KR880002705B1 - 치환된 2-페닐-2-(피리딜옥시)-에틸아민, 그의 등배전자 화합물 및 그의 산부가염의 제조방법 - Google Patents
치환된 2-페닐-2-(피리딜옥시)-에틸아민, 그의 등배전자 화합물 및 그의 산부가염의 제조방법 Download PDFInfo
- Publication number
- KR880002705B1 KR880002705B1 KR8204342A KR820004342A KR880002705B1 KR 880002705 B1 KR880002705 B1 KR 880002705B1 KR 8204342 A KR8204342 A KR 8204342A KR 820004342 A KR820004342 A KR 820004342A KR 880002705 B1 KR880002705 B1 KR 880002705B1
- Authority
- KR
- South Korea
- Prior art keywords
- ethylamine
- dimethyl
- pyridyl
- acid
- amino
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/64—One oxygen atom attached in position 2 or 6
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/26—Psychostimulants, e.g. nicotine, ***e
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/65—One oxygen atom attached in position 3 or 5
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/68—One oxygen atom attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/70—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
Abstract
내용 없음.
Description
[발명의 명칭]
치환된 2-페닐-2-(피리딜옥시)-에틸아민, 그의 등배전자 화합물 및 그의 산부가염의 제조방법
[발명의 상세한 설명]
본 발명은 다음 일반식(Ⅰ)의 치환된 2-2-(피리딜옥시)-에틸아민, 그의 등배전자 화합물 및 그의 산부가염을 제조하는 방법에 관한 것이다.
상기 식에서, R1및 R2는 동일하거나 상이할 수 있으며, 수소, 할로겐원자, 메틸 메톡시, 아미노 또는 니트로를 나타내고 : R3는 수소, 할로겐 또는 메틸을 나타내며 : R4및 R5는 동일하거나 상이할 수 있으며 수소 또는 탄소수 1 내지 2의 알킬그룹을 나타내거나, 질소원자와 함께 피롤리디노 또는 모르폴리노환을 형성할 수 있으며 : X는 산소,NH 또는 S를 나타낸다.
본 발명은 또한 약제학적 조성물중에서 활성물질로서의 본 발명의 화합물의 용도에 관한 것이다.
본 발명에 따른 신규의 화합물은 일반식(Ⅱ)의 페닐에틸아민 또는 그의 산부가염을 하기 일반식(Ⅲ)의 피리딘 유도체와 반응시킴으로써 수득할 수 있다.
상기 식에서, R1,R2,R3,R4및 R5는 상기 정의한 바와 같고 : Y는 할로겐원자 또는 히드록시그룹을 나타내며 : Z는 히드록시, 아미노 또는 머캅토그룹을 나타낸다.
Y가 히드록시그룹을 나타내는 일반식(Ⅱ)의 화합물을 출발물질로 사용하는 경우에, 축합반응은 산성매질중, 승온에서 일반식(Ⅲ)의 화합물을 사용하여 수행한다. 이 축합반응을 위해 강한 무기 또는 유기산, 예를들면 염화수소산, 브롬화수소산, 황산 또는 폴리포스포린산과 같은 농 무기산, 아세트산무수물, 오산화인 또는 트리플루오로아세트산을 사용할 수 있다.
Y가 할로겐원자를 나타내는 일반식(Ⅱ)의 페닐에틸아민은 염기성 물질을 사용하여 바람직하게는 상전이 조건하에 즉, 벤질트리부틸-암모늄 할라이드 또는 테트라부틸-암모늄 할라이드와 같은 장쇄 제3급 아민 1종 이상을 가하거나, 벤질-트리페닐-포스포늄클로라이드를 사용하여 일반식(Ⅲ)의 피리딘 유도체와 반응시키는 것이 바람직하다.
적당한 염기성 물질의 예로는 알칼리 또는 알칼리토금속 수산화물 또는 탄산염과 같은 무기염기, 피리딘, 피페리딘 또는 제3급 아민과 같은 유기염기 및 알칼리금속 알콕사이드가 있다.
R4및/또는 R5가 수소를 나타내는 일반식(Ⅰ)의 화합물은 그 자체가 공지된 방법으로 예를들어 이들 화합물을 디알킬술페이트 또는 알킬할라이드와 반응시킴으로써 알킬화시킬 수 있다.
