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 (36)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009045539A2 (en) * | 2007-10-05 | 2009-04-09 | Nektar Therapeutics Al, Corporation | Oligomer-corticosteroid conjugates |
| US10155063B2 (en) | 2015-11-12 | 2018-12-18 | University Of Virginia Patent Foundation | Methods for vas-occlusive contraception and reversal thereof |
| KR20190074310A (ko) | 2016-11-08 | 2019-06-27 | 리제너론 파마슈티칼스 인코포레이티드 | 스테로이드 및 이의 단백질-접합체 |
| US12383421B2 (en) | 2017-01-05 | 2025-08-12 | Contraline, Inc. | Contraceptive devices |
| CA3053451A1 (en) | 2017-01-05 | 2018-07-12 | Contraline, Inc. | Methods for implanting and reversing stimuli-responsive implants |
| ES2983582T3 (es) | 2017-04-07 | 2024-10-23 | Tambo Inc | Composiciones bioortogonales |
| JP7364471B2 (ja) | 2017-05-18 | 2023-10-18 | レゲネロン ファーマシューティカルス，インコーポレーテッド | シクロデキストリンタンパク質薬物コンジュゲート |
| WO2019094395A2 (en) | 2017-11-07 | 2019-05-16 | Regeneron Pharmaceuticals, Inc. | Hydrophilic linkers for antibody drug conjugates |
| AU2019205542B2 (en) | 2018-01-08 | 2025-10-23 | Regeneron Pharmaceuticals, Inc. | Steroids and antibody-conjugates thereof |
| 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 |
| WO2019144859A1 (zh) * | 2018-01-24 | 2019-08-01 | 南京柯菲平盛辉制药有限公司 | 吲哚胺2,3-双加氧酶调节剂，其制备方法及用途 |
| 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 |
| SG11202010909RA (en) | 2018-05-09 | 2020-12-30 | Regeneron Pharma | 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 |
| US20210330798A1 (en) * | 2018-09-26 | 2021-10-28 | Ascendis Pharma A/S | Treatment of infections |
| JP7650228B2 (ja) | 2018-10-10 | 2025-03-24 | タンボ・インコーポレイテッド | 官能化シクロオクテンを調製するためのプロセス |
| US11253391B2 (en) | 2018-11-13 | 2022-02-22 | 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 |
| CA3145889A1 (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 |
| 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 |
| 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 |
| 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 |
| EP4192506A1 (en) * | 2020-08-07 | 2023-06-14 | Tambo, Inc. | Trans-cyclooctene bioorthogonal agents and uses in cancer and immunotherapy |
| EP4422693A1 (en) | 2021-10-29 | 2024-09-04 | Tambo, Inc. | Trans-cyclooctene conjugates |
| EP4422696A1 (en) | 2021-10-29 | 2024-09-04 | Tambo, Inc. | Tetrazine conjugates for in vivo targeted delivery of a payload |
| US20250009890A1 (en) | 2021-11-05 | 2025-01-09 | Tambo, Inc. | Trans-cyclooctene-modified bispecific antibodies |
| CN120129533A (zh) | 2022-09-20 | 2025-06-10 | 瓦朗斯生物技术有限公司 | 点击释放蛋白质和肽 |
| 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 |
| CN121001752A (zh) | 2023-02-21 | 2025-11-21 | 坦博公司 | 反式环辛烯缀合物 |
| WO2024210956A1 (en) * | 2023-04-05 | 2024-10-10 | Rutgers, The State University Of New Jersey | Biogel, compositions and methods of use the same |
| WO2024229427A1 (en) | 2023-05-04 | 2024-11-07 | Tambo, Inc. | Tetrazine-based targeting agents for in vivo delivery of a payload |
| WO2024238969A1 (en) | 2023-05-18 | 2024-11-21 | Tambo, Inc. | Trans-cyclooctene-modified targeted protein degrader conjugates |
| WO2025059685A1 (en) | 2023-09-15 | 2025-03-20 | Tambo, Inc. | Methods for in vivo targeted delivery of a payload |
Family Cites Families (40)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE69530553T2 (de) | 1994-05-13 | 2004-03-25 | KURARAY CO., LTD, Kurashiki | Medizinisches polymergel |
| AU2002315414B2 (en) | 2001-06-21 | 2008-02-07 | Clontech Laboratories, Inc. | Water-soluble polymeric metal ion affinity compositions and methods for using the same |
| JPWO2003084571A1 (ja) | 2002-04-08 | 2005-08-11 | 電気化学工業株式会社 | 骨感染症治療用組成物 |
| 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 |
| WO2011127149A1 (en) | 2010-04-06 | 2011-10-13 | University Of Utah Research Foundation | Controlled release combination biomaterials |
