RU2016124135A - METHODS OF APPLICATION (+) - 1,4-DIHYDRO-7 - [(3S, 4S) -3-METOXY-4- (METHYLAMINO) -1-Pyrrolidinyl] -4-OXO-1- (2-THIAZOLYL) -1, 8-NAFTIRIDIN-3-CARBONIC ACID FOR CANCER TREATMENT - Google Patents

METHODS OF APPLICATION (+) - 1,4-DIHYDRO-7 - [(3S, 4S) -3-METOXY-4- (METHYLAMINO) -1-Pyrrolidinyl] -4-OXO-1- (2-THIAZOLYL) -1, 8-NAFTIRIDIN-3-CARBONIC ACID FOR CANCER TREATMENT Download PDF

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RU2016124135A
RU2016124135A RU2016124135A RU2016124135A RU2016124135A RU 2016124135 A RU2016124135 A RU 2016124135A RU 2016124135 A RU2016124135 A RU 2016124135A RU 2016124135 A RU2016124135 A RU 2016124135A RU 2016124135 A RU2016124135 A RU 2016124135A
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pyrrolidinyl
methylamino
thiazolyl
dihydro
oxo
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RU2016124135A
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Russian (ru)
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Дэниел С. ЭЙДЕЛМАН
Джеффри А. СИЛВЕРМАН
Майкл АРКИН
Дженнифер ХАЙД
Дункан УОЛКЕР
Жасмин РАЙТ
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Санесис Фармасьютикалз, Инк.
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Publication of RU2016124135A publication Critical patent/RU2016124135A/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4375—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • 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
    • A61K31/425—Thiazoles
    • A61K31/427—Thiazoles not condensed and containing further heterocyclic rings

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Claims (19)


