AU2005212409C1 - Pyrazolopyrimidine-derivatives as cyclin dependent kinase inhibitors - Google Patents

Info

Publication number

AU2005212409C1

AU2005212409C1 AU2005212409A AU2005212409A AU2005212409C1 AU 2005212409 C1 AU2005212409 C1 AU 2005212409C1 AU 2005212409 A AU2005212409 A AU 2005212409A AU 2005212409 A AU2005212409 A AU 2005212409A AU 2005212409 C1 AU2005212409 C1 AU 2005212409C1

Authority

AU

Australia

Prior art keywords

compound

pct

yield

mmol

lcms

Prior art date

2004-02-11

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Active

Links

• Espacenet
• Global Dossier
• Discuss

• 229940043378 cyclin-dependent kinase inhibitor Drugs 0.000 title description 8
• 239000002875 cyclin dependent kinase inhibitor Substances 0.000 title description 4
• 150000001875 compounds Chemical class 0.000 claims abstract description 429
• 238000000034 method Methods 0.000 claims abstract description 225
• 102000003903 Cyclin-dependent kinases Human genes 0.000 claims abstract description 34
• 108090000266 Cyclin-dependent kinases Proteins 0.000 claims abstract description 34
• 238000011282 treatment Methods 0.000 claims abstract description 27
• 108091007914 CDKs Proteins 0.000 claims abstract description 25
• 201000010099 disease Diseases 0.000 claims abstract description 23
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 23
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 14
• 230000005764 inhibitory process Effects 0.000 claims abstract description 5
• 229910052757 nitrogen Inorganic materials 0.000 claims description 112
• 150000003839 salts Chemical class 0.000 claims description 75
• -1 camptostar Chemical compound 0.000 claims description 63
• 239000012453 solvate Substances 0.000 claims description 58
• 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 30
• 206010028980 Neoplasm Diseases 0.000 claims description 21
• 108010024986 Cyclin-Dependent Kinase 2 Proteins 0.000 claims description 18
• 239000003814 drug Substances 0.000 claims description 16
• 239000002246 antineoplastic agent Substances 0.000 claims description 14
• 210000004027 cell Anatomy 0.000 claims description 14
• 230000002401 inhibitory effect Effects 0.000 claims description 14
• 201000011510 cancer Diseases 0.000 claims description 12
• 102000043136 MAP kinase family Human genes 0.000 claims description 11
• 108091054455 MAP kinase family Proteins 0.000 claims description 11
• CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 10
• 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 10
• 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 10
• 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 10
• 229930012538 Paclitaxel Natural products 0.000 claims description 10
• 108091000080 Phosphotransferase Proteins 0.000 claims description 10
• 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 10
• 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 claims description 10
• 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 10
• DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims description 10
• 229960004316 cisplatin Drugs 0.000 claims description 10
• 229960004679 doxorubicin Drugs 0.000 claims description 10
• GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 claims description 10
• 229960001592 paclitaxel Drugs 0.000 claims description 10
• FPVKHBSQESCIEP-JQCXWYLXSA-N pentostatin Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CNC[C@H]2O)=C2N=C1 FPVKHBSQESCIEP-JQCXWYLXSA-N 0.000 claims description 10
• 102000020233 phosphotransferase Human genes 0.000 claims description 10
• 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 10
• WYWHKKSPHMUBEB-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 claims description 10
• 101150073133 Cpt1a gene Proteins 0.000 claims description 9
• GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 9
• 238000004519 manufacturing process Methods 0.000 claims description 8
• 206010025323 Lymphomas Diseases 0.000 claims description 7
• HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical compound ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 claims description 7
• 230000001225 therapeutic effect Effects 0.000 claims description 7
• 208000024893 Acute lymphoblastic leukemia Diseases 0.000 claims description 6
• 208000014697 Acute lymphocytic leukaemia Diseases 0.000 claims description 6
• 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 claims description 6
• BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 claims description 6
• 239000000824 cytostatic agent Substances 0.000 claims description 6
• 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 claims description 6
• 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 claims description 6
• 210000001685 thyroid gland Anatomy 0.000 claims description 6
• FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 claims description 5
• 102100025573 1-alkyl-2-acetylglycerophosphocholine esterase Human genes 0.000 claims description 5
• VSNHCAURESNICA-NJFSPNSNSA-N 1-oxidanylurea Chemical compound N[14C](=O)NO VSNHCAURESNICA-NJFSPNSNSA-N 0.000 claims description 5
• GCKMFJBGXUYNAG-UHFFFAOYSA-N 17alpha-methyltestosterone Natural products C1CC2=CC(=O)CCC2(C)C2C1C1CCC(C)(O)C1(C)CC2 GCKMFJBGXUYNAG-UHFFFAOYSA-N 0.000 claims description 5
• DBPWSSGDRRHUNT-CEGNMAFCSA-N 17α-hydroxyprogesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)C)(O)[C@@]1(C)CC2 DBPWSSGDRRHUNT-CEGNMAFCSA-N 0.000 claims description 5
• NDMPLJNOPCLANR-UHFFFAOYSA-N 3,4-dihydroxy-15-(4-hydroxy-18-methoxycarbonyl-5,18-seco-ibogamin-18-yl)-16-methoxy-1-methyl-6,7-didehydro-aspidospermidine-3-carboxylic acid methyl ester Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 NDMPLJNOPCLANR-UHFFFAOYSA-N 0.000 claims description 5
• 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 claims description 5
• IDPUKCWIGUEADI-UHFFFAOYSA-N 5-[bis(2-chloroethyl)amino]uracil Chemical compound ClCCN(CCCl)C1=CNC(=O)NC1=O IDPUKCWIGUEADI-UHFFFAOYSA-N 0.000 claims description 5
• 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 5
• 108010024976 Asparaginase Proteins 0.000 claims description 5
• OLCWFLWEHWLBTO-HSZRJFAPSA-N BMS-214662 Chemical compound C=1C=CSC=1S(=O)(=O)N([C@@H](C1)CC=2C=CC=CC=2)CC2=CC(C#N)=CC=C2N1CC1=CN=CN1 OLCWFLWEHWLBTO-HSZRJFAPSA-N 0.000 claims description 5
• 108010006654 Bleomycin Proteins 0.000 claims description 5
• COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 claims description 5
• GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 claims description 5
• GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 claims description 5
• DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 claims description 5
• JWBOIMRXGHLCPP-UHFFFAOYSA-N Chloditan Chemical compound C=1C=CC=C(Cl)C=1C(C(Cl)Cl)C1=CC=C(Cl)C=C1 JWBOIMRXGHLCPP-UHFFFAOYSA-N 0.000 claims description 5
• 108010092160 Dactinomycin Proteins 0.000 claims description 5
• 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 claims description 5
• 102000019058 Glycogen Synthase Kinase 3 beta Human genes 0.000 claims description 5
• 108010051975 Glycogen Synthase Kinase 3 beta Proteins 0.000 claims description 5
• BLCLNMBMMGCOAS-URPVMXJPSA-N Goserelin Chemical compound C([C@@H](C(=O)N[C@H](COC(C)(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1[C@@H](CCC1)C(=O)NNC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 BLCLNMBMMGCOAS-URPVMXJPSA-N 0.000 claims description 5
• 108010069236 Goserelin Proteins 0.000 claims description 5
• 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 5
• 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 5
• FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 claims description 5
• 239000005411 L01XE02 - Gefitinib Substances 0.000 claims description 5
• 239000005551 L01XE03 - Erlotinib Substances 0.000 claims description 5
• 108010000817 Leuprolide Proteins 0.000 claims description 5
• HLFSDGLLUJUHTE-SNVBAGLBSA-N Levamisole Chemical compound C1([C@H]2CN3CCSC3=N2)=CC=CC=C1 HLFSDGLLUJUHTE-SNVBAGLBSA-N 0.000 claims description 5
• GQYIWUVLTXOXAJ-UHFFFAOYSA-N Lomustine Chemical compound ClCCN(N=O)C(=O)NC1CCCCC1 GQYIWUVLTXOXAJ-UHFFFAOYSA-N 0.000 claims description 5
• 241000124008 Mammalia Species 0.000 claims description 5
• FQISKWAFAHGMGT-SGJOWKDISA-M Methylprednisolone sodium succinate Chemical compound [Na+].C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2[C@@H](O)C[C@]2(C)[C@@](O)(C(=O)COC(=O)CCC([O-])=O)CC[C@H]21 FQISKWAFAHGMGT-SGJOWKDISA-M 0.000 claims description 5
• GCKMFJBGXUYNAG-HLXURNFRSA-N Methyltestosterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@](C)(O)[C@@]1(C)CC2 GCKMFJBGXUYNAG-HLXURNFRSA-N 0.000 claims description 5
• JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 claims description 5
• 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 5
• 229940009456 adriamycin Drugs 0.000 claims description 5
• 229960000473 altretamine Drugs 0.000 claims description 5
• ROBVIMPUHSLWNV-UHFFFAOYSA-N aminoglutethimide Chemical compound C=1C=C(N)C=CC=1C1(CC)CCC(=O)NC1=O ROBVIMPUHSLWNV-UHFFFAOYSA-N 0.000 claims description 5
• 229960003437 aminoglutethimide Drugs 0.000 claims description 5
• 229960001220 amsacrine Drugs 0.000 claims description 5
• 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 5
• 229960002932 anastrozole Drugs 0.000 claims description 5
• 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 5
• 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 claims description 5
• 229960001561 bleomycin Drugs 0.000 claims description 5
• OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 claims description 5
• 229960002092 busulfan Drugs 0.000 claims description 5
• 229960004117 capecitabine Drugs 0.000 claims description 5
• 229960004562 carboplatin Drugs 0.000 claims description 5
• 229960005243 carmustine Drugs 0.000 claims description 5
• 229960004630 chlorambucil Drugs 0.000 claims description 5
• JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 claims description 5
• BFPSDSIWYFKGBC-UHFFFAOYSA-N chlorotrianisene Chemical compound C1=CC(OC)=CC=C1C(Cl)=C(C=1C=CC(OC)=CC=1)C1=CC=C(OC)C=C1 BFPSDSIWYFKGBC-UHFFFAOYSA-N 0.000 claims description 5
• 229960002559 chlorotrianisene Drugs 0.000 claims description 5
• 229960004397 cyclophosphamide Drugs 0.000 claims description 5
• 229960000684 cytarabine Drugs 0.000 claims description 5
• 229960003901 dacarbazine Drugs 0.000 claims description 5
• 229960000640 dactinomycin Drugs 0.000 claims description 5
• 229960000975 daunorubicin Drugs 0.000 claims description 5
• 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 5
• 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 claims description 5
• RGLYKWWBQGJZGM-ISLYRVAYSA-N diethylstilbestrol Chemical compound C=1C=C(O)C=CC=1C(/CC)=C(\CC)C1=CC=C(O)C=C1 RGLYKWWBQGJZGM-ISLYRVAYSA-N 0.000 claims description 5
• 229960000452 diethylstilbestrol Drugs 0.000 claims description 5
• 229960003668 docetaxel Drugs 0.000 claims description 5
• NOTIQUSPUUHHEH-UXOVVSIBSA-N dromostanolone propionate Chemical compound C([C@@H]1CC2)C(=O)[C@H](C)C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](OC(=O)CC)[C@@]2(C)CC1 NOTIQUSPUUHHEH-UXOVVSIBSA-N 0.000 claims description 5
• 229950004683 drostanolone propionate Drugs 0.000 claims description 5
• 239000003937 drug carrier Substances 0.000 claims description 5
• 229960001904 epirubicin Drugs 0.000 claims description 5
• 229930013356 epothilone Natural products 0.000 claims description 5
• HESCAJZNRMSMJG-KKQRBIROSA-N epothilone A Chemical class C/C([C@@H]1C[C@@H]2O[C@@H]2CCC[C@@H]([C@@H]([C@@H](C)C(=O)C(C)(C)[C@@H](O)CC(=O)O1)O)C)=C\C1=CSC(C)=N1 HESCAJZNRMSMJG-KKQRBIROSA-N 0.000 claims description 5
• AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 claims description 5
• 229960001842 estramustine Drugs 0.000 claims description 5
• FRPJXPJMRWBBIH-RBRWEJTLSA-N estramustine Chemical compound ClCCN(CCCl)C(=O)OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 FRPJXPJMRWBBIH-RBRWEJTLSA-N 0.000 claims description 5
• 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 5
• 229960005420 etoposide Drugs 0.000 claims description 5
• ODKNJVUHOIMIIZ-RRKCRQDMSA-N floxuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 ODKNJVUHOIMIIZ-RRKCRQDMSA-N 0.000 claims description 5
• 229960000961 floxuridine Drugs 0.000 claims description 5
• GIUYCYHIANZCFB-FJFJXFQQSA-N fludarabine phosphate Chemical compound C1=NC=2C(N)=NC(F)=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@@H]1O GIUYCYHIANZCFB-FJFJXFQQSA-N 0.000 claims description 5
• 229960005304 fludarabine phosphate Drugs 0.000 claims description 5
• 229960002949 fluorouracil Drugs 0.000 claims description 5
• YLRFCQOZQXIBAB-RBZZARIASA-N fluoxymesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1CC[C@](C)(O)[C@@]1(C)C[C@@H]2O YLRFCQOZQXIBAB-RBZZARIASA-N 0.000 claims description 5
• 229960001751 fluoxymesterone Drugs 0.000 claims description 5
• 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 5
