JPWO2021226092A5 - - Google Patents
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- JPWO2021226092A5 JPWO2021226092A5 JP2022567136A JP2022567136A JPWO2021226092A5 JP WO2021226092 A5 JPWO2021226092 A5 JP WO2021226092A5 JP 2022567136 A JP2022567136 A JP 2022567136A JP 2022567136 A JP2022567136 A JP 2022567136A JP WO2021226092 A5 JPWO2021226092 A5 JP WO2021226092A5
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- 150000003384 small molecules Chemical class 0.000 claims description 11
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- 125000003342 alkenyl group Chemical group 0.000 claims description 6
- 125000000304 alkynyl group Chemical group 0.000 claims description 6
- PKVRCIRHQMSYJX-AIFWHQITSA-N trabectedin Chemical compound C([C@@]1(C(OC2)=O)NCCC3=C1C=C(C(=C3)O)OC)S[C@@H]1C3=C(OC(C)=O)C(C)=C4OCOC4=C3[C@H]2N2[C@@H](O)[C@H](CC=3C4=C(O)C(OC)=C(C)C=3)N(C)[C@H]4[C@@H]21 PKVRCIRHQMSYJX-AIFWHQITSA-N 0.000 claims description 6
- 229960000977 trabectedin Drugs 0.000 claims description 6
- 102000039446 nucleic acids Human genes 0.000 claims description 5
- 108020004707 nucleic acids Proteins 0.000 claims description 5
- 150000007523 nucleic acids Chemical class 0.000 claims description 5
- 102000004169 proteins and genes Human genes 0.000 claims description 5
- 108090000623 proteins and genes Proteins 0.000 claims description 5
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- 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 4
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- 125000000217 alkyl group Chemical group 0.000 claims description 4
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- 229960001904 epirubicin Drugs 0.000 claims description 4
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- 150000003839 salts Chemical class 0.000 claims description 4
- -1 streptozotecin Chemical compound 0.000 claims description 4
- AQTQHPDCURKLKT-JKDPCDLQSA-N vincristine sulfate Chemical compound OS(O)(=O)=O.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=O)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 AQTQHPDCURKLKT-JKDPCDLQSA-N 0.000 claims description 4
- 229960002110 vincristine sulfate Drugs 0.000 claims description 4
- 239000002245 particle Substances 0.000 claims description 3
- NAALWFYYHHJEFQ-ZASNTINBSA-N (2s,5r,6r)-6-[[(2r)-2-[[6-[4-[bis(2-hydroxyethyl)sulfamoyl]phenyl]-2-oxo-1h-pyridine-3-carbonyl]amino]-2-(4-hydroxyphenyl)acetyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid Chemical compound N([C@@H](C(=O)N[C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C=1C=CC(O)=CC=1)C(=O)C(C(N1)=O)=CC=C1C1=CC=C(S(=O)(=O)N(CCO)CCO)C=C1 NAALWFYYHHJEFQ-ZASNTINBSA-N 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
- QRBLKGHRWFGINE-UGWAGOLRSA-N 2-[2-[2-[[2-[[4-[[2-[[6-amino-2-[3-amino-1-[(2,3-diamino-3-oxopropyl)amino]-3-oxopropyl]-5-methylpyrimidine-4-carbonyl]amino]-3-[(2r,3s,4s,5s,6s)-3-[(2s,3r,4r,5s)-4-carbamoyl-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-4,5-dihydroxy-6-(hydroxymethyl)- Chemical compound N=1C(C=2SC=C(N=2)C(N)=O)CSC=1CCNC(=O)C(C(C)=O)NC(=O)C(C)C(O)C(C)NC(=O)C(C(O[C@H]1[C@@]([C@@H](O)[C@H](O)[C@H](CO)O1)(C)O[C@H]1[C@@H]([C@](O)([C@@H](O)C(CO)O1)C(N)=O)O)C=1NC=NC=1)NC(=O)C1=NC(C(CC(N)=O)NCC(N)C(N)=O)=NC(N)=C1C QRBLKGHRWFGINE-UGWAGOLRSA-N 0.000 claims description 2
- ZGCSNRKSJLVANE-UHFFFAOYSA-N Aglycone-Rebeccamycin Natural products N1C2=C3NC4=C(Cl)C=CC=C4C3=C(C(=O)NC3=O)C3=C2C2=C1C(Cl)=CC=C2 ZGCSNRKSJLVANE-UHFFFAOYSA-N 0.000 claims description 2
