 229910006074 SO2NH2 Inorganic materials 0.000 description 1
• 206010039710 Scleroderma Diseases 0.000 description 1
• 201000010208 Seminoma Diseases 0.000 description 1
• 206010040070 Septic Shock Diseases 0.000 description 1
• 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 1
• 241000710960 Sindbis virus Species 0.000 description 1
• 206010041067 Small cell lung cancer Diseases 0.000 description 1
• 101100054666 Streptomyces halstedii sch3 gene Proteins 0.000 description 1
• 208000006011 Stroke Diseases 0.000 description 1
• 101000996723 Sus scrofa Gonadotropin-releasing hormone receptor Proteins 0.000 description 1
• 206010042971 T-cell lymphoma Diseases 0.000 description 1
• 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 description 1
• 206010052779 Transplant rejections Diseases 0.000 description 1
• 239000007983 Tris buffer Substances 0.000 description 1
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
• 102000004504 Urokinase Plasminogen Activator Receptors Human genes 0.000 description 1
• 108010042352 Urokinase Plasminogen Activator Receptors Proteins 0.000 description 1
• 108091008605 VEGF receptors Proteins 0.000 description 1
• 241000700647 Variola virus Species 0.000 description 1
• 102000016549 Vascular Endothelial Growth Factor Receptor-2 Human genes 0.000 description 1
• 102000016663 Vascular Endothelial Growth Factor Receptor-3 Human genes 0.000 description 1
• 229940122803 Vinca alkaloid Drugs 0.000 description 1
• 208000036142 Viral infection Diseases 0.000 description 1
• 238000007239 Wittig reaction Methods 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
• PYZPABZGIRHQTA-UHFFFAOYSA-N [2-(4-methyl-2-phenylpiperazin-1-yl)pyridin-3-yl]methanol Chemical compound C1N(C)CCN(C=2C(=CC=CN=2)CO)C1C1=CC=CC=C1 PYZPABZGIRHQTA-UHFFFAOYSA-N 0.000 description 1
• ASDRDNCEDOIZHV-UHFFFAOYSA-N [N+](#[C-])CC(=O)OCC.C(C)OC(=O)C=1NC=C(C1CC)C(=O)OCC Chemical compound [N+](#[C-])CC(=O)OCC.C(C)OC(=O)C=1NC=C(C1CC)C(=O)OCC ASDRDNCEDOIZHV-UHFFFAOYSA-N 0.000 description 1
• SZRXMVSIOWLREA-UHFFFAOYSA-N [N+](#[C-])CC(=O)OCC.C(C)OC(=O)C=1NC=C(C1CCC)C(=O)OCC Chemical compound [N+](#[C-])CC(=O)OCC.C(C)OC(=O)C=1NC=C(C1CCC)C(=O)OCC SZRXMVSIOWLREA-UHFFFAOYSA-N 0.000 description 1
• 230000002159 abnormal effect Effects 0.000 description 1
• IKHGUXGNUITLKF-XPULMUKRSA-N acetaldehyde Chemical compound [14CH]([14CH3])=O IKHGUXGNUITLKF-XPULMUKRSA-N 0.000 description 1
• 229960001138 acetylsalicylic acid Drugs 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• 239000013543 active substance Substances 0.000 description 1
• 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• 150000003838 adenosines Chemical class 0.000 description 1
• 230000011759 adipose tissue development Effects 0.000 description 1
• 238000012382 advanced drug delivery Methods 0.000 description 1
• 238000001042 affinity chromatography Methods 0.000 description 1
• 239000000556 agonist Substances 0.000 description 1
• 229910052783 alkali metal Inorganic materials 0.000 description 1
• 150000001340 alkali metals Chemical class 0.000 description 1
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
• 150000001342 alkaline earth metals Chemical class 0.000 description 1
• 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
• 150000001350 alkyl halides Chemical class 0.000 description 1
• 230000029936 alkylation Effects 0.000 description 1
• 238000005804 alkylation reaction Methods 0.000 description 1
• 230000004075 alteration Effects 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• DQPBABKTKYNPMH-UHFFFAOYSA-N amino hydrogen sulfate Chemical compound NOS(O)(=O)=O DQPBABKTKYNPMH-UHFFFAOYSA-N 0.000 description 1
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 1
• 239000000908 ammonium hydroxide Substances 0.000 description 1
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
• 208000007502 anemia Diseases 0.000 description 1
• 230000002491 angiogenic effect Effects 0.000 description 1
• 238000002399 angioplasty Methods 0.000 description 1
• 150000001448 anilines Chemical class 0.000 description 1
• 239000005557 antagonist Substances 0.000 description 1
• 229940045799 anthracyclines and related substance Drugs 0.000 description 1
• 239000003242 anti bacterial agent Substances 0.000 description 1
• 229940046836 anti-estrogen Drugs 0.000 description 1
• 230000001833 anti-estrogenic effect Effects 0.000 description 1
• 230000003432 anti-folate effect Effects 0.000 description 1
• 230000003388 anti-hormonal effect Effects 0.000 description 1
• 230000001740 anti-invasion Effects 0.000 description 1
• 230000000340 anti-metabolite Effects 0.000 description 1
• 230000000692 anti-sense effect Effects 0.000 description 1
• 229940088710 antibiotic agent Drugs 0.000 description 1
• 229940127074 antifolate Drugs 0.000 description 1
• 229940100197 antimetabolite Drugs 0.000 description 1