• 229960002074 flutamide Drugs 0.000 claims description 5
• XGALLCVXEZPNRQ-UHFFFAOYSA-N gefitinib Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 claims description 5
• 229960005277 gemcitabine Drugs 0.000 claims description 5
• SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 claims description 5
• 229960002913 goserelin Drugs 0.000 claims description 5
• UUVWYPNAQBNQJQ-UHFFFAOYSA-N hexamethylmelamine Chemical compound CN(C)C1=NC(N(C)C)=NC(N(C)C)=N1 UUVWYPNAQBNQJQ-UHFFFAOYSA-N 0.000 claims description 5
• 229960002899 hydroxyprogesterone Drugs 0.000 claims description 5
• 229960000908 idarubicin Drugs 0.000 claims description 5
• HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 claims description 5
• 229960001101 ifosfamide Drugs 0.000 claims description 5
• 229940084651 iressa Drugs 0.000 claims description 5
• 229960004768 irinotecan Drugs 0.000 claims description 5
• 229960003881 letrozole Drugs 0.000 claims description 5
• 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 5
• GFIJNRVAKGFPGQ-LIJARHBVSA-N leuprolide Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 GFIJNRVAKGFPGQ-LIJARHBVSA-N 0.000 claims description 5
• 229960004338 leuprorelin Drugs 0.000 claims description 5
• 229960001614 levamisole Drugs 0.000 claims description 5
• 229960002247 lomustine Drugs 0.000 claims description 5
• DHMTURDWPRKSOA-RUZDIDTESA-N lonafarnib Chemical compound C1CN(C(=O)N)CCC1CC(=O)N1CCC([C@@H]2C3=C(Br)C=C(Cl)C=C3CCC3=CC(Br)=CN=C32)CC1 DHMTURDWPRKSOA-RUZDIDTESA-N 0.000 claims description 5
• 229960004961 mechlorethamine Drugs 0.000 claims description 5
• PSGAAPLEWMOORI-PEINSRQWSA-N medroxyprogesterone acetate Chemical compound C([C@@]12C)CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2CC[C@]2(C)[C@@](OC(C)=O)(C(C)=O)CC[C@H]21 PSGAAPLEWMOORI-PEINSRQWSA-N 0.000 claims description 5
• 229960002985 medroxyprogesterone acetate Drugs 0.000 claims description 5
• 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 5
• 229960004296 megestrol acetate Drugs 0.000 claims description 5
• 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 5
• 229960001924 melphalan Drugs 0.000 claims description 5
• 229960001428 mercaptopurine Drugs 0.000 claims description 5
• 229960000485 methotrexate Drugs 0.000 claims description 5
• 229960004584 methylprednisolone Drugs 0.000 claims description 5
• 229960001566 methyltestosterone Drugs 0.000 claims description 5
• 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 5
• 229960004857 mitomycin Drugs 0.000 claims description 5
• 229960000350 mitotane Drugs 0.000 claims description 5
• KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 claims description 5
• 229960001156 mitoxantrone Drugs 0.000 claims description 5
• YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 claims description 5
• 229960002340 pentostatin Drugs 0.000 claims description 5
• 229960000952 pipobroman Drugs 0.000 claims description 5
• NJBFOOCLYDNZJN-UHFFFAOYSA-N pipobroman Chemical compound BrCCC(=O)N1CCN(C(=O)CCBr)CC1 NJBFOOCLYDNZJN-UHFFFAOYSA-N 0.000 claims description 5
• 229960003171 plicamycin Drugs 0.000 claims description 5
• OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 claims description 5
• 229960005205 prednisolone Drugs 0.000 claims description 5
• XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 claims description 5
• 229960004618 prednisone Drugs 0.000 claims description 5
• 229960000624 procarbazine Drugs 0.000 claims description 5
• CPTBDICYNRMXFX-UHFFFAOYSA-N procarbazine Chemical compound CNNCC1=CC=C(C(=O)NC(C)C)C=C1 CPTBDICYNRMXFX-UHFFFAOYSA-N 0.000 claims description 5
• 229960001052 streptozocin Drugs 0.000 claims description 5
• ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 claims description 5
• 229960001603 tamoxifen Drugs 0.000 claims description 5
• 229940120982 tarceva Drugs 0.000 claims description 5
• 229940063683 taxotere Drugs 0.000 claims description 5
• 229960004964 temozolomide Drugs 0.000 claims description 5
• 229960001278 teniposide Drugs 0.000 claims description 5
• 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 5
• BPEWUONYVDABNZ-DZBHQSCQSA-N testolactone Chemical compound O=C1C=C[C@]2(C)[C@H]3CC[C@](C)(OC(=O)CC4)[C@@H]4[C@@H]3CCC2=C1 BPEWUONYVDABNZ-DZBHQSCQSA-N 0.000 claims description 5
• 229960005353 testolactone Drugs 0.000 claims description 5
• 229960003604 testosterone Drugs 0.000 claims description 5
• 229960003087 tioguanine Drugs 0.000 claims description 5
• 229960000303 topotecan Drugs 0.000 claims description 5
• 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 5
• 229960005026 toremifene Drugs 0.000 claims description 5
• 229950001353 tretamine Drugs 0.000 claims description 5
• IUCJMVBFZDHPDX-UHFFFAOYSA-N tretamine Chemical compound C1CN1C1=NC(N2CC2)=NC(N2CC2)=N1 IUCJMVBFZDHPDX-UHFFFAOYSA-N 0.000 claims description 5
• GFNANZIMVAIWHM-OBYCQNJPSA-N triamcinolone Chemical compound O=C1C=C[C@]2(C)[C@@]3(F)[C@@H](O)C[C@](C)([C@@]([C@H](O)C4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 GFNANZIMVAIWHM-OBYCQNJPSA-N 0.000 claims description 5
• 229960005294 triamcinolone Drugs 0.000 claims description 5
• 229960001055 uracil mustard Drugs 0.000 claims description 5
• 229960003048 vinblastine Drugs 0.000 claims description 5
• JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 claims description 5
• 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 5
• 229960004528 vincristine Drugs 0.000 claims description 5
• 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 5
• UGGWPQSBPIFKDZ-KOTLKJBCSA-N vindesine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(N)=O)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1N=C1[C]2C=CC=C1 UGGWPQSBPIFKDZ-KOTLKJBCSA-N 0.000 claims description 5
• 229960004355 vindesine Drugs 0.000 claims description 5
• BFPYWIDHMRZLRN-SLHNCBLASA-N Ethinyl estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 BFPYWIDHMRZLRN-SLHNCBLASA-N 0.000 claims description 4
• 239000005517 L01XE01 - Imatinib Substances 0.000 claims description 4
• 201000003793 Myelodysplastic syndrome Diseases 0.000 claims description 4
• 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims description 4
• 210000000481 breast Anatomy 0.000 claims description 4
• 210000001072 colon Anatomy 0.000 claims description 4
• 229940080856 gleevec Drugs 0.000 claims description 4
• 210000003734 kidney Anatomy 0.000 claims description 4
• 208000032839 leukemia Diseases 0.000 claims description 4
• 210000004072 lung Anatomy 0.000 claims description 4
• DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 claims description 4
• 229960001756 oxaliplatin Drugs 0.000 claims description 4
• 210000002307 prostate Anatomy 0.000 claims description 4
• PLHJCIYEEKOWNM-HHHXNRCGSA-N tipifarnib Chemical compound CN1C=NC=C1[C@](N)(C=1C=C2C(C=3C=C(Cl)C=CC=3)=CC(=O)N(C)C2=CC=1)C1=CC=C(Cl)C=C1 PLHJCIYEEKOWNM-HHHXNRCGSA-N 0.000 claims description 4
• 208000031261 Acute myeloid leukaemia Diseases 0.000 claims description 3
• 206010003571 Astrocytoma Diseases 0.000 claims description 3
• 208000003950 B-cell lymphoma Diseases 0.000 claims description 3
• 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 claims description 3
• 201000008808 Fibrosarcoma Diseases 0.000 claims description 3
• 208000032612 Glial tumor Diseases 0.000 claims description 3
• 206010018338 Glioma Diseases 0.000 claims description 3
• 208000017604 Hodgkin disease Diseases 0.000 claims description 3
• 208000021519 Hodgkin lymphoma Diseases 0.000 claims description 3
• 208000010747 Hodgkins lymphoma Diseases 0.000 claims description 3
• 208000007766 Kaposi sarcoma Diseases 0.000 claims description 3
• 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 claims description 3
• 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims description 3
• 206010029260 Neuroblastoma Diseases 0.000 claims description 3
• 201000010208 Seminoma Diseases 0.000 claims description 3
• 206010041067 Small cell lung cancer Diseases 0.000 claims description 3
• 230000001154 acute effect Effects 0.000 claims description 3
• 210000003679 cervix uteri Anatomy 0.000 claims description 3
• 210000003238 esophagus Anatomy 0.000 claims description 3
• 230000003325 follicular Effects 0.000 claims description 3
• 210000000232 gallbladder Anatomy 0.000 claims description 3
• 210000004185 liver Anatomy 0.000 claims description 3
• 201000001441 melanoma Diseases 0.000 claims description 3
• 208000007538 neurilemmoma Diseases 0.000 claims description 3
• 201000008968 osteosarcoma Diseases 0.000 claims description 3
• 210000001672 ovary Anatomy 0.000 claims description 3
• 210000000496 pancreas Anatomy 0.000 claims description 3
• 238000001959 radiotherapy Methods 0.000 claims description 3
• 201000009410 rhabdomyosarcoma Diseases 0.000 claims description 3
• 208000000587 small cell lung carcinoma Diseases 0.000 claims description 3
• 206010041823 squamous cell carcinoma Diseases 0.000 claims description 3
• 210000002784 stomach Anatomy 0.000 claims description 3
• 208000001608 teratocarcinoma Diseases 0.000 claims description 3
• 208000036762 Acute promyelocytic leukaemia Diseases 0.000 claims description 2
• 208000010833 Chronic myeloid leukaemia Diseases 0.000 claims description 2
• 229920002527 Glycogen Polymers 0.000 claims description 2
• 206010042971 T-cell lymphoma Diseases 0.000 claims description 2
• 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 claims description 2
• 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 2
• 229940125773 compound 10 Drugs 0.000 claims description 2
• 229940125758 compound 15 Drugs 0.000 claims description 2
• 229940120655 eloxatin Drugs 0.000 claims description 2
• 229940096919 glycogen Drugs 0.000 claims description 2
• ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 claims description 2
• KTUFNOKKBVMGRW-UHFFFAOYSA-N imatinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 claims 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 2
• UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 claims 2
• GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 claims 1
• 102000015792 Cyclin-Dependent Kinase 2 Human genes 0.000 claims 1
• 239000003112 inhibitor Substances 0.000 abstract description 16
• 230000002265 prevention Effects 0.000 abstract description 5
• LDIJKUBTLZTFRG-UHFFFAOYSA-N pyrazolo[1,5-a]pyrimidine Chemical class N1=CC=CN2N=CC=C21 LDIJKUBTLZTFRG-UHFFFAOYSA-N 0.000 abstract description 4
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical class OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 467
• 239000000047 product Substances 0.000 description 388
• 239000000460 chlorine Substances 0.000 description 331
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 215
• 239000000243 solution Substances 0.000 description 209
• 239000000203 mixture Substances 0.000 description 198
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 195
• 238000005481 NMR spectroscopy Methods 0.000 description 141
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 134
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 113
• 239000007787 solid Substances 0.000 description 94
• 229910052739 hydrogen Inorganic materials 0.000 description 83
• 230000002829 reductive effect Effects 0.000 description 81
• 239000011734 sodium Substances 0.000 description 76
• 125000000217 alkyl group Chemical group 0.000 description 70
• 239000011541 reaction mixture Substances 0.000 description 67
• 235000019439 ethyl acetate Nutrition 0.000 description 62
• 239000012044 organic layer Substances 0.000 description 54
• 239000003480 eluent Substances 0.000 description 53
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 51
• 239000012043 crude product Substances 0.000 description 50
• 238000006243 chemical reaction Methods 0.000 description 49
• 125000003118 aryl group Chemical group 0.000 description 47
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 45
• 239000010410 layer Substances 0.000 description 45
• 239000002904 solvent Substances 0.000 description 45
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 44
• 238000003818 flash chromatography Methods 0.000 description 44
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 44
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 43
• 238000002000 high resolution fast-atom bombardment mass spectrometry Methods 0.000 description 43
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 42
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical class CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 39
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 39
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 38
• 150000001412 amines Chemical class 0.000 description 37
• 239000011347 resin Substances 0.000 description 37
• 229920005989 resin Polymers 0.000 description 37
• 125000001072 heteroaryl group Chemical group 0.000 description 34
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 32
• 201000007224 Myeloproliferative neoplasm Diseases 0.000 description 31
