KR101104991B1 - (+)―2―〔1―(3―에톡시―4―메톡시페닐)―2―메틸설포닐에틸〕―4―아세틸아미노이소인돌린―1,3―디온: 그것의 조성물 및 사용 방법 - Google Patents
(+)―2―〔1―(3―에톡시―4―메톡시페닐)―2―메틸설포닐에틸〕―4―아세틸아미노이소인돌린―1,3―디온: 그것의 조성물 및 사용 방법 Download PDFInfo
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- KR101104991B1 KR101104991B1 KR1020107003988A KR20107003988A KR101104991B1 KR 101104991 B1 KR101104991 B1 KR 101104991B1 KR 1020107003988 A KR1020107003988 A KR 1020107003988A KR 20107003988 A KR20107003988 A KR 20107003988A KR 101104991 B1 KR101104991 B1 KR 101104991B1
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- Prior art keywords
- ethoxy
- methoxyphenyl
- dione
- methylsulfonylethyl
- acetylaminoisoindolin
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Abstract
Description
도 1은 (+)-2-[1-(3-에톡시-4-메톡시페닐)-2-메틸설포닐에틸]-4-아세틸아미노이소인돌린-1,3-디온(2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione)의 (+) 에난티오머(enantiomer)의 제법을 설명하기 위한 것이다.
도 2는 지각 능력이 있는 흰족제비의 폐의 LPS-유도 호중성백혈구증가증(neutrophilia) 상에서 본 발명의 에난티오머의 효과를 설명하기 위한 것이다.
Claims (42)
- 입체이성질체적으로 순수한 (+)-2-[1-(3-에톡시-4-메톡시페닐)-2-메틸설포닐에틸]-4-아세틸아미노이소인돌린-1,3-디온, 또는 그것의 약학적으로 허용가능한 염, 용매화물 또는 수화물을 유효성분으로 포함하는 것을 특징으로 하며,
입체이성질체적으로 순수한 (+)-2-[1-(3-에톡시-4-메톡시페닐)-2-메틸설포닐에틸]-4-아세틸아미노이소인돌린-1,3-디온은 (-)-2-[1-(3-에톡시-4-메톡시페닐)-2-메틸설포닐에틸]-4-아세틸아미노이소인돌린-1,3-디온을 20중량% 이하로 포함하는 것을 의미하는
암, 심장쇠약, 울혈성 심부전, 심근증, 폐부종, 독소-중화 패혈증성 쇼크, 급성 바이러스성 심근염, 심장 타가이식 거부, 심근경색, 발열, 급성 감염 및 쇼크 상태로 구성된 군으로부터 선택된 질병 또는 장애의 치료 또는 예방용 약학 제제. - 제 1항에 있어서, 상기 질병 또는 장애는 암이며, 상기 약학 제제는 알킬화제, 질소 머스타드, c-Jun N-말단 키나제(JNK) 억제제, 항생제, 항종양제, 에틸렌이민, 메틸멜라민 알킬 설포네이트, 니트로소우레아, 트리아젠, 엽산 아나로그, 피리미딘 아나로그, 퓨린 아나로그, 빈카 알카로이드, 에피포도필로톡신, 국소이성화효소 억제제 또는 항암 백신을 더 포함하는 것을 특징으로 하는 약학 제제.
- 제 1항에 있어서, 상기 암은 고형 종양인 것을 특징으로 하는 약학 제제.
- 제 3항에 있어서, 상기 고형 종양은 유방, 결장, 직장, 대장 또는 신장의 종양, 또는 신경아교종인 것을 특징으로 하는 약학 제제.
- 제 1항에 있어서, 상기 암은 혈액 유래 종양인 것을 특징으로 하는 약학 제제.
- 제 1항에 있어서, 상기 암은 다발성 골수종, 급성 백혈병, 림프 모세포성 백혈병, 골수성 백혈병, 림프성 백혈병 또는 골수구성 백혈병인 것을 특징으로 하는 약학 제제.
- 제 6항에 있어서, 상기 림프성 백혈병은 만성 림프성 백혈병인 것을 특징으로 하는 약학 제제.
- 입체이성질체적으로 순수한 (+)-2-[1-(3-에톡시-4-메톡시페닐)-2-메틸설포닐에틸]-4-아세틸아미노이소인돌린-1,3-디온, 또는 그것의 약학적으로 허용가능한 염, 용매화물 또는 수화물을 유효성분으로 포함하는 것을 특징으로 하며,
입체이성질체적으로 순수한 (+)-2-[1-(3-에톡시-4-메톡시페닐)-2-메틸설포닐에틸]-4-아세틸아미노이소인돌린-1,3-디온은 (-)-2-[1-(3-에톡시-4-메톡시페닐)-2-메틸설포닐에틸]-4-아세틸아미노이소인돌린-1,3-디온을 20중량% 이하로 포함하는 것을 의미하는
인간 면역결핍 바이러스(HIV) 질환, 박테리아 감염, 균에 의한 전염병, 말라리아, 마이코박테리움 질환, 간염, 성인 호흡 곤란 증후군, 뼈흡수병(bone-resorption disease), 낭포성 섬유증, 패혈증성 쇼크, 패혈증, 내독성 충격(endotoxic shock), 혈류역학적 쇼크(hemodynamic shock), 패혈증 증후군, 후허혈성 재관류 손상(post ischemic reperfusion injury), 뇌막염, 섬유 질병(fibrotic disease), 카케시아(cachexia), 이식편대숙주질환을 포함하는 이식 거부, 자기 면역 질병, 류머티즘 척추염, 골다공증, 다발성 경화증, 나병결절홍반(erythema nodosum leprosum), 방사선 장애 또는 고농도산소 꽈리 손상(hyperoxic alveolar injury)의 치료 또는 예방용 약학 제제. - 제 8항에 있어서, 상기 제제는 항히스타민제, 항염증제, 비스테로이드성 항염증제 또는 스테로이드를 더 포함하는 것을 특징으로 하는 약학 제제.