• 239000002256 antimetabolite Substances 0.000 description 1
• 239000003080 antimitotic agent Substances 0.000 description 1
• 229940045719 antineoplastic alkylating agent nitrosoureas Drugs 0.000 description 1
• 229940041181 antineoplastic drug Drugs 0.000 description 1
• 230000005735 apoptotic response Effects 0.000 description 1
• 125000005140 aralkylsulfonyl group Chemical group 0.000 description 1
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
• 239000003886 aromatase inhibitor Substances 0.000 description 1
• 229940046844 aromatase inhibitors Drugs 0.000 description 1
• 125000002029 aromatic hydrocarbon group Chemical group 0.000 description 1
• 125000005239 aroylamino group Chemical group 0.000 description 1
• 230000006793 arrhythmia Effects 0.000 description 1
• 206010003119 arrhythmia Diseases 0.000 description 1
• 125000005418 aryl aryl group Chemical group 0.000 description 1
• 125000004391 aryl sulfonyl group Chemical group 0.000 description 1
• 125000005110 aryl thio group Chemical group 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• 125000003289 ascorbyl group Chemical class [H]O[C@@]([H])(C([H])([H])O*)[C@@]1([H])OC(=O)C(O*)=C1O* 0.000 description 1
• FZCSTZYAHCUGEM-UHFFFAOYSA-N aspergillomarasmine B Natural products OC(=O)CNC(C(O)=O)CNC(C(O)=O)CC(O)=O FZCSTZYAHCUGEM-UHFFFAOYSA-N 0.000 description 1
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
• 230000001363 autoimmune Effects 0.000 description 1
• 230000035578 autophosphorylation Effects 0.000 description 1
• 125000002785 azepinyl group Chemical group 0.000 description 1
• 150000001541 aziridines Chemical group 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
• 229940092714 benzenesulfonic acid Drugs 0.000 description 1
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
• 125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 description 1
• 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 description 1
• 125000004602 benzodiazinyl group Chemical group N1=NC(=CC2=C1C=CC=C2)* 0.000 description 1
• 125000004601 benzofurazanyl group Chemical group N1=C2C(=NO1)C(=CC=C2)* 0.000 description 1
• 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
• 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 description 1
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 125000004600 benzothiopyranyl group Chemical group S1C(C=CC2=C1C=CC=C2)* 0.000 description 1
• RROBIDXNTUAHFW-UHFFFAOYSA-N benzotriazol-1-yloxy-tris(dimethylamino)phosphanium Chemical compound C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1 RROBIDXNTUAHFW-UHFFFAOYSA-N 0.000 description 1
• 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
• AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
• 125000002618 bicyclic heterocycle group Chemical group 0.000 description 1
• 239000012867 bioactive agent Substances 0.000 description 1
• 230000005540 biological transmission Effects 0.000 description 1
• 239000004305 biphenyl Substances 0.000 description 1
• 235000010290 biphenyl Nutrition 0.000 description 1
• 125000006267 biphenyl group Chemical group 0.000 description 1
• 210000001109 blastomere Anatomy 0.000 description 1
• 238000009835 boiling Methods 0.000 description 1
• 150000001642 boronic acid derivatives Chemical class 0.000 description 1
• 229940098773 bovine serum albumin Drugs 0.000 description 1
• 210000000133 brain stem Anatomy 0.000 description 1
• 239000007853 buffer solution Substances 0.000 description 1
• 125000006309 butyl amino group Chemical group 0.000 description 1
• 239000002775 capsule Substances 0.000 description 1
• 125000004181 carboxyalkyl group Chemical group 0.000 description 1
• BUZRUIZTMOKRPB-UHFFFAOYSA-N carboxycarbamic acid Chemical compound OC(=O)NC(O)=O BUZRUIZTMOKRPB-UHFFFAOYSA-N 0.000 description 1
• 239000012876 carrier material Substances 0.000 description 1
• 230000022131 cell cycle Effects 0.000 description 1
• 230000001413 cellular effect Effects 0.000 description 1
• 230000036755 cellular response Effects 0.000 description 1
• 210000003169 central nervous system Anatomy 0.000 description 1
• 208000025434 cerebellar degeneration Diseases 0.000 description 1
• 210000003679 cervix uteri Anatomy 0.000 description 1
• 238000010568 chiral column chromatography Methods 0.000 description 1
• 229910052801 chlorine Inorganic materials 0.000 description 1
• GGRHYQCXXYLUTL-UHFFFAOYSA-N chloromethyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OCCl GGRHYQCXXYLUTL-UHFFFAOYSA-N 0.000 description 1
• 125000004617 chromonyl group Chemical group O1C(=CC(C2=CC=CC=C12)=O)* 0.000 description 1
• 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
• 150000001860 citric acid derivatives Chemical class 0.000 description 1
• 201000011024 colonic benign neoplasm Diseases 0.000 description 1
• 208000029742 colonic neoplasm Diseases 0.000 description 1
• 239000012230 colorless oil Substances 0.000 description 1