• 125000000753 cycloalkyl group Chemical group 0.000 description 31
• 125000000623 heterocyclic group Chemical group 0.000 description 31
• 229910052740 iodine Inorganic materials 0.000 description 26
• 238000010992 reflux Methods 0.000 description 25
• 229920006395 saturated elastomer Polymers 0.000 description 25
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 24
• 229910052794 bromium Inorganic materials 0.000 description 24
• 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 24
• 238000012746 preparative thin layer chromatography Methods 0.000 description 24
• 239000000741 silica gel Substances 0.000 description 24
• 229910002027 silica gel Inorganic materials 0.000 description 24
• 229960001866 silicon dioxide Drugs 0.000 description 24
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 24
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 23
• 239000012267 brine Substances 0.000 description 23
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 23
• 125000003710 aryl alkyl group Chemical group 0.000 description 22
• 230000000704 physical effect Effects 0.000 description 22
• 239000000706 filtrate Substances 0.000 description 19
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 19
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 18
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 17
• 102100036239 Cyclin-dependent kinase 2 Human genes 0.000 description 17
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 17
• 125000000304 alkynyl group Chemical group 0.000 description 17
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 16
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 16
• 239000000908 ammonium hydroxide Substances 0.000 description 16
• 230000015572 biosynthetic process Effects 0.000 description 15
• 229910052736 halogen Inorganic materials 0.000 description 15
• 150000002367 halogens Chemical class 0.000 description 15
• 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 14
• 125000004432 carbon atom Chemical group C* 0.000 description 14
• 239000003921 oil Substances 0.000 description 14
• 235000019198 oils Nutrition 0.000 description 14
• 238000000746 purification Methods 0.000 description 14
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 12
• 238000003786 synthesis reaction Methods 0.000 description 12
• 238000004809 thin layer chromatography Methods 0.000 description 12
• 239000002253 acid Substances 0.000 description 11
• 229910052799 carbon Inorganic materials 0.000 description 11
• 125000004446 heteroarylalkyl group Chemical group 0.000 description 11
• 125000004415 heterocyclylalkyl group Chemical group 0.000 description 11
• 229910052760 oxygen Inorganic materials 0.000 description 11
• 238000003756 stirring Methods 0.000 description 11
• 229910052717 sulfur Inorganic materials 0.000 description 11
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
• 239000004743 Polypropylene Substances 0.000 description 10
• 150000001805 chlorine compounds Chemical class 0.000 description 10
• 239000013058 crude material Substances 0.000 description 10
• 125000004122 cyclic group Chemical group 0.000 description 10
• 229910052731 fluorine Inorganic materials 0.000 description 10
• 239000012458 free base Substances 0.000 description 10
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
• 229920001155 polypropylene Polymers 0.000 description 10
• 229940002612 prodrug Drugs 0.000 description 10
• 239000000651 prodrug Substances 0.000 description 10
• 239000000725 suspension Substances 0.000 description 10
• 238000005160 1H NMR spectroscopy Methods 0.000 description 9
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
• 239000001301 oxygen Substances 0.000 description 9
• 238000002360 preparation method Methods 0.000 description 9
• 239000000376 reactant Substances 0.000 description 9
• 125000006413 ring segment Chemical group 0.000 description 9
• MZSREVLQRIKFFY-UHFFFAOYSA-N 3-bromo-7-chloro-5-(2-chlorophenyl)pyrazolo[1,5-a]pyrimidine Chemical compound ClC1=CC=CC=C1C1=NC2=C(Br)C=NN2C(Cl)=C1 MZSREVLQRIKFFY-UHFFFAOYSA-N 0.000 description 8
• NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 8
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 8
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 8
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
• RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 8
• 125000001424 substituent group Chemical group 0.000 description 8
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 7
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 7
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 7
• 125000000066 S-methyl group Chemical group [H]C([H])([H])S* 0.000 description 7
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
• 125000002768 hydroxyalkyl group Chemical group 0.000 description 7
• NIZHERJWXFHGGU-UHFFFAOYSA-N isocyanato(trimethyl)silane Chemical compound C[Si](C)(C)N=C=O NIZHERJWXFHGGU-UHFFFAOYSA-N 0.000 description 7
• 239000007788 liquid Substances 0.000 description 7
• ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 7
• 239000000463 material Substances 0.000 description 7
• GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 description 6
• KCALNMIVFNPSCQ-UHFFFAOYSA-N 3-(2-aminoethyl)piperidine-1-carboxamide Chemical compound NCCC1CCCN(C(N)=O)C1 KCALNMIVFNPSCQ-UHFFFAOYSA-N 0.000 description 6
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 6
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 6
• 101150065749 Churc1 gene Proteins 0.000 description 6
• 102000004190 Enzymes Human genes 0.000 description 6
• 108090000790 Enzymes Proteins 0.000 description 6
• 102100038239 Protein Churchill Human genes 0.000 description 6
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 6
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
• 125000005038 alkynylalkyl group Chemical group 0.000 description 6
• 238000003556 assay Methods 0.000 description 6
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 6
• 230000000694 effects Effects 0.000 description 6
• 229940088598 enzyme Drugs 0.000 description 6
• 239000012948 isocyanate Substances 0.000 description 6
• HSZCZNFXUDYRKD-UHFFFAOYSA-M lithium iodide Chemical compound [Li+].[I-] HSZCZNFXUDYRKD-UHFFFAOYSA-M 0.000 description 6
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 6
• 235000019341 magnesium sulphate Nutrition 0.000 description 6
• 239000012074 organic phase Substances 0.000 description 6
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
• 235000017557 sodium bicarbonate Nutrition 0.000 description 6
• 239000011593 sulfur Substances 0.000 description 6
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 6
• JVVRJMXHNUAPHW-UHFFFAOYSA-N 1h-pyrazol-5-amine Chemical class NC=1C=CNN=1 JVVRJMXHNUAPHW-UHFFFAOYSA-N 0.000 description 5
• SBKQYEDAEHMIOI-UHFFFAOYSA-N 3-(aminomethyl)piperidine-1-carboxamide Chemical compound NCC1CCCN(C(N)=O)C1 SBKQYEDAEHMIOI-UHFFFAOYSA-N 0.000 description 5
• UPHKMPGSQIOAPM-UHFFFAOYSA-N 3-bromo-7-chloro-5-phenylpyrazolo[1,5-a]pyrimidine Chemical compound N=1C2=C(Br)C=NN2C(Cl)=CC=1C1=CC=CC=C1 UPHKMPGSQIOAPM-UHFFFAOYSA-N 0.000 description 5
• 229910014265 BrCl Inorganic materials 0.000 description 5
• 229910020314 ClBr Inorganic materials 0.000 description 5
• 102000003909 Cyclin E Human genes 0.000 description 5
• 108090000257 Cyclin E Proteins 0.000 description 5
• 102100038353 Gremlin-2 Human genes 0.000 description 5
• 101001032861 Homo sapiens Gremlin-2 Proteins 0.000 description 5
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
• 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 5
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 5
• 125000003342 alkenyl group Chemical group 0.000 description 5
• 125000003545 alkoxy group Chemical group 0.000 description 5
• 125000002877 alkyl aryl group Chemical group 0.000 description 5
• 229910052786 argon Inorganic materials 0.000 description 5
• 206010003246 arthritis Diseases 0.000 description 5
• 239000011324 bead Substances 0.000 description 5
• CODNYICXDISAEA-UHFFFAOYSA-N bromine monochloride Chemical compound BrCl CODNYICXDISAEA-UHFFFAOYSA-N 0.000 description 5
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 5
• 239000003795 chemical substances by application Substances 0.000 description 5
• 238000004587 chromatography analysis Methods 0.000 description 5
• 238000009833 condensation Methods 0.000 description 5
• 230000005494 condensation Effects 0.000 description 5
• 239000000284 extract Substances 0.000 description 5
• XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 5
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
• NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 5
• 208000015122 neurodegenerative disease Diseases 0.000 description 5
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 5
• 239000002244 precipitate Substances 0.000 description 5
• UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical class OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 5
• 239000000377 silicon dioxide Substances 0.000 description 5
• 238000006467 substitution reaction Methods 0.000 description 5
• 229960000281 trometamol Drugs 0.000 description 5
• KEDTYNCWGSIWBK-UHFFFAOYSA-N (1-methylpiperidin-3-yl)methanamine Chemical compound CN1CCCC(CN)C1 KEDTYNCWGSIWBK-UHFFFAOYSA-N 0.000 description 4
• AGTPSAZJSOQXHJ-UHFFFAOYSA-N (1-methylpiperidin-4-yl)methanamine Chemical compound CN1CCC(CN)CC1 AGTPSAZJSOQXHJ-UHFFFAOYSA-N 0.000 description 4
• LFIWXXXFJFOECP-UHFFFAOYSA-N 4-(aminomethyl)benzonitrile Chemical compound NCC1=CC=C(C#N)C=C1 LFIWXXXFJFOECP-UHFFFAOYSA-N 0.000 description 4
• ZKHQWZAMYRWXGA-KQYNXXCUSA-N Adenosine triphosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-N 0.000 description 4
• ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 4
• 208000024827 Alzheimer disease Diseases 0.000 description 4
• 101150041968 CDC13 gene Proteins 0.000 description 4
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
• 208000031888 Mycoses Diseases 0.000 description 4
• JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 4
• PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
• 102000001253 Protein Kinase Human genes 0.000 description 4
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
• 125000002252 acyl group Chemical group 0.000 description 4
• 229960001456 adenosine triphosphate Drugs 0.000 description 4
• 125000004453 alkoxycarbonyl group Chemical group 0.000 description 4
• 125000004414 alkyl thio group Chemical group 0.000 description 4
• 150000001408 amides Chemical class 0.000 description 4
• 230000001093 anti-cancer Effects 0.000 description 4
• 229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 description 4
• 125000004429 atom Chemical group 0.000 description 4
• WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 4
• 229910052796 boron Inorganic materials 0.000 description 4
• 239000000872 buffer Substances 0.000 description 4
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 4
• 239000003153 chemical reaction reagent Substances 0.000 description 4
• 229910052801 chlorine Inorganic materials 0.000 description 4
• 229940127089 cytotoxic agent Drugs 0.000 description 4
• 239000002254 cytotoxic agent Substances 0.000 description 4
• 231100000599 cytotoxic agent Toxicity 0.000 description 4
• 239000000839 emulsion Substances 0.000 description 4
• 125000005842 heteroatom Chemical group 0.000 description 4
• 125000004435 hydrogen atom Chemical class [H]* 0.000 description 4
• 150000002513 isocyanates Chemical class 0.000 description 4
• 150000002576 ketones Chemical class 0.000 description 4
• 239000002480 mineral oil Substances 0.000 description 4
• 235000010446 mineral oil Nutrition 0.000 description 4
• 230000000144 pharmacologic effect Effects 0.000 description 4
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
• 239000000843 powder Substances 0.000 description 4
• 108060006633 protein kinase Proteins 0.000 description 4
• 239000003909 protein kinase inhibitor Substances 0.000 description 4
• 102000004169 proteins and genes Human genes 0.000 description 4
• 108090000623 proteins and genes Proteins 0.000 description 4
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
• 125000004076 pyridyl group Chemical group 0.000 description 4
• 239000002002 slurry Substances 0.000 description 4
• 229910052708 sodium Inorganic materials 0.000 description 4
• 125000004434 sulfur atom Chemical group 0.000 description 4
• 239000003039 volatile agent Substances 0.000 description 4
• BTVJTKWOCSGJDQ-UHFFFAOYSA-N 1-methylpiperidine-4-carboxamide Chemical compound CN1CCC(C(N)=O)CC1 BTVJTKWOCSGJDQ-UHFFFAOYSA-N 0.000 description 3
• DGHHQBMTXTWTJV-BQAIUKQQSA-N 119413-54-6 Chemical compound Cl.C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 DGHHQBMTXTWTJV-BQAIUKQQSA-N 0.000 description 3
• XFKPORAVEUOIRF-UHFFFAOYSA-N 3-(aminomethyl)benzonitrile Chemical compound NCC1=CC=CC(C#N)=C1 XFKPORAVEUOIRF-UHFFFAOYSA-N 0.000 description 3
