JP2018536012A5 - - Google Patents
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- Publication number
- JP2018536012A5 JP2018536012A5 JP2018532532A JP2018532532A JP2018536012A5 JP 2018536012 A5 JP2018536012 A5 JP 2018536012A5 JP 2018532532 A JP2018532532 A JP 2018532532A JP 2018532532 A JP2018532532 A JP 2018532532A JP 2018536012 A5 JP2018536012 A5 JP 2018536012A5
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- aryl
- heteroalkyl
- pharmaceutically acceptable
- functionalized payload
- Prior art date
- 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
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- 239000000203 mixture Substances 0.000 claims description 59
- 125000000217 alkyl group Chemical group 0.000 claims description 46
- 125000003118 aryl group Chemical group 0.000 claims description 42
- 125000004404 heteroalkyl group Chemical group 0.000 claims description 37
- 125000003342 alkenyl group Chemical group 0.000 claims description 34
- 125000000304 alkynyl group Chemical group 0.000 claims description 34
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 34
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 34
- 125000001072 heteroaryl group Chemical group 0.000 claims description 34
- 125000000623 heterocyclic group Chemical group 0.000 claims description 34
- 229910052739 hydrogen Inorganic materials 0.000 claims description 28
- 239000001257 hydrogen Substances 0.000 claims description 28
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 28
- -1 alkoxyfluoroalkyl Chemical group 0.000 claims description 24
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 24
- 229910052736 halogen Inorganic materials 0.000 claims description 24
- 150000002367 halogens Chemical class 0.000 claims description 24
- 125000005647 linker group Chemical group 0.000 claims description 24
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 20
- 239000003937 drug carrier Substances 0.000 claims description 19
- 206010028980 Neoplasm Diseases 0.000 claims description 11
- 125000001188 haloalkyl group Chemical group 0.000 claims description 10
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 claims description 10
- 125000001424 substituent group Chemical group 0.000 claims description 10
- 201000011510 cancer Diseases 0.000 claims description 9
- 239000003795 chemical substances by application Substances 0.000 claims description 9
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 9
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 7
- 125000002947 alkylene group Chemical group 0.000 claims description 7
- DPOPAJRDYZGTIR-UHFFFAOYSA-N Tetrazine Chemical compound C1=CN=NN=N1 DPOPAJRDYZGTIR-UHFFFAOYSA-N 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 5
- 125000002252 acyl group Chemical group 0.000 claims description 5
- 125000004442 acylamino group Chemical group 0.000 claims description 5
- 125000003282 alkyl amino group Chemical group 0.000 claims description 5
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 5
- 125000004414 alkyl thio group Chemical group 0.000 claims description 5
- 150000001408 amides Chemical class 0.000 claims description 5
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 5
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 5
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 5
- 125000001769 aryl amino group Chemical group 0.000 claims description 5