상기 기술된 방법을 사용하여 하기의 최종 생성물들을 경우에 따라서는 그들의 산부가염 형태로 수득할 수 있다 : 2-페닐-2-(피리딜-(3)-옥시)-N,N-디메틸-에틸아민, 2-페닐-2-(피리딜(2)-옥시)-N,N-디메틸-에틸아민, 2-(P-브로모페닐)-2-(피리딜-(2)-옥시)-N,N-디메틸-에틸아민, 2-(P-브로모페닐)-2-(피리딜-(3)-옥시)-N,N-디메틸-에틸아민, 2-(P-브로모페닐)-2-(2-클로로피리딜-(3)-옥시)-N,N-디메틸-에틸아민, 2- (P-브로모페닐)-2-(5-클로로-피리딜-(2)-옥시)-N,N-디메틸-에틸아민, 2-(P-브로모페닐)-2-(6-클로로-피리딜-(2)-옥시)-N,N-디메틸-에틸아민, 2-(P-브로모페닐)-2-(피 리딜-(4)-옥시)-N,N-디메틸-에틸아민, 2-(P-클로로페닐)-2-(피리딜-(3)-옥시)-N,N-디메틸-에틸아민, 2-(m,P-디클로로페닐)-2-(피리딜-(3)-옥시)-N,N-디메틸-에틸아민, 2-페닐-2-(피리딜-(2)-아미노)-N, N-디메틸-에틸아민, 2-페닐-2-(피리딜-(3)-아미노)-N,N-디메틸-에틸아민, 2-(P-브로모페닐)-2-(피리딜-(2)-아미노)-N,N-메틸-에틸아민, 2-(P-브로모페닐)-2-(피리딜-(2)-아미노)-N,N-디메틸-에틸아민, 2-(P-브로모페 닐)-2-(피리딜-(3)-아미노)-N,N-디메틸-에틸아민, 2-페닐-2-(4-메틸-피리딜-(2)-아미노)-N, N-디메틸-에틸아민, 2-(P-브로모페닐)-2-(5-메틸-피리딜-(2)-아미노)-N, N-디메틸-에틸아민, 2- (P-브로모페닐)-2- (6-메틸-피리딜-(2)-아미노)-N,N-디메틸-에틸아민, 2-(4-P-브로모페닐)-2-(5-클로로-피리딜-(2)-아미노)-N,N-디메딜-에틸 아민, 2-(4-P-브로모페닐)-2-(피리딜-(2)-티오)-N,N-디메틸-에틸아민, 2-(P-브로모페닐)-2-(피리딜-(3)-옥시)-모르폴리노-에틸아민, 2-(P-브로모페닐)-2-(피리딜-(3)-옥시)-피롤리디노-에틸아민, 2- (P-브로모페닐)-2-(피리딜-(2)-아미노)-모르폴리노-에틸아민, 2-(P-브로모페닐)-2-(피리딜-(2)-아미노)-피롤리디노-에틸아민, 2-(P-메톡시페닐)-2-(피리딜-(3)-옥시)-N, N-디메틸-에틸아민, 2-(P-히드록시페닐)-2-피리딜- (3)-옥시) -N, N-디메틸-에틸아민, 2-(P-톨릴)-2-(피리딜-(3)-옥시)-N, N-디메틸-에 틸아민, 2-(P-니트로페닐)-2-(피리딜-(2)-옥시 )-N, N-디메틸-에틸아민, 2- (4-아미노페닐)-2-(피리딜-(2)-옥시)-N, N-디메틸-에틸아민, 2-(m, P-디클로로페닐)-2-(피리딜-(3)-아미노)-N, N-디메틸-에틸아민, 2-(m, P-디메톡시페닐)-2-(피리딜-(3)-옥시)-N, N-디메틸-에틸아민.
출발물질로는 시판품으로 구입할 수 있거나 통상적으로 알려진 방법을 사용하여 제조할 수 있는 화학물질을 광범위하게 사용한다.
일반식(Ⅰ)외 목적 생성물을 필요에 따라 통상의 방법으로 생리학적 허용되는 그의 산부가염으로 전환시킬 수 있다.
적합한 산의 예로는 할로겐화수소산, 황산, 인산 또는 술폰산과 같은 무기산, 및 포름산, 아세트산. 프로피온산, 락트산, 글리콜산, 글루콘산, 말레산, 숙신산, 타타르산, 벤조산, 살리실산, 시트르산, 아스코르브산, P-톨루엔술폰산 또는 옥시에탄술폰산과 같은 유기산이 있다.