- APKFDSVGJQXUKY-KKGHZKTASA-N Amphotericin-B Natural products O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1C=CC=CC=CC=CC=CC=CC=C[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-KKGHZKTASA-N 0.000 claims description 2
- 108010006654 Bleomycin Proteins 0.000 claims description 2
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 claims description 2
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 claims description 2
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 2
- 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 2
- 108010092160 Dactinomycin Proteins 0.000 claims description 2
- HKVAMNSJSFKALM-GKUWKFKPSA-N Everolimus Chemical compound C1C[C@@H](OCCO)[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 HKVAMNSJSFKALM-GKUWKFKPSA-N 0.000 claims description 2
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 2
- 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 2
- 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 2
- 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 2
- 239000005517 L01XE01 - Imatinib Substances 0.000 claims description 2
- 239000005411 L01XE02 - Gefitinib Substances 0.000 claims description 2
- 239000005551 L01XE03 - Erlotinib Substances 0.000 claims description 2
- 239000005536 L01XE08 - Nilotinib Substances 0.000 claims description 2
- 239000002144 L01XE18 - Ruxolitinib Substances 0.000 claims description 2
- 239000002177 L01XE27 - Ibrutinib Substances 0.000 claims description 2
- 229930012538 Paclitaxel Natural products 0.000 claims description 2
- MHRARRIFWSILEQ-UHFFFAOYSA-N Pederin Natural products COCC(CC1OC2C(NC(=O)C(O)C3(CC(=O)C(C)C(C)O3)OC)OCOC2C(OC)C1(C)C)OC MHRARRIFWSILEQ-UHFFFAOYSA-N 0.000 claims description 2
- LTQCLFMNABRKSH-UHFFFAOYSA-N Phleomycin Natural products N=1C(C=2SC=C(N=2)C(N)=O)CSC=1CCNC(=O)C(C(O)C)NC(=O)C(C)C(O)C(C)NC(=O)C(C(OC1C(C(O)C(O)C(CO)O1)OC1C(C(OC(N)=O)C(O)C(CO)O1)O)C=1NC=NC=1)NC(=O)C1=NC(C(CC(N)=O)NCC(N)C(N)=O)=NC(N)=C1C LTQCLFMNABRKSH-UHFFFAOYSA-N 0.000 claims description 2
- 108010035235 Phleomycins Proteins 0.000 claims description 2
- KMSKQZKKOZQFFG-HSUXVGOQSA-N Pirarubicin Chemical compound O([C@H]1[C@@H](N)C[C@@H](O[C@H]1C)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]1CCCCO1 KMSKQZKKOZQFFG-HSUXVGOQSA-N 0.000 claims description 2
- QEHOIJJIZXRMAN-UHFFFAOYSA-N Rebeccamycin Natural products OC1C(O)C(OC)C(CO)OC1N1C2=C3NC4=C(Cl)C=CC=C4C3=C3C(=O)NC(=O)C3=C2C2=CC=CC(Cl)=C21 QEHOIJJIZXRMAN-UHFFFAOYSA-N 0.000 claims description 2
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 claims description 2
- UVIQSJCZCSLXRZ-UBUQANBQSA-N abiraterone acetate Chemical compound C([C@@H]1[C@]2(C)CC[C@@H]3[C@@]4(C)CC[C@@H](CC4=CC[C@H]31)OC(=O)C)C=C2C1=CC=CN=C1 UVIQSJCZCSLXRZ-UBUQANBQSA-N 0.000 claims description 2
- 229960004103 abiraterone acetate Drugs 0.000 claims description 2
- 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 2
- 229960001686 afatinib Drugs 0.000 claims description 2
- ULXXDDBFHOBEHA-CWDCEQMOSA-N afatinib Chemical compound N1=CN=C2C=C(O[C@@H]3COCC3)C(NC(=O)/C=C/CN(C)C)=CC2=C1NC1=CC=C(F)C(Cl)=C1 ULXXDDBFHOBEHA-CWDCEQMOSA-N 0.000 claims description 2
- APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 claims description 2
- 229960003942 amphotericin b Drugs 0.000 claims description 2
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- VJZITPJGSQKZMX-XDPRQOKASA-N amrubicin Chemical compound O([C@H]1C[C@](CC2=C(O)C=3C(=O)C4=CC=CC=C4C(=O)C=3C(O)=C21)(N)C(=O)C)[C@H]1C[C@H](O)[C@H](O)CO1 VJZITPJGSQKZMX-XDPRQOKASA-N 0.000 claims description 2