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 5
- 125000004104 aryloxy group Chemical group 0.000 claims description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 5
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 5
- 125000004428 fluoroalkoxy group Chemical group 0.000 claims description 5
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 5
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 5
- 150000002576 ketones Chemical class 0.000 claims description 5
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 5
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 claims description 5
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 5
- 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
- 206010039491 Sarcoma Diseases 0.000 claims description 4
- 208000021712 Soft tissue sarcoma Diseases 0.000 claims description 4
- 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 4
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 4
- 229940124597 therapeutic agent Drugs 0.000 claims description 4
- 206010033128 Ovarian cancer Diseases 0.000 claims description 3
- 206010060862 Prostate cancer Diseases 0.000 claims description 3
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 3
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 3
- UIAGMCDKSXEBJQ-IBGZPJMESA-N 3-o-(2-methoxyethyl) 5-o-propan-2-yl (4s)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COCCOC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)C)[C@H]1C1=CC=CC([N+]([O-])=O)=C1 UIAGMCDKSXEBJQ-IBGZPJMESA-N 0.000 claims description 2
- 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 2
- FJHBVJOVLFPMQE-QFIPXVFZSA-N 7-Ethyl-10-Hydroxy-Camptothecin Chemical compound C1=C(O)C=C2C(CC)=C(CN3C(C4=C([C@@](C(=O)OC4)(O)CC)C=C33)=O)C3=NC2=C1 FJHBVJOVLFPMQE-QFIPXVFZSA-N 0.000 claims description 2
- ZGXJTSGNIOSYLO-UHFFFAOYSA-N 88755TAZ87 Chemical compound NCC(=O)CCC(O)=O ZGXJTSGNIOSYLO-UHFFFAOYSA-N 0.000 claims description 2
- 229930183010 Amphotericin Natural products 0.000 claims description 2
- QGGFZZLFKABGNL-UHFFFAOYSA-N Amphotericin A Natural products OC1C(N)C(O)C(C)OC1OC1C=CC=CC=CC=CCCC=CC=CC(C)C(O)C(C)C(C)OC(=O)CC(O)CC(O)CCC(O)C(O)CC(O)CC(O)(CC(O)C2C(O)=O)OC2C1 QGGFZZLFKABGNL-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
- 206010006187 Breast cancer Diseases 0.000 claims description 2
- 208000026310 Breast neoplasm Diseases 0.000 claims description 2
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 claims description 2
- 108010078777 Colistin Proteins 0.000 claims description 2
- 229930105110 Cyclosporin A Natural products 0.000 claims description 2
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 claims description 2
- 108010036949 Cyclosporine Proteins 0.000 claims description 2
- 108010013198 Daptomycin Proteins 0.000 claims description 2
- XQSPYNMVSIKCOC-NTSWFWBYSA-N Emtricitabine Chemical compound C1=C(F)C(N)=NC(=O)N1[C@H]1O[C@@H](CO)SC1 XQSPYNMVSIKCOC-NTSWFWBYSA-N 0.000 claims description 2
- 201000008808 Fibrosarcoma Diseases 0.000 claims description 2
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 claims description 2
- 229930182566 Gentamicin Natural products 0.000 claims description 2
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 2
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 claims description 2