• VZYZKPJAXWDZFT-UHFFFAOYSA-N 3-(bromomethyl)-1-methylpiperidine Chemical compound CN1CCCC(CBr)C1 VZYZKPJAXWDZFT-UHFFFAOYSA-N 0.000 description 3
• ROHXIBFCVMNBDP-UHFFFAOYSA-N 3-bromo-5-(2-chlorophenyl)-n-(piperidin-4-ylmethyl)pyrazolo[1,5-a]pyrimidin-7-amine Chemical compound ClC1=CC=CC=C1C1=NC2=C(Br)C=NN2C(NCC2CCNCC2)=C1 ROHXIBFCVMNBDP-UHFFFAOYSA-N 0.000 description 3
• YFCIFWOJYYFDQP-PTWZRHHISA-N 4-[3-amino-6-[(1S,3S,4S)-3-fluoro-4-hydroxycyclohexyl]pyrazin-2-yl]-N-[(1S)-1-(3-bromo-5-fluorophenyl)-2-(methylamino)ethyl]-2-fluorobenzamide Chemical compound CNC[C@@H](NC(=O)c1ccc(cc1F)-c1nc(cnc1N)[C@H]1CC[C@H](O)[C@@H](F)C1)c1cc(F)cc(Br)c1 YFCIFWOJYYFDQP-PTWZRHHISA-N 0.000 description 3
• OXTGVBZVABBYHU-UHFFFAOYSA-N 4-[[[3-bromo-5-(2-chlorophenyl)pyrazolo[1,5-a]pyrimidin-7-yl]amino]methyl]piperidine-1-carboxamide Chemical compound C1CN(C(=O)N)CCC1CNC1=CC(C=2C(=CC=CC=2)Cl)=NC2=C(Br)C=NN12 OXTGVBZVABBYHU-UHFFFAOYSA-N 0.000 description 3
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
• 101100439662 Arabidopsis thaliana CHR5 gene Proteins 0.000 description 3
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
• 208000024172 Cardiovascular disease Diseases 0.000 description 3
• 102000016736 Cyclin Human genes 0.000 description 3
• 108050006400 Cyclin Proteins 0.000 description 3
• 102000002554 Cyclin A Human genes 0.000 description 3
• 108010068192 Cyclin A Proteins 0.000 description 3
• 108010025464 Cyclin-Dependent Kinase 4 Proteins 0.000 description 3
• 108010025454 Cyclin-Dependent Kinase 5 Proteins 0.000 description 3
• 102100032857 Cyclin-dependent kinase 1 Human genes 0.000 description 3
• 102100036252 Cyclin-dependent kinase 4 Human genes 0.000 description 3
• 102100026805 Cyclin-dependent-like kinase 5 Human genes 0.000 description 3
• 101100520660 Drosophila melanogaster Poc1 gene Proteins 0.000 description 3
• GISRWBROCYNDME-PELMWDNLSA-N F[C@H]1[C@H]([C@H](NC1=O)COC1=NC=CC2=CC(=C(C=C12)OC)C(=O)N)C Chemical compound F[C@H]1[C@H]([C@H](NC1=O)COC1=NC=CC2=CC(=C(C=C12)OC)C(=O)N)C GISRWBROCYNDME-PELMWDNLSA-N 0.000 description 3
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
• 102000002254 Glycogen Synthase Kinase 3 Human genes 0.000 description 3
• 108010014905 Glycogen Synthase Kinase 3 Proteins 0.000 description 3
• 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 3
• 206010061218 Inflammation Diseases 0.000 description 3
• 150000001204 N-oxides Chemical class 0.000 description 3
• 101100520662 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) PBA1 gene Proteins 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
• 239000007983 Tris buffer Substances 0.000 description 3
• 241001125929 Trisopterus luscus Species 0.000 description 3
• 229960000583 acetic acid Drugs 0.000 description 3
• 230000010933 acylation Effects 0.000 description 3
• 238000005917 acylation reaction Methods 0.000 description 3
• QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
• 238000004458 analytical method Methods 0.000 description 3
• 230000006907 apoptotic process Effects 0.000 description 3
• 125000005018 aryl alkenyl group Chemical group 0.000 description 3
• 125000004659 aryl alkyl thio group Chemical group 0.000 description 3
• 125000005161 aryl oxy carbonyl group Chemical group 0.000 description 3
• 125000005110 aryl thio group Chemical group 0.000 description 3
• 125000004104 aryloxy group Chemical group 0.000 description 3
• SJSWRKNSCWKNIR-UHFFFAOYSA-N azane;dihydrochloride Chemical compound N.Cl.Cl SJSWRKNSCWKNIR-UHFFFAOYSA-N 0.000 description 3
• 239000002585 base Substances 0.000 description 3
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
• UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 3
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
• 150000001649 bromium compounds Chemical class 0.000 description 3
• 244000309464 bull Species 0.000 description 3
• 239000003054 catalyst Substances 0.000 description 3
• 230000022131 cell cycle Effects 0.000 description 3
• 230000004663 cell proliferation Effects 0.000 description 3
• 238000003776 cleavage reaction Methods 0.000 description 3
• 238000004440 column chromatography Methods 0.000 description 3
• 230000008878 coupling Effects 0.000 description 3
• 238000010168 coupling process Methods 0.000 description 3
• 238000005859 coupling reaction Methods 0.000 description 3
• 208000037765 diseases and disorders Diseases 0.000 description 3
• 238000006073 displacement reaction Methods 0.000 description 3
• 239000012153 distilled water Substances 0.000 description 3
• 238000007345 electrophilic aromatic substitution reaction Methods 0.000 description 3
• 238000003683 electrophilic halogenation reaction Methods 0.000 description 3
• 150000002148 esters Chemical class 0.000 description 3
• 238000001704 evaporation Methods 0.000 description 3
• 230000008020 evaporation Effects 0.000 description 3
• WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 3
• 238000009472 formulation Methods 0.000 description 3
• 125000002541 furyl group Chemical group 0.000 description 3
• 125000005843 halogen group Chemical group 0.000 description 3
• 238000010438 heat treatment Methods 0.000 description 3
• 125000004475 heteroaralkyl group Chemical group 0.000 description 3
• 239000001257 hydrogen Substances 0.000 description 3
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
• 238000010348 incorporation Methods 0.000 description 3
• 230000004054 inflammatory process Effects 0.000 description 3
• 239000004615 ingredient Substances 0.000 description 3
• GURKHSYORGJETM-WAQYZQTGSA-N irinotecan hydrochloride (anhydrous) Chemical compound Cl.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 GURKHSYORGJETM-WAQYZQTGSA-N 0.000 description 3
• 239000012139 lysis buffer Substances 0.000 description 3
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 3
• 150000002825 nitriles Chemical class 0.000 description 3
• 125000004433 nitrogen atom Chemical group N* 0.000 description 3
• 230000037361 pathway Effects 0.000 description 3
• 239000008188 pellet Substances 0.000 description 3
• 239000012071 phase Substances 0.000 description 3
• 230000008569 process Effects 0.000 description 3
• 108090000765 processed proteins & peptides Proteins 0.000 description 3
• 230000002062 proliferating effect Effects 0.000 description 3
• 125000006239 protecting group Chemical group 0.000 description 3
• 239000003528 protein farnesyltransferase inhibitor Substances 0.000 description 3
• TXQWFIVRZNOPCK-UHFFFAOYSA-N pyridin-4-ylmethanamine Chemical compound NCC1=CC=NC=C1 TXQWFIVRZNOPCK-UHFFFAOYSA-N 0.000 description 3
• 230000007017 scission Effects 0.000 description 3
• 239000011780 sodium chloride Substances 0.000 description 3
• 239000000758 substrate Substances 0.000 description 3
• 229940124530 sulfonamide Drugs 0.000 description 3
• 150000003456 sulfonamides Chemical class 0.000 description 3
• CKRMNVOOGVCVNY-UHFFFAOYSA-N tert-butyl 2-[2-[[3-bromo-5-(2-chlorophenyl)pyrazolo[1,5-a]pyrimidin-7-yl]amino]ethyl]piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCCC1CCNC1=CC(C=2C(=CC=CC=2)Cl)=NC2=C(Br)C=NN12 CKRMNVOOGVCVNY-UHFFFAOYSA-N 0.000 description 3
• OTUYHXHSMKRCDK-UHFFFAOYSA-N tert-butyl 4-[[[3-bromo-5-(2-chlorophenyl)pyrazolo[1,5-a]pyrimidin-7-yl]amino]methyl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1CNC1=CC(C=2C(=CC=CC=2)Cl)=NC2=C(Br)C=NN12 OTUYHXHSMKRCDK-UHFFFAOYSA-N 0.000 description 3
• UPFVGJRYWFWDNT-UHFFFAOYSA-N tert-butyl n-(3-cyanophenyl)-n-[(2-methylpropan-2-yl)oxycarbonyl]carbamate Chemical compound CC(C)(C)OC(=O)N(C(=O)OC(C)(C)C)C1=CC=CC(C#N)=C1 UPFVGJRYWFWDNT-UHFFFAOYSA-N 0.000 description 3
• XCAQIUOFDMREBA-UHFFFAOYSA-N tert-butyl n-[(2-methylpropan-2-yl)oxycarbonyl]carbamate Chemical compound CC(C)(C)OC(=O)NC(=O)OC(C)(C)C XCAQIUOFDMREBA-UHFFFAOYSA-N 0.000 description 3
• AJILWPCUWOPSPC-UHFFFAOYSA-N tert-butyl n-[2-(1-carbamoylpiperidin-3-yl)ethyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCC1CCCN(C(N)=O)C1 AJILWPCUWOPSPC-UHFFFAOYSA-N 0.000 description 3
• YMCRUAXNVIVQOF-UHFFFAOYSA-N tert-butyl n-[2-(1-carbamoylpiperidin-4-yl)ethyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCC1CCN(C(N)=O)CC1 YMCRUAXNVIVQOF-UHFFFAOYSA-N 0.000 description 3
• 125000001544 thienyl group Chemical group 0.000 description 3
• 230000003612 virological effect Effects 0.000 description 3
• MJUVRTYWUMPBTR-MRXNPFEDSA-N 1-(2,2-difluoro-1,3-benzodioxol-5-yl)-n-[1-[(2r)-2,3-dihydroxypropyl]-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)indol-5-yl]cyclopropane-1-carboxamide Chemical compound FC=1C=C2N(C[C@@H](O)CO)C(C(C)(CO)C)=CC2=CC=1NC(=O)C1(C=2C=C3OC(F)(F)OC3=CC=2)CC1 MJUVRTYWUMPBTR-MRXNPFEDSA-N 0.000 description 2
• APXRHPDHORGIEB-UHFFFAOYSA-N 1H-pyrazolo[4,3-d]pyrimidine Chemical class N1=CN=C2C=NNC2=C1 APXRHPDHORGIEB-UHFFFAOYSA-N 0.000 description 2
• WOXFMYVTSLAQMO-UHFFFAOYSA-N 2-Pyridinemethanamine Chemical compound NCC1=CC=CC=N1 WOXFMYVTSLAQMO-UHFFFAOYSA-N 0.000 description 2
• PTHDBHDZSMGHKF-ZETCQYMHSA-N 2-[(2s)-piperidin-2-yl]ethanol Chemical compound OCC[C@@H]1CCCCN1 PTHDBHDZSMGHKF-ZETCQYMHSA-N 0.000 description 2
• GIWZCVPVXRTNOA-UHFFFAOYSA-N 2-[2-[[3-bromo-5-(2-chlorophenyl)pyrazolo[1,5-a]pyrimidin-7-yl]amino]ethyl]piperidine-1-carboxamide Chemical compound NC(=O)N1CCCCC1CCNC1=CC(C=2C(=CC=CC=2)Cl)=NC2=C(Br)C=NN12 GIWZCVPVXRTNOA-UHFFFAOYSA-N 0.000 description 2
• PTHDBHDZSMGHKF-UHFFFAOYSA-N 2-piperidin-2-ylethanol Chemical compound OCCC1CCCCN1 PTHDBHDZSMGHKF-UHFFFAOYSA-N 0.000 description 2
• OTFSNWHSDVUQIU-UHFFFAOYSA-N 4-(1,3-oxazol-5-yl)benzamide Chemical compound C1=CC(C(=O)N)=CC=C1C1=CN=CO1 OTFSNWHSDVUQIU-UHFFFAOYSA-N 0.000 description 2
• JPXBDUADRDXVGV-UHFFFAOYSA-N 4-(2-aminoethyl)piperidine-1-carboxamide Chemical compound NCCC1CCN(C(N)=O)CC1 JPXBDUADRDXVGV-UHFFFAOYSA-N 0.000 description 2
• XYWIPYBIIRTJMM-IBGZPJMESA-N 4-[[(2S)-2-[4-[5-chloro-2-[4-(trifluoromethyl)triazol-1-yl]phenyl]-5-methoxy-2-oxopyridin-1-yl]butanoyl]amino]-2-fluorobenzamide Chemical compound CC[C@H](N1C=C(OC)C(=CC1=O)C1=C(C=CC(Cl)=C1)N1C=C(N=N1)C(F)(F)F)C(=O)NC1=CC(F)=C(C=C1)C(N)=O XYWIPYBIIRTJMM-IBGZPJMESA-N 0.000 description 2
• JVVRCYWZTJLJSG-UHFFFAOYSA-N 4-dimethylaminophenol Chemical compound CN(C)C1=CC=C(O)C=C1 JVVRCYWZTJLJSG-UHFFFAOYSA-N 0.000 description 2
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 2
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-dimethylaminopyridine Substances CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
• GYFGZFJGMRRTTP-UHFFFAOYSA-N 4-imidazol-1-ylbenzonitrile Chemical compound C1=CC(C#N)=CC=C1N1C=NC=C1 GYFGZFJGMRRTTP-UHFFFAOYSA-N 0.000 description 2
• CCMRFUCSFRRPNT-UHFFFAOYSA-N 4-pyridin-2-ylbenzonitrile Chemical compound C1=CC(C#N)=CC=C1C1=CC=CC=N1 CCMRFUCSFRRPNT-UHFFFAOYSA-N 0.000 description 2
• ZRPZPNYZFSJUPA-UHFFFAOYSA-N ARS-1620 Chemical compound Oc1cccc(F)c1-c1c(Cl)cc2c(ncnc2c1F)N1CCN(CC1)C(=O)C=C ZRPZPNYZFSJUPA-UHFFFAOYSA-N 0.000 description 2
• 208000032467 Aplastic anaemia Diseases 0.000 description 2
• 201000001320 Atherosclerosis Diseases 0.000 description 2
• 208000023275 Autoimmune disease Diseases 0.000 description 2
• LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 2
• 101100167062 Caenorhabditis elegans chch-3 gene Proteins 0.000 description 2
• KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 2
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
• 108010025468 Cyclin-Dependent Kinase 6 Proteins 0.000 description 2
• 102100026804 Cyclin-dependent kinase 6 Human genes 0.000 description 2
• 102100026810 Cyclin-dependent kinase 7 Human genes 0.000 description 2
• 102100024456 Cyclin-dependent kinase 8 Human genes 0.000 description 2
• MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 2
• GKKZMYDNDDMXSE-UHFFFAOYSA-N Ethyl 3-oxo-3-phenylpropanoate Chemical compound CCOC(=O)CC(=O)C1=CC=CC=C1 GKKZMYDNDDMXSE-UHFFFAOYSA-N 0.000 description 2
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
• 206010018364 Glomerulonephritis Diseases 0.000 description 2
• 101000868333 Homo sapiens Cyclin-dependent kinase 1 Proteins 0.000 description 2
• 101000911952 Homo sapiens Cyclin-dependent kinase 7 Proteins 0.000 description 2
• 101000980937 Homo sapiens Cyclin-dependent kinase 8 Proteins 0.000 description 2
• 101000909198 Homo sapiens DNA polymerase delta catalytic subunit Proteins 0.000 description 2
• 101000632319 Homo sapiens Septin-7 Proteins 0.000 description 2
• 241000701044 Human gammaherpesvirus 4 Species 0.000 description 2
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
• 208000022559 Inflammatory bowel disease Diseases 0.000 description 2
• 229930194542 Keto Natural products 0.000 description 2
• 229910010082 LiAlH Inorganic materials 0.000 description 2
• 241001465754 Metazoa Species 0.000 description 2
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
• FEYNFHSRETUBEM-UHFFFAOYSA-N N-[3-(1,1-difluoroethyl)phenyl]-1-(4-methoxyphenyl)-3-methyl-5-oxo-4H-pyrazole-4-carboxamide Chemical compound COc1ccc(cc1)N1N=C(C)C(C(=O)Nc2cccc(c2)C(C)(F)F)C1=O FEYNFHSRETUBEM-UHFFFAOYSA-N 0.000 description 2
• LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical group IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 2
• PLYSRROVZCWHDU-UHFFFAOYSA-N N.CF Chemical compound N.CF PLYSRROVZCWHDU-UHFFFAOYSA-N 0.000 description 2
• 235000019502 Orange oil Nutrition 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• 241001465382 Physalis alkekengi Species 0.000 description 2
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 2
• 201000004681 Psoriasis Diseases 0.000 description 2
• 229910019020 PtO2 Inorganic materials 0.000 description 2
• 102100027981 Septin-7 Human genes 0.000 description 2
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
• 241000534944 Thia Species 0.000 description 2
• 208000036142 Viral infection Diseases 0.000 description 2
• 230000002378 acidificating effect Effects 0.000 description 2
• YKIOKAURTKXMSB-UHFFFAOYSA-N adams's catalyst Chemical compound O=[Pt]=O YKIOKAURTKXMSB-UHFFFAOYSA-N 0.000 description 2
• 239000000443 aerosol Substances 0.000 description 2
• 125000001931 aliphatic group Chemical group 0.000 description 2
• 150000001447 alkali salts Chemical class 0.000 description 2
• 125000004390 alkyl sulfonyl group Chemical group 0.000 description 2
• BIIVYFLTOXDAOV-YVEFUNNKSA-N alvocidib Chemical compound O[C@@H]1CN(C)CC[C@@H]1C1=C(O)C=C(O)C2=C1OC(C=1C(=CC=CC=1)Cl)=CC2=O BIIVYFLTOXDAOV-YVEFUNNKSA-N 0.000 description 2
• 229950010817 alvocidib Drugs 0.000 description 2
• 239000007864 aqueous solution Substances 0.000 description 2
• 125000003435 aroyl group Chemical group 0.000 description 2
• 125000002102 aryl alkyloxo group Chemical group 0.000 description 2
• 125000004391 aryl sulfonyl group Chemical group 0.000 description 2
• 239000012298 atmosphere Substances 0.000 description 2
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 2
• 230000000903 blocking effect Effects 0.000 description 2
• 230000037396 body weight Effects 0.000 description 2
• 229910000085 borane Inorganic materials 0.000 description 2
• ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
• 229910000024 caesium carbonate Inorganic materials 0.000 description 2
• 239000002775 capsule Substances 0.000 description 2
• 239000004202 carbamide Substances 0.000 description 2
• 239000000969 carrier Substances 0.000 description 2
• 230000003197 catalytic effect Effects 0.000 description 2
• 230000002113 chemopreventative effect Effects 0.000 description 2
• 229940125898 compound 5 Drugs 0.000 description 2
• 239000006071 cream Substances 0.000 description 2
• 239000013078 crystal Substances 0.000 description 2
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
• IGSKHXTUVXSOMB-UHFFFAOYSA-N cyclopropylmethanamine Chemical compound NCC1CC1 IGSKHXTUVXSOMB-UHFFFAOYSA-N 0.000 description 2
• 238000011161 development Methods 0.000 description 2
• BEPAFCGSDWSTEL-UHFFFAOYSA-N dimethyl malonate Chemical compound COC(=O)CC(=O)OC BEPAFCGSDWSTEL-UHFFFAOYSA-N 0.000 description 2
• 231100000673 dose–response relationship Toxicity 0.000 description 2
• 238000001035 drying Methods 0.000 description 2
• 238000005516 engineering process Methods 0.000 description 2
• 239000011737 fluorine Substances 0.000 description 2
• 230000006870 function Effects 0.000 description 2
• 239000007789 gas Substances 0.000 description 2
• 239000000499 gel Substances 0.000 description 2
• 201000005787 hematologic cancer Diseases 0.000 description 2
• 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 2
• 125000004447 heteroarylalkenyl group Chemical group 0.000 description 2
• IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
• 150000003840 hydrochlorides Chemical class 0.000 description 2
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
• CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 2
• YLMAHDNUQAMNNX-UHFFFAOYSA-N imatinib methanesulfonate Chemical compound CS(O)(=O)=O.C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 YLMAHDNUQAMNNX-UHFFFAOYSA-N 0.000 description 2
• 150000004694 iodide salts Chemical class 0.000 description 2
• PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 description 2
• 238000002955 isolation Methods 0.000 description 2
• 238000000021 kinase assay Methods 0.000 description 2
• 230000000670 limiting effect Effects 0.000 description 2
• 239000012280 lithium aluminium hydride Substances 0.000 description 2
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
• 238000003760 magnetic stirring Methods 0.000 description 2
• 239000002609 medium Substances 0.000 description 2
• QSRRZKPKHJHIRB-UHFFFAOYSA-N methyl 4-[(2,5-dichloro-4-methylthiophen-3-yl)sulfonylamino]-2-hydroxybenzoate Chemical compound C1=C(O)C(C(=O)OC)=CC=C1NS(=O)(=O)C1=C(Cl)SC(Cl)=C1C QSRRZKPKHJHIRB-UHFFFAOYSA-N 0.000 description 2
• 230000004048 modification Effects 0.000 description 2
• 238000012986 modification Methods 0.000 description 2
• 230000004770 neurodegeneration Effects 0.000 description 2
• 239000012038 nucleophile Substances 0.000 description 2
• GTVPOLSIJWJJNY-UHFFFAOYSA-N olomoucine Chemical compound N1=C(NCCO)N=C2N(C)C=NC2=C1NCC1=CC=CC=C1 GTVPOLSIJWJJNY-UHFFFAOYSA-N 0.000 description 2
• 239000010502 orange oil Substances 0.000 description 2
• 150000007530 organic bases Chemical class 0.000 description 2
• 125000002971 oxazolyl group Chemical group 0.000 description 2
• HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 2
• BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
• IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 2
• 229910000027 potassium carbonate Inorganic materials 0.000 description 2
• 150000003138 primary alcohols Chemical class 0.000 description 2
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
• 125000003373 pyrazinyl group Chemical group 0.000 description 2
• 125000003226 pyrazolyl group Chemical group 0.000 description 2
• 150000003230 pyrimidines Chemical class 0.000 description 2
• 230000001105 regulatory effect Effects 0.000 description 2
• 239000007858 starting material Substances 0.000 description 2
• 150000003457 sulfones Chemical class 0.000 description 2
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 2
• 150000003462 sulfoxides Chemical class 0.000 description 2
• YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 2
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
• MYSCGCDVRLGCPL-UHFFFAOYSA-N tert-butyl n-(1-methylpiperidin-3-yl)-n-[(2-methylpropan-2-yl)oxycarbonyl]carbamate Chemical compound CN1CCCC(N(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C)C1 MYSCGCDVRLGCPL-UHFFFAOYSA-N 0.000 description 2
• MZDXQPKJGLGAOI-UHFFFAOYSA-N tert-butyl n-[(1-carbamoylpiperidin-3-yl)methyl]carbamate Chemical compound CC(C)(C)OC(=O)NCC1CCCN(C(N)=O)C1 MZDXQPKJGLGAOI-UHFFFAOYSA-N 0.000 description 2
• XAMAFLWCELXNAY-UHFFFAOYSA-N tert-butyl n-[(4-cyanophenyl)methyl]-n-[(2-methylpropan-2-yl)oxycarbonyl]carbamate Chemical compound CC(C)(C)OC(=O)N(C(=O)OC(C)(C)C)CC1=CC=C(C#N)C=C1 XAMAFLWCELXNAY-UHFFFAOYSA-N 0.000 description 2
• CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 2
• 238000002560 therapeutic procedure Methods 0.000 description 2
• QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
• PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 2
• IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 2
• 241000701161 unidentified adenovirus Species 0.000 description 2
• 241000701447 unidentified baculovirus Species 0.000 description 2
• 230000009385 viral infection Effects 0.000 description 2
• 238000005406 washing Methods 0.000 description 2
• LSPHULWDVZXLIL-UHFFFAOYSA-N (+/-)-Camphoric acid Chemical class CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
• 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
• UGXQXVDTGJCQHR-UHFFFAOYSA-N (1-methylpiperidin-3-yl)methanol Chemical compound CN1CCCC(CO)C1 UGXQXVDTGJCQHR-UHFFFAOYSA-N 0.000 description 1
• SOCAXRLFGRNEPK-IFZYUDKTSA-N (1r,3s,5r)-2-n-[1-carbamoyl-5-(cyanomethoxy)indol-3-yl]-3-n-[(3-chloro-2-fluorophenyl)methyl]-2-azabicyclo[3.1.0]hexane-2,3-dicarboxamide Chemical compound O=C([C@@H]1C[C@H]2C[C@H]2N1C(=O)NC1=CN(C2=CC=C(OCC#N)C=C21)C(=O)N)NCC1=CC=CC(Cl)=C1F SOCAXRLFGRNEPK-IFZYUDKTSA-N 0.000 description 1
• JIMSXLUBRRQALI-RYUDHWBXSA-N (1s,2s)-2-phenylmethoxycyclopentan-1-amine Chemical compound N[C@H]1CCC[C@@H]1OCC1=CC=CC=C1 JIMSXLUBRRQALI-RYUDHWBXSA-N 0.000 description 1
• BSVHTRRLCAVQCZ-JDEXMCKMSA-N (2s)-1-[(2s)-1-[(2s)-1-[(2s)-1-[(2s)-1-[(2s)-1-[(2s)-2-[[(2s)-1-[(2s)-2-[[(2s)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-3-carboxypropanoyl]pyrrolidine-2-carbonyl]amino]propanoyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carbonyl]pyrro Chemical compound C([C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(O)=O)C1=CC=C(O)C=C1 BSVHTRRLCAVQCZ-JDEXMCKMSA-N 0.000 description 1
• CEBAHYWORUOILU-UHFFFAOYSA-N (4-cyanophenyl)boronic acid Chemical compound OB(O)C1=CC=C(C#N)C=C1 CEBAHYWORUOILU-UHFFFAOYSA-N 0.000 description 1
• MACCCEHTOQDLIP-UHFFFAOYSA-N (4-imidazol-1-ylphenyl)methanamine Chemical compound C1=CC(CN)=CC=C1N1C=NC=C1 MACCCEHTOQDLIP-UHFFFAOYSA-N 0.000 description 1
• KPPVNWGJXFMGAM-UUILKARUSA-N (e)-2-methyl-1-(6-methyl-3,4-dihydro-2h-quinolin-1-yl)but-2-en-1-one Chemical compound CC1=CC=C2N(C(=O)C(/C)=C/C)CCCC2=C1 KPPVNWGJXFMGAM-UUILKARUSA-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
• KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 1
• SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
• 125000004514 1,2,4-thiadiazolyl group Chemical group 0.000 description 1
• 125000004530 1,2,4-triazinyl group Chemical group N1=NC(=NC=C1)* 0.000 description 1
• NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
• XGYCWCIGCYGQFU-UHFFFAOYSA-N 1,2-thiazolidine 1,1-dioxide Chemical compound O=S1(=O)CCCN1 XGYCWCIGCYGQFU-UHFFFAOYSA-N 0.000 description 1
• RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical class NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 description 1
• 125000005940 1,4-dioxanyl group Chemical group 0.000 description 1
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
• PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
• VFWCMGCRMGJXDK-UHFFFAOYSA-N 1-chlorobutane Chemical class CCCCCl VFWCMGCRMGJXDK-UHFFFAOYSA-N 0.000 description 1
• VUQPJRPDRDVQMN-UHFFFAOYSA-N 1-chlorooctadecane Chemical class CCCCCCCCCCCCCCCCCCCl VUQPJRPDRDVQMN-UHFFFAOYSA-N 0.000 description 1
• 125000001088 1-naphthoyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 description 1
• LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 description 1
• YQGHJCYLMLPCCB-UHFFFAOYSA-N 2,4-diaminopyrimidin-5-ol Chemical compound NC1=NC=C(O)C(N)=N1 YQGHJCYLMLPCCB-UHFFFAOYSA-N 0.000 description 1
• PTHDBHDZSMGHKF-SSDOTTSWSA-N 2-[(2r)-piperidin-2-yl]ethanol Chemical group OCC[C@H]1CCCCN1 PTHDBHDZSMGHKF-SSDOTTSWSA-N 0.000 description 1
• NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
• IMRWILPUOVGIMU-UHFFFAOYSA-N 2-bromopyridine Chemical compound BrC1=CC=CC=N1 IMRWILPUOVGIMU-UHFFFAOYSA-N 0.000 description 1
• 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
• RPCLPGKRXFYJKP-UHFFFAOYSA-N 2-chloro-5-(chloromethyl)-1-oxidopyridin-1-ium Chemical compound [O-][N+]1=CC(CCl)=CC=C1Cl RPCLPGKRXFYJKP-UHFFFAOYSA-N 0.000 description 1
• IOOJBDSYMIVHQI-UHFFFAOYSA-N 2-cyclopentylguanidine;hydrochloride Chemical compound Cl.NC(N)=NC1CCCC1 IOOJBDSYMIVHQI-UHFFFAOYSA-N 0.000 description 1
• FAUQRRGKJKMEIW-UHFFFAOYSA-N 2-cyclopropylacetonitrile Chemical compound N#CCC1CC1 FAUQRRGKJKMEIW-UHFFFAOYSA-N 0.000 description 1
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
• ASUDFOJKTJLAIK-UHFFFAOYSA-N 2-methoxyethanamine Chemical compound COCCN ASUDFOJKTJLAIK-UHFFFAOYSA-N 0.000 description 1
• CESUXLKAADQNTB-ZETCQYMHSA-N 2-methylpropane-2-sulfinamide Chemical compound CC(C)(C)[S@@](N)=O CESUXLKAADQNTB-ZETCQYMHSA-N 0.000 description 1
• CESUXLKAADQNTB-SSDOTTSWSA-N 2-methylpropane-2-sulfinamide Chemical group CC(C)(C)[S@](N)=O CESUXLKAADQNTB-SSDOTTSWSA-N 0.000 description 1
• 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
• WMPPDTMATNBGJN-UHFFFAOYSA-N 2-phenylethylbromide Chemical class BrCCC1=CC=CC=C1 WMPPDTMATNBGJN-UHFFFAOYSA-N 0.000 description 1
• HCDMJFOHIXMBOV-UHFFFAOYSA-N 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one Chemical compound C=1C2=C3N(CC)C(=O)N(C=4C(=C(OC)C=C(OC)C=4F)F)CC3=CN=C2NC=1CN1CCOCC1 HCDMJFOHIXMBOV-UHFFFAOYSA-N 0.000 description 1
• 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 1
• CVKOOKPNCVYHNY-UHFFFAOYSA-N 3-(bromomethyl)benzonitrile Chemical compound BrCC1=CC=CC(C#N)=C1 CVKOOKPNCVYHNY-UHFFFAOYSA-N 0.000 description 1
• RUJYJCANMOTJMO-UHFFFAOYSA-N 3-(trifluoromethyl)benzoyl chloride Chemical compound FC(F)(F)C1=CC=CC(C(Cl)=O)=C1 RUJYJCANMOTJMO-UHFFFAOYSA-N 0.000 description 1
