RU2003127391A - Лечение рака - Google Patents
Лечение рака Download PDFInfo
- Publication number
- RU2003127391A RU2003127391A RU2003127391/15A RU2003127391A RU2003127391A RU 2003127391 A RU2003127391 A RU 2003127391A RU 2003127391/15 A RU2003127391/15 A RU 2003127391/15A RU 2003127391 A RU2003127391 A RU 2003127391A RU 2003127391 A RU2003127391 A RU 2003127391A
- Authority
- RU
- Russia
- Prior art keywords
- inhibitor
- pharmaceutical composition
- rapamycin
- compound
- formula
- Prior art date
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- 206010028980 Neoplasm Diseases 0.000 title claims 6
- 201000011510 cancer Diseases 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims 9
- 239000008194 pharmaceutical composition Substances 0.000 claims 8
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[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 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 claims 8
- 238000000034 method Methods 0.000 claims 5
- 239000002246 antineoplastic agent Substances 0.000 claims 4
- 229940127089 cytotoxic agent Drugs 0.000 claims 4
- 239000003112 inhibitor Substances 0.000 claims 4
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 claims 4
- 229960002930 sirolimus Drugs 0.000 claims 4
- 230000001771 impaired effect Effects 0.000 claims 3
- 230000006884 regulation of angiogenesis Effects 0.000 claims 3
- 239000000969 carrier Substances 0.000 claims 2
- 239000003795 chemical substances by application Substances 0.000 claims 2
- 239000003085 diluting agent Substances 0.000 claims 2
- 230000000694 effects Effects 0.000 claims 2
- 150000002632 lipids Chemical class 0.000 claims 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims 2
- 102000004169 proteins and genes Human genes 0.000 claims 2
- 108090000623 proteins and genes Proteins 0.000 claims 2
- 229940097396 Aminopeptidase inhibitor Drugs 0.000 claims 1
- 229940122815 Aromatase inhibitor Drugs 0.000 claims 1
- 229940122361 Bisphosphonate Drugs 0.000 claims 1
- 102400000967 Bradykinin Human genes 0.000 claims 1
- 101800004538 Bradykinin Proteins 0.000 claims 1
- 229940122204 Cyclooxygenase inhibitor Drugs 0.000 claims 1
- 229940123780 DNA topoisomerase I inhibitor Drugs 0.000 claims 1
- 229940124087 DNA topoisomerase II inhibitor Drugs 0.000 claims 1
- 102400000932 Gonadoliberin-1 Human genes 0.000 claims 1
- QXZGBUJJYSLZLT-UHFFFAOYSA-N H-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg-OH Natural products NC(N)=NCCCC(N)C(=O)N1CCCC1C(=O)N1C(C(=O)NCC(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CO)C(=O)N2C(CCC2)C(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CCCN=C(N)N)C(O)=O)CCC1 QXZGBUJJYSLZLT-UHFFFAOYSA-N 0.000 claims 1
- 229940122588 Heparanase inhibitor Drugs 0.000 claims 1
- 101500026183 Homo sapiens Gonadoliberin-1 Proteins 0.000 claims 1
- 101710181812 Methionine aminopeptidase Proteins 0.000 claims 1
- 102000029749 Microtubule Human genes 0.000 claims 1
- 108091022875 Microtubule Proteins 0.000 claims 1
- 102000045595 Phosphoprotein Phosphatases Human genes 0.000 claims 1
- 108700019535 Phosphoprotein Phosphatases Proteins 0.000 claims 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 claims 1
- 102000001708 Protein Isoforms Human genes 0.000 claims 1
- 108010029485 Protein Isoforms Proteins 0.000 claims 1
- 102000001253 Protein Kinase Human genes 0.000 claims 1
- 229940123582 Telomerase inhibitor Drugs 0.000 claims 1
- 239000000365 Topoisomerase I Inhibitor Substances 0.000 claims 1
- 239000000317 Topoisomerase II Inhibitor Substances 0.000 claims 1
- 102000044159 Ubiquitin Human genes 0.000 claims 1
- 108090000848 Ubiquitin Proteins 0.000 claims 1
- 101000998548 Yersinia ruckeri Alkaline proteinase inhibitor Proteins 0.000 claims 1
- 239000000556 agonist Substances 0.000 claims 1
- 229940100198 alkylating agent Drugs 0.000 claims 1
- 239000002168 alkylating agent Substances 0.000 claims 1
- 239000002333 angiotensin II receptor antagonist Substances 0.000 claims 1
- 229940126317 angiotensin II receptor antagonist Drugs 0.000 claims 1
- 230000002280 anti-androgenic effect Effects 0.000 claims 1
- 230000001772 anti-angiogenic effect Effects 0.000 claims 1
- 230000009949 anti-apoptotic pathway Effects 0.000 claims 1
- 229940046836 anti-estrogen Drugs 0.000 claims 1
- 230000001833 anti-estrogenic effect Effects 0.000 claims 1
- 239000000051 antiandrogen Substances 0.000 claims 1
- 239000002814 antineoplastic antimetabolite Substances 0.000 claims 1
- 239000003886 aromatase inhibitor Substances 0.000 claims 1
- 230000008512 biological response Effects 0.000 claims 1
- 150000004663 bisphosphonates Chemical class 0.000 claims 1
- QXZGBUJJYSLZLT-FDISYFBBSA-N bradykinin Chemical compound NC(=N)NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(=O)NCC(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CO)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)CCC1 QXZGBUJJYSLZLT-FDISYFBBSA-N 0.000 claims 1
- 230000024245 cell differentiation Effects 0.000 claims 1
- 239000000328 estrogen antagonist Substances 0.000 claims 1