- 229940121375 antifungal agent Drugs 0.000 claims description 2
- 239000003429 antifungal agent Substances 0.000 claims description 2
- 239000002246 antineoplastic agent Substances 0.000 claims description 2
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 claims description 2
- 229960001561 bleomycin Drugs 0.000 claims description 2
- 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 2
- GXJABQQUPOEUTA-RDJZCZTQSA-N bortezomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)B(O)O)NC(=O)C=1N=CC=NC=1)C1=CC=CC=C1 GXJABQQUPOEUTA-RDJZCZTQSA-N 0.000 claims description 2
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- WXCXUHSOUPDCQV-UHFFFAOYSA-N enzalutamide Chemical compound C1=C(F)C(C(=O)NC)=CC=C1N1C(C)(C)C(=O)N(C=2C=C(C(C#N)=CC=2)C(F)(F)F)C1=S WXCXUHSOUPDCQV-UHFFFAOYSA-N 0.000 claims description 2
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- 125000004404 heteroalkyl group Chemical group 0.000 claims description 2
- 229940088013 hycamtin Drugs 0.000 claims description 2
- 229960001507 ibrutinib Drugs 0.000 claims description 2
- XYFPWWZEPKGCCK-GOSISDBHSA-N ibrutinib Chemical compound C1=2C(N)=NC=NC=2N([C@H]2CN(CCC2)C(=O)C=C)N=C1C(C=C1)=CC=C1OC1=CC=CC=C1 XYFPWWZEPKGCCK-GOSISDBHSA-N 0.000 claims description 2
- 229960000908 idarubicin Drugs 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 description 2
- 229960002411 imatinib Drugs 0.000 claims description 2
- 229960000779 irinotecan hydrochloride Drugs 0.000 claims description 2
- 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 claims description 2
- 229960002014 ixabepilone Drugs 0.000 claims description 2
- FABUFPQFXZVHFB-CFWQTKTJSA-N ixabepilone Chemical compound C/C([C@@H]1C[C@@H]2O[C@]2(C)CCC[C@@H]([C@@H]([C@H](C)C(=O)C(C)(C)[C@H](O)CC(=O)N1)O)C)=C\C1=CSC(C)=N1 FABUFPQFXZVHFB-CFWQTKTJSA-N 0.000 claims description 2
- 150000002596 lactones Chemical class 0.000 claims description 2
- GOTYRUGSSMKFNF-UHFFFAOYSA-N lenalidomide Chemical compound C1C=2C(N)=CC=CC=2C(=O)N1C1CCC(=O)NC1=O GOTYRUGSSMKFNF-UHFFFAOYSA-N 0.000 claims description 2
- 229960004942 lenalidomide Drugs 0.000 claims description 2
- 239000003120 macrolide antibiotic agent Substances 0.000 claims description 2
- 229950002736 marizomib Drugs 0.000 claims description 2
- 229960000485 methotrexate Drugs 0.000 claims description 2
- 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 2
- 229960004857 mitomycin Drugs 0.000 claims description 2
- 239000002858 neurotransmitter agent Substances 0.000 claims description 2
- HHZIURLSWUIHRB-UHFFFAOYSA-N nilotinib Chemical compound C1=NC(C)=CN1C1=CC(NC(=O)C=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)=CC(C(F)(F)F)=C1 HHZIURLSWUIHRB-UHFFFAOYSA-N 0.000 claims description 2
- 229960001346 nilotinib Drugs 0.000 claims description 2
- DUYJMQONPNNFPI-UHFFFAOYSA-N osimertinib Chemical compound COC1=CC(N(C)CCN(C)C)=C(NC(=O)C=C)C=C1NC1=NC=CC(C=2C3=CC=CC=C3N(C)C=2)=N1 DUYJMQONPNNFPI-UHFFFAOYSA-N 0.000 claims description 2
- 229960003278 osimertinib Drugs 0.000 claims description 2
- 229960001592 paclitaxel Drugs 0.000 claims description 2
- AHJRHEGDXFFMBM-UHFFFAOYSA-N palbociclib Chemical compound N1=C2N(C3CCCC3)C(=O)C(C(=O)C)=C(C)C2=CN=C1NC(N=C1)=CC=C1N1CCNCC1 AHJRHEGDXFFMBM-UHFFFAOYSA-N 0.000 claims description 2
- 229960004390 palbociclib Drugs 0.000 claims description 2