• 229940046044 combinations of antineoplastic agent Drugs 0.000 description 1
• 229940127573 compound 38 Drugs 0.000 description 1
• 229940124558 contraceptive agent Drugs 0.000 description 1
• 239000003433 contraceptive agent Substances 0.000 description 1
• 239000006184 cosolvent Substances 0.000 description 1
• 125000000332 coumarinyl group Chemical group O1C(=O)C(=CC2=CC=CC=C12)* 0.000 description 1
• 230000008878 coupling Effects 0.000 description 1
• 238000010168 coupling process Methods 0.000 description 1
• 125000000753 cycloalkyl group Chemical group 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
• 238000006114 decarboxylation reaction Methods 0.000 description 1
• 238000005828 desilylation reaction Methods 0.000 description 1
• PGBYJSOGWLPFLS-UHFFFAOYSA-N diethyl 1-amino-3-methoxypyrrole-2,4-dicarboxylate Chemical compound CCOC(=O)C1=CN(N)C(C(=O)OCC)=C1OC PGBYJSOGWLPFLS-UHFFFAOYSA-N 0.000 description 1
• DHJFMUPNQKBJTG-UHFFFAOYSA-N diethyl 1-amino-3-propylpyrrole-2,4-dicarboxylate Chemical compound CCCC=1C(C(=O)OCC)=CN(N)C=1C(=O)OCC DHJFMUPNQKBJTG-UHFFFAOYSA-N 0.000 description 1
• IJQUVMMGXHGEBN-UHFFFAOYSA-N diethyl 1-benzyl-3-hydroxypyrrole-2,4-dicarboxylate Chemical compound CCOC(=O)C1=C(O)C(C(=O)OCC)=CN1CC1=CC=CC=C1 IJQUVMMGXHGEBN-UHFFFAOYSA-N 0.000 description 1
• LXEGDWJIWBTXFM-UHFFFAOYSA-N diethyl 3-methoxy-1h-pyrrole-2,4-dicarboxylate Chemical compound CCOC(=O)C1=CNC(C(=O)OCC)=C1OC LXEGDWJIWBTXFM-UHFFFAOYSA-N 0.000 description 1
• YONIZNXARZVZOF-UHFFFAOYSA-N diethyl 4-(2-oxo-1,3-dihydroindol-3-yl)pyrrolo[2,1-f][1,2,4]triazine-5,6-dicarboxylate Chemical compound O=C1NC2=CC=CC=C2C1C1=NC=NN2C=C(C(=O)OCC)C(C(=O)OCC)=C21 YONIZNXARZVZOF-UHFFFAOYSA-N 0.000 description 1
• 125000004598 dihydrobenzofuryl group Chemical group O1C(CC2=C1C=CC=C2)* 0.000 description 1
• 125000004586 dihydrobenzopyranyl group Chemical group O1C(CCC2=C1C=CC=C2)* 0.000 description 1
• 125000004582 dihydrobenzothienyl group Chemical group S1C(CC2=C1C=CC=C2)* 0.000 description 1
• 125000004597 dihydrobenzothiopyranyl group Chemical group S1C(CCC2=C1C=CC=C2)* 0.000 description 1
• WOKPSXJEBSRSAT-UHFFFAOYSA-N dihydrobenzothiopyranyl sulfone group Chemical group S1C(CCC2=C1C=CC=C2)S(=O)(=O)C2SC1=C(CC2)C=CC=C1 WOKPSXJEBSRSAT-UHFFFAOYSA-N 0.000 description 1
• 125000004611 dihydroisoindolyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
• 125000004609 dihydroquinazolinyl group Chemical group N1(CN=CC2=CC=CC=C12)* 0.000 description 1
• 238000006471 dimerization reaction Methods 0.000 description 1
• QUIWKVDFKYXEFF-UHFFFAOYSA-N dimethyl 3-methyl-1h-pyrrole-2,4-dicarboxylate Chemical compound COC(=O)C1=CNC(C(=O)OC)=C1C QUIWKVDFKYXEFF-UHFFFAOYSA-N 0.000 description 1
• SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
• 125000000532 dioxanyl group Chemical group 0.000 description 1
• 230000008034 disappearance Effects 0.000 description 1
• VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
• 239000003534 dna topoisomerase inhibitor Substances 0.000 description 1
• 230000007783 downstream signaling Effects 0.000 description 1
• 229940079593 drug Drugs 0.000 description 1
• 238000009510 drug design Methods 0.000 description 1
• 238000009509 drug development Methods 0.000 description 1
• 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
• XOPYFXBZMVTEJF-PDACKIITSA-N eleutherobin Chemical class C(/[C@H]1[C@H](C(=CC[C@@H]1C(C)C)C)C[C@@H]([C@@]1(C)O[C@@]2(C=C1)OC)OC(=O)\C=C\C=1N=CN(C)C=1)=C2\CO[C@@H]1OC[C@@H](O)[C@@H](O)[C@@H]1OC(C)=O XOPYFXBZMVTEJF-PDACKIITSA-N 0.000 description 1
• XOPYFXBZMVTEJF-UHFFFAOYSA-N eleutherobin Chemical class C1=CC2(OC)OC1(C)C(OC(=O)C=CC=1N=CN(C)C=1)CC(C(=CCC1C(C)C)C)C1C=C2COC1OCC(O)C(O)C1OC(C)=O XOPYFXBZMVTEJF-UHFFFAOYSA-N 0.000 description 1
• 230000010595 endothelial cell migration Effects 0.000 description 1
• 229940116977 epidermal growth factor Drugs 0.000 description 1
• 125000003700 epoxy group Chemical group 0.000 description 1
• 210000003238 esophagus Anatomy 0.000 description 1
• 125000004185 ester group Chemical group 0.000 description 1
• 239000000328 estrogen antagonist Substances 0.000 description 1
• AGMKVZDPATUSMS-AATRIKPKSA-N ethyl (e)-pent-2-enoate Chemical compound CCOC(=O)\C=C\CC AGMKVZDPATUSMS-AATRIKPKSA-N 0.000 description 1
• FOLSVRXVBVWZIK-UHFFFAOYSA-N ethyl 1-amino-5-cyano-4-phenylpyrrole-3-carboxylate Chemical compound CCOC(=O)C1=CN(N)C(C#N)=C1C1=CC=CC=C1 FOLSVRXVBVWZIK-UHFFFAOYSA-N 0.000 description 1
• FPULFENIJDPZBX-UHFFFAOYSA-N ethyl 2-isocyanoacetate Chemical compound CCOC(=O)C[N+]#[C-] FPULFENIJDPZBX-UHFFFAOYSA-N 0.000 description 1
• ZCKGARDCKJFLRH-UHFFFAOYSA-N ethyl 4-(3-bromoanilino)-5-ethylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(CC)C(C(=O)OCC)=CN2N=CN=C1NC1=CC=CC(Br)=C1 ZCKGARDCKJFLRH-UHFFFAOYSA-N 0.000 description 1