1     1. Способ лечения острого миелогенного лейкоза, включающий введение человеку (+)-1,4-дигидро-7-[(3S,4S)-3-метокси-4-(метиламино)-1-пирролидинил]-4-оксо-1-(2-тиазолил)-1,8-нафтиридин-3-карбоновой кислоты в дозе от примерно 10 до примерно 100 мг/м2 и терапевтически эффективной дозы второго средства, выбранного из децитабина и азацитидина.
1 1. A method of treating acute myelogenous leukemia, comprising administering to a person (+) - 1,4-dihydro-7 - [(3S, 4S) -3-methoxy-4- (methylamino) -1-pyrrolidinyl] -4-oxo- 1- (2-thiazolyl) -1,8-naphthyridine-3-carboxylic acid in a dose of from about 10 to about 100 mg / m 2 and a therapeutically effective dose of a second agent selected from decitabine and azacytidine.
2     2. Способ по п.1, где лейкоз является рецидивирующим, рефракторным или устойчивым к обычному лечению.
2 2. The method according to claim 1, where the leukemia is recurrent, refractory or resistant to conventional treatment.
3     3. Способ по п.1 или 2, где доза (+)-1,4-дигидро-7-[(3S,4S)-3-метокси-4-(метиламино)-1-пирролидинил]-4-оксо-1-(2-тиазолил)-1,8-нафтиридин-3-карбоновой кислоты составляет от примерно 50 до примерно 90 мг/м2.
3 3. The method according to claim 1 or 2, where the dose of (+) - 1,4-dihydro-7 - [(3S, 4S) -3-methoxy-4- (methylamino) -1-pyrrolidinyl] -4-oxo -1- (2-thiazolyl) -1,8-naphthyridine-3-carboxylic acid is from about 50 to about 90 mg / m 2.
4     4. Способ по п.3, где доза (+)-1,4-дигидро-7-[(3S,4S)-3-метокси-4-(метиламино)-1-пирролидинил]-4-оксо-1-(2-тиазолил)-1,8-нафтиридин-3-карбоновой кислоты составляет от примерно 55 до примерно 75 мг/м2.
4 4. The method according to claim 3, where the dose of (+) - 1,4-dihydro-7 - [(3S, 4S) -3-methoxy-4- (methylamino) -1-pyrrolidinyl] -4-oxo-1 - (2-thiazolyl) -1,8-naphthyridine-3-carboxylic acid is from about 55 to about 75 mg / m 2 .
5     5. Способ по п.3, где доза (+)-1,4-дигидро-7-[(3S,4S)-3-метокси-4-(метиламино)-1-пирролидинил]-4-оксо-1-(2-тиазолил)-1,8-нафтиридин-3-карбоновой кислоты составляет примерно 60 мг/м2.
5 5. The method according to claim 3, where the dose of (+) - 1,4-dihydro-7 - [(3S, 4S) -3-methoxy-4- (methylamino) -1-pyrrolidinyl] -4-oxo-1 - (2-thiazolyl) -1,8-naphthyridine-3-carboxylic acid is about 60 mg / m 2 .
6     6. Способ по п.3, где доза (+)-1,4-дигидро-7-[(3S,4S)-3-метокси-4-(метиламино)-1-пирролидинил]-4-оксо-1-(2-тиазолил)-1,8-нафтиридин-3-карбоновой кислоты составляет примерно 65 мг/м2.
6 6. The method according to claim 3, where the dose of (+) - 1,4-dihydro-7 - [(3S, 4S) -3-methoxy-4- (methylamino) -1-pyrrolidinyl] -4-oxo-1 - (2-thiazolyl) -1,8-naphthyridine-3-carboxylic acid is about 65 mg / m 2 .
7     7. Способ по п.3, где доза (+)-1,4-дигидро-7-[(3S,4S)-3-метокси-4-(метиламино)-1-пирролидинил]-4-оксо-1-(2-тиазолил)-1,8-нафтиридин-3-карбоновой кислоты составляет примерно 70 мг/м2.
7 7. The method according to claim 3, where the dose of (+) - 1,4-dihydro-7 - [(3S, 4S) -3-methoxy-4- (methylamino) -1-pyrrolidinyl] -4-oxo-1 - (2-thiazolyl) -1,8-naphthyridine-3-carboxylic acid is about 70 mg / m 2 .
8     8. Способ по п.3, где доза (+)-1,4-дигидро-7-[(3S,4S)-3-метокси-4-(метиламино)-1-пирролидинил]-4-оксо-1-(2-тиазолил)-1,8-нафтиридин-3-карбоновой кислоты составляет примерно 75 мг/м2.
8 8. The method according to claim 3, where the dose of (+) - 1,4-dihydro-7 - [(3S, 4S) -3-methoxy-4- (methylamino) -1-pyrrolidinyl] -4-oxo-1 - (2-thiazolyl) -1,8-naphthyridine-3-carboxylic acid is about 75 mg / m 2 .
9     9. Способ по п.1, где доза (+)-1,4-дигидро-7-[(3S,4S)-3-метокси-4-(метиламино)-1-пирролидинил]-4-оксо-1-(2-тиазолил)-1,8-нафтиридин-3-карбоновой кислоты вводится 1 раз в неделю в течение 3 недель.
9 9. The method according to claim 1, where the dose of (+) - 1,4-dihydro-7 - [(3S, 4S) -3-methoxy-4- (methylamino) -1-pyrrolidinyl] -4-oxo-1 - (2-thiazolyl) -1,8-naphthyridine-3-carboxylic acid is administered once a week for 3 weeks.
10     10. Способ по п.1, где доза (+)-1,4-дигидро-7-[(3S,4S)-3-метокси-4-(метиламино)-1-пирролидинил]-4-оксо-1-(2-тиазолил)-1,8-нафтиридин-3-карбоновой кислоты вводится 2 раза в неделю.
10 10. The method according to claim 1, where the dose of (+) - 1,4-dihydro-7 - [(3S, 4S) -3-methoxy-4- (methylamino) -1-pyrrolidinyl] -4-oxo-1 - (2-thiazolyl) -1,8-naphthyridine-3-carboxylic acid is administered 2 times a week.
11     11. Способ по п.10, где доза (+)-1,4-дигидро-7-[(3S,4S)-3-метокси-4-(метиламино)-1-пирролидинил]-4-оксо-1-(2-тиазолил)-1,8-нафтиридин-3-карбоновой кислоты составляет от примерно 80 до примерно 90 мг/м2.
11 11. The method of claim 10, where the dose of (+) - 1,4-dihydro-7 - [(3S, 4S) -3-methoxy-4- (methylamino) -1-pyrrolidinyl] -4-oxo-1 - (2-thiazolyl) -1,8-naphthyridine-3-carboxylic acid is from about 80 to about 90 mg / m 2 .
12     12. Способ по п.10, где доза (+)-1,4-дигидро-7-[(3S,4S)-3-метокси-4-(метиламино)-1-пирролидинил]-4-оксо-1-(2-тиазолил)-1,8-нафтиридин-3-карбоновой кислоты составляет от примерно 65 до примерно 75 мг/м2.
12 12. The method according to claim 10, where the dose (+) - 1,4-dihydro-7 - [(3S, 4S) -3-methoxy-4- (methylamino) -1-pyrrolidinyl] -4-oxo-1 - (2-thiazolyl) -1,8-naphthyridine-3-carboxylic acid is from about 65 to about 75 mg / m 2 .
13     13. Способ по любому из пп.10-12, где доза (+)-1,4-дигидро-7-[(3S,4S)-3-метокси-4-(метиламино)-1-пирролидинил]-4-оксо-1-(2-тиазолил)-1,8-нафтиридин-3-карбоновой кислоты вводится в течение 2 недель.
13 13. The method according to any one of claims 10-12, where the dose of (+) - 1,4-dihydro-7 - [(3S, 4S) -3-methoxy-4- (methylamino) -1-pyrrolidinyl] -4 -oxo-1- (2-thiazolyl) -1,8-naphthyridine-3-carboxylic acid is administered over 2 weeks.
14     14. Способ по п.1, где доза (+)-1,4-дигидро-7-[(3S,4S)-3-метокси-4-(метиламино)-1-пирролидинил]-4-оксо-1-(2-тиазолил)-1,8-нафтиридин-3-карбоновой кислоты вводится в виде внутривенной инъекции.
14 14. The method according to claim 1, where the dose of (+) - 1,4-dihydro-7 - [(3S, 4S) -3-methoxy-4- (methylamino) -1-pyrrolidinyl] -4-oxo-1 - (2-thiazolyl) -1,8-naphthyridine-3-carboxylic acid is administered as an intravenous injection.
15     15. Способ по п.14, где доза (+)-1,4-дигидро-7-[(3S,4S)-3-метокси-4-(метиламино)-1-пирролидинил]-4-оксо-1-(2-тиазолил)-1,8-нафтиридин-3-карбоновой кислоты вводится в виде внутривенного вливания длительностью 10-15 минут.
15 15. The method according to 14, where the dose of (+) - 1,4-dihydro-7 - [(3S, 4S) -3-methoxy-4- (methylamino) -1-pyrrolidinyl] -4-oxo-1 - (2-thiazolyl) -1,8-naphthyridine-3-carboxylic acid is administered as an intravenous infusion lasting 10-15 minutes.
16     16. Способ по п.1, где второе средство представляет собой децитабин.
16 16. The method according to claim 1, where the second agent is decitabine.
17     17. Способ по п.1, где второе средство представляет собой азацитидин.
17 17. The method according to claim 1, where the second agent is azacytidine.
18     18. Способ по п.1, где (+)-1,4-дигидро-7-[(3S,4S)-3-метокси-4-(метиламино)-1-пирролидинил]-4-оксо-1-(2-тиазолил)-1,8-нафтиридин-3-карбоновой кислоту вводят пациенту раз в неделю, где период 1 неделя представляет собой цикл лечения, и цикл лечения повторяется, по меньшей мере, 3 раза.
18 18. The method according to claim 1, where (+) - 1,4-dihydro-7 - [(3S, 4S) -3-methoxy-4- (methylamino) -1-pyrrolidinyl] -4-oxo-1- (2-thiazolyl) -1,8-naphthyridine-3-carboxylic acid is administered to the patient once a week, where a period of 1 week is a treatment cycle and the treatment cycle is repeated at least 3 times.
19     19. Способ по п.1, где (+)-1,4-дигидро-7-[(3S,4S)-3-метокси-4-(метиламино)-1-пирролидинил]-4-оксо-1-(2-тиазолил)-1,8-нафтиридин-3-карбоновой кислоты вводят в количестве от примерно 1 до примерно 75г/м2 в комбинации со вторым активным средством перед, во время или после применения обычного лечения.
19 19. The method according to claim 1, where (+) - 1,4-dihydro-7 - [(3S, 4S) -3-methoxy-4- (methylamino) -1-pyrrolidinyl] -4-oxo-1- (2-thiazolyl) -1,8-naphthyridine-3-carboxylic acid is administered in an amount of about 1 to about 75 g / m 2 in combination with a second active agent before, during or after the usual treatment.
RU2016124135A 2005-09-02 2016-06-17 METHODS OF APPLICATION (+) - 1,4-DIHYDRO-7 - [(3S, 4S) -3-METOXY-4- (METHYLAMINO) -1-Pyrrolidinyl] -4-OXO-1- (2-THIAZOLYL) -1, 8-NAFTIRIDIN-3-CARBONIC ACID FOR CANCER TREATMENT RU2016124135A (en)

