JP2015512953A5 - - Google Patents

Info

Publication number

JP2015512953A5

JP2015512953A5 JP2015505991A JP2015505991A JP2015512953A5 JP 2015512953 A5 JP2015512953 A5 JP 2015512953A5 JP 2015505991 A JP2015505991 A JP 2015505991A JP 2015505991 A JP2015505991 A JP 2015505991A JP 2015512953 A5 JP2015512953 A5 JP 2015512953A5

Authority

JP

Japan

Prior art keywords

sdc

trap

trap according

moiety

daltons

Prior art date

2013-04-16

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.)

Granted

Links

• Espacenet
• Global Dossier
• Discuss

• 239000012636 effector Substances 0.000 claims description 107
• 102100034051 Heat shock protein HSP 90-alpha Human genes 0.000 claims description 78
• 101001016865 Homo sapiens Heat shock protein HSP 90-alpha Proteins 0.000 claims description 78
• 231100000433 cytotoxic Toxicity 0.000 claims description 64
• 230000001472 cytotoxic effect Effects 0.000 claims description 64
• 238000000034 method Methods 0.000 claims description 45
• 239000003481 heat shock protein 90 inhibitor Substances 0.000 claims description 34
• 230000001225 therapeutic effect Effects 0.000 claims description 34
• 239000003446 ligand Substances 0.000 claims description 32
• 238000003384 imaging method Methods 0.000 claims description 23
• MWTUOSWPJOUADP-XDJHFCHBSA-N (5z)-5-(4-hydroxy-6-oxo-3-propan-2-ylcyclohexa-2,4-dien-1-ylidene)-4-(1-methylindol-5-yl)-1,2,4-triazolidin-3-one Chemical group O=C1C=C(O)C(C(C)C)=C\C1=C\1N(C=2C=C3C=CN(C)C3=CC=2)C(=O)NN/1 MWTUOSWPJOUADP-XDJHFCHBSA-N 0.000 claims description 17
• 229950004161 ganetespib Drugs 0.000 claims description 17
• 229940002612 prodrug Drugs 0.000 claims description 16
• 239000000651 prodrug Substances 0.000 claims description 16
• 108050001186 Chaperonin Cpn60 Proteins 0.000 claims description 10
• 102000052603 Chaperonins Human genes 0.000 claims description 10
• 102000004169 proteins and genes Human genes 0.000 claims description 9
• 108090000623 proteins and genes Proteins 0.000 claims description 9
• 239000003814 drug Substances 0.000 claims description 3
• 239000008194 pharmaceutical composition Substances 0.000 claims description 3
• 230000009056 active transport Effects 0.000 claims description 2
• 238000003745 diagnosis Methods 0.000 claims description 2
• 238000009792 diffusion process Methods 0.000 claims description 2
• 229940079593 drug Drugs 0.000 claims description 2
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
• 229940124531 pharmaceutical excipient Drugs 0.000 claims description 2
• AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 32
• AYUNIORJHRXIBJ-TXHRRWQRSA-N tanespimycin Chemical compound N1C(=O)\C(C)=C\C=C/[C@H](OC)[C@@H](OC(N)=O)\C(C)=C\[C@H](C)[C@@H](O)[C@@H](OC)C[C@H](C)CC2=C(NCC=C)C(=O)C=C1C2=O AYUNIORJHRXIBJ-TXHRRWQRSA-N 0.000 description 32
• 229950007866 tanespimycin Drugs 0.000 description 32
• 210000004027 cell Anatomy 0.000 description 26
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical group NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 16
• GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 16
• JRZJKWGQFNTSRN-UHFFFAOYSA-N Geldanamycin Natural products C1C(C)CC(OC)C(O)C(C)C=C(C)C(OC(N)=O)C(OC)CCC=C(C)C(=O)NC2=CC(=O)C(OC)=C1C2=O JRZJKWGQFNTSRN-UHFFFAOYSA-N 0.000 description 16
• 239000002146 L01XE16 - Crizotinib Substances 0.000 description 16
• 229930195248 Macbecin Natural products 0.000 description 16
• PLTGBUPHJAKFMA-UHFFFAOYSA-N Macbecin I Natural products N1C(=O)C(C)=CC=CC(C)C(OC(N)=O)C(C)=CC(C)C(OC)C(OC)CC(C)C(OC)C2=CC(=O)C=C1C2=O PLTGBUPHJAKFMA-UHFFFAOYSA-N 0.000 description 16
• ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 16
• 206010028980 Neoplasm Diseases 0.000 description 16