• AQOVLSUINZASEY-UHFFFAOYSA-N ethyl 4-(3-hydroxy-4-methylanilino)-5-phenylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C=3C=CC=CC=3)C(C(=O)OCC)=CN2N=CN=C1NC1=CC=C(C)C(O)=C1 AQOVLSUINZASEY-UHFFFAOYSA-N 0.000 description 1
• VPESUWVCPICSPO-UHFFFAOYSA-N ethyl 4-ethyl-1h-pyrrole-3-carboxylate Chemical compound CCOC(=O)C1=CNC=C1CC VPESUWVCPICSPO-UHFFFAOYSA-N 0.000 description 1
• XLUCRSMGHKJWSF-UHFFFAOYSA-N ethyl 5-cyano-4-phenyl-1h-pyrrole-3-carboxylate Chemical compound CCOC(=O)C1=CNC(C#N)=C1C1=CC=CC=C1 XLUCRSMGHKJWSF-UHFFFAOYSA-N 0.000 description 1
• JLRNNJCMROTZGX-UHFFFAOYSA-N ethyl 5-ethyl-4-(1h-indazol-6-ylamino)pyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C1=C2C=NNC2=CC(NC2=NC=NN3C=C(C(=C32)CC)C(=O)OCC)=C1 JLRNNJCMROTZGX-UHFFFAOYSA-N 0.000 description 1
• BGUPXCWDFRSPDW-UHFFFAOYSA-N ethyl 5-formyl-4-phenyl-1h-pyrrole-3-carboxylate Chemical compound CCOC(=O)C1=CNC(C=O)=C1C1=CC=CC=C1 BGUPXCWDFRSPDW-UHFFFAOYSA-N 0.000 description 1
• 125000004494 ethyl ester group Chemical group 0.000 description 1
• IYPLKUJAMNCWEI-UHFFFAOYSA-N ethyl triazine-4-carboxylate Chemical compound C(C)OC(=O)C1=CC=NN=N1 IYPLKUJAMNCWEI-UHFFFAOYSA-N 0.000 description 1
• 239000013604 expression vector Substances 0.000 description 1
• 230000008175 fetal development Effects 0.000 description 1
• 239000011737 fluorine Substances 0.000 description 1
• 229910052731 fluorine Inorganic materials 0.000 description 1
• 150000005699 fluoropyrimidines Chemical class 0.000 description 1
• 239000004052 folic acid antagonist Substances 0.000 description 1
• 230000003325 follicular Effects 0.000 description 1
• 230000022244 formylation Effects 0.000 description 1
• 238000006170 formylation reaction Methods 0.000 description 1
• 238000001640 fractional crystallisation Methods 0.000 description 1
• 125000004615 furo[2,3-b]pyridinyl group Chemical group O1C(=CC=2C1=NC=CC2)* 0.000 description 1
• 125000004613 furo[2,3-c]pyridinyl group Chemical group O1C(=CC=2C1=CN=CC2)* 0.000 description 1
• 125000004614 furo[3,1-b]pyridinyl group Chemical group 0.000 description 1
• 125000004612 furopyridinyl group Chemical group O1C(=CC2=C1C=CC=N2)* 0.000 description 1
• 108020001507 fusion proteins Proteins 0.000 description 1
• 102000037865 fusion proteins Human genes 0.000 description 1
• 210000000232 gallbladder Anatomy 0.000 description 1
• 230000014509 gene expression Effects 0.000 description 1
• XLXSAKCOAKORKW-UHFFFAOYSA-N gonadorelin Chemical compound C1CCC(C(=O)NCC(N)=O)N1C(=O)C(CCCN=C(N)N)NC(=O)C(CC(C)C)NC(=O)CNC(=O)C(NC(=O)C(CO)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C(CC=1NC=NC=1)NC(=O)C1NC(=O)CC1)CC1=CC=C(O)C=C1 XLXSAKCOAKORKW-UHFFFAOYSA-N 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 208000014951 hematologic disease Diseases 0.000 description 1
• 150000002391 heterocyclic compounds Chemical class 0.000 description 1
• 150000004677 hydrates Chemical class 0.000 description 1
• 150000004678 hydrides Chemical class 0.000 description 1
• 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
• 150000002440 hydroxy compounds Chemical class 0.000 description 1
• 230000003463 hyperproliferative effect Effects 0.000 description 1
• 230000001969 hypertrophic effect Effects 0.000 description 1
• 125000002632 imidazolidinyl group Chemical group 0.000 description 1
• 125000002636 imidazolinyl group Chemical group 0.000 description 1
• 239000000367 immunologic factor Substances 0.000 description 1
• 238000002513 implantation Methods 0.000 description 1
• 238000000338 in vitro Methods 0.000 description 1
• 238000011534 incubation Methods 0.000 description 1
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
• 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
• 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
• 102000006495 integrins Human genes 0.000 description 1
• 108010044426 integrins Proteins 0.000 description 1
• 238000009830 intercalation Methods 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 239000011630 iodine Substances 0.000 description 1
• 229910052740 iodine Inorganic materials 0.000 description 1
• 238000004255 ion exchange chromatography Methods 0.000 description 1
• 208000037906 ischaemic injury Diseases 0.000 description 1
• 125000003384 isochromanyl group Chemical group C1(OCCC2=CC=CC=C12)* 0.000 description 1
• 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
• 125000001786 isothiazolyl group Chemical group 0.000 description 1
• 125000003971 isoxazolinyl group Chemical group 0.000 description 1
• 125000000842 isoxazolyl group Chemical group 0.000 description 1
• 210000003734 kidney Anatomy 0.000 description 1
• 229940043355 kinase inhibitor Drugs 0.000 description 1
• 206010023841 laryngeal neoplasm Diseases 0.000 description 1
• 210000000867 larynx Anatomy 0.000 description 1
• 201000004962 larynx cancer Diseases 0.000 description 1
• 208000032839 leukemia Diseases 0.000 description 1
