JP2015513315A5 - - Google Patents
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- JP2015513315A5 JP2015513315A5 JP2014553496A JP2014553496A JP2015513315A5 JP 2015513315 A5 JP2015513315 A5 JP 2015513315A5 JP 2014553496 A JP2014553496 A JP 2014553496A JP 2014553496 A JP2014553496 A JP 2014553496A JP 2015513315 A5 JP2015513315 A5 JP 2015513315A5
- Authority
- JP
- Japan
- Prior art keywords
- phorbol
- pharmaceutical composition
- deoxyphorbol
- formula
- derivative
- 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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- PHEDXBVPIONUQT-RGYGYFBISA-N phorbol 13-acetate 12-myristate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCCCCCCCCCCCC)C(CO)=C[C@H]1[C@H]1[C@]2(OC(C)=O)C1(C)C PHEDXBVPIONUQT-RGYGYFBISA-N 0.000 claims description 167
- 239000002644 phorbol ester Substances 0.000 claims description 153
- 238000000034 method Methods 0.000 claims description 139
- 239000000203 mixture Substances 0.000 claims description 87
- -1 isomers Chemical class 0.000 claims description 84
- 229910052739 hydrogen Inorganic materials 0.000 claims description 82
- 239000001257 hydrogen Substances 0.000 claims description 82
- 239000003814 drug Substances 0.000 claims description 71
- 229940124597 therapeutic agent Drugs 0.000 claims description 71
- 150000002431 hydrogen Chemical class 0.000 claims description 58
- 208000024891 symptom Diseases 0.000 claims description 49
- 239000002671 adjuvant Substances 0.000 claims description 46
- GZNWHPFWQMQXII-UHFFFAOYSA-N 1-(2-ethylphenyl)pyrrole-2,5-dione Chemical compound CCC1=CC=CC=C1N1C(=O)C=CC1=O GZNWHPFWQMQXII-UHFFFAOYSA-N 0.000 claims description 36
- 150000003839 salts Chemical class 0.000 claims description 34
- 238000011282 treatment Methods 0.000 claims description 30
- 229940002612 prodrug Drugs 0.000 claims description 29
- 239000000651 prodrug Substances 0.000 claims description 29
- 239000012453 solvate Substances 0.000 claims description 29
- 230000002265 prevention Effects 0.000 claims description 27
- 230000000694 effects Effects 0.000 claims description 26
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 24
- 206010028980 Neoplasm Diseases 0.000 claims description 22
- 150000004633 phorbol derivatives Chemical class 0.000 claims description 21
- 230000027939 micturition Effects 0.000 claims description 20
- 238000009472 formulation Methods 0.000 claims description 19
- VCQRVYCLJARKLE-XQOWHXTBSA-N (1ar,1bs,4ar,7as,7bs,8r,9r,9as)-3-[(acetyloxy)methyl]-4a,7b,9-trihydroxy-1,1,6,8-tetramethyl-5-oxo-1,1a,1b,4,4a,5,7a,7b,8,9-decahydro-9ah-cyclopropa[3,4]benzo[1,2-e]azulen-9a-yl acetate Chemical compound C1=C(COC(C)=O)C[C@]2(O)C(=O)C(C)=C[C@H]2[C@@]2(O)[C@H](C)[C@@H](O)[C@@]3(OC(C)=O)C(C)(C)[C@H]3[C@@H]21 VCQRVYCLJARKLE-XQOWHXTBSA-N 0.000 claims description 18
- HJEHMBCPVHLCOG-UHFFFAOYSA-N 1-ethynyl-4-propan-2-yloxybenzene Chemical compound CC(C)OC1=CC=C(C#C)C=C1 HJEHMBCPVHLCOG-UHFFFAOYSA-N 0.000 claims description 18