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US92150105P 2005-09-02 2005-09-02
US92150005P 2005-09-02 2005-09-02
US60/921,501 2005-09-02
US60/921,500 2005-09-02
US78892706P 2006-04-03 2006-04-03
US78909306P 2006-04-03 2006-04-03
US60/788,927 2006-04-03
US60/789,093 2006-04-03
US81028506P 2006-06-01 2006-06-01
US60/810,285 2006-06-01

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RU2016124135A RU2016124135A (en) 2005-09-02 2016-06-17 METHODS OF APPLICATION (+) - 1,4-DIHYDRO-7 - [(3S, 4S) -3-METOXY-4- (METHYLAMINO) -1-Pyrrolidinyl] -4-OXO-1- (2-THIAZOLYL) -1, 8-NAFTIRIDIN-3-CARBONIC ACID FOR CANCER TREATMENT

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US6458810B1 (en) * 2000-11-14 2002-10-01 George Muller Pharmaceutically active isoindoline derivatives
US6740757B2 (en) * 2001-08-29 2004-05-25 Pfizer Inc Enantiomers of 6-[(4-chloro-phenyl)-hydroxy-(3-methyl-3h-imidazol-4-yl)-methyl]-4-[3-(3-hydroxy-3-methyl-but-1-ynyl)-phenyl]-1-methyl-1h-quinolin-2-one and salts thereof, useful in the treatment of cancer
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