• 150000007517 lewis acids Chemical class 0.000 description 1
• 108020001756 ligand binding domains Proteins 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• 229910052744 lithium Inorganic materials 0.000 description 1
• YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
• 210000004185 liver Anatomy 0.000 description 1
• 208000019423 liver disease Diseases 0.000 description 1
• 208000037841 lung tumor Diseases 0.000 description 1
• 210000004324 lymphatic system Anatomy 0.000 description 1
• 208000002780 macular degeneration Diseases 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
• 235000019341 magnesium sulphate Nutrition 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
• 239000011976 maleic acid Substances 0.000 description 1
• 239000011572 manganese Substances 0.000 description 1
• 239000011565 manganese chloride Substances 0.000 description 1
• 235000002867 manganese chloride Nutrition 0.000 description 1
• OCSMOTCMPXTDND-OUAUKWLOSA-N marimastat Chemical compound CNC(=O)[C@H](C(C)(C)C)NC(=O)[C@H](CC(C)C)[C@H](O)C(=O)NO OCSMOTCMPXTDND-OUAUKWLOSA-N 0.000 description 1
• 229950008959 marimastat Drugs 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• 229960004961 mechlorethamine Drugs 0.000 description 1
• HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical class ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 description 1
• 230000001404 mediated effect Effects 0.000 description 1
• 201000001441 melanoma Diseases 0.000 description 1
• 239000003475 metalloproteinase inhibitor Substances 0.000 description 1
• 230000009401 metastasis Effects 0.000 description 1
• 230000001394 metastastic effect Effects 0.000 description 1
• 229940098779 methanesulfonic acid Drugs 0.000 description 1
• GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
• MCVVUJPXSBQTRZ-ONEGZZNKSA-N methyl (e)-but-2-enoate Chemical compound COC(=O)\C=C\C MCVVUJPXSBQTRZ-ONEGZZNKSA-N 0.000 description 1
• QJLVOOSVISKFQY-UHFFFAOYSA-N methyl 4-(1,3-benzothiazol-2-ylamino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C1=CC=C2SC(NC3=NC=NN4C=C(C(=C43)C)C(=O)OC)=NC2=C1 QJLVOOSVISKFQY-UHFFFAOYSA-N 0.000 description 1
• ROFJWTANRAQMGO-UHFFFAOYSA-N methyl 4-(1h-indazol-6-ylamino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C1=C2C=NNC2=CC(NC2=NC=NN3C=C(C(=C32)C)C(=O)OC)=C1 ROFJWTANRAQMGO-UHFFFAOYSA-N 0.000 description 1
• AGAAWXGEIGAJBE-UHFFFAOYSA-N methyl 4-(2-oxo-1,3-dihydroindol-3-yl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound O=C1NC2=CC=CC=C2C1C1=NC=NN2C1=CC(C(=O)OC)=C2 AGAAWXGEIGAJBE-UHFFFAOYSA-N 0.000 description 1
• FFOHMEIHKYAANS-UHFFFAOYSA-N methyl 4-(2h-benzotriazol-5-ylamino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C1=C2NN=NC2=CC(NC2=NC=NN3C=C(C(=C32)C)C(=O)OC)=C1 FFOHMEIHKYAANS-UHFFFAOYSA-N 0.000 description 1
• JMSXXXONKQOXOT-UHFFFAOYSA-N methyl 4-(3,4-dimethylanilino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C)C(C(=O)OC)=CN2N=CN=C1NC1=CC=C(C)C(C)=C1 JMSXXXONKQOXOT-UHFFFAOYSA-N 0.000 description 1
• CJHLDECNXNRHRZ-UHFFFAOYSA-N methyl 4-(3-amino-4-methylanilino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C)C(C(=O)OC)=CN2N=CN=C1NC1=CC=C(C)C(N)=C1 CJHLDECNXNRHRZ-UHFFFAOYSA-N 0.000 description 1
• IYPMLBBCOSZMAE-UHFFFAOYSA-N methyl 4-(3-cyanoanilino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C)C(C(=O)OC)=CN2N=CN=C1NC1=CC=CC(C#N)=C1 IYPMLBBCOSZMAE-UHFFFAOYSA-N 0.000 description 1
• GBXXNMWVJNHKTA-UHFFFAOYSA-N methyl 4-(3-fluoro-4-methylanilino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C)C(C(=O)OC)=CN2N=CN=C1NC1=CC=C(C)C(F)=C1 GBXXNMWVJNHKTA-UHFFFAOYSA-N 0.000 description 1
• FJRJHNCPMQHVRO-UHFFFAOYSA-N methyl 4-[(1-acetyl-2,3-dihydroindol-6-yl)amino]-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C1=C2CCN(C(C)=O)C2=CC(NC2=NC=NN3C=C(C(=C32)C)C(=O)OC)=C1 FJRJHNCPMQHVRO-UHFFFAOYSA-N 0.000 description 1
• INVMEKIXYDZXNQ-UHFFFAOYSA-N methyl 4-[(3-hydroxy-4-methylphenyl)methylamino]-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C)C(C(=O)OC)=CN2N=CN=C1NCC1=CC=C(C)C(O)=C1 INVMEKIXYDZXNQ-UHFFFAOYSA-N 0.000 description 1
• KYLFAIGRMTXKCK-UHFFFAOYSA-N methyl 4-[4-(benzenesulfonamido)-3-hydroxyanilino]-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C)C(C(=O)OC)=CN2N=CN=C1NC(C=C1O)=CC=C1NS(=O)(=O)C1=CC=CC=C1 KYLFAIGRMTXKCK-UHFFFAOYSA-N 0.000 description 1
• AIMDSXKCSQCTRF-UHFFFAOYSA-N methyl 4-[5-(dimethylsulfamoyl)-2-oxo-1,3-dihydroindol-3-yl]-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound O=C1NC2=CC=C(S(=O)(=O)N(C)C)C=C2C1C1=NC=NN2C=C(C(=O)OC)C(C)=C21 AIMDSXKCSQCTRF-UHFFFAOYSA-N 0.000 description 1
• XFQMHQALFSWUAC-UHFFFAOYSA-N methyl 4-[5-(methanesulfonamido)-2-oxo-1,3-dihydroindol-3-yl]-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound O=C1NC2=CC=C(NS(C)(=O)=O)C=C2C1C1=NC=NN2C=C(C(=O)OC)C(C)=C21 XFQMHQALFSWUAC-UHFFFAOYSA-N 0.000 description 1
