JP2019535710A5 - - Google Patents

Info

Publication number

JP2019535710A5

JP2019535710A5 JP2019524935A JP2019524935A JP2019535710A5 JP 2019535710 A5 JP2019535710 A5 JP 2019535710A5 JP 2019524935 A JP2019524935 A JP 2019524935A JP 2019524935 A JP2019524935 A JP 2019524935A JP 2019535710 A5 JP2019535710 A5 JP 2019535710A5

Authority

JP

Japan

Prior art keywords

polymer

formula

drug conjugate

null

natural number

Prior art date

2017-11-16

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
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• 239000000580 polymer-drug conjugate Substances 0.000 claims 14
• 239000003814 drug Substances 0.000 claims 10
• 229920000642 polymer Chemical class 0.000 claims 10
• 229940124597 therapeutic agent Drugs 0.000 claims 7
• AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 claims 6
• GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims 5
• 239000012986 chain transfer agent Substances 0.000 claims 5
• 239000000562 conjugate Substances 0.000 claims 5
• 229960002949 fluorouracil Drugs 0.000 claims 5
• WHTVZRBIWZFKQO-AWEZNQCLSA-N (S)-chloroquine Chemical compound ClC1=CC=C2C(N[C@@H](C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-AWEZNQCLSA-N 0.000 claims 4
• 229960003677 chloroquine Drugs 0.000 claims 4
• WHTVZRBIWZFKQO-UHFFFAOYSA-N chloroquine Natural products ClC1=CC=C2C(NC(C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-UHFFFAOYSA-N 0.000 claims 4
• 239000012634 fragment Substances 0.000 claims 4
• 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 4
• 229960005277 gemcitabine Drugs 0.000 claims 4
• 239000003999 initiator Substances 0.000 claims 4
• 239000000178 monomer Substances 0.000 claims 4
• 108090000765 processed proteins & peptides Proteins 0.000 claims 4
• LGZKGOGODCLQHG-CYBMUJFWSA-N 5-[(2r)-2-hydroxy-2-(3,4,5-trimethoxyphenyl)ethyl]-2-methoxyphenol Chemical compound C1=C(O)C(OC)=CC=C1C[C@@H](O)C1=CC(OC)=C(OC)C(OC)=C1 LGZKGOGODCLQHG-CYBMUJFWSA-N 0.000 claims 3
• NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 claims 3
• LGZKGOGODCLQHG-UHFFFAOYSA-N combretastatin Natural products C1=C(O)C(OC)=CC=C1CC(O)C1=CC(OC)=C(OC)C(OC)=C1 LGZKGOGODCLQHG-UHFFFAOYSA-N 0.000 claims 3
• 229960004679 doxorubicin Drugs 0.000 claims 3
• 229940079593 drug Drugs 0.000 claims 3
• 125000000524 functional group Chemical group 0.000 claims 3
• 238000000034 method Methods 0.000 claims 3
• 229920001223 polyethylene glycol Polymers 0.000 claims 3
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims 2
• 206010028980 Neoplasm Diseases 0.000 claims 2
• -1 Platinumates Substances 0.000 claims 2
• 201000011510 cancer Diseases 0.000 claims 2
• 229930195733 hydrocarbon Natural products 0.000 claims 2
• 150000002430 hydrocarbons Chemical class 0.000 claims 2
• 238000006116 polymerization reaction Methods 0.000 claims 2
• 230000002265 prevention Effects 0.000 claims 2
• 102000004196 processed proteins & peptides Human genes 0.000 claims 2
• KQRHTCDQWJLLME-XUXIUFHCSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-aminopropanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-4-methylpentanoic acid Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)N KQRHTCDQWJLLME-XUXIUFHCSA-N 0.000 claims 1
• AGGWFDNPHKLBBV-YUMQZZPRSA-N (2s)-2-[[(2s)-2-amino-3-methylbutanoyl]amino]-5-(carbamoylamino)pentanoic acid Chemical compound CC(C)[C@H](N)C(=O)N[C@H](C(O)=O)CCCNC(N)=O AGGWFDNPHKLBBV-YUMQZZPRSA-N 0.000 claims 1
• NVHPXYIRNJFKTE-HAGHYFMRSA-N 2-[(2s,5r,8s,11s)-8-(4-aminobutyl)-5-benzyl-11-[3-(diaminomethylideneamino)propyl]-3,6,9,12,15-pentaoxo-1,4,7,10,13-pentazacyclopentadec-2-yl]acetic acid Chemical compound N1C(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H]1CC1=CC=CC=C1 NVHPXYIRNJFKTE-HAGHYFMRSA-N 0.000 claims 1