- GFAGCYRBGVCTPP-UHFFFAOYSA-N 12-deoxyphorbol 13-angelate Natural products C1C(C)C2(O)C3C=C(C)C(=O)C3(O)CC(CO)=CC2C2C1(OC(=O)C(C)=CC)C2(C)C GFAGCYRBGVCTPP-UHFFFAOYSA-N 0.000 claims description 18
- GFAGCYRBGVCTPP-APZZYBINSA-N 12-deoxyphorbol-13-angelate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)C2)C(CO)=C[C@H]1[C@H]1[C@]2(OC(=O)C(\C)=C/C)C1(C)C GFAGCYRBGVCTPP-APZZYBINSA-N 0.000 claims description 18
- QSTFRCUXCBXJAW-UHFFFAOYSA-N 12-deoxyphorbol-13-isobutyrate Natural products C1C(C)C2(O)C3C=C(C)C(=O)C3(O)CC(CO)=CC2C2C1(OC(=O)C(C)C)C2(C)C QSTFRCUXCBXJAW-UHFFFAOYSA-N 0.000 claims description 18
- ZZTJICHINNSOQL-LWYYLCCUSA-N 12-deoxyphorbol-13-tiglate-20-acetate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)C2)C(COC(C)=O)=C[C@H]1[C@H]1[C@]2(OC(=O)C(/C)=C/C)C1(C)C ZZTJICHINNSOQL-LWYYLCCUSA-N 0.000 claims description 18
- SDSVJYOOAPRSDA-RPCQODIISA-N 13-Acetylphorbol Chemical compound C1=C(CO)C[C@]2(O)C(=O)C(C)=C[C@H]2[C@@]2(O)[C@H](C)[C@@H](O)[C@@]3(OC(C)=O)C(C)(C)[C@H]3[C@@H]21 SDSVJYOOAPRSDA-RPCQODIISA-N 0.000 claims description 18
- NQSPTMFCJGKOQJ-UHFFFAOYSA-N 2,2,2-trifluoro-1-(3-fluorophenyl)ethanone Chemical compound FC1=CC=CC(C(=O)C(F)(F)F)=C1 NQSPTMFCJGKOQJ-UHFFFAOYSA-N 0.000 claims description 18
- MGWGTDCOSWKYIL-UHFFFAOYSA-N 2-amino-4-(diaminomethylideneamino)butanoic acid;hydrochloride Chemical compound Cl.OC(=O)C(N)CCN=C(N)N MGWGTDCOSWKYIL-UHFFFAOYSA-N 0.000 claims description 18
- 208000002193 Pain Diseases 0.000 claims description 18
- QWYNFKKVBDGBLL-UBDSXHIHSA-N Phorbol 12-tiglate 13-decanoate Natural products O=C(O[C@H]1[C@@H](C)[C@@]2(O)[C@H]3[C@@](O)(C(=O)C(C)=C3)CC(CO)=C[C@H]2[C@H]2C(C)(C)[C@]12OC(=O)CCCCCCCCC)/C(=C\C)/C QWYNFKKVBDGBLL-UBDSXHIHSA-N 0.000 claims description 18
- NUQJULCGNZMBEF-UHFFFAOYSA-N Prostratin Natural products COC(=O)C12CC(C)C3(O)C(C=C(CO)CC4(O)C3C=C(C)C4=O)C1C2(C)C NUQJULCGNZMBEF-UHFFFAOYSA-N 0.000 claims description 18
- YJFFPVQHOKPCRV-LKSXOGJWSA-N [(1S,2S,6R,10S,11R,13S,14R,15R)-1,6,14-trihydroxy-8-(hydroxymethyl)-4,12,12,15-tetramethyl-5-oxo-13-tetracyclo[8.5.0.02,6.011,13]pentadeca-3,8-dienyl] decanoate Chemical compound C1=C(CO)C[C@]2(O)C(=O)C(C)=C[C@H]2[C@@]2(O)[C@H](C)[C@@H](O)[C@@]3(OC(=O)CCCCCCCCC)C(C)(C)[C@H]3[C@@H]21 YJFFPVQHOKPCRV-LKSXOGJWSA-N 0.000 claims description 18
- CESGKXMBHGUQTB-VONOSFMSSA-N [(1S,2S,6R,10S,11R,13S,14R,15R)-1,6,14-trihydroxy-8-(hydroxymethyl)-4,12,12,15-tetramethyl-5-oxo-13-tetracyclo[8.5.0.02,6.011,13]pentadeca-3,8-dienyl] tetradecanoate Chemical compound C1=C(CO)C[C@]2(O)C(=O)C(C)=C[C@H]2[C@@]2(O)[C@H](C)[C@@H](O)[C@@]3(OC(=O)CCCCCCCCCCCCC)C(C)(C)[C@H]3[C@@H]21 CESGKXMBHGUQTB-VONOSFMSSA-N 0.000 claims description 18
- LMLOFRDITXUVHZ-BPNNYVJBSA-N ac1l3xbq Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CC)C(CO)=C[C@H]1[C@H]1[C@]2(OC(=O)CC)C1(C)C LMLOFRDITXUVHZ-BPNNYVJBSA-N 0.000 claims description 18
- FDFRQMKAXPLXFL-UZAJRZOCSA-N ac1l576h Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)C2)C(CO)=C[C@H]1[C@H]1[C@]2(OC(=O)CCCCCCCCCCCCC)C1(C)C FDFRQMKAXPLXFL-UZAJRZOCSA-N 0.000 claims description 18