• CXMYWJRJTQUXQD-UHFFFAOYSA-N methyl 4-methyl-1h-pyrrole-3-carboxylate Chemical compound COC(=O)C1=CNC=C1C CXMYWJRJTQUXQD-UHFFFAOYSA-N 0.000 description 1
• ZSDGVRHWVXBRDS-UHFFFAOYSA-N methyl 5-methyl-4-(1-methyl-2-oxo-3h-indol-3-yl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound O=C1N(C)C2=CC=CC=C2C1C1=NC=NN2C=C(C(=O)OC)C(C)=C21 ZSDGVRHWVXBRDS-UHFFFAOYSA-N 0.000 description 1
• MJBVBHIMQBVWOJ-UHFFFAOYSA-N methyl 5-methyl-4-(2-oxo-1,3-dihydroindol-3-yl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound O=C1NC2=CC=CC=C2C1C1=NC=NN2C=C(C(=O)OC)C(C)=C21 MJBVBHIMQBVWOJ-UHFFFAOYSA-N 0.000 description 1
• DJKXWQNKGUHXMA-UHFFFAOYSA-N methyl 5-methyl-4-(2-oxo-3h-benzimidazol-1-yl)pyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=CC=CC=C2NC(=O)N1C1=NC=NN2C=C(C(=O)OC)C(C)=C21 DJKXWQNKGUHXMA-UHFFFAOYSA-N 0.000 description 1
• HSGHODFJKOHCLO-UHFFFAOYSA-N methyl 5-methyl-4-[(5-methyl-1h-pyrazol-3-yl)amino]pyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C)C(C(=O)OC)=CN2N=CN=C1NC=1C=C(C)NN=1 HSGHODFJKOHCLO-UHFFFAOYSA-N 0.000 description 1
• OGRZUAZSYFSVDR-UHFFFAOYSA-N methyl 5-methyl-4-[5-(2-morpholin-4-ylethylsulfamoyl)-2-oxo-1,3-dihydroindol-3-yl]pyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C12=C(C)C(C(=O)OC)=CN2N=CN=C1C(C1=C2)C(=O)NC1=CC=C2S(=O)(=O)NCCN1CCOCC1 OGRZUAZSYFSVDR-UHFFFAOYSA-N 0.000 description 1
• BHTATNLRPITTOG-UHFFFAOYSA-N methyl 5-methyl-4-[5-(methylsulfamoyl)-2-oxo-1,3-dihydroindol-3-yl]pyrrolo[2,1-f][1,2,4]triazine-6-carboxylate Chemical compound C1=NN2C=C(C(=O)OC)C(C)=C2C(C2C(=O)NC3=CC=C(C=C32)S(=O)(=O)NC)=N1 BHTATNLRPITTOG-UHFFFAOYSA-N 0.000 description 1
• BYTPHJAFXFEZLP-UHFFFAOYSA-N methyl triazine-4-carboxylate Chemical compound COC(=O)C1=CC=NN=N1 BYTPHJAFXFEZLP-UHFFFAOYSA-N 0.000 description 1
• 210000004688 microtubule Anatomy 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 238000003032 molecular docking Methods 0.000 description 1
• 238000012544 monitoring process Methods 0.000 description 1
• 125000002911 monocyclic heterocycle group Chemical group 0.000 description 1
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
• 125000002757 morpholinyl group Chemical group 0.000 description 1
• 239000012452 mother liquor Substances 0.000 description 1
• 201000006417 multiple sclerosis Diseases 0.000 description 1
• 210000002346 musculoskeletal system Anatomy 0.000 description 1
• 230000035772 mutation Effects 0.000 description 1
• 208000010125 myocardial infarction Diseases 0.000 description 1
• SBULNBMWGLBIMA-UHFFFAOYSA-N n,n-dimethyl-2-oxo-1,3-dihydroindole-5-sulfonamide Chemical compound CN(C)S(=O)(=O)C1=CC=C2NC(=O)CC2=C1 SBULNBMWGLBIMA-UHFFFAOYSA-N 0.000 description 1
• AHSIJGGJRZIVRW-UHFFFAOYSA-N n-(2-morpholin-4-ylethyl)-2-oxo-1,3-dihydroindole-5-sulfonamide Chemical compound C=1C=C2NC(=O)CC2=CC=1S(=O)(=O)NCCN1CCOCC1 AHSIJGGJRZIVRW-UHFFFAOYSA-N 0.000 description 1
• PEMGGJDINLGTON-UHFFFAOYSA-N n-(3-aminophenyl)acetamide Chemical compound CC(=O)NC1=CC=CC(N)=C1 PEMGGJDINLGTON-UHFFFAOYSA-N 0.000 description 1
• UQRRCQRFQGOHAI-UHFFFAOYSA-N n-(3-aminophenyl)methanesulfonamide Chemical compound CS(=O)(=O)NC1=CC=CC(N)=C1 UQRRCQRFQGOHAI-UHFFFAOYSA-N 0.000 description 1
• SXGURHSLXPDJBC-UHFFFAOYSA-N n-(5-aminopyridin-2-yl)acetamide Chemical compound CC(=O)NC1=CC=C(N)C=N1 SXGURHSLXPDJBC-UHFFFAOYSA-N 0.000 description 1
• XFOSBARPNHJHHD-UHFFFAOYSA-N n-methyl-2-oxo-1,3-dihydroindole-5-sulfonamide Chemical compound CNS(=O)(=O)C1=CC=C2NC(=O)CC2=C1 XFOSBARPNHJHHD-UHFFFAOYSA-N 0.000 description 1
• GYGYDOOXVKDZCF-UHFFFAOYSA-N n-methyl-2-pyrrolidin-1-ylethanamine Chemical compound CNCCN1CCCC1 GYGYDOOXVKDZCF-UHFFFAOYSA-N 0.000 description 1
• 125000001624 naphthyl group Chemical group 0.000 description 1
• 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
• 208000007538 neurilemmoma Diseases 0.000 description 1
• 201000004931 neurofibromatosis Diseases 0.000 description 1
• 150000002823 nitrates Chemical class 0.000 description 1
• 150000002825 nitriles Chemical class 0.000 description 1
• 125000004433 nitrogen atom Chemical group N* 0.000 description 1
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
• 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
• 231100000252 nontoxic Toxicity 0.000 description 1
• 230000003000 nontoxic effect Effects 0.000 description 1
• 239000010502 orange oil Substances 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 150000007530 organic bases Chemical class 0.000 description 1
• 201000008968 osteosarcoma Diseases 0.000 description 1
• 230000002018 overexpression Effects 0.000 description 1
• 125000001715 oxadiazolyl group Chemical group 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• 125000000160 oxazolidinyl group Chemical group 0.000 description 1
• 125000002971 oxazolyl group Chemical group 0.000 description 1
• 125000003566 oxetanyl 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
• 150000005623 oxindoles Chemical class 0.000 description 1