• WNEODWDFDXWOLU-QHCPKHFHSA-N 3-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2s)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl]amino]-6-oxopyridin-3-yl]pyridin-2-yl]-7,7-dimethyl-1,2,6,8-tetrahydrocyclopenta[3,4]pyrrolo[3,5-b]pyrazin-4-one Chemical compound C([C@@H](N(CC1)C=2C=NC(NC=3C(N(C)C=C(C=3)C=3C(=C(N4C(C5=CC=6CC(C)(C)CC=6N5CC4)=O)N=CC=3)CO)=O)=CC=2)C)N1C1COC1 WNEODWDFDXWOLU-QHCPKHFHSA-N 0.000 description 1
• GXOIDFYMHQTHBA-UHFFFAOYSA-N 3-bromo-5-(2-chlorophenyl)-n-(2-piperidin-2-ylethyl)pyrazolo[1,5-a]pyrimidin-7-amine Chemical compound ClC1=CC=CC=C1C1=NC2=C(Br)C=NN2C(NCCC2NCCCC2)=C1 GXOIDFYMHQTHBA-UHFFFAOYSA-N 0.000 description 1
• URQJLEHTWPIESE-UHFFFAOYSA-N 3-chloro-2h-pyrazolo[4,3-d]pyrimidine Chemical compound N1=CN=C2C(Cl)=NNC2=C1 URQJLEHTWPIESE-UHFFFAOYSA-N 0.000 description 1
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
• MCPBXFWYUHYSIZ-UHFFFAOYSA-N 4-(1,3-oxazol-5-yl)benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C1=CN=CO1 MCPBXFWYUHYSIZ-UHFFFAOYSA-N 0.000 description 1
• UMLFTCYAQPPZER-UHFFFAOYSA-N 4-(bromomethyl)benzonitrile Chemical compound BrCC1=CC=C(C#N)C=C1 UMLFTCYAQPPZER-UHFFFAOYSA-N 0.000 description 1
• DPBWFNDFMCCGGJ-UHFFFAOYSA-N 4-Piperidine carboxamide Chemical compound NC(=O)C1CCNCC1 DPBWFNDFMCCGGJ-UHFFFAOYSA-N 0.000 description 1
• VJPPLCNBDLZIFG-ZDUSSCGKSA-N 4-[(3S)-3-(but-2-ynoylamino)piperidin-1-yl]-5-fluoro-2,3-dimethyl-1H-indole-7-carboxamide Chemical compound C(C#CC)(=O)N[C@@H]1CN(CCC1)C1=C2C(=C(NC2=C(C=C1F)C(=O)N)C)C VJPPLCNBDLZIFG-ZDUSSCGKSA-N 0.000 description 1
• SPBWHPXCWJLQRU-FITJORAGSA-N 4-amino-8-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound C12=NC=NC(N)=C2C(=O)C(C(=O)N)=CN1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O SPBWHPXCWJLQRU-FITJORAGSA-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
• RDCODVKTTJWFAR-UHFFFAOYSA-N 4-ethyl-1h-pyrazol-5-amine Chemical compound CCC=1C=NNC=1N RDCODVKTTJWFAR-UHFFFAOYSA-N 0.000 description 1
• AEKVBBNGWBBYLL-UHFFFAOYSA-N 4-fluorobenzonitrile Chemical compound FC1=CC=C(C#N)C=C1 AEKVBBNGWBBYLL-UHFFFAOYSA-N 0.000 description 1
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
• FFNKBQRKZRMYCL-UHFFFAOYSA-N 5-amino-1h-pyrazole-4-carbonitrile Chemical compound NC1=NNC=C1C#N FFNKBQRKZRMYCL-UHFFFAOYSA-N 0.000 description 1
• CVICEEPAFUYBJG-UHFFFAOYSA-N 5-chloro-2,2-difluoro-1,3-benzodioxole Chemical group C1=C(Cl)C=C2OC(F)(F)OC2=C1 CVICEEPAFUYBJG-UHFFFAOYSA-N 0.000 description 1
• ZIJAZUBWHAZHPL-UHFFFAOYSA-N 6-chloropyridine-3-carboxamide Chemical compound NC(=O)C1=CC=C(Cl)N=C1 ZIJAZUBWHAZHPL-UHFFFAOYSA-N 0.000 description 1
• UNQYAAAWKOOBFQ-UHFFFAOYSA-N 7-[(4-chlorophenyl)methyl]-8-[4-chloro-3-(trifluoromethoxy)phenoxy]-1-(3-hydroxypropyl)-3-methylpurine-2,6-dione Chemical compound C=1C=C(Cl)C=CC=1CN1C=2C(=O)N(CCCO)C(=O)N(C)C=2N=C1OC1=CC=C(Cl)C(OC(F)(F)F)=C1 UNQYAAAWKOOBFQ-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
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
• 208000030507 AIDS Diseases 0.000 description 1
• 206010065040 AIDS dementia complex Diseases 0.000 description 1
• 201000004384 Alopecia Diseases 0.000 description 1
• 101100439663 Arabidopsis thaliana CHR7 gene Proteins 0.000 description 1
• 101100244083 Arabidopsis thaliana PKL gene Proteins 0.000 description 1
• 239000004475 Arginine Substances 0.000 description 1
• 102000014654 Aromatase Human genes 0.000 description 1
• 108010078554 Aromatase Proteins 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
• ZMOUVWHDCOZPGR-UHFFFAOYSA-N BNBr Chemical compound BNBr ZMOUVWHDCOZPGR-UHFFFAOYSA-N 0.000 description 1
• 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 1
• VTZFRRICNUUBRJ-UHFFFAOYSA-N BrIBr Chemical compound BrIBr VTZFRRICNUUBRJ-UHFFFAOYSA-N 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
• 229940126074 CDK kinase inhibitor Drugs 0.000 description 1
• 101100037762 Caenorhabditis elegans rnh-2 gene Proteins 0.000 description 1
• 101100314454 Caenorhabditis elegans tra-1 gene Proteins 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• 206010058019 Cancer Pain Diseases 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
• 201000009030 Carcinoma Diseases 0.000 description 1
• UWNXGZKSIKQKAH-UHFFFAOYSA-N Cc1cc(CNC(CO)C(O)=O)c(OCc2cccc(c2)C#N)cc1OCc1cccc(c1C)-c1ccc2OCCOc2c1 Chemical compound Cc1cc(CNC(CO)C(O)=O)c(OCc2cccc(c2)C#N)cc1OCc1cccc(c1C)-c1ccc2OCCOc2c1 UWNXGZKSIKQKAH-UHFFFAOYSA-N 0.000 description 1
• DALOIWZUIXBBIU-UHFFFAOYSA-N ClC1=NN2C(N=C(C=C2)C2=CC=CC=C2)=C1 Chemical compound ClC1=NN2C(N=C(C=C2)C2=CC=CC=C2)=C1 DALOIWZUIXBBIU-UHFFFAOYSA-N 0.000 description 1
• 101710106279 Cyclin-dependent kinase 1 Proteins 0.000 description 1
• 102100036329 Cyclin-dependent kinase 3 Human genes 0.000 description 1
• 102100034770 Cyclin-dependent kinase inhibitor 3 Human genes 0.000 description 1
• 201000003883 Cystic fibrosis Diseases 0.000 description 1
• 108020004414 DNA Proteins 0.000 description 1
• 230000006820 DNA synthesis Effects 0.000 description 1
• 229940123780 DNA topoisomerase I inhibitor Drugs 0.000 description 1
• 229940124087 DNA topoisomerase II inhibitor Drugs 0.000 description 1
• XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical class C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
• 102100031480 Dual specificity mitogen-activated protein kinase kinase 1 Human genes 0.000 description 1
• 101710146526 Dual specificity mitogen-activated protein kinase kinase 1 Proteins 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
• 102000001301 EGF receptor Human genes 0.000 description 1
• 108060006698 EGF receptor Proteins 0.000 description 1
• 102100030013 Endoribonuclease Human genes 0.000 description 1
• 101710199605 Endoribonuclease Proteins 0.000 description 1
• 206010014824 Endotoxic shock Diseases 0.000 description 1
• KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
• BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
• 206010017533 Fungal infection Diseases 0.000 description 1
• 102100030500 Heparin cofactor 2 Human genes 0.000 description 1
• 101710153650 Heparin cofactor 2 Proteins 0.000 description 1
• 108010033040 Histones Proteins 0.000 description 1
• 102000006947 Histones Human genes 0.000 description 1
• 241000282412 Homo Species 0.000 description 1
• 101000715946 Homo sapiens Cyclin-dependent kinase 3 Proteins 0.000 description 1
• 101000945639 Homo sapiens Cyclin-dependent kinase inhibitor 3 Proteins 0.000 description 1
• 241000701806 Human papillomavirus Species 0.000 description 1
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
• AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
• 108010050904 Interferons Proteins 0.000 description 1
• 102000014150 Interferons Human genes 0.000 description 1
• 150000000994 L-ascorbates Chemical class 0.000 description 1
• 102100020870 La-related protein 6 Human genes 0.000 description 1
• 108050008265 La-related protein 6 Proteins 0.000 description 1
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
• 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
• 229940124647 MEK inhibitor Drugs 0.000 description 1
• 206010027476 Metastases Diseases 0.000 description 1
• LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 1
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 1
• AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 1
• 229910017974 NH40H Inorganic materials 0.000 description 1
• 208000012902 Nervous system disease Diseases 0.000 description 1
• 208000009905 Neurofibromatoses Diseases 0.000 description 1
• 102100026379 Neurofibromin Human genes 0.000 description 1
• 208000025966 Neurological disease Diseases 0.000 description 1
• PCKPVGOLPKLUHR-UHFFFAOYSA-N OH-Indolxyl Natural products C1=CC=C2C(O)=CNC2=C1 PCKPVGOLPKLUHR-UHFFFAOYSA-N 0.000 description 1
• 208000001132 Osteoporosis Diseases 0.000 description 1
• 108091008606 PDGF receptors Proteins 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 208000018737 Parkinson disease Diseases 0.000 description 1
• 101150003085 Pdcl gene Proteins 0.000 description 1
• 108091005804 Peptidases Proteins 0.000 description 1
• 108010077495 Peptide oostatic hormone Proteins 0.000 description 1
• 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
• 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
• 102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical class CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
• 239000004365 Protease Substances 0.000 description 1
• 108090000315 Protein Kinase C Proteins 0.000 description 1
• 102000003923 Protein Kinase C Human genes 0.000 description 1
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
• 102100033479 RAF proto-oncogene serine/threonine-protein kinase Human genes 0.000 description 1
• 101710141955 RAF proto-oncogene serine/threonine-protein kinase Proteins 0.000 description 1
• 206010063837 Reperfusion injury Diseases 0.000 description 1
• 208000017442 Retinal disease Diseases 0.000 description 1
• 208000007014 Retinitis pigmentosa Diseases 0.000 description 1
• 206010038923 Retinopathy Diseases 0.000 description 1
• 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
• 235000016588 Rosa centifolia Nutrition 0.000 description 1
• 244000052585 Rosa centifolia Species 0.000 description 1
• 230000018199 S phase Effects 0.000 description 1
• 206010040070 Septic Shock Diseases 0.000 description 1
• 101710113029 Serine/threonine-protein kinase Proteins 0.000 description 1
• 241000580858 Simian-Human immunodeficiency virus Species 0.000 description 1
• 241000710960 Sindbis virus Species 0.000 description 1
• 208000006011 Stroke Diseases 0.000 description 1
• 229940123237 Taxane Drugs 0.000 description 1
• IOYNQIMAUDJVEI-BMVIKAAMSA-N Tepraloxydim Chemical compound C1C(=O)C(C(=N/OC\C=C\Cl)/CC)=C(O)CC1C1CCOCC1 IOYNQIMAUDJVEI-BMVIKAAMSA-N 0.000 description 1
• 239000000365 Topoisomerase I Inhibitor Substances 0.000 description 1
• 239000000317 Topoisomerase II Inhibitor Substances 0.000 description 1
• DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
• 229920004890 Triton X-100 Polymers 0.000 description 1
• 239000013504 Triton X-100 Substances 0.000 description 1
• 102000004243 Tubulin Human genes 0.000 description 1
• 108090000704 Tubulin Proteins 0.000 description 1
• 108010040002 Tumor Suppressor Proteins Proteins 0.000 description 1
• 102000001742 Tumor Suppressor Proteins Human genes 0.000 description 1
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
• 241000700605 Viruses Species 0.000 description 1
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 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
• BRQFIORUNWWNBM-KBPBESRZSA-N [(1r,2s)-2-(benzylamino)cyclohexyl]methanol Chemical compound OC[C@@H]1CCCC[C@@H]1NCC1=CC=CC=C1 BRQFIORUNWWNBM-KBPBESRZSA-N 0.000 description 1
• MIOPJNTWMNEORI-MHPPCMCBSA-N [(4r)-7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl]methanesulfonic acid Chemical group C1C[C@]2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-MHPPCMCBSA-N 0.000 description 1
• MIOPJNTWMNEORI-OMNKOJBGSA-N [(4s)-7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl]methanesulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-OMNKOJBGSA-N 0.000 description 1
• ACDMHVQYOFHZJF-UHFFFAOYSA-N [Na]C1=NC=CN1 Chemical compound [Na]C1=NC=CN1 ACDMHVQYOFHZJF-UHFFFAOYSA-N 0.000 description 1
• WREOTYWODABZMH-DTZQCDIJSA-N [[(2r,3s,4r,5r)-3,4-dihydroxy-5-[2-oxo-4-(2-phenylethoxyamino)pyrimidin-1-yl]oxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O[C@H]1N(C=C\1)C(=O)NC/1=N\OCCC1=CC=CC=C1 WREOTYWODABZMH-DTZQCDIJSA-N 0.000 description 1
• 230000001594 aberrant effect Effects 0.000 description 1
• 230000002159 abnormal effect Effects 0.000 description 1
• 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 1
• 150000001242 acetic acid derivatives Chemical class 0.000 description 1
• DSRXQXXHDIAVJT-UHFFFAOYSA-N acetonitrile;n,n-dimethylformamide Chemical compound CC#N.CN(C)C=O DSRXQXXHDIAVJT-UHFFFAOYSA-N 0.000 description 1
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
• 229960001138 acetylsalicylic acid Drugs 0.000 description 1
• 150000008043 acidic salts Chemical class 0.000 description 1
• 150000007513 acids Chemical class 0.000 description 1
• 239000004480 active ingredient Substances 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
• 229910052783 alkali metal Inorganic materials 0.000 description 1
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
• 125000004946 alkenylalkyl group Chemical group 0.000 description 1
• 150000001350 alkyl halides Chemical class 0.000 description 1
• 125000005213 alkyl heteroaryl group Chemical group 0.000 description 1
• 229940100198 alkylating agent Drugs 0.000 description 1
• 239000002168 alkylating agent Substances 0.000 description 1
• 231100000360 alopecia Toxicity 0.000 description 1
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
• 229910052782 aluminium Inorganic materials 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 238000010640 amide synthesis reaction Methods 0.000 description 1
• 229940024606 amino acid Drugs 0.000 description 1
• 150000001413 amino acids Chemical class 0.000 description 1
• 150000001414 amino alcohols Chemical class 0.000 description 1