- XLXSAKCOAKORKW-AQJXLSMYSA-N gonadorelin Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 XLXSAKCOAKORKW-AQJXLSMYSA-N 0.000 claims 1
- 229960001442 gonadorelin Drugs 0.000 claims 1
- 239000002474 gonadorelin antagonist Substances 0.000 claims 1
- 229940121372 histone deacetylase inhibitor Drugs 0.000 claims 1
- 239000003276 histone deacetylase inhibitor Substances 0.000 claims 1
- 230000001939 inductive effect Effects 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 claims 1
- 230000005764 inhibitory process Effects 0.000 claims 1
- 230000009545 invasion Effects 0.000 claims 1
- 239000011159 matrix material Substances 0.000 claims 1
- 239000003475 metalloproteinase inhibitor Substances 0.000 claims 1
- 210000004688 microtubule Anatomy 0.000 claims 1
- 239000003607 modifier Substances 0.000 claims 1
- 231100000590 oncogenic Toxicity 0.000 claims 1
- 230000002246 oncogenic effect Effects 0.000 claims 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 claims 1
- 229910052697 platinum Inorganic materials 0.000 claims 1
- 239000002599 prostaglandin synthase inhibitor Substances 0.000 claims 1
- 108060006633 protein kinase Proteins 0.000 claims 1
- 208000024891 symptom Diseases 0.000 claims 1
- 239000003277 telomerase inhibitor Substances 0.000 claims 1
Classifications
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- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
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- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4196—1,2,4-Triazoles
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Claims (10)
1. Применение соединения формулы I
где r1 обозначает СН3 или С3-С6алкинил,
R2 обозначает Н или –СН2-СН2-ОН, и
Х обозначает =О, (Н, Н) или (Н, ОН)
при условии, что R2 не обозначает Н, если Х обозначает=0 и r1 обозначает СН3, для приготовления фармацевтической композиции, предназначенной для лечения плотных опухолей.
2. Применение соединения формулы I по п.1 для приготовления фармацевтической композиции, предназначенной для лечения инвазии плотных опухолей или симптомов, связанных с ростом такой опухоли.
3. Применение рапамицина или производного рапамицина для приготовления фармацевтической композиции, предназначенной для ингибирования или контроля нарушенной регуляции ангиогенеза.
4. Фармацевтическая композиция, предназначенная для лечения плотных опухолей, содержащая соединение формулы I по п.1 в сочетании с одним или несколькими фармацевтически приемлемыми разбавителями или носителями.
5. Фармацевтическая композиция, предназначенная для ингибирования или контроля нарушенной регуляции ангиогенеза, содержащая рапамицин или производное рапамицина в сочетании с одним или несколькими фармацевтически приемлемыми разбавителями или носителями.
6. Фармацевтическая композиция, содержащая а) соединение формулы I по п.1 и б) коагент, представляющий собой химиотерапевтический агент.
7. Фармацевтическая композиция по п.6, где коагент выбирают из группы, включающей
I. ингибитор ароматазы,
II. антиэстроген, антиандроген или агонист гонадорелина,
III. ингибитор топоизомеразы I или ингибитор топоизомеразы II,
IV. агент, обладающий активностью в отношении микротрубочек, алкилирующий агент, антинеопластический антиметаболит или содержащее платину соединение,
V. соединение, обладающее способностью воздействовать на/понижать активность протеин- или липидкиназы, или протеин- или липидфосфатазы, другое антиангиогенное соединение или соединение, индуцирующее процессы дифференцировки клеток,
VI. антагонист рецептора брадикинина 1 или ангиотензина II,
VII. ингибитор циклооксигеназы, бисфосфонат, ингибитор гистон-деацетилазы, ингибитор гепараназы, модификатор биологической реакции, ингибитор убиквитина, или ингибитор, блокирующий антиапоптозные пути,
VIII. ингибитор онкогенных изоформ Ras,
IX. ингибитор теломеразы и
X. ингибитор протеазы, ингибитор матриксной металлопротеазы, ингибитор метионинаминопептидазы или ингибитор протеосомы.
8. Фармацевтическая композиция, содержащая а) рапамицин или производное рапамицина и б) коагент, представляющий собой химиотерапевтический агент, выбранный из агентов, перечисленных в разделах (I.) и (V)-(X.) по п.7.
9. Способ лечения плотных опухолей у пациента, нуждающегося в таком лечении, заключающийся в том, что пациенту вводят терапевтически эффективное количество соединения формулы I по п.1 необязательно одновременно или последовательно в сочетании с химиотерапевтическим агентом.
10. Способ ингибирования или контроля нарушенной регуляции ангиогенеза у пациента, нуждающегося в таком лечении, заключающийся в том, что пациенту вводят терапевтически эффективное количество рапамицина или производного рапамицина необязательно одновременно или последовательно с введением химиотерапевтического агента.
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RU2011138835/15A RU2483727C1 (ru) | 2001-02-19 | 2011-09-22 | Применение производного рапамицина |
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2005
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