- ZNEZZONMADKYTB-VRCUBXEUSA-N pederin Chemical compound C1[C@@H](O)C(C)(C)[C@@H](C[C@@H](COC)OC)O[C@@H]1[C@H](OC)NC(=O)[C@@H](O)[C@]1(OC)O[C@H](C)[C@H](C)C(=C)C1 ZNEZZONMADKYTB-VRCUBXEUSA-N 0.000 claims description 2
- 229960005079 pemetrexed Drugs 0.000 claims description 2
- 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 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 229960001221 pirarubicin Drugs 0.000 claims description 2
- 229960003171 plicamycin Drugs 0.000 claims description 2
- 229950008499 plitidepsin Drugs 0.000 claims description 2
- UUSZLLQJYRSZIS-LXNNNBEUSA-N plitidepsin Chemical compound CN([C@H](CC(C)C)C(=O)N[C@@H]1C(=O)N[C@@H]([C@H](CC(=O)O[C@H](C(=O)[C@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N2CCC[C@H]2C(=O)N(C)[C@@H](CC=2C=CC(OC)=CC=2)C(=O)O[C@@H]1C)C(C)C)O)[C@@H](C)CC)C(=O)[C@@H]1CCCN1C(=O)C(C)=O UUSZLLQJYRSZIS-LXNNNBEUSA-N 0.000 claims description 2
- 108010049948 plitidepsin Proteins 0.000 claims description 2
- 229960005567 rebeccamycin Drugs 0.000 claims description 2
- INSACQSBHKIWNS-QZQSLCQPSA-N rebeccamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](OC)[C@@H](CO)O[C@H]1N1C2=C3N=C4[C](Cl)C=CC=C4C3=C3C(=O)NC(=O)C3=C2C2=CC=CC(Cl)=C21 INSACQSBHKIWNS-QZQSLCQPSA-N 0.000 claims description 2
- 229960000215 ruxolitinib Drugs 0.000 claims description 2
- HFNKQEVNSGCOJV-OAHLLOKOSA-N ruxolitinib Chemical compound C1([C@@H](CC#N)N2N=CC(=C2)C=2C=3C=CNC=3N=CN=2)CCCC1 HFNKQEVNSGCOJV-OAHLLOKOSA-N 0.000 claims description 2
- NGWSFRIPKNWYAO-SHTIJGAHSA-N salinosporamide A Chemical compound C([C@@H]1[C@H](O)[C@]23C(=O)O[C@]2([C@H](C(=O)N3)CCCl)C)CCC=C1 NGWSFRIPKNWYAO-SHTIJGAHSA-N 0.000 claims description 2
- NGWSFRIPKNWYAO-UHFFFAOYSA-N salinosporamide A Natural products N1C(=O)C(CCCl)C2(C)OC(=O)C21C(O)C1CCCC=C1 NGWSFRIPKNWYAO-UHFFFAOYSA-N 0.000 claims description 2
- 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 2
- 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 2
- 229960001278 teniposide Drugs 0.000 claims description 2
- 229930187659 theopederin Natural products 0.000 claims description 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 description 2
- 229960000653 valrubicin Drugs 0.000 claims description 2
- ZOCKGBMQLCSHFP-KQRAQHLDSA-N valrubicin Chemical compound O([C@H]1C[C@](CC2=C(O)C=3C(=O)C4=CC=CC(OC)=C4C(=O)C=3C(O)=C21)(O)C(=O)COC(=O)CCCC)[C@H]1C[C@H](NC(=O)C(F)(F)F)[C@H](O)[C@H](C)O1 ZOCKGBMQLCSHFP-KQRAQHLDSA-N 0.000 claims description 2
- 229960003048 vinblastine Drugs 0.000 claims description 2
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 claims description 2
- 229960004528 vincristine Drugs 0.000 claims description 2
- 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 2
- 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 2
- GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 claims description 2
- 229960002066 vinorelbine Drugs 0.000 claims description 2
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
Description
当業者は、本明細書に記載される特定の実施形態に対する多くの等価物を認識するか、または単なる日常的な実験を使用して確認することができるであろう。本明細書に記載される本実施形態の範囲は、上記の説明に限定されることを意図するものではなく、添付の特許請求の範囲に記載される通りである。当業者は、以下の特許請求の範囲で規定される本発明の精神または範囲から逸脱することなく、この記載に対する様々な変更および修正を行うことができることを理解するであろう。
最後に、本発明の好ましい実施態様を項分け記載する。
［実施態様１］
式Ｉの化合物またはその薬学的に許容される塩：
Ｙは神経伝達物質に由来する部分であり；
Ｗは、－ＮＲ
２０
－、－Ｏ－、または－Ｓ－であり；
Ｒ
脂質
は、独立して、置換もしくは非置換のＣ
１－２０
アルキル、置換もしくは非置換のＣ
１－２０
アルケニル、置換もしくは非置換のＣ
１－２０
アルキニル、置換もしくは非置換のＣ
１－２０
ヘテロアルキル、置換もしくは非置換のＣ
１－２０
ヘテロアルケニル、または置換もしくは非置換のＣ
１－２０
ヘテロアルキニルであり；
Ｒ
２０
は、Ｒ
脂質
、Ｈ、Ｃ
１－６
アルキル、Ｃ
１－６
アルケニル、またはＣ
１－６
アルキニルである］。
［実施態様２］