• WEZDRVHTDXTVLT-GJZGRUSLSA-N 2-[[(2s)-2-[[(2s)-2-[(2-aminoacetyl)amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]acetic acid Chemical compound OC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)CN)CC1=CC=CC=C1 WEZDRVHTDXTVLT-GJZGRUSLSA-N 0.000 claims 1
• FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims 1
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims 1
• 239000004215 Carbon black (E152) Substances 0.000 claims 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims 1
• 102000004225 Cathepsin B Human genes 0.000 claims 1
• 108090000712 Cathepsin B Proteins 0.000 claims 1
• 229940123780 DNA topoisomerase I inhibitor Drugs 0.000 claims 1
• BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 claims 1
• 108010009504 Gly-Phe-Leu-Gly Proteins 0.000 claims 1
• 102000008394 Immunoglobulin Fragments Human genes 0.000 claims 1
• 108010021625 Immunoglobulin Fragments Proteins 0.000 claims 1
• FADYJNXDPBKVCA-UHFFFAOYSA-N L-Phenylalanyl-L-lysin Natural products NCCCCC(C(O)=O)NC(=O)C(N)CC1=CC=CC=C1 FADYJNXDPBKVCA-UHFFFAOYSA-N 0.000 claims 1
• FADYJNXDPBKVCA-STQMWFEESA-N Phe-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](N)CC1=CC=CC=C1 FADYJNXDPBKVCA-STQMWFEESA-N 0.000 claims 1
• 102000013530 TOR Serine-Threonine Kinases Human genes 0.000 claims 1
• 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 claims 1
• 239000000365 Topoisomerase I Inhibitor Substances 0.000 claims 1
• HSRXSKHRSXRCFC-WDSKDSINSA-N Val-Ala Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C)C(O)=O HSRXSKHRSXRCFC-WDSKDSINSA-N 0.000 claims 1
• 229940122803 Vinca alkaloid Drugs 0.000 claims 1
• DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims 1
• 150000001241 acetals Chemical class 0.000 claims 1
• 108010054982 alanyl-leucyl-alanyl-leucine Proteins 0.000 claims 1
• 229940100198 alkylating agent Drugs 0.000 claims 1
• 239000002168 alkylating agent Substances 0.000 claims 1
• 150000001408 amides Chemical class 0.000 claims 1
• 150000001413 amino acids Chemical class 0.000 claims 1
• 229940045799 anthracyclines and related substance Drugs 0.000 claims 1
• 230000003432 anti-folate effect Effects 0.000 claims 1
• 229940127074 antifolate Drugs 0.000 claims 1
• 239000013059 antihormonal agent Substances 0.000 claims 1
• 229920001400 block copolymer Polymers 0.000 claims 1
• 238000006243 chemical reaction Methods 0.000 claims 1
• 229920001577 copolymer Polymers 0.000 claims 1
• 150000002148 esters Chemical class 0.000 claims 1
• 239000004052 folic acid antagonist Substances 0.000 claims 1
• 229940121372 histone deacetylase inhibitor Drugs 0.000 claims 1
• 239000003276 histone deacetylase inhibitor Substances 0.000 claims 1
• 150000002466 imines Chemical class 0.000 claims 1
• 239000002955 immunomodulating agent Substances 0.000 claims 1
• 229940121354 immunomodulator Drugs 0.000 claims 1
• 239000003112 inhibitor Substances 0.000 claims 1
• 239000002207 metabolite Substances 0.000 claims 1
• 239000000693 micelle Substances 0.000 claims 1
• 239000002105 nanoparticle Substances 0.000 claims 1
• 239000002777 nucleoside Substances 0.000 claims 1
• 125000003835 nucleoside group Chemical class 0.000 claims 1
• 239000008194 pharmaceutical composition Substances 0.000 claims 1
• 230000004962 physiological condition Effects 0.000 claims 1
• 229920001308 poly(aminoacid) Polymers 0.000 claims 1
• 229940121896 radiopharmaceutical Drugs 0.000 claims 1
• 239000012217 radiopharmaceutical Substances 0.000 claims 1
• 230000002799 radiopharmaceutical effect Effects 0.000 claims 1
• ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 claims 1
• QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 claims 1
• 229960002930 sirolimus Drugs 0.000 claims 1
• 229940121358 tyrosine kinase inhibitor Drugs 0.000 claims 1
• 239000005483 tyrosine kinase inhibitor Substances 0.000 claims 1