일반식( I )의 신규한 화합물 및 그의 산부가염은 유용한 약제학적 조성물이며, 우울증 치료제에 대한 특이적 생화학 및 약물학적 시험에서 매우 효과적이다. 즉 이들 화합물은, 테트라벤자인으로 하수증을 유발시킨 생쥐에 있어서 하수증을 억제할 수 있으며, ED50은 1mg/kg정도이다. 이 시험은 우울중 치료 효과시험의 기준으로 사용되고 있다(International Journal of Neuropharmacology 8.73(1969) .
본 발명에 따른 화합물은 레세르핀 길항작용 즉 우을증 치료활성을 갖는 화합물의 사용에 의한, 레세르핀에 의해 야기된 저체온 작용의 반전에 대한 시험에 있어서 매우 바람직한 활성을 나타낸다. 또한 본 발명의 화합물들은 세로토닌 및 아드레날린의 뉴론에 재흡수 되는 것을 억제한다는 사실도 밝혀졌다.
본 발명의 화합물들은 종전의 우울증 치료제와 구조가 상이한 점에서 특히 유용하며, 시판품으로 구입할 수 있는 공지의 우울증 치료제에 비해 활성이 동등하거나 우수하며 독성기 보다 낮다.
특히 바람직한 화합물로는 R1이 P위치에서 브롬원자를 나타내고, X가 산소원자 또는 이미노그룹을 나타내며, R2가 수소를 나타내며, R3및 R4가 메틸그룹을 나타내는 일반식( I )의 화합물이 언급될 수 있다.
이들을 예시하면 다음과 같다 : 2-(P-브로모페닐)-2-(피리딜-(3)-옥시)-N,N-디메틸-에틸아민, 2-(P-브로모페닐)-2-(피리딜-(2)-아미노)-N,N-디메틸-에틸아민, 2- (P-브로모페닐)-2-(피리딜-(2)-아미노)-N,N-디메틸-에틸아민.
다음 실시예는 본 발명을 보다 상세히 설명하고자 한다.
[실시예 1]
2-P-브로모페닐-2-(3-피리딜옥시)-N,N-디메틸-에틸아민 이염산염
2-클로로-2-P-브로모페닐-N,N-디메틸에틸아민 염산염 29.9g 및 3-히드록시피리딘 14.3g(0.15몰)을 25%수산화나트륨 용액 150ml 및 톨루엔 150m1중에서 벤질트리폐닐포스포늄 클로라이드 0.5g과 함께 16시간 동안 환류시킨다. 용매를 유기층으로부터 증류시켜 제거한 후, 남은 잔사는 알코올에 용해시킨다. 표제 화할물의 이염산염은 염산에 의해 수득된다. 표제화합물을 시클로헥산중에서 활성목탄과 규조토로 처리하여정제하여 융점 128 내지 129℃ (에탄올)의 이염산염 20g(이론치의 44%)을 수득한다.
[실시예 2]
2-P-브로모페닐-2-(2-피리딜아미노)-N, N-디메틸-에틸아민 이옥살산염
2-P-브로모페닐-N,N-디메틸 에탄올아민 24.5g(0.1몰) 및 2-아미노피리딘 11g(0.11몰)을 메탄술폰산 50㎖중에서 30분 동안 60℃로 가열한다. 가온하면서 반응혼합물이 여전히 따뜻할때, 이를 얼음에 부어, 암모니아를 가하여 알칼리성으로 되게한 다음 에틸아세테이트로 추출한다. 생성물을 실리카겔 염화메틸렌-에틸아세테이트 메탄올상에서 컬럼 크로마토그래피하여 정제한다. 그 다음, 알코올성 옥살산을 가하여 융점 170 내지 171℃의 표제화합물의 결정성 이옥살산염 21g(이론치의 42%)을 수득한다.
상기 기술한 방법을 사용하여 일반식( I )의 하기 화합물을 수득한다.