- 입체이성질체적으로 순수한 (+)-2-[1-(3-에톡시-4-메톡시페닐)-2-메틸설포닐에틸]-4-아세틸아미노이소인돌린-1,3-디온, 또는 그것의 약학적으로 허용가능한 염, 용매화물 또는 수화물을 유효성분으로 포함하는 것을 특징으로 하며,
입체이성질체적으로 순수한 (+)-2-[1-(3-에톡시-4-메톡시페닐)-2-메틸설포닐에틸]-4-아세틸아미노이소인돌린-1,3-디온은 (-)-2-[1-(3-에톡시-4-메톡시페닐)-2-메틸설포닐에틸]-4-아세틸아미노이소인돌린-1,3-디온을 20중량% 이하로 포함하는 것을 의미하는
아데노신 3',5'-시클릭 모노포스페이트(cAMP) 농도 조절에 의해 개선되는 질병인 천식 또는 염증의 치료 또는 예방용 약학 제제. - 제 1항 내지 제 10항 중 어느 한 항에 있어서, 상기 제제는 비경구, 경피, 국소, 점막, 비강, 구강, 혀 밑 또는 경구를 통해 투여되는 것을 특징으로 하는 약학 제제.
- 제 11항에 있어서, 상기 제제는 경구 투여되는 것을 특징으로 하는 약학 제제.
- 제 12항에 있어서, 상기 제제는 정제 또는 캡슐 형태인 것을 특징으로 하는 약학 제제.
- 제 11항에 있어서, 상기 제제는 안약 용액, 스프레이, 에어로졸, 크림, 로션, 연고, 겔, 용액, 에멀젼 또는 서스펜션의 형태인 것을 특징으로 하는 약학 제제.
- 제 1항 내지 제 10항 중 어느 한 항에 있어서, 상기 제제는 하루에 (+)-2-[1-(3-에톡시-4-메톡시페닐)-2-메틸설포닐에틸]-4-아세틸아미노이소인돌린-1,3-디온 1mg 내지 1000mg의 투여량을 갖도록 제조되는 것을 특징으로 하는 약학 제제.
- 제 15항에 있어서, 상기 제제는 하루에 (+)-2-[1-(3-에톡시-4-메톡시페닐)-2-메틸설포닐에틸]-4-아세틸아미노이소인돌린-1,3-디온 5mg 내지 500mg의 투여량을 갖도록 제조되는 것을 특징으로 하는 약학 제제.
- 제 16항에 있어서, 상기 제제는 하루에 (+)-2-[1-(3-에톡시-4-메톡시페닐)-2-메틸설포닐에틸]-4-아세틸아미노이소인돌린-1,3-디온 10mg 내지 200mg의 투여량을 갖도록 제조되는 것을 특징으로 하는 약학 제제.
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- 제 1항 내지 제 10항 중 어느 한 항에 있어서, 상기 입체이성질체적으로 순수한 (+)-2-[1-(3-에톡시-4-메톡시페닐)-2-메틸설포닐에틸]-4-아세틸아미노이소인돌린-1,3-디온은 (-)-2-[1-(3-에톡시-4-메톡시페닐)-2-메틸설포닐에틸]-4-아세틸아미노이소인돌린-1,3-디온을 10중량% 이하로 포함하는 것을 특징으로 하는 약학 제제.
- 제 19항에 있어서, 상기 입체이성질체적으로 순수한 (+)-2-[1-(3-에톡시-4-메톡시페닐)-2-메틸설포닐에틸]-4-아세틸아미노이소인돌린-1,3-디온은 (-)-2-[1-(3-에톡시-4-메톡시페닐)-2-메틸설포닐에틸]-4-아세틸아미노이소인돌린-1,3-디온을 5중량% 이하로 포함하는 것을 특징으로 하는 약학 제제.
- 제 20항에 있어서, 상기 입체이성질체적으로 순수한 (+)-2-[1-(3-에톡시-4-메톡시페닐)-2-메틸설포닐에틸]-4-아세틸아미노이소인돌린-1,3-디온은 (-)-2-[1-(3-에톡시-4-메톡시페닐)-2-메틸설포닐에틸]-4-아세틸아미노이소인돌린-1,3-디온을 3중량% 이하로 포함하는 것을 특징으로 하는 약학 제제.
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