KR100806464B1 - (-)-시스-2-(2-클로로페닐)-5,7-디하이드록시-8[4알-(3에스-하이드록시-1-메틸)피페리디닐]-4에이치-1-벤조피란-4-온의슈도폴리모프 - Google Patents
(-)-시스-2-(2-클로로페닐)-5,7-디하이드록시-8[4알-(3에스-하이드록시-1-메틸)피페리디닐]-4에이치-1-벤조피란-4-온의슈도폴리모프 Download PDFInfo
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- KR100806464B1 KR100806464B1 KR1020027009215A KR20027009215A KR100806464B1 KR 100806464 B1 KR100806464 B1 KR 100806464B1 KR 1020027009215 A KR1020027009215 A KR 1020027009215A KR 20027009215 A KR20027009215 A KR 20027009215A KR 100806464 B1 KR100806464 B1 KR 100806464B1
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- cis
- methyl
- dihydroxy
- benzopyran
- hydroxy
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P35/02—Antineoplastic agents specific for leukemia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P35/04—Antineoplastic agents specific for metastasis
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- A—HUMAN NECESSITIES
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Pyrane Compounds (AREA)
- Stereophonic System (AREA)
- Inorganic Insulating Materials (AREA)
Abstract
Description
2 세타각(°) | D 간격 - Å | 상대 강도 | 상대 강도(%) |
6.950 | 12.708 | 강 | 100.0 |
20.529 | 4.323 | 강 | 75.9 |
15.830 | 5.594 | 강 | 58.5 |
16.560 | 5.349 | 중 | 49.5 |
24.778 | 3.590 | 중 | 46.6 |
26.457 | 3.366 | 중 | 42.0 |
21.091 | 4.209 | 중 | 40.7 |
26.226 | 3.395 | 중 | 39.5 |
25.898 | 3.438 | 중 | 38.8 |
18.320 | 4.839 | 중 | 37.1 |
8.308 | 10.634 | 중 | 35.7 |
23.748 | 3.744 | 중 | 33.4 |
13.010 | 6.799 | 중 | 32.4 |
30.520 | 2.927 | 중 | 31.0 |
27.106 | 3.287 | 약 | 26.2 |
31.153 | 2.869 | 약 | 22.4 |
29.043 | 3.072 | 약 | 23.7 |
14.600 | 6.062 | 약 | 22.4 |
19.033 | 4.659 | 약 | 20.6 |
2 세타각(°) | D 간격 - Å | 상대 강도(%) |
6.920 | 12.763 | 100.0 |
13.850 | 6.389 | 35.7 |
27.908 | 3.194 | 22.2 |
6.669 | 13.244 | 18.0 |
20.838 | 4.259 | 13.8 |
7.339 | 12.036 | 13.8 |
31.660 | 2.824 | 9.5 |
10.208 | 8.659 | 8.3 |
14.722 | 6.012 | 7.2 |
16.413 | 5.397 | 6.9 |
25.829 | 3.447 | 6.5 |
Claims (24)
- "D" 간격으로 표시되는 x선 분말 회절 무늬를 가지는 (-)-시스-2-(2-클로로 페닐)-5,7-디하이드록시-8[4R-(3S-하이드록시-1-메틸)피페리디닐]-4H-1-벤조피란-4-온 하이드로클로라이드 화합물.D 간격 - Å12.7084.3235.5945.3493.590
- "D" 간격과 상대 강도로 표시되는 x선 분말 회절 무늬를 가지는(-)-시스-2-(2-클로로 페닐)-5,7-디하이드록시-8[4R-(3S-하이드록시-1-메틸)피페리디닐]-4H-1-벤조피란-4-온 하이드로클로라이드 화합물.D 간격 - Å 상대 강도12.708 강4.323 강5.594 강5.349 중3.590 중3.366 중4.209 중3.395 중3.438 중4.839 중
- "D" 간격과 이의 상대 강도 퍼센티지로 표시되는 x선 분말 회절 무늬를 가지는 (-)-시스-2-(2-클로로 페닐)-5,7-디하이드록시-8[4R-(3S-하이드록시-1-메틸)피페리디닐]-4H-1-벤조피란-4-온 하이드로클로라이드 화합물.D 간격 - Å 상대 강도 %12.708 100.04.323 75.95.594 58.55.349 49.53.590 46.63.366 42.04.209 40.73.395 39.53.438 38.84.839 37.1
- 하기 표 1에 정의되어 있는 x선 분말 회절 무늬를 가지는 (-)-시스-2-(2-클로로 페닐)-5,7-디하이드록시-8[4R-(3S-하이드록시-1-메틸)피페리디닐]-4H-1-벤조피란-4-온 하이드로클로라이드 화합물.표 1
2 세타각(°) D 간격 - Å 상대 강도 상대 강도(%) 6.950 12.708 강 100.0 20.529 4.323 강 75.9 15.830 5.594 강 58.5 16.560 5.349 중 49.5 24.778 3.590 중 46.6 26.457 3.366 중 42.0 21.091 4.209 중 40.7 26.226 3.395 중 39.5 25.898 3.438 중 38.8 18.320 4.839 중 37.1 8.308 10.634 중 35.7 23.748 3.744 중 33.4 13.010 6.799 중 32.4 30.520 2.927 중 31.0 27.106 3.287 약 26.2 31.153 2.869 약 22.4 29.043 3.072 약 23.7 14.600 6.062 약 22.4 19.033 4.659 약 20.6 - 제 1 항 내지 4 항 중 어느 한 항에 있어서, 플라보피리돌 하이드로클로라이드 에탄올/물 용매화물 형태를 0 내지 10% 미만으로 함유하는 (-)-시스-2-(2-클로로 페닐)-5,7-디하이드록시-8[4R-(3S-하이드록시-1-메틸)피페리디닐]-4H-1-벤조피란-4-온 하이드로클로라이드 화합물.