[제형화 실시예]
[a) 제피정제]
[1핵정당 조성]
본 발명에 따른 활성성분 25.0㎎
락토오스 50.0㎎
옥수수 전분 22.0㎎
젤라틴 2.0㎎
마그네슘 스테아레이트 1.0㎎
[제 조]
활성성분, 락토오스와 옥수수 전분의 혼합물을 1㎜ 메쉬의 스크린을 통해 10%젤라틴 수용액과 함께 과립화한 다음, 40℃에서 건조시키고 다시 스크린을 통과시킨다. 이와같이 하여 수득된 과립을 마그네슘 스테아레이트와 혼합하고 압착한다. 수득된 핵정을 설탕의 수성 현탁액, 이산화티탄, 활석 및 아라비아 고무를 사용하여 통상의 방법으로 피복시킨다. 그 다음, 최종 제피정을 밀납으로 시광하여 최종 중량이 200㎎인 제피정을 얻는다.
[b) 정 제]
본 발명에 따른 활성성분 10.0㎎
락토오스 40.0㎎
옥수수 전분 44.0㎎
가용성 전분 5.0㎎
마그네슘 스테아레이트 1.0㎎
방법 : 활성성분 및 마그네슘 스테아레이트를 가용성 전분의 수용액과 함께 과립화하여, 과립을 건조시킨 다음 락토오스 및 옥수수 전분과 함께 충분히 혼합한다. 그 다음, 혼합물을 압착시켜 활성물질 10㎎을 함유하는 100㎎ 중량의 정제를 얻는다.
[c)좌 제]
1좌제당 조성
본 발명에 따른 활성성분 10.0㎎
좌약 기제 1,690.0㎎
[방 법]
액침 균질기를 사용하여, 미세분쇄된 물질을 40℃로 냉각시킨 용융된 좌약 기제중에 넣고 교반한다. 35℃에서 이 덩어리를 약간 미리 냉각시킨 주형에 붓는다.
[d) 앰풀제(주사용액제)]
[조성]
본 발명에 따른 활성성분 5.0중량부
나트륨 피로술파이트 1.0중량부
에틸렌디아민 테트라아세트산의 이나트륨염 0.5중량부
염화나트륨 8.5중량부
증류수(2회 증류시킴) 전체 1,000중량부가 되도록 하는 적당량
[방 법]
활성성분 및 부형제를 충분한 양의 물에 용해시키고 필요한 양의 물을 가하여 목적 농도로 조정한다. 용액을 여과하여 무균 조건하에서 1㎖들이 앰풀이 옮긴다. 최종적으로 앰풀을 멸균 시키고 밀봉한다. 각 앰풀은 5.0㎎의 활성성분을 함유한다.
Claims (2)
- 일반식(Ⅱ)의 페닐에틸아민 또는 그의 산부가염을 일반식(Ⅲ)의 피리딘 유도체와 반응시킨 다음, 필요한 경우 수득된 목적생성물을 생리학적으로 허용되는 그의 산부가염으로 전환시킴을 특징으로 하여, 일반식(Ⅰ)의 치환된 2-페닐-2-(피리딜옥시)-에틸아민, 그의 등배전자 화합물 및 그의 산부가염을 제조하는 방법.
상기 식에서, R1및 R2는 동일하거나 상이할 수 있으며, 수소, 할로겐원자. 메틸, 메톡시, 아미노 또는 니트로를 나타내고 : R3는 수소, 할로겐 또는 메틸을 나타내며 : R4및 R5는 동일하거나 상이할 수 있으며 수소 또는 탄소수 1 내지 2의 알킬그룹을 나타내거나, 질소원자와 함께 피롤리디노 또는 모노폴리노환을 형성할 수 있으며 : X는 산소, NH 또는 S를 나타내고 : Y는 할로겐원자 또는 히르록시그룹을 나타내며 : Z는 히드록시, 아미노 또는 머캅토그룹을 나타낸다. - 제1항에 있어서, R4및/또는 R5가 수소를 나타내는 일반식(Ⅰ)의 화합물을 공지된 방법으로 알킬화시킴을 특징으로 하는 방법.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19813138550 DE3138550A1 (de) | 1981-09-28 | 1981-09-28 | Substituierte 2-phenyl-2-(pyridyloxy)-ethylamine und isostere verbindungen, verfahren zu ihrer herstellung und verwendung |
| DEP.3138550.8 | 1981-09-28 | ||
| DEP3138550.8 | 1981-09-28 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR840001555A KR840001555A (ko) | 1984-05-07 |
| KR880002705B1 true KR880002705B1 (ko) | 1988-12-26 |
Family
ID=6142812
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR8204342A KR880002705B1 (ko) | 1981-09-28 | 1982-09-27 | 치환된 2-페닐-2-(피리딜옥시)-에틸아민, 그의 등배전자 화합물 및 그의 산부가염의 제조방법 |
Country Status (21)
| Country | Link |
|---|---|
| US (1) | US4666910A (ko) |
| EP (1) | EP0075752B1 (ko) |
| JP (1) | JPS5869865A (ko) |
| KR (1) | KR880002705B1 (ko) |
| AR (1) | AR231534A1 (ko) |
| AT (1) | ATE18551T1 (ko) |
| AU (1) | AU550614B2 (ko) |
| CA (1) | CA1171086A (ko) |
| DE (2) | DE3138550A1 (ko) |
| DK (1) | DK156718C (ko) |
| ES (1) | ES515972A0 (ko) |
| FI (1) | FI78074C (ko) |
| GB (1) | GB2106902B (ko) |
| GR (1) | GR77657B (ko) |
| IE (1) | IE53959B1 (ko) |
| IL (1) | IL66870A (ko) |
| NO (1) | NO159999C (ko) |
| NZ (1) | NZ202015A (ko) |
| PH (1) | PH23219A (ko) |
| PT (1) | PT75611B (ko) |
