RU2018108884A - Композиции и способы применения форболовых сложных эфиров - Google Patents
Композиции и способы применения форболовых сложных эфиров Download PDFInfo
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- RU2018108884A RU2018108884A RU2018108884A RU2018108884A RU2018108884A RU 2018108884 A RU2018108884 A RU 2018108884A RU 2018108884 A RU2018108884 A RU 2018108884A RU 2018108884 A RU2018108884 A RU 2018108884A RU 2018108884 A RU2018108884 A RU 2018108884A
- Authority
- RU
- Russia
- Prior art keywords
- phorbol
- deoxyphorbol
- acetate
- formula
- ester
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims 17
- 239000000203 mixture Substances 0.000 title claims 7
- 150000002170 ethers Chemical class 0.000 title 1
- 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 10
- 239000003814 drug Substances 0.000 claims 9
- 230000000694 effects Effects 0.000 claims 9
- 229940124597 therapeutic agent Drugs 0.000 claims 9
- 229910052739 hydrogen Inorganic materials 0.000 claims 8
- 239000001257 hydrogen Substances 0.000 claims 8
- 239000002644 phorbol ester Substances 0.000 claims 8
- 238000002512 chemotherapy Methods 0.000 claims 6
- 150000002148 esters Chemical class 0.000 claims 6
- 229910052736 halogen Inorganic materials 0.000 claims 6
- 150000002367 halogens Chemical class 0.000 claims 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 6
- 125000001424 substituent group Chemical group 0.000 claims 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 5
- 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 4
- 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 4
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- 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 4
- 150000001875 compounds Chemical class 0.000 claims 4
- QGVLYPPODPLXMB-UBTYZVCOSA-N (1aR,1bS,4aR,7aS,7bS,8R,9R,9aS)-4a,7b,9,9a-tetrahydroxy-3-(hydroxymethyl)-1,1,6,8-tetramethyl-1,1a,1b,4,4a,7a,7b,8,9,9a-decahydro-5H-cyclopropa[3,4]benzo[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@@H](O)[C@@]3(O)C(C)(C)[C@H]3[C@@H]21 QGVLYPPODPLXMB-UBTYZVCOSA-N 0.000 claims 3
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- QGVLYPPODPLXMB-QXYKVGAMSA-N phorbol Natural products C[C@@H]1[C@@H](O)[C@]2(O)[C@H]([C@H]3C=C(CO)C[C@@]4(O)[C@H](C=C(C)C4=O)[C@@]13O)C2(C)C QGVLYPPODPLXMB-QXYKVGAMSA-N 0.000 claims 3
- 238000001959 radiotherapy Methods 0.000 claims 3
- 150000003839 salts Chemical class 0.000 claims 3
- 239000012453 solvate Substances 0.000 claims 3
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- 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 2
- 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 2
- 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 2
- 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 2
- 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 2
- 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 2
- MTXOHECJOIIIJM-PHFLZNSYSA-N 12-deoxyphorbol-13-isobutyrate-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)C1(C)C MTXOHECJOIIIJM-PHFLZNSYSA-N 0.000 claims 2
- MTXOHECJOIIIJM-UHFFFAOYSA-N 12-deoxyphorbol-13-isobutyrate-20-acetate Natural products C1C(C)C2(O)C3C=C(C)C(=O)C3(O)CC(COC(C)=O)=CC2C2C1(OC(=O)C(C)C)C2(C)C MTXOHECJOIIIJM-UHFFFAOYSA-N 0.000 claims 2
- 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 2
- 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 2
- 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 2
- 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 2
- WYWHKKSPHMUBEB-UHFFFAOYSA-N 6-Mercaptoguanine Natural products N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 claims 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 2
- 102000015790 Asparaginase Human genes 0.000 claims 2
- 108010024976 Asparaginase Proteins 0.000 claims 2
- 208000014644 Brain disease Diseases 0.000 claims 2
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims 2
- 208000032274 Encephalopathy Diseases 0.000 claims 2
- 206010018852 Haematoma Diseases 0.000 claims 2
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- 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 2
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- 206010062016 Immunosuppression Diseases 0.000 claims 2
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- 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 2