• 125000004043 oxo group Chemical group O=* 0.000 description 1
• 125000005476 oxopyrrolidinyl group Chemical group 0.000 description 1
• 239000001301 oxygen Substances 0.000 description 1
• 125000004430 oxygen atom Chemical group O* 0.000 description 1
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
• 210000000496 pancreas Anatomy 0.000 description 1
• 201000002528 pancreatic cancer Diseases 0.000 description 1
• 230000036961 partial effect Effects 0.000 description 1
• 230000001575 pathological effect Effects 0.000 description 1
• 230000035778 pathophysiological process Effects 0.000 description 1
• 210000001428 peripheral nervous system Anatomy 0.000 description 1
• ISWSIDIOOBJBQZ-UHFFFAOYSA-M phenolate Chemical compound [O-]C1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-M 0.000 description 1
• WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
• 235000021317 phosphate Nutrition 0.000 description 1
• DCWXELXMIBXGTH-QMMMGPOBSA-N phosphonotyrosine Chemical group OC(=O)[C@@H](N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-QMMMGPOBSA-N 0.000 description 1
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
• LFGREXWGYUGZLY-UHFFFAOYSA-N phosphoryl Chemical group [P]=O LFGREXWGYUGZLY-UHFFFAOYSA-N 0.000 description 1
• 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
• 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
• 238000000053 physical method Methods 0.000 description 1
• 125000004193 piperazinyl group Chemical group 0.000 description 1
• 125000003386 piperidinyl group Chemical group 0.000 description 1
• 229960005235 piperonyl butoxide Drugs 0.000 description 1
• 125000004591 piperonyl group Chemical group C(C1=CC=2OCOC2C=C1)* 0.000 description 1
• 150000003057 platinum Chemical class 0.000 description 1
• 208000015768 polyposis Diseases 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 235000015497 potassium bicarbonate Nutrition 0.000 description 1
• 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
• 239000011736 potassium bicarbonate Substances 0.000 description 1
• TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
• 239000000843 powder Substances 0.000 description 1
• 239000000583 progesterone congener Substances 0.000 description 1
• 229940095055 progestogen systemic hormonal contraceptives Drugs 0.000 description 1
• 201000008171 proliferative glomerulonephritis Diseases 0.000 description 1
• BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
• 239000003528 protein farnesyltransferase inhibitor Substances 0.000 description 1
• 208000005069 pulmonary fibrosis Diseases 0.000 description 1
• 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
• 125000003373 pyrazinyl group Chemical group 0.000 description 1
• 125000002755 pyrazolinyl group Chemical group 0.000 description 1
• 125000003226 pyrazolyl group Chemical group 0.000 description 1
• 125000002098 pyridazinyl group Chemical group 0.000 description 1
• 125000004590 pyridopyridyl group Chemical group N1=C(C=CC2=C1C=CC=N2)* 0.000 description 1
• SFUIIJZOWVIBHA-UHFFFAOYSA-N pyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid Chemical compound C1=NC=NN2C=C(C(=O)O)C=C21 SFUIIJZOWVIBHA-UHFFFAOYSA-N 0.000 description 1
• 125000006085 pyrrolopyridyl group Chemical group 0.000 description 1
• 150000003921 pyrrolotriazines Chemical class 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• 238000011002 quantification Methods 0.000 description 1
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
• 125000004620 quinolinyl-N-oxide group Chemical group 0.000 description 1
• 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
• 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
• 238000001959 radiotherapy Methods 0.000 description 1
• BMKDZUISNHGIBY-UHFFFAOYSA-N razoxane Chemical compound C1C(=O)NC(=O)CN1C(C)CN1CC(=O)NC(=O)C1 BMKDZUISNHGIBY-UHFFFAOYSA-N 0.000 description 1
• 229960000460 razoxane Drugs 0.000 description 1
• 230000000306 recurrent effect Effects 0.000 description 1
• 238000006268 reductive amination reaction Methods 0.000 description 1
• 230000002829 reductive effect Effects 0.000 description 1
• 230000001105 regulatory effect Effects 0.000 description 1
• 238000011160 research Methods 0.000 description 1
• 208000037803 restenosis Diseases 0.000 description 1
• 230000002441 reversible effect Effects 0.000 description 1
• 201000009410 rhabdomyosarcoma Diseases 0.000 description 1
• 150000003873 salicylate salts Chemical class 0.000 description 1
• 230000037390 scarring Effects 0.000 description 1
• 230000019491 signal transduction Effects 0.000 description 1
• 201000009890 sinusitis Diseases 0.000 description 1
• 239000002002 slurry Substances 0.000 description 1
• 208000000587 small cell lung carcinoma Diseases 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
• QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