- RTJAYUGZUOLFMY-UHFFFAOYSA-N deoxyphorbol Natural products C1=C(CO)CC2C(=O)C(C)=CC2C2(O)C(C)C(O)C3(O)C(C)(C)C3C21 RTJAYUGZUOLFMY-UHFFFAOYSA-N 0.000 claims description 18
- LASMKIAVFGUYEG-SEYWVDNQSA-N phorbol 12,13,20-triacetate Chemical compound C1=C(COC(C)=O)C[C@]2(O)C(=O)C(C)=C[C@H]2[C@@]2(O)[C@H](C)[C@@H](OC(C)=O)[C@@]3(OC(C)=O)C(C)(C)[C@H]3[C@@H]21 LASMKIAVFGUYEG-SEYWVDNQSA-N 0.000 claims description 18
- BQJRUJTZSGYBEZ-YVQNUNKESA-N phorbol 12,13-dibutanoate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCC)C(CO)=C[C@H]1[C@H]1[C@]2(OC(=O)CCC)C1(C)C BQJRUJTZSGYBEZ-YVQNUNKESA-N 0.000 claims description 18
- NVKVYBPQQUTLSY-RPCQODIISA-N phorbol 12-acetate Chemical compound C1=C(CO)C[C@]2(O)C(=O)C(C)=C[C@H]2[C@@]2(O)[C@H](C)[C@@H](OC(C)=O)[C@@]3(O)C(C)(C)[C@H]3[C@@H]21 NVKVYBPQQUTLSY-RPCQODIISA-N 0.000 claims description 18
- LXYSVTVLQYLWKR-LKSXOGJWSA-N phorbol 12-decanoate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCCCCCCCC)C(CO)=C[C@H]1[C@H]1[C@]2(O)C1(C)C LXYSVTVLQYLWKR-LKSXOGJWSA-N 0.000 claims description 18
- FZXHDWWEDNRATG-JUDMOCROSA-N phorbol 13-butanoate Chemical group C1=C(CO)C[C@]2(O)C(=O)C(C)=C[C@H]2[C@@]2(O)[C@H](C)[C@@H](O)[C@@]3(OC(=O)CCC)C(C)(C)[C@H]3[C@@H]21 FZXHDWWEDNRATG-JUDMOCROSA-N 0.000 claims description 18
- QWYNFKKVBDGBLL-KFWZAFQTSA-N phorbol 13-decanoate 12-tiglate Chemical compound C1=C(CO)C[C@]2(O)C(=O)C(C)=C[C@H]2[C@@]2(O)[C@H](C)[C@@H](OC(=O)C(\C)=C\C)[C@@]3(OC(=O)CCCCCCCCC)C(C)(C)[C@H]3[C@@H]21 QWYNFKKVBDGBLL-KFWZAFQTSA-N 0.000 claims description 18
- DGOSGFYDFDYMCW-MWRBZVGOSA-N phorbol dicaprate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCCCCCCCC)C(CO)=C[C@H]1[C@H]1[C@]2(OC(=O)CCCCCCCCC)C1(C)C DGOSGFYDFDYMCW-MWRBZVGOSA-N 0.000 claims description 18
- XGPRSRGBAHBMAF-NQWCLMGHSA-N phorbol-12,13-dihexanoate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCCCC)C(CO)=C[C@H]1[C@H]1[C@]2(OC(=O)CCCCC)C1(C)C XGPRSRGBAHBMAF-NQWCLMGHSA-N 0.000 claims description 18
- XLCISDOVNFLSGO-VONOSFMSSA-N phorbol-12-myristate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCCCCCCCCCCCC)C(CO)=C[C@H]1[C@H]1[C@]2(O)C1(C)C XLCISDOVNFLSGO-VONOSFMSSA-N 0.000 claims description 18
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 17
- 208000035269 cancer or benign tumor Diseases 0.000 claims description 16
- 201000010099 disease Diseases 0.000 claims description 16
- 230000036407 pain Effects 0.000 claims description 16
- 230000001613 neoplastic effect Effects 0.000 claims description 15
- FXEDIXLHKQINFP-UHFFFAOYSA-N 12-O-tetradecanoylphorbol-13-acetate Natural products CCCCCCCCCCCCCC(=O)OC1CC2(O)C(C=C(CO)CC3(O)C2C=C(C)C3=O)C4C(C)(C)C14OC(=O)C FXEDIXLHKQINFP-UHFFFAOYSA-N 0.000 claims description 14
- 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 14
- 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 14
- 230000004596 appetite loss Effects 0.000 claims description 12
- 206010016256 fatigue Diseases 0.000 claims description 12