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 claims description 2
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 claims description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 2
- 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 2
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 2
- 229930012538 Paclitaxel Natural products 0.000 claims description 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 2
- 206010038389 Renal cancer Diseases 0.000 claims description 2
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 claims description 2
- 108010059993 Vancomycin Proteins 0.000 claims description 2
- 229960004150 aciclovir Drugs 0.000 claims description 2
- MKUXAQIIEYXACX-UHFFFAOYSA-N aciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCO)C=N2 MKUXAQIIEYXACX-UHFFFAOYSA-N 0.000 claims description 2
- 229960002749 aminolevulinic acid Drugs 0.000 claims description 2
- 229940009444 amphotericin Drugs 0.000 claims description 2
- 229960003942 amphotericin b Drugs 0.000 claims description 2
- 239000003242 anti bacterial agent Substances 0.000 claims description 2
- 230000001387 anti-histamine Effects 0.000 claims description 2
- 239000002260 anti-inflammatory agent Substances 0.000 claims description 2
- 229940121363 anti-inflammatory agent Drugs 0.000 claims description 2
- 230000003110 anti-inflammatory effect Effects 0.000 claims description 2
- 229940124346 antiarthritic agent Drugs 0.000 claims description 2
- 239000003429 antifungal agent Substances 0.000 claims description 2
- 229940121375 antifungal agent Drugs 0.000 claims description 2
- 239000000739 antihistaminic agent Substances 0.000 claims description 2
- 239000003409 antileprotic agent Substances 0.000 claims description 2
- 239000002246 antineoplastic agent Substances 0.000 claims description 2
- 239000003435 antirheumatic agent Substances 0.000 claims description 2
- 239000003699 antiulcer agent Substances 0.000 claims description 2
- 239000003443 antiviral agent Substances 0.000 claims description 2
- 230000003115 biocidal effect Effects 0.000 claims description 2
- 229960005243 carmustine Drugs 0.000 claims description 2
- 229960004755 ceftriaxone Drugs 0.000 claims description 2
- VAAUVRVFOQPIGI-SPQHTLEESA-N ceftriaxone Chemical compound S([C@@H]1[C@@H](C(N1C=1C(O)=O)=O)NC(=O)\C(=N/OC)C=2N=C(N)SC=2)CC=1CSC1=NC(=O)C(=O)NN1C VAAUVRVFOQPIGI-SPQHTLEESA-N 0.000 claims description 2
- RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 claims description 2
- 229960000590 celecoxib Drugs 0.000 claims description 2
- 229940106164 cephalexin Drugs 0.000 claims description 2
- ZAIPMKNFIOOWCQ-UEKVPHQBSA-N cephalexin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CC=CC=C1 ZAIPMKNFIOOWCQ-UEKVPHQBSA-N 0.000 claims description 2
- 229960001265 ciclosporin Drugs 0.000 claims description 2
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- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 2
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- 235000018417 cysteine Nutrition 0.000 claims description 2
- DOAKLVKFURWEDJ-QCMAZARJSA-N daptomycin Chemical compound C([C@H]1C(=O)O[C@H](C)[C@@H](C(NCC(=O)N[C@@H](CCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@H](CO)C(=O)N[C@H](C(=O)N1)[C@H](C)CC(O)=O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](CC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)CCCCCCCCC)C(=O)C1=CC=CC=C1N DOAKLVKFURWEDJ-QCMAZARJSA-N 0.000 claims description 2