| US8574629B2 (en) | 2008-08-01 | 2013-11-05 | Anteis S.A. | Injectable hydrogel with an enhanced remanence and with an enhanced ability to create volume |
| 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 |
| JP2012509273A (ja) | 2008-11-17 | 2012-04-19 | エンゾン ファーマシューティカルズ，インコーポレーテッド | 核酸送達系のための放出可能融合性脂質 |
| BRPI1006246A2 (pt) | 2009-04-16 | 2020-02-04 | Koninl Philips Electronics Nv | "kit para imagem médica marcada e/ou terapias, sonda efetora e método" |
| 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 |
| JP6063384B2 (ja) | 2010-10-14 | 2017-01-18 | コーニンクレッカ フィリップス エヌ ヴェＫｏｎｉｎｋｌｉｊｋｅ Ｐｈｉｌｉｐｓ Ｎ．Ｖ． | プレターゲットキット、プレターゲット方法及びその使用試薬 |
| US9649394B2 (en) | 2010-11-22 | 2017-05-16 | The General Hospital Corporation | Compositions and methods for in vivo imaging |
| EP2654796A1 (en) | 2010-12-21 | 2013-10-30 | Koninklijke Philips N.V. | Agents for clearing biomolecules from circulation |
| EP2522369A1 (en) | 2011-05-09 | 2012-11-14 | Koninklijke Philips Electronics N.V. | Pretargeting kit, method and agents used therein |
| CA2836338C (en) | 2011-05-16 | 2022-05-03 | Koninklijke Philips N.V. | Tetrazine derivatives used in bio-orthogonal drug activation |
| JPWO2012165462A1 (ja) | 2011-05-31 | 2015-02-23 | 国立大学法人 東京大学 | ハイドロゲル及びその製造方法 |
| ES2393602B1 (es) | 2011-06-09 | 2013-10-02 | Universidad Complutense De Madrid | Materiales biocerámicos para el tratamiento de la osteomielitis. |
| US20140303123A1 (en) | 2011-11-22 | 2014-10-09 | The Regents Of The University Of Michigan | Synthesizing functionalized dendrimers within biological settings |
| MX366864B (es) | 2012-02-27 | 2019-07-26 | Amunix Operating Inc | Composiciones de conjugados de xten y métodos para realizarlas. |
| 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) |
| WO2013187954A1 (en) * | 2012-06-12 | 2013-12-19 | 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 |
| EP4245744A3 (en) * | 2012-11-22 | 2024-05-01 | Tagworks Pharmaceuticals B.V. | Chemically cleavable group |
| WO2014081299A1 (en) | 2012-11-22 | 2014-05-30 | Tagworks Pharmaceuticals B.V. | Activatable liposomes |
| WO2014081300A1 (en) | 2012-11-22 | 2014-05-30 | Tagworks Pharmaceuticals B.V. | Channel protein activatable liposomes |
| US20150297741A1 (en) * | 2012-11-22 | 2015-10-22 | Tagworks Pharmaceuticals B.V. | Bio-orthogonal drug activation |
| EP2948186A4 (en) | 2013-01-25 | 2016-10-05 | Sloan Kettering Inst Cancer | TETRAZINE / TRANSCYCLOOKTENE IN SOLID PHASE SYNTHESIS MARKED PEPTIDE |
| WO2014138186A1 (en) | 2013-03-05 | 2014-09-12 | The Johns Hopkins University | Bioorthogonal two-component delivery systems for enhanced internalization of nanotherapeutics |
| WO2014134689A1 (en) | 2013-03-08 | 2014-09-12 | Polyactiva Pty Ltd | Polymer conjugate for delivery of a bioactive agent |
| EP3008201B1 (en) | 2013-06-12 | 2019-08-07 | The General Hospital Corporation | Methods for multiplexed detection of target molecules and uses thereof |
| WO2014205126A1 (en) * | 2013-06-19 | 2014-12-24 | The Regents Of The University Of California | Chemical structures for localized delivery of therapeutic agents |
| US20160346409A1 (en) | 2014-02-10 | 2016-12-01 | Mcmaster University | Targeted molecular imaging contrast agents |
| ES2880468T3 (es) * | 2014-03-14 | 2021-11-24 | Univ California | Conjugados de TCO y métodos para el suministro de agentes terapéuticos |
| WO2015154078A1 (en) * | 2014-04-04 | 2015-10-08 | President And Fellows Of Harvard College | Click-crosslinked hydrogels and methods of use |
| US20170119892A1 (en) | 2014-04-04 | 2017-05-04 | President And Fellows Of Harvard College | Refillable drug delivery devices and methods of use thereof |
| ES2983582T3 (es) * | 2017-04-07 | 2024-10-23 | Tambo Inc | Composiciones bioortogonales |
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2020
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2021
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