| ZA (1) | ZA827055B (ko) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8320699D0 (en) * | 1983-08-01 | 1983-09-01 | Wellcome Found | Ethylenediamines |
| GB0004152D0 (en) | 2000-02-23 | 2000-04-12 | Astrazeneca Uk Ltd | Novel compounds |
| GB0004151D0 (en) * | 2000-02-23 | 2000-04-12 | Astrazeneca Uk Ltd | Novel use |
| GB0004153D0 (en) * | 2000-02-23 | 2000-04-12 | Astrazeneca Uk Ltd | Novel use |
| AR035700A1 (es) * | 2001-05-08 | 2004-06-23 | Astrazeneca Ab | Derivados de arilheteroalquilamina, composicion farmaceutica, usos de estos derivados para la fabricacion de medicamentos, metodos de tratamiento, y proceso para la preparacion de estos derivados |
| SE0102640D0 (sv) * | 2001-07-31 | 2001-07-31 | Astrazeneca Ab | Novel compounds |
| SE0102641D0 (sv) * | 2001-07-31 | 2001-07-31 | Astrazeneca Ab | Novel compounds |
| SE0102639D0 (sv) * | 2001-07-31 | 2001-07-31 | Astrazeneca Ab | Novel compounds |
| GB0219154D0 (en) * | 2002-08-16 | 2002-09-25 | Pfizer Ltd | Diaryl compounds |
| US6800652B2 (en) | 2002-08-16 | 2004-10-05 | Pfizer Inc. | Diaryl compounds |
| SE0203304D0 (sv) * | 2002-11-07 | 2002-11-07 | Astrazeneca Ab | Novel Coumpounds |
| ATE453626T1 (de) * | 2003-10-09 | 2010-01-15 | Millennium Pharm Inc | Thioethersubstituierte benzamide als inhibitoren von faktor xa |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2734845A (en) * | 1956-02-14 | Aqueous suspension of procaine penicil- | ||
| US2734846A (en) * | 1956-02-14 | Aqueous suspension of procaine penicil- | ||
| FR1511398A (fr) * | 1966-02-16 | 1968-01-26 | Takeda Chemical Industries Ltd | Procédé de préparation de nouveaux dérivés de picoline |
| BE790592A (ko) * | 1971-10-28 | 1973-04-26 | Oreal | |
| US4011324A (en) * | 1976-01-20 | 1977-03-08 | Pfizer Inc. | Esters and amides of pyrimido[4,5-b]quinolin-4(3H)-one-2-carboxylic acids as antiulcer agents |
| JPS53141271A (en) * | 1977-05-13 | 1978-12-08 | Yamanouchi Pharmaceut Co Ltd | Heterocyclic compounds and process for their preparation |
-
1981
- 1981-09-28 DE DE19813138550 patent/DE3138550A1/de not_active Withdrawn
-
1982
- 1982-09-06 EP EP82108196A patent/EP0075752B1/de not_active Expired
- 1982-09-06 DE DE8282108196T patent/DE3269839D1/de not_active Expired
- 1982-09-06 AT AT82108196T patent/ATE18551T1/de not_active IP Right Cessation
- 1982-09-22 FI FI823246A patent/FI78074C/fi not_active IP Right Cessation
- 1982-09-24 AR AR290759A patent/AR231534A1/es active
- 1982-09-24 IL IL66870A patent/IL66870A/xx unknown
- 1982-09-27 NO NO823253A patent/NO159999C/no unknown
- 1982-09-27 KR KR8204342A patent/KR880002705B1/ko active
- 1982-09-27 IE IE2330/82A patent/IE53959B1/en not_active IP Right Cessation
- 1982-09-27 AU AU88738/82A patent/AU550614B2/en not_active Ceased
- 1982-09-27 DK DK428582A patent/DK156718C/da not_active IP Right Cessation