- 208000019017 loss of appetite Diseases 0.000 claims description 12
- 235000021266 loss of appetite Nutrition 0.000 claims description 12
- 230000001939 inductive effect Effects 0.000 claims description 11
- QVRQIOGZIFABFD-UHFFFAOYSA-N 2-hydroxybenzoic acid;magnesium Chemical compound [Mg].OC(=O)C1=CC=CC=C1O.OC(=O)C1=CC=CC=C1O.OC(=O)C1=CC=CC=C1O QVRQIOGZIFABFD-UHFFFAOYSA-N 0.000 claims description 10
- 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 10
- 208000018737 Parkinson disease Diseases 0.000 claims description 10
- 206010046543 Urinary incontinence Diseases 0.000 claims description 10
- 238000002512 chemotherapy Methods 0.000 claims description 10
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 claims description 10
- 229960001231 choline Drugs 0.000 claims description 10
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 claims description 10
- 229960003957 dexamethasone Drugs 0.000 claims description 10
- 229960000485 methotrexate Drugs 0.000 claims description 10
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 10
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 claims description 9
- 208000004403 Prostatic Hyperplasia Diseases 0.000 claims description 9
- 208000017169 kidney disease Diseases 0.000 claims description 9
- 206010028417 myasthenia gravis Diseases 0.000 claims description 9
- 238000011477 surgical intervention Methods 0.000 claims description 9
- 210000002700 urine Anatomy 0.000 claims description 9
- 206010028813 Nausea Diseases 0.000 claims description 8
- 208000003251 Pruritus Diseases 0.000 claims description 8
- 206010037660 Pyrexia Diseases 0.000 claims description 8
- 206010040844 Skin exfoliation Diseases 0.000 claims description 8
- 206010047700 Vomiting Diseases 0.000 claims description 8
- 230000008693 nausea Effects 0.000 claims description 8
- 238000001959 radiotherapy Methods 0.000 claims description 8
- 230000008673 vomiting Effects 0.000 claims description 8
- CBDIJHBGVGPIIE-MCDHERAVSA-N 1,1a,1b,4,4a,7a,7b,8,9,9a-decahydro-4a,7b,9a-trihydroxy-3-(hydroxymethyl)-1,1,6,8-tetramethyl-,(1ar,1bs,4ar,7as,7br,8r,9as)-5h-cyclopropa(3,4)benz(1,2-e)azulen-5-one Chemical compound C1=C(CO)C[C@]2(O)C(=O)C(C)=C[C@H]2[C@@]2(O)[C@H](C)C[C@@]3(O)C(C)(C)[C@H]3[C@@H]21 CBDIJHBGVGPIIE-MCDHERAVSA-N 0.000 claims description 7
- WYWHKKSPHMUBEB-UHFFFAOYSA-N 6-Mercaptoguanine Natural products N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 claims description 7
- 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 7
- 102000015790 Asparaginase Human genes 0.000 claims description 7
- 108010024976 Asparaginase Proteins 0.000 claims description 7
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 7
- 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 7
- 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 7
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 claims description 7
- 229960005310 aldesleukin Drugs 0.000 claims description 7