- 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 2
- 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 2
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- 229960003272 asparaginase Drugs 0.000 claims 2
- DCXYFEDJOCDNAF-UHFFFAOYSA-M asparaginate Chemical compound [O-]C(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-M 0.000 claims 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 2
- CNBGNNVCVSKAQZ-UHFFFAOYSA-N benzydamine Chemical compound C12=CC=CC=C2C(OCCCN(C)C)=NN1CC1=CC=CC=C1 CNBGNNVCVSKAQZ-UHFFFAOYSA-N 0.000 claims 2
- 208000034158 bleeding Diseases 0.000 claims 2
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- 239000000812 cholinergic antagonist Substances 0.000 claims 2
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- 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 2
- 229960000752 etoposide phosphate Drugs 0.000 claims 2
- 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 2
- 206010016256 fatigue Diseases 0.000 claims 2
- 229960000390 fludarabine Drugs 0.000 claims 2
- 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 2
- 229960003297 gemtuzumab ozogamicin Drugs 0.000 claims 2
- 231100000234 hepatic damage Toxicity 0.000 claims 2
- 229960000908 idarubicin Drugs 0.000 claims 2
- 230000001506 immunosuppresive effect Effects 0.000 claims 2
- 239000003018 immunosuppressive agent Substances 0.000 claims 2
- 239000003112 inhibitor Substances 0.000 claims 2
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- 208000004235 neutropenia Diseases 0.000 claims 2
- 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 2
- 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 2
- 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 2
- 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 2
- 150000004633 phorbol derivatives Chemical class 0.000 claims 2
- 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 2
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Claims (32)
1. Способ лечения или профилактики одного или нескольких побочных эффектов химиотерапии или одного или более побочных эффектов радиотерапии у субъекта-млекопитающего, нуждающегося в этом, включающий введение эффективного количества форболового сложного эфира формулы I или его фармацевтически приемлемой соли, энантиомера, сольвата или гидрата указанному субъекту-млекопитающему,
где формула I представлена:
Формула I
где R1 и R2 выбраны из группы, содержащей водород, 
, 
, 
, и их замещенные производные, где заместители выбраны из группы, состоящей из галогена, нитро и амино; R3 выбран из водорода, 
и их замещенных производных, где заместители выбраны из группы, состоящей из галогена, нитро и амино; и, необходимости, по меньшей мере, одного вспомогательного или добавочного терапевтического агента, причем, если осуществляют введение для лечения или профилактики одного или более побочных эффектов химиотерапии, указанный сложный эфир форбола формулы I проводят перед или после каждого химиотерапевтического применения многократно, по меньшей мере дважды в неделю.
2. Способ лечения или профилактики одного или нескольких побочных эффектов химиотерапии у субъекта-млекопитающего, нуждающегося в этом, включающий введение эффективного количества форболового сложного эфира формулы I или его фармацевтически приемлемой соли, энантиомера, сольвата или гидрата указанному субъекту-млекопитающему,
где формула I представлена:
Формула I
где R1 и R2 выбраны из группы, содержащей водород, , , , и их замещенные производные, где заместители выбраны из группы, состоящей из галогена, нитро и амино; R3 выбран из водорода, и их замещенных производных, где заместители выбраны из группы, состоящей из галогена, нитро и амино; и, необходимости, по меньшей мере, одного вспомогательного или добавочного терапевтического агента, причем указанный сложный эфир формулы I вводят перед и/или после каждого химиотерапевтического воздействия, а один или несколько побочных эффектов химиотерапии выбирают из группы, состоящей из облысения, тошноты, рвоты, плохого аппетита, болезненности, нейтропении, анемии, тромбоцитопении, головокружения, утомляемости, запора, язвы полости рта, зудящей кожи, шелушащейся кожи, лепрозного повреждения нерва и мышцы, слуховых изменений, потери массы тела, диареи, иммуносупрессии, гематомы, кровоточивости, повреждения сердца, повреждения печени, повреждения почки, вертиго и энцефалопатии.