- 229960005484 daptomycin Drugs 0.000 claims description 2
- 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 2
- 229960000975 daunorubicin Drugs 0.000 claims description 2
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- 229960004679 doxorubicin Drugs 0.000 claims description 2
- 229960003722 doxycycline Drugs 0.000 claims description 2
- XQTWDDCIUJNLTR-CVHRZJFOSA-N doxycycline monohydrate Chemical compound O.O=C1C2=C(O)C=CC=C2[C@H](C)[C@@H]2C1=C(O)[C@]1(O)C(=O)C(C(N)=O)=C(O)[C@@H](N(C)C)[C@@H]1[C@H]2O XQTWDDCIUJNLTR-CVHRZJFOSA-N 0.000 claims description 2
- 230000002526 effect on cardiovascular system Effects 0.000 claims description 2
- 229960000366 emtricitabine Drugs 0.000 claims description 2
- YJGVMLPVUAXIQN-UHFFFAOYSA-N epipodophyllotoxin Natural products COC1=C(OC)C(OC)=CC(C2C3=CC=4OCOC=4C=C3C(O)C3C2C(OC3)=O)=C1 YJGVMLPVUAXIQN-UHFFFAOYSA-N 0.000 claims description 2
- 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 2
- 229960005420 etoposide Drugs 0.000 claims description 2
- XRECTZIEBJDKEO-UHFFFAOYSA-N flucytosine Chemical compound NC1=NC(=O)NC=C1F XRECTZIEBJDKEO-UHFFFAOYSA-N 0.000 claims description 2
- 229960004413 flucytosine Drugs 0.000 claims description 2
- 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 2
- 229960005277 gemcitabine Drugs 0.000 claims description 2
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- 229940125721 immunosuppressive agent Drugs 0.000 claims description 2
- 239000003018 immunosuppressive agent Substances 0.000 claims description 2
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 claims description 2
- 229960004768 irinotecan Drugs 0.000 claims description 2
- 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
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- JORAUNFTUVJTNG-BSTBCYLQSA-N n-[(2s)-4-amino-1-[[(2s,3r)-1-[[(2s)-4-amino-1-oxo-1-[[(3s,6s,9s,12s,15r,18s,21s)-6,9,18-tris(2-aminoethyl)-3-[(1r)-1-hydroxyethyl]-12,15-bis(2-methylpropyl)-2,5,8,11,14,17,20-heptaoxo-1,4,7,10,13,16,19-heptazacyclotricos-21-yl]amino]butan-2-yl]amino]-3-h Chemical compound CC(C)CCCCC(=O)N[C@@H](CCN)C(=O)N[C@H]([C@@H](C)O)CN[C@@H](CCN)C(=O)N[C@H]1CCNC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCN)NC(=O)[C@H](CCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CCN)NC1=O.CCC(C)CCCCC(=O)N[C@@H](CCN)C(=O)N[C@H]([C@@H](C)O)CN[C@@H](CCN)C(=O)N[C@H]1CCNC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCN)NC(=O)[C@H](CCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CCN)NC1=O JORAUNFTUVJTNG-BSTBCYLQSA-N 0.000 claims description 2
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- YVCVYCSAAZQOJI-UHFFFAOYSA-N podophyllotoxin Natural products COC1=C(O)C(OC)=CC(C2C3=CC=4OCOC=4C=C3C(O)C3C2C(OC3)=O)=C1 YVCVYCSAAZQOJI-UHFFFAOYSA-N 0.000 claims description 2
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Families Citing this family (38)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8796248B2 (en) * | 2007-10-05 | 2014-08-05 | Nektar Therapeutics | Oligomer-corticosteroid conjugates |
| CN108135857A (zh) | 2015-09-10 | 2018-06-08 | 沙思奇公司 | 生物正交组合物 |
| US20170136144A1 (en) | 2015-11-12 | 2017-05-18 | John C. Herr | Compositions and methods for vas-occlusive contraception |
| CA3042428A1 (en) | 2016-11-08 | 2018-05-17 | Regeneron Pharmaceuticals, Inc. | Steroids and protein-conjugates thereof |