• 229910021529 ammonia Inorganic materials 0.000 description 1
• 235000019270 ammonium chloride Nutrition 0.000 description 1
• 150000003863 ammonium salts Chemical class 0.000 description 1
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
• 208000007502 anemia Diseases 0.000 description 1
• 238000002399 angioplasty Methods 0.000 description 1
• 150000001448 anilines Chemical class 0.000 description 1
• 230000000340 anti-metabolite Effects 0.000 description 1
• 230000000118 anti-neoplastic effect Effects 0.000 description 1
• 230000001028 anti-proliverative effect Effects 0.000 description 1
• 238000011319 anticancer therapy Methods 0.000 description 1
• 238000011394 anticancer treatment Methods 0.000 description 1
• 229940100197 antimetabolite Drugs 0.000 description 1
• 239000002256 antimetabolite Substances 0.000 description 1
• 229940034982 antineoplastic agent Drugs 0.000 description 1
• 230000001640 apoptogenic effect Effects 0.000 description 1
• 239000012736 aqueous medium Substances 0.000 description 1
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
• 239000012300 argon atmosphere Substances 0.000 description 1
• 230000006793 arrhythmia Effects 0.000 description 1
• 206010003119 arrhythmia Diseases 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• 230000001363 autoimmune Effects 0.000 description 1
• 125000005334 azaindolyl group Chemical group N1N=C(C2=CC=CC=C12)* 0.000 description 1
• 230000008901 benefit Effects 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical class OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
• 125000005513 benzoazaindolyl group Chemical group 0.000 description 1
• 125000004601 benzofurazanyl group Chemical group N1=C2C(=NO1)C(=CC=C2)* 0.000 description 1
• 150000001558 benzoic acid derivatives Chemical class 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
• WTEPWWCRWNCUNA-UHFFFAOYSA-M benzyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)CC1=CC=CC=C1 WTEPWWCRWNCUNA-UHFFFAOYSA-M 0.000 description 1
• 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
• 230000033228 biological regulation Effects 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-M bisulphate group Chemical group S([O-])(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
• 150000001642 boronic acid derivatives Chemical class 0.000 description 1
• 230000005587 bubbling Effects 0.000 description 1
• 150000004648 butanoic acid derivatives Chemical class 0.000 description 1
• 125000004744 butyloxycarbonyl group Chemical group 0.000 description 1
• KVNRLNFWIYMESJ-UHFFFAOYSA-N butyronitrile Chemical compound CCCC#N KVNRLNFWIYMESJ-UHFFFAOYSA-N 0.000 description 1
• 239000006227 byproduct Substances 0.000 description 1
• 229910052792 caesium Inorganic materials 0.000 description 1
• TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical compound [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical class C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
• 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
• IGAAUQWWGNYORG-UHFFFAOYSA-N carbonochloridoyl 2-methylpropanoate Chemical compound CC(C)C(=O)OC(Cl)=O IGAAUQWWGNYORG-UHFFFAOYSA-N 0.000 description 1
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
• 230000006369 cell cycle progression Effects 0.000 description 1
• 108091092328 cellular RNA Proteins 0.000 description 1
• 210000003169 central nervous system Anatomy 0.000 description 1
• 238000005119 centrifugation Methods 0.000 description 1
• 208000025434 cerebellar degeneration Diseases 0.000 description 1
• PBAYDYUZOSNJGU-UHFFFAOYSA-N chelidonic acid Natural products OC(=O)C1=CC(=O)C=C(C(O)=O)O1 PBAYDYUZOSNJGU-UHFFFAOYSA-N 0.000 description 1
• DGLFSNZWRYADFC-UHFFFAOYSA-N chembl2334586 Chemical compound C1CCC2=CN=C(N)N=C2C2=C1NC1=CC=C(C#CC(C)(O)C)C=C12 DGLFSNZWRYADFC-UHFFFAOYSA-N 0.000 description 1
• SFZULDYEOVSIKM-UHFFFAOYSA-N chembl321317 Chemical compound C1=CC(C(=N)NO)=CC=C1C1=CC=C(C=2C=CC(=CC=2)C(=N)NO)O1 SFZULDYEOVSIKM-UHFFFAOYSA-N 0.000 description 1
• 238000001311 chemical methods and process Methods 0.000 description 1
• FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
• 150000001860 citric acid derivatives Chemical class 0.000 description 1
• 230000003081 coactivator Effects 0.000 description 1
• 239000012230 colorless oil Substances 0.000 description 1
• 230000002860 competitive effect Effects 0.000 description 1
• 230000009918 complex formation Effects 0.000 description 1
• 239000012141 concentrate Substances 0.000 description 1
• 239000000470 constituent Substances 0.000 description 1
• 238000006880 cross-coupling reaction Methods 0.000 description 1
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 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
• NISGSNTVMOOSJQ-UHFFFAOYSA-N cyclopentanamine Chemical compound NC1CCCC1 NISGSNTVMOOSJQ-UHFFFAOYSA-N 0.000 description 1
• 230000001472 cytotoxic effect Effects 0.000 description 1
• 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 230000001419 dependent effect Effects 0.000 description 1
• 150000008050 dialkyl sulfates Chemical class 0.000 description 1
• OCXGTPDKNBIOTF-UHFFFAOYSA-N dibromo(triphenyl)-$l^{5}-phosphane Chemical compound C=1C=CC=CC=1P(Br)(C=1C=CC=CC=1)(Br)C1=CC=CC=C1 OCXGTPDKNBIOTF-UHFFFAOYSA-N 0.000 description 1
• LMEDOLJKVASKTP-UHFFFAOYSA-N dibutyl sulfate Chemical class CCCCOS(=O)(=O)OCCCC LMEDOLJKVASKTP-UHFFFAOYSA-N 0.000 description 1
• 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• ZHXTWWCDMUWMDI-UHFFFAOYSA-N dihydroxyboron Chemical compound O[B]O ZHXTWWCDMUWMDI-UHFFFAOYSA-N 0.000 description 1
• 125000005594 diketone group Chemical group 0.000 description 1
• 239000003085 diluting agent Substances 0.000 description 1
• IFBVBPACKYFTOF-UHFFFAOYSA-N dimethyl 2-oxocyclopentane-1,1-dicarboxylate Chemical compound COC(=O)C1(C(=O)OC)CCCC1=O IFBVBPACKYFTOF-UHFFFAOYSA-N 0.000 description 1
• 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
• VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
• 230000008034 disappearance Effects 0.000 description 1
• 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 239000002552 dosage form Substances 0.000 description 1
• 229940079593 drug Drugs 0.000 description 1
• 238000001647 drug administration Methods 0.000 description 1
• 238000009510 drug design Methods 0.000 description 1
• 238000010828 elution Methods 0.000 description 1
• 150000002085 enols Chemical class 0.000 description 1
• VVDUZZGYBOWDSQ-UHFFFAOYSA-M eschenmoser's salt Chemical compound [I-].C[N+](C)=C VVDUZZGYBOWDSQ-UHFFFAOYSA-M 0.000 description 1
• 229960002568 ethinylestradiol Drugs 0.000 description 1
• 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
• 239000002024 ethyl acetate extract Substances 0.000 description 1
• UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 1
• 125000004705 ethylthio group Chemical group C(C)S* 0.000 description 1
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
• 238000000605 extraction Methods 0.000 description 1
• 239000012065 filter cake Substances 0.000 description 1
• 238000001914 filtration Methods 0.000 description 1
• 239000006260 foam Substances 0.000 description 1
• 235000003599 food sweetener Nutrition 0.000 description 1
• 238000004108 freeze drying Methods 0.000 description 1
• VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
• 125000000524 functional group Chemical group 0.000 description 1
• 125000003838 furazanyl group Chemical group 0.000 description 1
• 230000002496 gastric effect Effects 0.000 description 1
• 239000012362 glacial acetic acid Substances 0.000 description 1
• 239000011521 glass Substances 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 229940093915 gynecological organic acid Drugs 0.000 description 1
• 150000004820 halides Chemical class 0.000 description 1
• 125000001188 haloalkyl group Chemical group 0.000 description 1
• 208000014951 hematologic disease Diseases 0.000 description 1
• 125000005312 heteroarylalkynyl group Chemical group 0.000 description 1
• 125000005143 heteroarylsulfonyl group Chemical group 0.000 description 1
• 125000005368 heteroarylthio group Chemical group 0.000 description 1
• 239000008241 heterogeneous mixture Substances 0.000 description 1
• 238000004896 high resolution mass spectrometry Methods 0.000 description 1
• 238000002114 high-resolution electrospray ionisation mass spectrometry Methods 0.000 description 1
• 229940125697 hormonal agent Drugs 0.000 description 1
• 238000001794 hormone therapy Methods 0.000 description 1
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical class I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
• 238000005984 hydrogenation reaction Methods 0.000 description 1
• 230000007062 hydrolysis Effects 0.000 description 1
• 238000006460 hydrolysis reaction Methods 0.000 description 1
• RCCPEORTSYDPMB-UHFFFAOYSA-N hydroxy benzenecarboximidothioate Chemical compound OSC(=N)C1=CC=CC=C1 RCCPEORTSYDPMB-UHFFFAOYSA-N 0.000 description 1
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
• 230000001969 hypertrophic effect Effects 0.000 description 1
• 239000005457 ice water Substances 0.000 description 1
• 125000002883 imidazolyl group Chemical group 0.000 description 1
• 125000005945 imidazopyridyl group Chemical group 0.000 description 1
• 238000000338 in vitro Methods 0.000 description 1
• 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
• JYGFTBXVXVMTGB-UHFFFAOYSA-N indolin-2-one Chemical compound C1=CC=C2NC(=O)CC2=C1 JYGFTBXVXVMTGB-UHFFFAOYSA-N 0.000 description 1
• 125000001041 indolyl group Chemical group 0.000 description 1
• 230000001939 inductive effect Effects 0.000 description 1
• 208000015181 infectious disease Diseases 0.000 description 1
• 230000000977 initiatory effect Effects 0.000 description 1
• 238000002347 injection Methods 0.000 description 1
• 239000007924 injection Substances 0.000 description 1
• 150000007529 inorganic bases Chemical class 0.000 description 1
• 230000002452 interceptive effect Effects 0.000 description 1
• 229940047124 interferons Drugs 0.000 description 1
• 239000011630 iodine Substances 0.000 description 1
• 239000003456 ion exchange resin Substances 0.000 description 1
• 229920003303 ion-exchange polymer Polymers 0.000 description 1
• 150000002500 ions Chemical class 0.000 description 1
• 208000037906 ischaemic injury Diseases 0.000 description 1
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
• 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 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
• 125000000842 isoxazolyl group Chemical group 0.000 description 1
• 125000000468 ketone group Chemical group 0.000 description 1
• 229940043355 kinase inhibitor Drugs 0.000 description 1
• 150000003951 lactams Chemical class 0.000 description 1
• 150000003893 lactate salts Chemical class 0.000 description 1
• 150000002596 lactones Chemical class 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 229910052744 lithium Inorganic materials 0.000 description 1
• 229910003002 lithium salt Inorganic materials 0.000 description 1
• 159000000002 lithium salts Chemical class 0.000 description 1
• SBNKPLLRLXWYQI-UHFFFAOYSA-N lithium;di(propan-2-yl)azanide;ethyl acetate Chemical compound [Li+].CCOC(C)=O.CC(C)[N-]C(C)C SBNKPLLRLXWYQI-UHFFFAOYSA-N 0.000 description 1
• 208000019423 liver disease Diseases 0.000 description 1
• 239000006210 lotion Substances 0.000 description 1
• 206010025135 lupus erythematosus Diseases 0.000 description 1
• 239000006166 lysate Substances 0.000 description 1
• ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
• 239000001095 magnesium carbonate Substances 0.000 description 1
• 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
• 159000000003 magnesium salts Chemical class 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• GFTXWCQFWLOXAT-UHFFFAOYSA-M magnesium;cyclohexane;bromide Chemical compound [Mg+2].[Br-].C1CC[CH-]CC1 GFTXWCQFWLOXAT-UHFFFAOYSA-M 0.000 description 1
• VFZXMEQGIIWBFJ-UHFFFAOYSA-M magnesium;cyclopropane;bromide Chemical compound [Mg+2].[Br-].C1C[CH-]1 VFZXMEQGIIWBFJ-UHFFFAOYSA-M 0.000 description 1
• BRKADVNLTRCLOW-UHFFFAOYSA-M magnesium;fluorobenzene;bromide Chemical compound [Mg+2].[Br-].FC1=CC=[C-]C=C1 BRKADVNLTRCLOW-UHFFFAOYSA-M 0.000 description 1
• 230000014759 maintenance of location Effects 0.000 description 1
• 150000002688 maleic acid derivatives Chemical class 0.000 description 1
• 230000003211 malignant effect Effects 0.000 description 1
• 239000011159 matrix material Substances 0.000 description 1
• 230000001404 mediated effect Effects 0.000 description 1
• 230000002503 metabolic effect Effects 0.000 description 1
• LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 description 1
• 230000009401 metastasis Effects 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
• HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical class CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 description 1