3. Способ по п. 1 или 2, где R1 или R2 обозначает 
, оставшиеся R1 или R2 обозначают 
, и R3 обозначает водород.
4. Способ по п. 1 или 2, где форболовый сложный эфир обозначает форбол 13-бутират, форбол 12-деканоат, форбол 13-деканоат, форбол 12,13-диацетат, форбол 13,20-диацетат, форбол 12,13-дибензоат, форбол 12,13-дибутират, форбол 12,13-дидеканоат, форбол 12,13-дигексаноат, форбол 12,13-дипропионат, форбол 12-миристат, форбол 13-миристат, форбол 12,13,20-триацетат, 12-деоксифорбол 13-ангелат, 12-деоксифорбол 13-ангелат 20-ацетат, 12-деоксифорбол 13-изобутират, 12-деоксифорбол 13-изобутират-20-ацетат, 12-деоксифорбол 13-фенилацетат, 12-деоксифорбол 13-фенилацетат 20-ацетат, 12-деоксифорбол 13-тетрадеканоат, форбол 12-тиглиат 13-деканоат, 12-деоксифорбол 13-ацетат, форбол 12-ацетат, или форбол 13-ацетат.
5. Способ по п. 1 или 2, где форболовый сложный эфир представляет собой 12-O-тетрадеканоилфорбол-13-ацетат.
6. Способ по п. 1 или 2, где, по меньшей мере, один вспомогательный или добавочный терапевтический агент вводят указанному субъекту в координационном протоколе введения, одновременно, до, или после введения указанного форболового сложного эфира указанному субъекту.
7. Способ по п. 1 или 2, где по меньшей мере один вспомогательный или добавочный терапевтический агент выбран из группы, состоящей из: доксорубицина, витамина D3, цитарабина, цитозина арабинозида, даунорубицина, циклофосфамида, гемтузумаба озогамицина, идарубицина, меркаптопурина, митоксантрона, тиогуанина, альдеслейкина, аспарагиназы, карбоплатина, этопозида фосфата, флударабина, метотрексата, этопозида, дексаметазона, и холин магний трисалицилата.
8. Способ по п. 1 или 2, где два вспомогательных или добавочных терапевтических агента вводят указанному субъекту.
9. Способ по п. 8, где два вспомогательных или добавочных терапевтических агента представляют собою дексаметазон и холин магния трисалицилат.
10. Способ по п. 1 или 2, где указанное эффективное количество составляет между приблизительно 10 и 1500 мкг/день указанного форболового сложного эфира или производного соединения формулы I.
11. Способ по п. 1 или 2, где указанное эффективное количество составляет между приблизительно 125 и 500 мкг/день указанного форболового сложного эфира или производного соединения формулы I.
12. Композиция, содержащая эффективное количество форболового сложного эфира формулы I или его фармацевтически приемлемой соли, энантиомера, сольвата или гидрата
Формула I
где R1 и R2 выбраны из группы, содержащей водород, 
, , , и их замещенные производные, где заместители выбраны из группы, состоящей из галогена, нитро и амино; R3 обозначает водород, 
и их замещенные производные, где заместители выбраны из группы, состоящей из галогена, нитро и амино; и, по меньшей мере, одного вспомогательного или добавочного терапевтического агента для лечения или предотвращения одного или нескольких побочных эффектов химиотерапии или одного или более побочных эффектов радиотерапии в способе по п. 1.
13. Композиция по п. 12, где R1 или R2 представляют собой, оставшиеся R1 или R2 обозначают , и R3 обозначает водород.
14. Композиция по п. 12, где форболовый сложный эфир представляет собой форбол 13-бутират, форбол 12-деканоат, форбол 13-деканоат, форбол 12,13-диацетат, форбол 13,20-диацетат, форбол 12,13-дибензоат, форбол 12,13-дибутират, форбол 12,13-дидеканоат, форбол 12,13-дигексаноат, форбол 12,13-дипропионат, форбол 12-миристат, форбол 13-миристат, форбол 12,13,20-триацетат, 12-деоксифорбол 13-ангелат, 12-деоксифорбол 13-ангелат 20-ацетат, 12-деоксифорбол 13-изобутират, 12-деоксифорбол 13-изобутират-20-ацетат, 12-деоксифорбол 13-фенилацетат, 12-деоксифорбол 13-фенилацетат 20-ацетат, 12-деоксифорбол 13-тетрадеканоат, форбол 12-тиглиат 13-деканоат, 12-деоксифорбол 13-ацетат, форбол 12-ацетат, или форбол 13-ацетат.