- 1982-09-27 CA CA000412268A patent/CA1171086A/en not_active Expired
- 1982-09-27 PT PT75611A patent/PT75611B/pt not_active IP Right Cessation
- 1982-09-27 ZA ZA827055A patent/ZA827055B/xx unknown
- 1982-09-27 JP JP57168221A patent/JPS5869865A/ja active Granted
- 1982-09-27 NZ NZ202015A patent/NZ202015A/en unknown
- 1982-09-27 ES ES515972A patent/ES515972A0/es active Granted
- 1982-09-27 GB GB08227449A patent/GB2106902B/en not_active Expired
- 1982-09-28 GR GR69383A patent/GR77657B/el unknown
-
1984
- 1984-08-28 US US06/645,007 patent/US4666910A/en not_active Expired - Fee Related
-
1985
- 1985-03-07 PH PH31952A patent/PH23219A/en unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US4675319A (en) | Antianaphylactic and antibronchospastic piperazinyl-(N-substituted phenyl)carboxamides, compositions and use | |
| KR880002705B1 (ko) | 치환된 2-페닐-2-(피리딜옥시)-에틸아민, 그의 등배전자 화합물 및 그의 산부가염의 제조방법 | |
| US4202896A (en) | N-Benzhydryloxyethyl-N-phenylpropyl-piperazines | |
| US6410582B1 (en) | Thienylazolylalcoxyethanamines, their preparation and their application as medicaments | |
| AU712056B2 (en) | Benzofuryl derivatives and their use | |
| KR0155543B1 (ko) | 1-[모노-또는 비스(트리플루오로메틸)-2-피리디닐]피페라진을 함유한 약학조성물 | |
| IE55156B1 (en) | Pharmacologically active pyrazolo(4,3-c)pyridines | |
| JPS5988481A (ja) | 新規な４−（１Ｈ−インド−ル−３−イル）−α−メチルピペリジン−１−エタノ−ル誘導体、その塩、製造方法、薬剤としての用途および該新規な化合物を含有する組成物 | |
| CA1082699A (en) | Fused pyrimidine derivatives and process for the preparation thereof | |
| IE46802B1 (en) | 2-methoxy-5-chloro aniline derivatives | |
| Manoury et al. | Synthesis and analgesic activities of some (4-substituted phenyl-1-piperazinyl) alkyl 2-aminobenzoates and 2-aminonicotinates | |
| GB1593651A (en) | Amides | |
| US4330546A (en) | 3-Aryl-3-aryloxypropylamines | |
| KR100248643B1 (ko) | 아릴 및 헤테로아릴 알콕시나프탈렌 유도체 | |
| US4381305A (en) | Ethylenediamine derivatives and pharmaceutical compositions containing same | |
| US4528299A (en) | 1-(2,3-Dimethyl-4-methoxyphenyl)-2-methyl-3-(1-pyrrolidinyl)-1-propanone and anti-spastic use thereof | |
| US3970661A (en) | 2-Amino, 5-carbamoyl pyridine compounds | |
| CS237337B2 (en) | Processing of new basicaly substituted 4-phenyl-4,5,6,7-tetrahydrothiene/2,3-c-pyridine | |
| Hayes et al. | Some Furan Antihistaminic Agents | |
| US4276297A (en) | Pyridylaminotriazole therapeutic agents | |
| US4013670A (en) | Derivatives of pyrrolidine and piperidine | |
| US4285942A (en) | Cyclododecanone oximes | |
| RU2058985C1 (ru) | Производные индола, способ их получения и фармацевтическая композиция для лечения психических расстройств на их основе | |
| US3777027A (en) | Anorectic compositions comprising n-pyridylalkyl-beta-alkoxy-beta-trifluoro-methylphenalkylamines | |
| US4100349A (en) | α-Acetylenic derivatives of histamine and related compounds |