Ｙは
［実施態様３］
Ｙは
［実施態様４］
Ｗは、－ＮＲ
２０
－または－Ｓ－である、実施態様１～３のいずれかに記載の化合物。
［実施態様５］
Ｗは－ＮＲ
２０
－である、実施態様４に記載の化合物。
［実施態様６］
Ｗは－Ｓ－である、実施態様４に記載の化合物。
［実施態様７］
Ｗは－ＮＲ
２０
－であり、Ｒ
２０
はＲ
脂質
である、実施態様１に記載の化合物。
［実施態様８］
Ｙは
Ｗは－ＮＲ
２０
－であり、
Ｒ
２０
はＲ
脂質
である
実施態様１に記載の化合物。
［実施態様９］
Ｒ
脂質
は、下記構造：
Ｒ
１
およびＲ
２
の各例は、独立して、－Ｈ、－ＯＨ、－ＮＨＲ
３０
、または－ＳＨであり；
Ｒ
３
およびＲ
４
は共に－Ｈである；または、Ｒ
３
およびＲ
４
は一緒にオキソ（＝Ｏ）基を形成し；
Ｚは、－ＣＨ
２
－、－Ｏ－、－ＮＲ
３０
－、または－Ｓ－であり；
ＸおよびＹは、独立して、－ＣＨ
２
－、－ＮＲ
３０
－、－Ｏ－、－Ｓ－、または－Ｓｅ－であり；
ｍは１～３から選択される整数であり；
ｎは１～１４から選択される整数であり；
ｐは０または１であり；
ｑは１～１０から選択される整数であり；
ｔは０または１であり；
Ｒ
３０
は、－Ｈ、Ｃ
１－６
アルキル、Ｃ
１－６
アルケニル、またはＣ
１－６
アルキニルである］
のものである、実施態様１～８のいずれかに記載の化合物。
［実施態様１０］
Ｒ
１
およびＲ
２
の各例は、独立して、－Ｈまたは－ＯＨである、実施態様９に記載の化合物。
［実施態様１１］
Ｒ
１
およびＲ
２
は－Ｈである、実施態様１０に記載の化合物。
［実施態様１２］
Ｒ
１
は－Ｈであり；Ｒ
２
は－ＯＨである、実施態様１０に記載の化合物。
［実施態様１３］
Ｒ
３
およびＲ
４
は－Ｈである、実施態様９～１２のいずれかに記載の化合物。
［実施態様１４］
Ｒ
３
およびＲ
４
は一緒にオキソ（＝Ｏ）基を形成する、実施態様９～１２のいずれかに記載の化合物。
［実施態様１５］
Ｚは、－ＣＨ
２
－、－Ｏ－、または－ＮＲ
３０
－である、実施態様９～１４のいずれかに記載の化合物。
［実施態様１６］
Ｚは－ＣＨ
２
－である、実施態様１５に記載の化合物。
［実施態様１７］
Ｚは－Ｏ－である、実施態様１５に記載の化合物。
［実施態様１８］
Ｚは－ＮＲ
３０
－である、実施態様１５に記載の化合物。
［実施態様１９］
Ｒ
１
およびＲ
２
は－Ｈであり、Ｒ
３
およびＲ
４
は一緒にオキソ（＝Ｏ）基を形成し、ＺはＯである、実施態様９に記載の化合物。
［実施態様２０］
Ｒ
１
は－Ｈであり、Ｒ
２
は－ＯＨであり、Ｒ
３
およびＲ
４
は－Ｈであり、Ｚは－ＣＨ
２
－である、実施態様９に記載の化合物。
［実施態様２１］
ＸおよびＹは、独立して、－ＣＨ
２
－または－Ｏ－である、実施態様９～２０のいずれかに記載の化合物。
［実施態様２２］
ＸおよびＹは、独立して、－ＣＨ
２
－または－Ｏ－であり、ＸとＹは同じではない、実施態様２１に記載の化合物。
［実施態様２３］
ＸおよびＹは、独立して、－ＣＨ
２
－または－Ｓ－である、実施態様９～２０のいずれかに記載の化合物。
［実施態様２４］
ＸおよびＹは両方とも－ＣＨ
２
－である、実施態様２３に記載の化合物。
［実施態様２５］
ＸおよびＹは両方とも－Ｓ－である、実施態様２３に記載の化合物。
［実施態様２６］
ｍは１または２である、実施態様９～２５のいずれかに記載の化合物。
［実施態様２７］
ｍは１である、実施態様２６に記載の化合物。
［実施態様２８］
ｍは２である、実施態様２６に記載の化合物。
［実施態様２９］
ｎは４～１２から選択される整数である、実施態様９～２８のいずれかに記載の化合物。
［実施態様３０］
ｎは６～１０から選択される整数である、実施態様２９に記載の化合物。
［実施態様３１］
ｐは０である、実施態様９～３０のいずれかに記載の化合物。
［実施態様３２］
ｐは１である、実施態様９～３０のいずれかに記載の化合物。
［実施態様３３］
ｑは２～８から選択される整数である、実施態様９～３２のいずれかに記載の化合物。
［実施態様３４］
ｑは４～８から選択される整数である、実施態様３３に記載の化合物。
［実施態様３５］
ｔは０である、実施態様９～３４のいずれかに記載の化合物。
［実施態様３６］
ｔは１である、実施態様９～３４のいずれかに記載の化合物。
［実施態様３７］
［実施態様３８］
実施態様１～３７のいずれかに記載の化合物を含む、リピドイドナノ粒子。
［実施態様３９］
タンパク質をさらに含む、実施態様３８に記載のリピドイドナノ粒子。
［実施態様４０］
前記タンパク質はＧＦＰ－Ｃｒｅである、実施態様３９に記載のリピドイドナノ粒子。
［実施態様４１］
核酸をさらに含む、実施態様３８～４０のいずれかに記載のリピドイドナノ粒子。
［実施態様４２］
前記核酸はタウ－ＡＳＯである、実施態様４１に記載のリピドイドナノ粒子。
［実施態様４３］
小分子をさらに含む、実施態様３８～４２のいずれかに記載のリピドイドナノ粒子。
［実施態様４４］
前記小分子は抗真菌剤または化学療法剤である、実施態様４３に記載のリピドイドナノ粒子。
［実施態様４５］
前記小分子は、ボルテゾミブ、イマチニブ、ゲフィチニブ、エルロチニブ、アファチニブ、オシメルチニブ、ダコミチニブ、ダウノルビシン塩酸塩、シタラビン、フルオロウラシル、イリノテカン塩酸塩、ビンクリスチン硫酸塩、メトトレキサート、パクリタキセル、ビンクリスチン硫酸塩、エピルビシン、ドセタキセル、シクロホスファミド、カルボプラチン、レナリドミド、イブルチニブ、酢酸アビラテロン、エンザルタミド、ペメトレキセド、パルボシクリブ、ニロチニブ、エベロリムス、ルキソリチニブ、エピルビシン、ピラルビシン、イダルビシン、バルルビシン、アムルビシン、ブレオマイシン、フレオマイシン、ダクチノマイシン、ミトラマイシン、ストレプトゾテシン、ペントスタチン、マイトサン マイトマイシンＣ、エンジイン カリケアマイシン、グリコシド レベッカマイシン、マクロライドラクトン エポチフィロン、イクサベピロン、ペントスタチン、サリノスポラミドＡ、ビンブラスチン、ビンクリスチン、エトポシド、テニポシド、ビノレルビン、ドセタキセル、カンプトテシン、ハイカムチン、ペデリン、テオペデリン、アンナミド（ａｎｎａｍｉｄｅ）、トラベクテジン、アプリジン、およびエクテイナシジン７４３（ＥＴ７４３）からなる群より選択される、実施態様４３に記載のリピドイドナノ粒子。
［実施態様４６］
前記小分子は、アムホテリシンＢまたはドキソルビシンである、実施態様４３に記載のリピドイドナノ粒子。
［実施態様４７］
約２５ｎｍ～約１０００ｎｍの粒径を有する、実施態様３８～４６のいずれかに記載のリピドイドナノ粒子。
［実施態様４８］
約５０ｎｍ～約５００ｎｍの粒径を有する、実施態様４７に記載のリピドイドナノ粒子。
［実施態様４９］
実施態様３８～４８のいずれかに記載のリピドイドナノ粒子、および薬学的に許容される担体または賦形剤を含む、医薬組成物。
Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments described herein. The scope of the embodiments described herein is not intended to be limited to the above description, but is as set forth in the appended claims. Those skilled in the art will appreciate that various changes and modifications to this description can be made without departing from the spirit or scope of the invention, as defined in the following claims.