• PLTGBUPHJAKFMA-BMJWZTMLSA-N [(2r,3s,5s,6r,7s,8e,10r,11s,12z,14e)-2,5,6-trimethoxy-3,7,9,11,15-pentamethyl-16,20,22-trioxo-17-azabicyclo[16.3.1]docosa-1(21),8,12,14,18-pentaen-10-yl] carbamate Chemical compound N1C(=O)\C(C)=C\C=C/[C@H](C)[C@@H](OC(N)=O)\C(C)=C\[C@H](C)[C@@H](OC)[C@@H](OC)C[C@H](C)[C@@H](OC)C2=CC(=O)C=C1C2=O PLTGBUPHJAKFMA-BMJWZTMLSA-N 0.000 description 16
• GZOSMCIZMLWJML-VJLLXTKPSA-N abiraterone Chemical compound C([C@H]1[C@H]2[C@@H]([C@]3(CC[C@H](O)CC3=CC2)C)CC[C@@]11C)C=C1C1=CC=CN=C1 GZOSMCIZMLWJML-VJLLXTKPSA-N 0.000 description 16
• 229960000853 abiraterone Drugs 0.000 description 16
• 150000001408 amides Chemical group 0.000 description 16
• YTKUWDBFDASYHO-UHFFFAOYSA-N bendamustine Chemical compound ClCCN(CCCl)C1=CC=C2N(C)C(CCCC(O)=O)=NC2=C1 YTKUWDBFDASYHO-UHFFFAOYSA-N 0.000 description 16
• 229960002707 bendamustine Drugs 0.000 description 16
• 201000011510 cancer Diseases 0.000 description 16
• KQJSQWZMSAGSHN-JJWQIEBTSA-N celastrol Chemical compound C([C@H]1[C@]2(C)CC[C@@]34C)[C@](C)(C(O)=O)CC[C@]1(C)CC[C@]2(C)C4=CC=C1C3=CC(=O)C(O)=C1C KQJSQWZMSAGSHN-JJWQIEBTSA-N 0.000 description 16
• KTEIFNKAUNYNJU-GFCCVEGCSA-N crizotinib Chemical compound O([C@H](C)C=1C(=C(F)C=CC=1Cl)Cl)C(C(=NC=1)N)=CC=1C(=C1)C=NN1C1CCNCC1 KTEIFNKAUNYNJU-GFCCVEGCSA-N 0.000 description 16
• 229960005061 crizotinib Drugs 0.000 description 16
• 125000002228 disulfide group Chemical group 0.000 description 16
• 229960003668 docetaxel Drugs 0.000 description 16
• 229960004679 doxorubicin Drugs 0.000 description 16
• 150000002148 esters Chemical group 0.000 description 16
• RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Chemical group CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
• 229960002949 fluorouracil Drugs 0.000 description 16
• 239000012634 fragment Substances 0.000 description 16
• QTQAWLPCGQOSGP-GBTDJJJQSA-N geldanamycin Chemical group N1C(=O)\C(C)=C/C=C\[C@@H](OC)[C@H](OC(N)=O)\C(C)=C/[C@@H](C)[C@@H](O)[C@H](OC)C[C@@H](C)CC2=C(OC)C(=O)C=C1C2=O QTQAWLPCGQOSGP-GBTDJJJQSA-N 0.000 description 16
• 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 description 16
• 229960004768 irinotecan Drugs 0.000 description 16
• GOTYRUGSSMKFNF-UHFFFAOYSA-N lenalidomide Chemical compound C1C=2C(N)=CC=CC=2C(=O)N1C1CCC(=O)NC1=O GOTYRUGSSMKFNF-UHFFFAOYSA-N 0.000 description 16
• 229960004942 lenalidomide Drugs 0.000 description 16
• VYGYNVZNSSTDLJ-HKCOAVLJSA-N monorden Natural products CC1CC2OC2C=C/C=C/C(=O)CC3C(C(=CC(=C3Cl)O)O)C(=O)O1 VYGYNVZNSSTDLJ-HKCOAVLJSA-N 0.000 description 16
• QOFFJEBXNKRSPX-ZDUSSCGKSA-N pemetrexed Chemical compound C1=N[C]2NC(N)=NC(=O)C2=C1CCC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 QOFFJEBXNKRSPX-ZDUSSCGKSA-N 0.000 description 16
• 229960005079 pemetrexed Drugs 0.000 description 16
• AECPBJMOGBFQDN-YMYQVXQQSA-N radicicol Chemical compound C1CCCC(=O)C[C@H]2[C@H](Cl)C(=O)CC(=O)[C@H]2C(=O)O[C@H](C)C[C@H]2O[C@@H]21 AECPBJMOGBFQDN-YMYQVXQQSA-N 0.000 description 16
• 229930192524 radicicol Natural products 0.000 description 16
• 230000001988 toxicity Effects 0.000 description 16
• 231100000419 toxicity Toxicity 0.000 description 16
• WAEXFXRVDQXREF-UHFFFAOYSA-N vorinostat Chemical compound ONC(=O)CCCCCCC(=O)NC1=CC=CC=C1 WAEXFXRVDQXREF-UHFFFAOYSA-N 0.000 description 16
• 229960000237 vorinostat Drugs 0.000 description 16
• 210000004881 tumor cell Anatomy 0.000 description 3
• 230000008685 targeting Effects 0.000 description 2
• 210000004899 c-terminal region Anatomy 0.000 description 1
• 230000000694 effects Effects 0.000 description 1
• 229940124597 therapeutic agent Drugs 0.000 description 1
• 231100000331 toxic Toxicity 0.000 description 1
• 230000002588 toxic effect Effects 0.000 description 1