• HQEIPVHJHZTMDP-JEDNCBNOSA-N methyl (2s)-pyrrolidine-2-carboxylate;hydrochloride Chemical compound Cl.COC(=O)[C@@H]1CCCN1 HQEIPVHJHZTMDP-JEDNCBNOSA-N 0.000 description 1
• PZBBESSUKAHBHD-UHFFFAOYSA-N methyl 2-oxocyclopentane-1-carboxylate Chemical compound COC(=O)C1CCCC1=O PZBBESSUKAHBHD-UHFFFAOYSA-N 0.000 description 1
• XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
• 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 125000002757 morpholinyl group Chemical group 0.000 description 1
• 201000006417 multiple sclerosis Diseases 0.000 description 1
• 210000002346 musculoskeletal system Anatomy 0.000 description 1
• 231100000219 mutagenic Toxicity 0.000 description 1
• 230000003505 mutagenic effect Effects 0.000 description 1
• 208000010125 myocardial infarction Diseases 0.000 description 1
• DILRJUIACXKSQE-UHFFFAOYSA-N n',n'-dimethylethane-1,2-diamine Chemical compound CN(C)CCN DILRJUIACXKSQE-UHFFFAOYSA-N 0.000 description 1
• WCZAXBXVDLKQGV-UHFFFAOYSA-N n,n-dimethyl-2-(7-oxobenzo[c]fluoren-5-yl)oxyethanamine oxide Chemical compound C12=CC=CC=C2C(OCC[N+](C)([O-])C)=CC2=C1C1=CC=CC=C1C2=O WCZAXBXVDLKQGV-UHFFFAOYSA-N 0.000 description 1
• FMASTMURQSHELY-UHFFFAOYSA-N n-(4-fluoro-2-methylphenyl)-3-methyl-n-[(2-methyl-1h-indol-4-yl)methyl]pyridine-4-carboxamide Chemical compound C1=CC=C2NC(C)=CC2=C1CN(C=1C(=CC(F)=CC=1)C)C(=O)C1=CC=NC=C1C FMASTMURQSHELY-UHFFFAOYSA-N 0.000 description 1
• 125000006606 n-butoxy group Chemical group 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical class C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
• 125000001624 naphthyl group Chemical group 0.000 description 1
• 125000005029 naphthylthio group Chemical group C1(=CC=CC2=CC=CC=C12)S* 0.000 description 1
• 230000001537 neural effect Effects 0.000 description 1
• 201000004931 neurofibromatosis Diseases 0.000 description 1
• 230000000926 neurological effect Effects 0.000 description 1
• 150000002823 nitrates Chemical class 0.000 description 1
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
• ODUCDPQEXGNKDN-UHFFFAOYSA-N nitroxyl Chemical compound O=N ODUCDPQEXGNKDN-UHFFFAOYSA-N 0.000 description 1
• 125000006574 non-aromatic ring group Chemical group 0.000 description 1
• 231100000252 nontoxic Toxicity 0.000 description 1
• 230000003000 nontoxic effect Effects 0.000 description 1
• 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
• 230000006508 oncogene activation Effects 0.000 description 1
• 239000003605 opacifier Substances 0.000 description 1
• 230000003287 optical effect Effects 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 125000001979 organolithium group Chemical group 0.000 description 1
• 125000002524 organometallic group Chemical group 0.000 description 1
• 230000002611 ovarian Effects 0.000 description 1
• WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
• 150000003891 oxalate salts Chemical class 0.000 description 1
• 125000004095 oxindolyl group Chemical group N1(C(CC2=CC=CC=C12)=O)* 0.000 description 1
• 125000004430 oxygen atom Chemical group O* 0.000 description 1
• NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 108010092851 peginterferon alfa-2b Proteins 0.000 description 1
• 229940106366 pegintron Drugs 0.000 description 1
• 210000001428 peripheral nervous system Anatomy 0.000 description 1
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
• 125000006678 phenoxycarbonyl group Chemical group 0.000 description 1
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
• 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
• 235000021317 phosphate Nutrition 0.000 description 1
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
• 230000026731 phosphorylation Effects 0.000 description 1
• 238000006366 phosphorylation reaction Methods 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
• 125000004193 piperazinyl group Chemical group 0.000 description 1
• JSPCTNUQYWIIOT-UHFFFAOYSA-N piperidine-1-carboxamide Chemical compound NC(=O)N1CCCCC1 JSPCTNUQYWIIOT-UHFFFAOYSA-N 0.000 description 1
• 125000005936 piperidyl group Chemical group 0.000 description 1
• 229910052697 platinum Inorganic materials 0.000 description 1
• 229920000642 polymer Polymers 0.000 description 1
• 208000015768 polyposis Diseases 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 159000000001 potassium salts Chemical class 0.000 description 1
• ZNNZYHKDIALBAK-UHFFFAOYSA-M potassium thiocyanate Chemical compound [K+].[S-]C#N ZNNZYHKDIALBAK-UHFFFAOYSA-M 0.000 description 1
• 229940116357 potassium thiocyanate Drugs 0.000 description 1
• 239000002243 precursor Substances 0.000 description 1
• 102000004196 processed proteins & peptides Human genes 0.000 description 1
• 230000035755 proliferation Effects 0.000 description 1
• ALDITMKAAPLVJK-UHFFFAOYSA-N prop-1-ene;hydrate Chemical group O.CC=C ALDITMKAAPLVJK-UHFFFAOYSA-N 0.000 description 1
• 125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
• DNIAPMSPPWPWGF-UHFFFAOYSA-N propylene glycol Substances CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 1
• 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
• 230000004224 protection Effects 0.000 description 1
• ROSDSFDQCJNGOL-UHFFFAOYSA-N protonated dimethyl amine Natural products CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 1
• 208000005069 pulmonary fibrosis Diseases 0.000 description 1
• 150000005230 pyrazolo[3,4-b]pyridines Chemical class 0.000 description 1
• 125000002098 pyridazinyl group Chemical group 0.000 description 1
• HDOUGSFASVGDCS-UHFFFAOYSA-N pyridin-3-ylmethanamine Chemical group NCC1=CC=CN=C1 HDOUGSFASVGDCS-UHFFFAOYSA-N 0.000 description 1
• 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
• 125000000714 pyrimidinyl group Chemical group 0.000 description 1
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
• 125000006085 pyrrolopyridyl group Chemical group 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 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
• 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
• 150000003254 radicals Chemical class 0.000 description 1
• 230000002285 radioactive effect Effects 0.000 description 1
• 108020003175 receptors Proteins 0.000 description 1
• 102000005962 receptors Human genes 0.000 description 1
• 238000005932 reductive alkylation reaction Methods 0.000 description 1
• 238000011160 research Methods 0.000 description 1
• 230000004044 response Effects 0.000 description 1
• 208000037803 restenosis Diseases 0.000 description 1
• 230000000717 retained effect Effects 0.000 description 1
• 230000002441 reversible effect Effects 0.000 description 1
• 206010039073 rheumatoid arthritis Diseases 0.000 description 1
• 150000003873 salicylate salts Chemical class 0.000 description 1
• 239000012047 saturated solution Substances 0.000 description 1
• 230000036573 scar formation Effects 0.000 description 1
• BTIHMVBBUGXLCJ-OAHLLOKOSA-N seliciclib Chemical compound C=12N=CN(C(C)C)C2=NC(N[C@@H](CO)CC)=NC=1NCC1=CC=CC=C1 BTIHMVBBUGXLCJ-OAHLLOKOSA-N 0.000 description 1
• 238000013207 serial dilution Methods 0.000 description 1
• 238000007086 side reaction Methods 0.000 description 1
• 230000019491 signal transduction Effects 0.000 description 1
• XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
• 201000009890 sinusitis Diseases 0.000 description 1
• 210000003491 skin Anatomy 0.000 description 1
• 229910000029 sodium carbonate Inorganic materials 0.000 description 1
• 229910052938 sodium sulfate Inorganic materials 0.000 description 1
• 235000011152 sodium sulphate Nutrition 0.000 description 1
• 239000007909 solid dosage form Substances 0.000 description 1
• 241000894007 species Species 0.000 description 1
• 238000001228 spectrum Methods 0.000 description 1
• 208000002320 spinal muscular atrophy Diseases 0.000 description 1
• 102000009076 src-Family Kinases Human genes 0.000 description 1
• 108010087686 src-Family Kinases Proteins 0.000 description 1
• 239000012258 stirred mixture Substances 0.000 description 1
• 239000000126 substance Substances 0.000 description 1
• 125000000547 substituted alkyl group Chemical group 0.000 description 1
• 125000004426 substituted alkynyl group Chemical group 0.000 description 1
• 150000003890 succinate salts Chemical class 0.000 description 1
• 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
• 239000006228 supernatant Substances 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 230000004083 survival effect Effects 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 208000024891 symptom Diseases 0.000 description 1
• 230000009885 systemic effect Effects 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 102000013498 tau Proteins Human genes 0.000 description 1
• 108010026424 tau Proteins Proteins 0.000 description 1
• 229940061353 temodar Drugs 0.000 description 1
• QLEBCEWTHGUFFL-UHFFFAOYSA-N tert-butyl 2-(2-aminoethyl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCCC1CCN QLEBCEWTHGUFFL-UHFFFAOYSA-N 0.000 description 1
• KLKBCNDBOVRQIJ-UHFFFAOYSA-N tert-butyl 4-(aminomethyl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CN)CC1 KLKBCNDBOVRQIJ-UHFFFAOYSA-N 0.000 description 1
• XQIKKZRRQGXGHF-UHFFFAOYSA-N tert-butyl n-(2-piperidin-3-ylethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCC1CCCNC1 XQIKKZRRQGXGHF-UHFFFAOYSA-N 0.000 description 1
• RQRMFFGCUUGYPC-UHFFFAOYSA-N tert-butyl n-(2-piperidin-4-ylethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCC1CCNCC1 RQRMFFGCUUGYPC-UHFFFAOYSA-N 0.000 description 1
• KHPQHXGYYXYTDN-UHFFFAOYSA-N tert-butyl n-(piperidin-3-ylmethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCC1CCCNC1 KHPQHXGYYXYTDN-UHFFFAOYSA-N 0.000 description 1
• IVXIXTAKKFLIIP-UHFFFAOYSA-N tert-butyl n-[(1-methylpiperidin-3-yl)methyl]-n-[(2-methylpropan-2-yl)oxycarbonyl]carbamate Chemical compound CN1CCCC(CN(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C)C1 IVXIXTAKKFLIIP-UHFFFAOYSA-N 0.000 description 1
• DAIKYASGECCERG-UHFFFAOYSA-N tert-butyl n-[(3-cyanophenyl)methyl]-n-[(2-methylpropan-2-yl)oxycarbonyl]carbamate Chemical compound CC(C)(C)OC(=O)N(C(=O)OC(C)(C)C)CC1=CC=CC(C#N)=C1 DAIKYASGECCERG-UHFFFAOYSA-N 0.000 description 1
• 150000003512 tertiary amines Chemical class 0.000 description 1
• 238000012360 testing method Methods 0.000 description 1
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
• 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
• 125000003507 tetrahydrothiofenyl group Chemical group 0.000 description 1
• 150000003536 tetrazoles Chemical class 0.000 description 1
• 229940124597 therapeutic agent Drugs 0.000 description 1
• 125000001984 thiazolidinyl group Chemical group 0.000 description 1
• 125000000335 thiazolyl group Chemical group 0.000 description 1
• 125000004588 thienopyridyl group Chemical group S1C(=CC2=C1C=CC=N2)* 0.000 description 1
• 150000003567 thiocyanates Chemical class 0.000 description 1
• 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
• 229950009158 tipifarnib Drugs 0.000 description 1
• LBLYYCQCTBFVLH-UHFFFAOYSA-M toluenesulfonate group Chemical group C=1(C(=CC=CC1)S(=O)(=O)[O-])C LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
• 125000003944 tolyl group Chemical group 0.000 description 1
• 125000005490 tosylate group Chemical group 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
• 238000012546 transfer Methods 0.000 description 1
• 238000002054 transplantation Methods 0.000 description 1
• 230000016596 traversing start control point of mitotic cell cycle Effects 0.000 description 1
• 125000001425 triazolyl group Chemical group 0.000 description 1
• QIWRFOJWQSSRJZ-UHFFFAOYSA-N tributyl(ethenyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C=C QIWRFOJWQSSRJZ-UHFFFAOYSA-N 0.000 description 1
• ZHSKFONQCREGOG-UHFFFAOYSA-N triethyl(trifluoromethyl)silane Chemical compound CC[Si](CC)(CC)C(F)(F)F ZHSKFONQCREGOG-UHFFFAOYSA-N 0.000 description 1
• ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
• CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Substances C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 1
• IIHPVYJPDKJYOU-UHFFFAOYSA-N triphenylcarbethoxymethylenephosphorane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=CC(=O)OCC)C1=CC=CC=C1 IIHPVYJPDKJYOU-UHFFFAOYSA-N 0.000 description 1
• 230000005747 tumor angiogenesis Effects 0.000 description 1
• 241001529453 unidentified herpesvirus Species 0.000 description 1
• 210000003932 urinary bladder Anatomy 0.000 description 1
• 229910052720 vanadium Inorganic materials 0.000 description 1
• 238000007631 vascular surgery Methods 0.000 description 1
• 239000003981 vehicle Substances 0.000 description 1
• 238000010626 work up procedure Methods 0.000 description 1
• 101150051200 yedS gene Proteins 0.000 description 1
• 229910052725 zinc Inorganic materials 0.000 description 1
• 239000011701 zinc Substances 0.000 description 1
• HMBFIVLHOWOJRD-UHFFFAOYSA-M zinc;benzonitrile;iodide Chemical compound I[Zn+].N#CC1=CC=C[C-]=C1 HMBFIVLHOWOJRD-UHFFFAOYSA-M 0.000 description 1