- 제 1 항 내지 4 항 중 어느 한 항에 있어서, 플라보피리돌 하이드로클로라이드 에탄올/물 용매화물 형태, 및 이의 염기, 염 형태, 수화물, 용매화물 및 용매화 수화물을 0 내지 10% 미만으로 함유하는 (-)-시스-2-(2-클로로 페닐)-5,7-디하이드록시-8[4R-(3S-하이드록시-1-메틸)피페리디닐]-4H-1-벤조피란-4-온 하이드로클로라이드 화합물.
- 제 1 항 내지 4 항 중 어느 한 항에 있어서, 플라보피리돌 하이드로클로라이드 에탄올/물 용매화물 형태, 및 이의 염기, 염 형태, 수화물, 용매화물 및 용매화 수화물을 0 내지 4% 미만으로 함유하는 (-)-시스-2-(2-클로로 페닐)-5,7-디하이드록시-8[4R-(3S-하이드록시-1-메틸)피페리디닐]-4H-1-벤조피란-4-온 하이드로클로라이드 화합물.
- 치료유효량의 제 1 항 내지 4 항 중 어느 한 항의 (-)-시스-2-(2-클로로 페닐)-5,7-디하이드록시-8[4R-(3S-하이드록시-1-메틸)피페리디닐]-4H-1-벤조피란-4-온 하이드로클로라이드 화합물 및 약학적으로 허용되는 담체를 포함하는 암 치료용 약학 조성물.
- 플라보피리돌 하이드로클로라이드 에탄올/물 용매화물 형태를 0 내지 10% 미만으로 포함하는 치료유효량의 제 1 항 내지 4 항 중 어느 한 항의 (-)-시스-2-(2-클로로 페닐)-5,7-디하이드록시-8[4R-(3S-하이드록시-1-메틸)피페리디닐]-4H-1-벤조피란-4-온 하이드로클로라이드 화합물, 및 약학적으로 허용되는 담체를 포함하는 암 치료용 약학 조성물.
- 플라보피리돌 하이드로클로라이드 에탄올/물 용매화물 형태, 및 이의 염기, 염 형태, 수화물, 용매화물 및 용매화 수화물을 0 내지 10% 미만으로 포함하는 치료유효량의 제 1 항 내지 4 항 중 어느 한 항의 (-)-시스-2-(2-클로로 페닐)-5,7-디하이드록시-8[4R-(3S-하이드록시-1-메틸)피페리디닐]-4H-1-벤조피란-4-온 하이드로클로라이드 화합물를 포함하는 암 치료용 약학 조성물.
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- (a) 플라보피리돌 하이드로클로라이드 에탄올/물 용매화물 형태 충분량을 적합한 공비 용매 충분량과 배합하여 공비 혼합물을 형성하고;(b) 공비 혼합물을 (-)-시스-2-(2-클로로 페닐)-5,7-디하이드록시-8[4R-(3S-하이드록시-1-메틸)피페리디닐]-4H-1-벤조피란-4-온 하이드로클로라이드를 형성하기에 충분한 공비 증류에 가한 다음;(c) 임의로 이로부터 (-)-시스-2-(2-클로로 페닐)-5,7-디하이드록시-8[4R-(3S-하이드록시-1-메틸)피페리디닐]-4H-1-벤조피란-4-온 하이드로클로라이드를 회수하는 단계를 포함하는제 1 항 내지 4 항 중 어느 한 항의 (-)-시스-2-(2-클로로 페닐)-5,7-디하이드록시-8[4R-(3S-하이드록시-1-메틸)피페리디닐]-4H-1-벤조피란-4-온 하이드로클로라이드 화합물의 제조방법.
- 제 17 항에 있어서, 용매가 케톤 용매인 방법.
- 제 17 항에 있어서, 용매가 메틸 에틸 케톤인 방법.
- 제 17 항에 있어서, 결정화된 (-)-시스-2-(2-클로로 페닐)-5,7-디하이드록시-8[4R-(3S-하이드록시-1-메틸)피페리디닐]-4H-1-벤조피란-4-온 하이드로클로라이드 화합물이 (-)-시스-2-(2-클로로 페닐)-5,7-디하이드록시-8[4R-(3S-하이드록시-1-메틸)피페리디닐]-4H-1-벤조피란-4-온 하이드로클로라이드 화합물을 여과함으로써 회수되는 방법.
- 제 17 항에 있어서, 공비 증류의 온도가 73℃ 내지 80℃인 방법.
- 75%의 상대습도에서 0 내지 5% 미만의 물로 인한 중량 증가를 특징으로 하는, (-)-시스-2-(2-클로로페닐)-5,7-디하이드록시-8[4R-(3S-하이드록시-1-메틸)피페리디닐]-4H-1-벤조피란-4-온 하이드로클로라이드 또는 이의 약학적으로 허용되는 염.
- 75%의 상대습도에서 0 내지 5% 미만의 물로 인한 중량 증가를 특징으로 하는, (-)-시스-2-(2-클로로페닐)-5,7-디하이드록시-8[4R-(3S-하이드록시-1-메틸)피페리디닐]4H-1-벤조피란-4-온 하이드로클로라이드 화합물.
- 약학적 활성 화합물로서 사용하기 위한 제 1 항 내지 4 항 중 어느 한 항의 (-)-시스-2-(2-클로로 페닐)-5,7-디하이드록시-8[4R-(3S-하이드록시-1-메틸)피페리디닐]-4H-1-벤조피란-4-온 하이드로클로라이드 화합물.
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