• 239000012418 sodium perborate tetrahydrate Substances 0.000 description 1
• RSIJVJUOQBWMIM-UHFFFAOYSA-L sodium sulfate decahydrate Chemical compound O.O.O.O.O.O.O.O.O.O.[Na+].[Na+].[O-]S([O-])(=O)=O RSIJVJUOQBWMIM-UHFFFAOYSA-L 0.000 description 1
• IBDSNZLUHYKHQP-UHFFFAOYSA-N sodium;3-oxidodioxaborirane;tetrahydrate Chemical compound O.O.O.O.[Na+].[O-]B1OO1 IBDSNZLUHYKHQP-UHFFFAOYSA-N 0.000 description 1
• 239000012453 solvate Substances 0.000 description 1
• 238000007614 solvation Methods 0.000 description 1
• 239000011877 solvent mixture Substances 0.000 description 1
• 208000002320 spinal muscular atrophy Diseases 0.000 description 1
• 206010041823 squamous cell carcinoma Diseases 0.000 description 1
• 239000007858 starting material Substances 0.000 description 1
• 230000000638 stimulation Effects 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 150000003890 succinate salts Chemical class 0.000 description 1
• 239000011593 sulfur Substances 0.000 description 1
• 125000004434 sulfur atom Chemical group 0.000 description 1
• YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
• 238000001356 surgical procedure Methods 0.000 description 1
• 229920001059 synthetic polymer Polymers 0.000 description 1
• 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
• 239000003826 tablet Substances 0.000 description 1
• 230000008685 targeting Effects 0.000 description 1
• 150000003892 tartrate salts Chemical class 0.000 description 1
• 230000002123 temporal effect Effects 0.000 description 1
• 208000001608 teratocarcinoma Diseases 0.000 description 1
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
• 229960003604 testosterone Drugs 0.000 description 1
• 125000006092 tetrahydro-1,1-dioxothienyl group Chemical group 0.000 description 1
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
• 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
• 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
• 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
• 150000003536 tetrazoles Chemical class 0.000 description 1
• 229940124597 therapeutic agent Drugs 0.000 description 1
• 230000001225 therapeutic effect Effects 0.000 description 1
• 238000002560 therapeutic procedure Methods 0.000 description 1
• 125000001113 thiadiazolyl group Chemical group 0.000 description 1
• 125000006090 thiamorpholinyl sulfone group Chemical group 0.000 description 1
• 125000006089 thiamorpholinyl sulfoxide group Chemical group 0.000 description 1
• 125000001984 thiazolidinyl group Chemical group 0.000 description 1
• 125000004589 thienofuryl group Chemical group O1C(=CC2=C1C=CS2)* 0.000 description 1
• 125000004588 thienopyridyl group Chemical group S1C(=CC2=C1C=CC=N2)* 0.000 description 1
• 125000004587 thienothienyl group Chemical group S1C(=CC2=C1C=CS2)* 0.000 description 1
• 125000002053 thietanyl group Chemical group 0.000 description 1
• 125000001730 thiiranyl group Chemical group 0.000 description 1
• 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
• 230000007838 tissue remodeling Effects 0.000 description 1
• 229940044693 topoisomerase inhibitor Drugs 0.000 description 1
• 239000003053 toxin Substances 0.000 description 1
• 231100000765 toxin Toxicity 0.000 description 1
• 108700012359 toxins Proteins 0.000 description 1
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
• ZFDIRQKJPRINOQ-UHFFFAOYSA-N transbutenic acid ethyl ester Natural products CCOC(=O)C=CC ZFDIRQKJPRINOQ-UHFFFAOYSA-N 0.000 description 1
• 125000004306 triazinyl group Chemical group 0.000 description 1
• 125000001425 triazolyl group Chemical group 0.000 description 1
• IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
• YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
• 238000001665 trituration Methods 0.000 description 1
• 230000005747 tumor angiogenesis Effects 0.000 description 1
• 210000004881 tumor cell Anatomy 0.000 description 1
• 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
• OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
• 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 1
• 239000005483 tyrosine kinase inhibitor Substances 0.000 description 1
• 241000701161 unidentified adenovirus Species 0.000 description 1
• 241000701447 unidentified baculovirus Species 0.000 description 1
• 241001529453 unidentified herpesvirus Species 0.000 description 1
• 208000010570 urinary bladder carcinoma Diseases 0.000 description 1
• 210000002229 urogenital system Anatomy 0.000 description 1
• HGBOYTHUEUWSSQ-UHFFFAOYSA-N valeric aldehyde Natural products CCCCC=O HGBOYTHUEUWSSQ-UHFFFAOYSA-N 0.000 description 1
• 208000019553 vascular disease Diseases 0.000 description 1
• 238000007631 vascular surgery Methods 0.000 description 1
• 210000005166 vasculature Anatomy 0.000 description 1
• 230000009385 viral infection Effects 0.000 description 1
• 210000003905 vulva Anatomy 0.000 description 1