Finally, preferred embodiments of the present invention are described in sections.
[Embodiment 1]
A compound of formula I or a pharma- ceutically acceptable salt thereof:
Y is a moiety derived from a neurotransmitter;
W is -NR 20 -, -O-, or -S-;
R lipid is independently a substituted or unsubstituted C 1-20 alkyl, a substituted or unsubstituted C 1-20 alkenyl, a substituted or unsubstituted C 1-20 alkynyl, a substituted or unsubstituted C 1-20 heteroalkyl, a substituted or unsubstituted C 1-20 heteroalkenyl, or a substituted or unsubstituted C 1-20 heteroalkynyl;
R20 is Rlipid , H, C1-6 alkyl, C1-6 alkenyl , or C1-6 alkynyl .
[Embodiment 2]
Y is
[Embodiment 3]
Y is
[Embodiment 4]
A compound according to any of embodiments 1 to 3, wherein W is --NR 20 -- or --S--.
[Embodiment 5]
The compound according to embodiment 4, wherein W is --NR.sup.20-- .
[Embodiment 6]
The compound according to embodiment 4, wherein W is -S-.
[Embodiment 7]
The compound according to embodiment 1, wherein W is --NR.sup.20-- and R.sup.20 is R lipid .
[Embodiment 8]
Y is
W is -NR20- ;
R20 is R lipid
2. The compound according to embodiment 1.
[Embodiment 9]
R lipid has the following structure:
Each instance of R 1 and R 2 is independently -H, -OH, -NHR 30 , or -SH;
R 3 and R 4 are both -H; or R 3 and R 4 together form an oxo (=O) group;
Z is -CH 2 -, -O-, -NR 30 -, or -S-;
X and Y are independently -CH 2 -, -NR 30 -, -O-, -S-, or -Se-;
m is an integer selected from 1 to 3;
n is an integer selected from 1 to 14;
p is 0 or 1;
q is an integer selected from 1 to 10;
t is 0 or 1;
R 30 is -H, C 1-6 alkyl, C 1-6 alkenyl, or C 1-6 alkynyl.
9. The compound according to any one of embodiments 1 to 8, wherein
[Embodiment 10]
The compound according to embodiment 9, wherein each instance of R 1 and R 2 is independently -H or -OH.
[Embodiment 11]
The compound according to embodiment 10, wherein R 1 and R 2 are -H.
[Embodiment 12]
The compound according to embodiment 10, wherein R 1 is --H; and R 2 is --OH.
[Embodiment 13]
13. The compound according to any of embodiments 9 to 12, wherein R 3 and R 4 are —H.
[Embodiment 14]
13. The compound according to any one of embodiments 9 to 12, wherein R 3 and R 4 together form an oxo (═O) group.
[Embodiment 15]
The compound according to any of embodiments 9 to 14, wherein Z is —CH 2 —, —O—, or —NR 30 —.
[Embodiment 16]
The compound according to embodiment 15, wherein Z is -CH 2 -.
[Embodiment 17]
The compound according to embodiment 15, wherein Z is --O--.
[Embodiment 18]
The compound according to embodiment 15, wherein Z is --NR 30 --.
[Embodiment 19]
The compound according to embodiment 9, wherein R 1 and R 2 are —H, R 3 and R 4 together form an oxo (═O) group, and Z is O.
[Embodiment 20]
The compound according to embodiment 9, wherein R 1 is -H, R 2 is -OH, R 3 and R 4 are -H, and Z is -CH 2 -.
[Embodiment 21]
21. A compound according to any of embodiments 9 to 20, wherein X and Y are independently -CH 2 - or -O-.
[Embodiment 22]
22. The compound according to embodiment 21, wherein X and Y are independently -CH 2 - or -O-, and X and Y are not the same.