| US12383421B2 (en) | 2017-01-05 | 2025-08-12 | Contraline, Inc. | Contraceptive devices |
| EP3565484B1 (en) | 2017-01-05 | 2024-04-03 | Contraline, Inc. | Compositions for implanting and reversing stimuli-responsive implants |
| AU2018250312C1 (en) * | 2017-04-07 | 2024-08-22 | Tambo, Inc. | Bioorthogonal compositions |
| KR20250008984A (ko) | 2017-05-18 | 2025-01-16 | 리제너론 파마슈티칼스 인코포레이티드 | 사이클로덱스트린 단백질 약물 접합체 |
| CA3247730A1 (en) | 2017-11-07 | 2025-10-30 | Regeneron Pharmaceuticals, Inc. | Hydrophilic linkers for antibody drug conjugates |
| MA50259A1 (fr) | 2018-01-08 | 2021-07-29 | Regeneron Pharma | Stéroïdes et leurs conjugués-anticorps |
| CN110066253B (zh) * | 2018-01-24 | 2023-06-23 | 江苏柯菲平医药股份有限公司 | 1,2,5-噁二唑类衍生物，其制备方法及其在医药中的应用 |
| CN110577501A (zh) * | 2018-06-07 | 2019-12-17 | 江苏柯菲平医药股份有限公司 | 吲哚胺2,3-双加氧酶调节剂，其制备方法及用途 |
| US11369589B2 (en) | 2018-01-24 | 2022-06-28 | Nanjing Carephar Shenghui Pharmaceutical Co., Ltd. | Modulator of indoleamine 2,3-dioxygenase, preparation method and use thereof |
| WO2019217591A1 (en) | 2018-05-09 | 2019-11-14 | Regeneron Pharmaceuticals, Inc. | Anti-msr1 antibodies and methods of use thereof |
| WO2020010560A1 (zh) * | 2018-07-12 | 2020-01-16 | 深圳华大生命科学研究院 | 一种亚磷酰胺类化合物、其制备方法及应用 |
| CA3114056A1 (en) * | 2018-09-26 | 2020-04-02 | Ascendis Pharma A/S | Treatment of infections |
| WO2020077140A1 (en) * | 2018-10-10 | 2020-04-16 | Tambo, Inc. | Processes for preparing functionalized cyclooctenes |
| AU2019380413B2 (en) | 2018-11-13 | 2025-04-17 | Contraline, Inc. | Systems and methods for delivering biomaterials |
| CN111662251A (zh) * | 2019-03-05 | 2020-09-15 | 国家纳米科学中心 | 一种紫杉醇前药及其制备方法和应用 |
| WO2021007160A1 (en) | 2019-07-05 | 2021-01-14 | Tambo, Inc. | Trans-cyclooctene bioorthogonal agents and uses in cancer and immunotherapy |
| CN111138337B (zh) * | 2019-12-26 | 2021-06-22 | 清华大学 | 用于生物正交反应的双环[4.1.0]庚烷亚硝基脲衍生物及其制备方法与应用 |
| SE2050204A1 (en) * | 2020-02-24 | 2021-08-25 | Oboe Ipr Ab | A system and method for releasing a species |
| CN113321702B (zh) * | 2020-02-28 | 2022-08-05 | 国家纳米科学中心 | 一种单甲基澳瑞他汀f甲酯前药及其制备方法和应用 |
| CN113321692B (zh) * | 2020-02-28 | 2022-10-14 | 国家纳米科学中心 | 一种阿霉素前药及其制备方法和应用 |
| CN113354657B (zh) * | 2020-03-05 | 2022-10-21 | 国家纳米科学中心 | 一种Mytoxin A前药及其制备方法和应用 |
| JP2023537066A (ja) | 2020-08-07 | 2023-08-30 | タンボ・インコーポレイテッド | トランス－シクロオクテン生体直交型薬剤並びに癌及び免疫療法における使用 |
| WO2023077129A1 (en) | 2021-10-29 | 2023-05-04 | Tambo, Inc. | Tetrazine conjugates for in vivo targeted delivery of a payload |
| CN118414169A (zh) | 2021-10-29 | 2024-07-30 | 坦博公司 | 反式环辛烯缀合物 |
| WO2023081809A1 (en) | 2021-11-05 | 2023-05-11 | Tambo, Inc. | Trans-cyclooctene-modified bispecific antibodies |
| JP2025531342A (ja) | 2022-09-20 | 2025-09-19 | バランクス・バイオテック・ゲーエムベーハー | タンパク質およびペプチドにおけるクリック－トゥ－リリース |
| WO2024130526A1 (en) * | 2022-12-20 | 2024-06-27 | Nanjing University | A bioorthogonal cycloaddition reaction and use thereof |
| WO2024168065A1 (en) | 2023-02-08 | 2024-08-15 | Tambo, Inc. | System comprising modified whole cell payloads for targeted delivery |
| JP2026508188A (ja) | 2023-02-21 | 2026-03-10 | タンボ・インコーポレイテッド | トランス－シクロオクテンコンジュゲート |
| KR20260007642A (ko) * | 2023-04-05 | 2026-01-14 | 럿거스, 더 스테이트 유니버시티 오브 뉴 저지 | 바이오겔, 조성물 및 이의 사용방법 |