15. Композиция по п. 12, где форболовый сложный эфир представляет собой 12-O-тетрадеканоилфорбол-13-ацетат.
16. Способ по п. 12, где указанное эффективное количество составляет между приблизительно 10 и 1500 мкг/день указанного форболового сложного эфира или производного соединения формулы I.
17. Способ по п. 16, где указанное эффективное количество составляет между приблизительно 125 и 500 мкг/день указанного форболового сложного эфира или производного соединения формулы I.
18. Композиция по п. 12, где, по меньшей мере, один вспомогательный или добавочный терапевтический агент выбран из группы, состоящей из: доксорубицина, витамина D3, цитарабина, цитозина арабинозида, даунорубицина, циклофосфамида, гемтузумаба озогамицина, идарубицина, меркаптопурина, митоксантрона, тиогуанина, альдеслейкина, аспарагиназы, карбоплатина, этопозида фосфата, флударабина, метотрексата, этопозида, дексаметазона, холин магний трисалицилата, пегфилграстима, эпоэтина альфа, дарбэпоэтина альфа, алендроната натрия, ризедроната, ибандроната, Г-КСФ, антагонистов рецептора 5-HT3, антагонистов NK1, оланзапина, кортикостероидов, антагонистов дофамина, антагонистов серотонина, бензодиазепинов, апрепитанта, каннабиноидов, стероидов, амифостина, хлоргексидина, бензидамина, сукральфата, ФРК, палифермина, Cu/Zn супероксиддисмутазы, интерлейкина 11, или простагландинов, тканевого активатора плазминогена, антикоагулянта, статина, блокаторов рецептора ангиотензина II, ингибитора ангиотензин-превращающего фермента, бета-блокатора, блокатора кальциевых каналов, диуретика, леводопы, карбидопы, пиридоксина, селейилина, разагилина, толкапона, агониста дофамина, ингибиторов MAO-B, амантидина, антихолинергических средств, финастерида, дутастерида, теразозина, доксазозина, тамсулозина, альфа-блокатора, нестероидного противовоспалительного средства, стероида; противоревматического препарата, модифицирующего течение болезни; иммуносупрессанта, ингибитора ФНО-α, адалимунаба, азатиоприна, хлорохина, гидроксихлорохина, циклоспорина, D-пеницилламина, этанерцепта, голимумаба, солей золота, инфликсимаба, лефлуномида, метотрексата, миноциклина, сульфасалазина, анакинры, абатацепта, ритуксимаба, тоцилизумаба, антихолинэстеразы, кортикостероида, иммуносупрессивного агента, антихолинергического средства, местного эстрогена, имипрамина или дулоксетина.
19. Композиция по п. 12, которая содержит, по меньшей мере, два вспомогательных или добавочных терапевтических агента.
20. Способ по п. 1, где один или несколько побочных эффектов лечения химиотерапией представляют собой облысение, тошноту, рвоту, плохой аппетит, болезненность, нейтропению, анемию, тромбоцитопению, головокружение, утомляемость, запор, язвы полости рта, зудящую кожу, шелушащуюся кожу, лепрозное повреждение нерва и мышцы, слуховые изменения, потерю массы тела, диарею, иммуносупрессию, гематомы, кровоточивость, повреждение сердца, повреждение печени, повреждение почки, вертиго и/или энцефалопатию.
21. Способ по п. 1, где один или несколько побочных эффектов радиотерапии представляют собой влажную десквамацию, болезненность, диарею, тошноту, рвоту, потерю аппетита, запор, зудящую кожу, шелушащуюся кожу, язвы рта и горла, отек, бесплодие, фиброз, выпадение волос, или сухость слизистых оболочек.
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