[Embodiment 23]
21. A compound according to any of embodiments 9 to 20, wherein X and Y are independently -CH 2 - or -S-.
[Embodiment 24]
24. A compound according to embodiment 23, wherein X and Y are both -CH 2 -.
[Embodiment 25]
24. The compound according to embodiment 23, wherein X and Y are both -S-.
[Embodiment 26]
26. The compound according to any one of embodiments 9 to 25, wherein m is 1 or 2.
[Embodiment 27]
27. The compound according to embodiment 26, wherein m is 1.
[Embodiment 28]
27. The compound according to embodiment 26, wherein m is 2.
[Embodiment 29]
29. The compound according to any one of embodiments 9 to 28, wherein n is an integer selected from 4 to 12.
[Embodiment 30]
30. The compound according to embodiment 29, wherein n is an integer selected from 6 to 10.
[Embodiment 31]
31. The compound according to any one of embodiments 9 to 30, wherein p is 0.
[Embodiment 32]
31. The compound according to any one of embodiments 9 to 30, wherein p is 1.
[Embodiment 33]
33. The compound according to any one of embodiments 9 to 32, wherein q is an integer selected from 2 to 8.
[Embodiment 34]
34. The compound according to embodiment 33, wherein q is an integer selected from 4 to 8.
[Embodiment 35]
35. The compound according to any one of embodiments 9 to 34, wherein t is 0.
[Embodiment 36]
The compound according to any one of embodiments 9 to 34, wherein t is 1.
[Embodiment 37]
[Embodiment 38]
38. A lipidoid nanoparticle comprising a compound according to any one of embodiments 1 to 37.
[Embodiment 39]
39. The lipidoid nanoparticle of embodiment 38, further comprising a protein.
[Embodiment 40]
40. The lipidoid nanoparticle of embodiment 39, wherein the protein is GFP-Cre.
[Embodiment 41]
41. The lipidoid nanoparticle of any of embodiments 38 to 40, further comprising a nucleic acid.
[Embodiment 42]
42. The lipidoid nanoparticle of embodiment 41, wherein the nucleic acid is a tau-ASO.
[Embodiment 43]
43. The lipidoid nanoparticle of any of embodiments 38 to 42, further comprising a small molecule.
[Embodiment 44]
The lipidoid nanoparticle of embodiment 43, wherein the small molecule is an antifungal agent or a chemotherapeutic agent.
[Embodiment 45]
The small molecule may be selected from the group consisting of bortezomib, imatinib, gefitinib, erlotinib, afatinib, osimertinib, dacomitinib, daunorubicin hydrochloride, cytarabine, fluorouracil, irinotecan hydrochloride, vincristine sulfate, methotrexate, paclitaxel, vincristine sulfate, epirubicin, docetaxel, cyclophosphamide, carboplatin, lenalidomide, ibrutinib, abiraterone acetate, enzalutamide, pemetrexed, palbociclib, nilotinib, everolimus, ruxolitinib, epirubicin, pirarubicin, idarubicin, valrubicin, amrubicin, bleomycin, phleomycin, dactinomycin, mithramycin, streptozotecin, pentostatin, mitosan mitomycin C, enediyne 44. The lipidoid nanoparticle of embodiment 43, selected from the group consisting of calicheamicin, glycoside rebeccamycin, macrolide lactone epothyfilone, ixabepilone, pentostatin, salinosporamide A, vinblastine, vincristine, etoposide, teniposide, vinorelbine, docetaxel, camptothecin, hycamtin, pederin, theopederin, annamid, trabectedin, aplidine, and ecteinascidin 743 (ET743).
[Embodiment 46]
The lipidoid nanoparticle of embodiment 43, wherein the small molecule is amphotericin B or doxorubicin.
[Embodiment 47]
47. The lipidoid nanoparticle according to any of embodiments 38 to 46, having a particle size of about 25 nm to about 1000 nm.
[Embodiment 48]
48. The lipidoid nanoparticles according to embodiment 47, having a particle size of about 50 nm to about 500 nm.
[Embodiment 49]
A pharmaceutical composition comprising the lipidoid nanoparticles according to any one of embodiments 38 to 48, and a pharma- ceutically acceptable carrier or excipient.
Claims (26)
Ｙは神経伝達物質に由来する部分であり；
Ｗは、－ＮＲ２０－、－Ｏ－、または－Ｓ－であり；
Ｒ脂質は、独立して、置換もしくは非置換のＣ１－２０アルキル、置換もしくは非置換のＣ１－２０アルケニル、置換もしくは非置換のＣ１－２０アルキニル、置換もしくは非置換のＣ１－２０ヘテロアルキル、置換もしくは非置換のＣ１－２０ヘテロアルケニル、または置換もしくは非置換のＣ１－２０ヘテロアルキニルであり；
Ｒ２０は、Ｒ脂質、Ｈ、Ｃ１－６アルキル、Ｃ１－６アルケニル、またはＣ１－６アルキニルである］。 A compound of formula I or a pharma- ceutically acceptable salt thereof:
Y is a moiety derived from a neurotransmitter;
W is -NR 20 -, -O-, or -S-;
R lipid is independently a substituted or unsubstituted C 1-20 alkyl, a substituted or unsubstituted C 1-20 alkenyl, a substituted or unsubstituted C 1-20 alkynyl, a substituted or unsubstituted C 1-20 heteroalkyl, a substituted or unsubstituted C 1-20 heteroalkenyl, or a substituted or unsubstituted C 1-20 heteroalkynyl;
R20 is Rlipid , H, C1-6 alkyl, C1-6 alkenyl, or C1-6 alkynyl.