| EP4704904A1 (en) | 2023-05-04 | 2026-03-11 | Tambo, Inc. | Tetrazine-based targeting agents for in vivo delivery of a payload |
| EP4713022A1 (en) | 2023-05-18 | 2026-03-25 | Tambo, Inc. | Trans-cyclooctene-modified targeted protein degrader conjugates |
| CN122138843A (zh) | 2023-09-15 | 2026-06-02 | 坦博公司 | 用于有效载荷的体内靶向递送的方法 |
| WO2025231424A1 (en) * | 2024-05-02 | 2025-11-06 | Arizona Board Of Regents On Behalf Of Arizona State University | Procapped mrna for targeted cell translation |
Family Cites Families (44)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5658592A (en) | 1994-05-13 | 1997-08-19 | Kuraray Co., Ltd. | Medical crosslinked polymer gel of carboxylic polysaccharide and diaminoalkane |
| CA2447594A1 (en) | 2001-06-21 | 2003-01-03 | Clontech Laboratories, Inc. | Water-soluble polymeric metal ion affinity compositions and methods for using the same |
| AU2003221078A1 (en) | 2002-04-08 | 2003-10-20 | Denki Kagaku Kogyo Kabushiki Kaisha | Therapeutic composition for bone infectious disease |
| US7445894B2 (en) | 2002-05-03 | 2008-11-04 | Molecular Probes, Inc. | Compositions and methods for detection and isolation of phosphorylated molecules |
| WO2007052267A2 (en) | 2005-11-01 | 2007-05-10 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Biodegradable composite for internal local radiotherapy |
| EP1867638A1 (de) | 2006-06-16 | 2007-12-19 | Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts | Verfahren zur kovalenten Verknüpfung zweier Moleküle mittels Diels-Alder-Reaktion mit inversem Elektronenbedarf |
| US8398956B2 (en) | 2007-01-11 | 2013-03-19 | Immunomedics, Inc. | In vivo copper-free click chemistry for delivery of therapeutic and/or diagnostic agents |
| US8236949B2 (en) | 2007-07-17 | 2012-08-07 | University Of Delaware | Tetrazine-based bio-orthogonal coupling reagents and methods |
| WO2009064738A2 (en) | 2007-11-12 | 2009-05-22 | Bipar Sciences, Inc. | Treatment of breast cancer with a parp inhibitor alone or in combination with anti-tumor agents |
| WO2011127149A1 (en) | 2010-04-06 | 2011-10-13 | University Of Utah Research Foundation | Controlled release combination biomaterials |
| JP5574083B2 (ja) | 2008-08-01 | 2014-08-20 | アンタイス エス．エイ． | 高い残留性及び容量を与える高い能力を有する注入可能なヒドロゲル |
| CN102271712B (zh) * | 2008-10-31 | 2015-11-25 | 通用医疗公司 | 用于将物质递送至生物靶标的组合物和方法 |
| US20110223257A1 (en) | 2008-11-17 | 2011-09-15 | Enzon Pharmaceuticals, Inc. | Releasable fusogenic lipids for nucleic acids delivery systems |
| WO2010119389A2 (en) | 2009-04-16 | 2010-10-21 | Koninklijke Philips Electronics N.V. | Pretargeting kit, method and agents used therein |
| CN103221398B (zh) | 2010-07-23 | 2016-03-23 | 特拉华大学 | 用于快速构建放射性核素标记探针的四嗪-反式环辛烯连接反应 |
| WO2012049624A1 (en) | 2010-10-14 | 2012-04-19 | Koninklijke Philips Electronics N.V. | Pretargeting kit, method and agents used therein |
| WO2012074840A2 (en) | 2010-11-22 | 2012-06-07 | The General Hospital Corporation | Compositions and methods for in vivo imaging |
| JP5992435B2 (ja) | 2010-12-21 | 2016-09-14 | コーニンクレッカ フィリップス エヌ ヴェＫｏｎｉｎｋｌｉｊｋｅ Ｐｈｉｌｉｐｓ Ｎ．Ｖ． | 循環からの生体分子の除去剤 |
| EP2522369A1 (en) | 2011-05-09 | 2012-11-14 | Koninklijke Philips Electronics N.V. | Pretargeting kit, method and agents used therein |
| EP2709666B1 (en) | 2011-05-16 | 2021-07-14 | Koninklijke Philips N.V. | Bio-orthogonal drug activation |
| US20140256831A1 (en) | 2011-05-31 | 2014-09-11 | The University Of Tokyo | Hydrogel and method for producing same |