- 108700025316 aldesleukin Proteins 0.000 claims description 7
- 229960003272 asparaginase Drugs 0.000 claims description 7
- DCXYFEDJOCDNAF-UHFFFAOYSA-M asparaginate Chemical compound [O-]C(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-M 0.000 claims description 7
- 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 7
- 229960004562 carboplatin Drugs 0.000 claims description 7
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- 229960000684 cytarabine Drugs 0.000 claims description 7
- 229960000975 daunorubicin Drugs 0.000 claims description 7
- 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 7
- 229960004679 doxorubicin Drugs 0.000 claims description 7
- 229960005420 etoposide Drugs 0.000 claims description 7
- 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 7
- 229960000752 etoposide phosphate Drugs 0.000 claims description 7
- LIQODXNTTZAGID-OCBXBXKTSA-N etoposide phosphate Chemical compound COC1=C(OP(O)(O)=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 LIQODXNTTZAGID-OCBXBXKTSA-N 0.000 claims description 7
- 229960000390 fludarabine Drugs 0.000 claims description 7
- GIUYCYHIANZCFB-FJFJXFQQSA-N fludarabine phosphate Chemical compound C1=NC=2C(N)=NC(F)=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@@H]1O GIUYCYHIANZCFB-FJFJXFQQSA-N 0.000 claims description 7
- 229960003297 gemtuzumab ozogamicin Drugs 0.000 claims description 7
- 229960000908 idarubicin Drugs 0.000 claims description 7
- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 claims description 7
- 229960001428 mercaptopurine Drugs 0.000 claims description 7
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 claims description 7
- 229960001156 mitoxantrone Drugs 0.000 claims description 7
- 210000003205 muscle Anatomy 0.000 claims description 7
- 229960003087 tioguanine Drugs 0.000 claims description 7
- QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-YRZJJWOYSA-N 0.000 claims description 7
- 235000005282 vitamin D3 Nutrition 0.000 claims description 7
- 239000011647 vitamin D3 Substances 0.000 claims description 7
- 229940021056 vitamin d3 Drugs 0.000 claims description 7
- 201000004384 Alopecia Diseases 0.000 claims description 6
- 208000006820 Arthralgia Diseases 0.000 claims description 6
- 206010010774 Constipation Diseases 0.000 claims description 6
- 206010012735 Diarrhoea Diseases 0.000 claims description 6
- 208000032843 Hemorrhage Diseases 0.000 claims description 6
- 229940121948 Muscarinic receptor antagonist Drugs 0.000 claims description 6
- 206010046555 Urinary retention Diseases 0.000 claims description 6
- CNBGNNVCVSKAQZ-UHFFFAOYSA-N benzydamine Chemical compound C12=CC=CC=C2C(OCCCN(C)C)=NN1CC1=CC=CC=C1 CNBGNNVCVSKAQZ-UHFFFAOYSA-N 0.000 claims description 6
- 230000000740 bleeding effect Effects 0.000 claims description 6
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| CN106420687A (zh) * | 2016-10-11 | 2017-02-22 | 孙君重 | 防护肠辐射损伤的方法及tpa的用途 |
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