Ｗは－ＮＲ２０－であり、
Ｒ２０はＲ脂質である、請求項１に記載の化合物。 Y is
W is -NR20- ;
2. The compound of claim 1, wherein R20 is an R lipid .
Ｒ１およびＲ２の各例は、独立して、－Ｈ、－ＯＨ、－ＮＨＲ３０、または－ＳＨであり；
Ｒ３およびＲ４は共に－Ｈである；または、Ｒ３およびＲ４は一緒にオキソ（＝Ｏ）基を形成し；
Ｚは、－ＣＨ２－、－Ｏ－、－ＮＲ３０－、または－Ｓ－であり；
ＸおよびＹは、独立して、－ＣＨ２－、－ＮＲ３０－、－Ｏ－、－Ｓ－、または－Ｓｅ－であり；
ｍは１～３から選択される整数であり；
ｎは１～１４から選択される整数であり；
ｐは０または１であり；
ｑは１～１０から選択される整数であり；
ｔは０または１であり；
Ｒ３０は、－Ｈ、Ｃ１－６アルキル、Ｃ１－６アルケニル、またはＣ１－６アルキニルである］
のものである、請求項１～５のいずれか一項に記載の化合物。 R lipids have the following structure:
Each instance of R 1 and R 2 is independently -H, -OH, -NHR 30 , or -SH;
R 3 and R 4 are both -H; or R 3 and R 4 together form an oxo (=O) group;
Z is -CH 2 -, -O-, -NR 30 -, or -S-;
X and Y are independently -CH 2 -, -NR 30 -, -O-, -S-, or -Se-;
m is an integer selected from 1 to 3;
n is an integer selected from 1 to 14;
p is 0 or 1;
q is an integer selected from 1 to 10;
t is 0 or 1;
R 30 is -H, C 1-6 alkyl, C 1-6 alkenyl, or C 1-6 alkynyl.
The compound according to any one of claims 1 to 5 ,
Ｒ １ は－Ｈであり、かつＲ ２ は－ＯＨである、請求項７に記載の化合物。 R 1 and R 2 are —H; or
The compound of claim 7 , wherein R 1 is -H and R 2 is -OH .
Ｒ １ は－Ｈであり、Ｒ ２ は－ＯＨであり、Ｒ ３ およびＲ ４ は－Ｈであり、Ｚは－ＣＨ ２ －である、請求項６に記載の化合物。 R 1 and R 2 are -H, R 3 and R 4 together form an oxo (=O) group, and Z is O; or
The compound of claim 6, wherein R 1 is -H, R 2 is -OH, R 3 and R 4 are -H, and Z is -CH 2 - .
ＸおよびＹは、独立して、－ＣＨ ２ －または－Ｓ－である、請求項６～１０のいずれか一項に記載の化合物。 X and Y are independently -CH 2 - or -O-;
The compound of any one of claims 6 to 10 , wherein X and Y are independently -CH 2 - or -S- .
ＸおよびＹは両方とも－Ｓ－である、請求項１１に記載の化合物。 X and Y are both -CH 2 -; or
The compound of claim 11 , wherein X and Y are both -S- .
A pharmaceutical composition comprising the lipidoid nanoparticles according to any one of claims 18 to 25 and a pharma- ceutically acceptable carrier or excipient.
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| CA3177508A1 (en) | 2020-05-04 | 2021-11-11 | Qiaobing Xu | Synthetic lipid-like materials for brain delivery |
| CN115232128B (en) * | 2022-08-15 | 2024-03-29 | 中国科学技术大学 | Imidazo-pyridinyl lipid compound, and preparation method and application thereof |
| CN116063245B (en) * | 2022-12-05 | 2024-09-10 | 南开大学 | MRNA liposome nano particle with degradable center and preparation method and application thereof |
| KR20240130926A (en) * | 2023-02-22 | 2024-08-30 | 주식회사 서지넥스 | Ionizable lipid comprising sulfide and lipid nanoparticle comprising thereof |
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| US3197274A (en) * | 1962-03-05 | 1965-07-27 | Gen Mills Inc | Liquid-liquid recovery of metal values using hydroxyamine extractants |
| JPWO2001083471A1 (en) * | 2000-05-02 | 2004-04-15 | 明治製菓株式会社 | Novel indole derivative having chymase inhibitory activity and method for producing indole derivative |
| JP2006206723A (en) * | 2005-01-27 | 2006-08-10 | Adeka Corp | Lubricant composition |
| EP2882706A1 (en) * | 2012-08-13 | 2015-06-17 | Massachusetts Institute of Technology | Amine-containing lipidoids and uses thereof |
| US20160346208A1 (en) * | 2015-05-28 | 2016-12-01 | University Of South Carolina | Dual responsive brain targeted nanoparticles and their applications |
| AU2019215157A1 (en) * | 2018-02-01 | 2020-08-13 | Trustees Of Tufts College | Lipid-like nanocomplexes and uses thereof |
| WO2021022121A1 (en) * | 2019-07-31 | 2021-02-04 | Trustees Of Tufts College | Nitrilotriacetic acid-containing lipidoid nanoparticles |
| CA3177508A1 (en) | 2020-05-04 | 2021-11-11 | Qiaobing Xu | Synthetic lipid-like materials for brain delivery |
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