| ES2393602B1 (es) | 2011-06-09 | 2013-10-02 | Universidad Complutense De Madrid | Materiales biocerámicos para el tratamiento de la osteomielitis. |
| WO2013115885A2 (en) * | 2011-11-22 | 2013-08-08 | The Regents Of The University Of Michigan | Synthesizing functionalized dendrimers within biological settings |
| CN104302408B (zh) | 2012-02-27 | 2016-12-14 | 阿穆尼克斯运营公司 | Xten缀合组合物和制造其的方法 |
| US9206271B2 (en) | 2012-03-25 | 2015-12-08 | Wisconsin Alumni Research Foundation | Fully backbone degradable and functionalizable polymers derived from the ring-opening metathesis polymerization (ROMP) |
| US10274490B2 (en) | 2012-06-12 | 2019-04-30 | The General Hospital Corporation | Magnetic labeling of bacteria |
| WO2014065860A1 (en) | 2012-10-24 | 2014-05-01 | The General Hospital Corporation | Functionalized 1,2,4,5-tetrazine compounds for use in bioorthogonal coupling reactions |
| US10927139B2 (en) | 2012-11-22 | 2021-02-23 | Tagworks Pharmaceuticals B.V. | Chemically cleavable group |
| WO2014081299A1 (en) | 2012-11-22 | 2014-05-30 | Tagworks Pharmaceuticals B.V. | Activatable liposomes |
| US20150297741A1 (en) * | 2012-11-22 | 2015-10-22 | Tagworks Pharmaceuticals B.V. | Bio-orthogonal drug activation |
| WO2014081300A1 (en) | 2012-11-22 | 2014-05-30 | Tagworks Pharmaceuticals B.V. | Channel protein activatable liposomes |
| US20150359913A1 (en) | 2013-01-25 | 2015-12-17 | Memorial Sloan-Kettering Cancer Center | Tetrazines/trans-cyclooctenes in solid phase synthesis of labeled peptides |
| WO2014138186A1 (en) | 2013-03-05 | 2014-09-12 | The Johns Hopkins University | Bioorthogonal two-component delivery systems for enhanced internalization of nanotherapeutics |
| FI2964224T3 (fi) * | 2013-03-08 | 2024-09-27 | Polyactiva Pty Ltd | Polymeerikonjugaatti bioaktiivisen aineen annostelemiseksi |
| JP6600302B2 (ja) | 2013-06-12 | 2019-10-30 | ザ ジェネラル ホスピタル コーポレイション | 標的分子のマルチプレックス検出のための方法、キット、およびシステム、ならびにそれらの使用 |
| EP3010486B1 (en) | 2013-06-19 | 2023-11-22 | The Regents of The University of California | Chemical structures for localized delivery of therapeutic agents |
| WO2015117235A1 (en) * | 2014-02-10 | 2015-08-13 | Mcmaster University | Targeted molecular imaging contrast agents |
| AU2015229014B2 (en) * | 2014-03-14 | 2019-07-25 | The Regents Of The University Of California | TCO conjugates and methods for delivery of therapeutic agents |
| EP3125960B1 (en) * | 2014-04-04 | 2020-06-03 | President and Fellows of Harvard College | Click-crosslinked hydrogels and methods of use |
| JP6787789B2 (ja) | 2014-04-04 | 2020-11-18 | プレジデント アンド フェローズ オブ ハーバード カレッジ | 詰め替え可能な薬物送達デバイスおよびその使用方法 |
| WO2016014799A1 (en) | 2014-07-23 | 2016-01-28 | University Of Iowa Research Foundation | Epidermal growth factor and blockade of immune checkpoints in cancer immunotherapy |
| EA201890161A1 (ru) | 2015-06-29 | 2018-06-29 | Верастэм, Инк. | Терапевтические композиции, комбинации и способы применения |
| CN108135857A (zh) | 2015-09-10 | 2018-06-08 | 沙思奇公司 | 生物正交组合物 |
| AU2018250312C1 (en) | 2017-04-07 | 2024-08-22 | Tambo, Inc. | Bioorthogonal compositions |
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2020
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2021
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2025
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