KR920005712A - 인체 호중구 엘라스타제의 억제제로서의 산화제 감수성 및 비감수성 방향족 에스테르 - Google Patents

인체 호중구 엘라스타제의 억제제로서의 산화제 감수성 및 비감수성 방향족 에스테르 Download PDF

Info

Publication number
KR920005712A
KR920005712A KR1019910008164A KR910008164A KR920005712A KR 920005712 A KR920005712 A KR 920005712A KR 1019910008164 A KR1019910008164 A KR 1019910008164A KR 910008164 A KR910008164 A KR 910008164A KR 920005712 A KR920005712 A KR 920005712A
Authority
KR
South Korea
Prior art keywords
carbon atoms
compound
alkyl
ring
phenyl
Prior art date
Application number
KR1019910008164A
Other languages
English (en)
Inventor
폴 커스첸휴터 게리
와렌 스프러스 라일
크리스 체로니스 죤
Original Assignee
죤 씨. 체로니스
코텍크, 인크.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 죤 씨. 체로니스, 코텍크, 인크. filed Critical 죤 씨. 체로니스
Publication of KR920005712A publication Critical patent/KR920005712A/ko

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/14—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D295/155—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
    • C07C205/49—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups
    • C07C205/57—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups having nitro groups and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
    • C07C205/59—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups having nitro groups and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton the carbon skeleton being further substituted by singly-bound oxygen atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/08—Vasodilators for multiple indications
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
    • C07C205/39—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by esterified hydroxy groups
    • C07C205/42—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by esterified hydroxy groups having nitro groups or esterified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
    • C07C205/43—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by esterified hydroxy groups having nitro groups or esterified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton to carbon atoms of the same non-condensed six-membered aromatic ring or to carbon atoms of six-membered aromatic rings being part of the same condensed ring system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
    • C07C205/49—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups
    • C07C205/56—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups having nitro groups bound to carbon atoms of six-membered aromatic rings and carboxyl groups bound to acyclic carbon atoms of the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
    • C07C309/01—Sulfonic acids
    • C07C309/28—Sulfonic acids having sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
    • C07C309/41—Sulfonic acids having sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing singly-bound oxygen atoms bound to the carbon skeleton
    • C07C309/42—Sulfonic acids having sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing singly-bound oxygen atoms bound to the carbon skeleton having the sulfo groups bound to carbon atoms of non-condensed six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C317/00—Sulfones; Sulfoxides
    • C07C317/16—Sulfones; Sulfoxides having sulfone or sulfoxide groups and singly-bound oxygen atoms bound to the same carbon skeleton
    • C07C317/22—Sulfones; Sulfoxides having sulfone or sulfoxide groups and singly-bound oxygen atoms bound to the same carbon skeleton with sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C317/00—Sulfones; Sulfoxides
    • C07C317/44—Sulfones; Sulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
    • C07C323/10—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton
    • C07C323/18—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton
    • C07C323/20—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton with singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
    • C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
    • C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
    • C07C323/52—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/45—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation
    • C07C45/46—Friedel-Crafts reactions
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/017—Esters of hydroxy compounds having the esterified hydroxy group bound to a carbon atom of a six-membered aromatic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/612—Esters of carboxylic acids having a carboxyl group bound to an acyclic carbon atom and having a six-membered aromatic ring in the acid moiety
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/04—Systems containing only non-condensed rings with a four-membered ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
    • C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/14—The ring being saturated

Abstract

내용 없음

Description

인체 호중구 엘라스타제의 억제제로서의 산화제 감수성 및 비감수성 방향족 에스테르
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음

Claims (26)

  1. 하기 일반식(Ⅵ)의 화합물 또는 그의 제약학상 허용되는 비독성 염.
    상기 식중, R1및 R2는 동일하거나 또는 상이한 것으로서, 수소원자, 탄소원자수가 1내지 6개인 알킬, 탄소원자수가 3내지 6개인 시클로알킬로 이루어진 군 중에서 선택되거나, 또는 R1및 R2는 함께 메틸렌기 -(CH2)n- (여기서, n은 1내지 6의 정수임)를 나타내고, R3은 수소원자, 할로겐, 탄소원자수가 1내지 12개인 할로알킬, 탄소원자수가 1내지 12개인 알킬, 탄소원자수가 1내지 12개인 알콕시, 탄소원자수가 2내지 12개인 알케닐, 탄소원자수가 3내지 12개인 시클로알킬, 일환식 또는 이환식 아릴, -ZR5(여기서, Z는 O,S,S(O) 또는 SO2이고 R5는 수소원자, 탄소원자수가 1내지 18개인 알킬, 탄소원자수가 3내지 12개인 시클로알킬이거나 또는 페닐임) -NR6R7[여기서, R6및 R7은 동일하거나 또는 상이한 것으로서, 수소 원자, 탄소원자수가 1내지 12개인 알킬, 탄소원자수가 1내지 12개인 알킬, 탄소원자수가 3내지 12개인 시클로알킬, 페닐, CH3OC(O)CH2CH2-, HOOCCH2CH2, NaO3SCH2CH2NHC(O)CH2CH2-임)의 아실이거나 또는 R6및 R7은 함께 -C(O)CH2CH2C(O), 0C(O)-C6H4- C(O)- 또는 -(CH2)x- (여기서, X는 2, 3, 4, 5, 또는 6임)을 나타냄], 질소원자를 통해 페닐 고리에 연결된 모르플리오, 이미다졸리노 또는 피페라지노로 이루어진 군중에서 선택된 1내지 5개의 치환체를 나타내거나 또는 R3은 인접한 고리 탄소원자들 사이에서 추가의 카르보시클릭 고리를 완성하는데 필요한 1내지 6개의 탄소원자로된 원자들이거나 또는 하나 이상의 O,S또는 N고리 원자들을 포함하는 5내지 6원 헤테로시클릭 고리를 나타내며, R4는 수소원자, 할로겐, 니트로, -C(O)CH3, S(O)pR9(여기서, p는 0,1 또는 2이고 R9는 히드록시, -ONa 또는 탄소원자수가 1내지 12개인 임의 치환된 알킬 또는 임의 치환된 시클로알킬임)중에서 선택된 1내지 5개의 치환체이다.
  2. 제1항에 있어서, R1및 R2중 하나가 수소 원자이고, 나머지 하나는 탄소 원자수가 1내지 6개인 알킬이고, R3이 수소원자, 저급알킬 또는 시킬로알킬, 저급알콕시, 페닐, 페닐고리의 인접한 탄소 원자와 함께 고리를 완성하는데 필요한 원자이거나 또는 -NR6R7[여기서, R6은 수소원자이고, R7은 -C(O)R6(여기서, R6은 페닐임)이거나, 또는 R6및 R7이 함께 -(CH2)x- (여기서, x는 2내지 6임)를 나타냄]인 화합물.
  3. 제2항에 있어서,R4가 -S(O)pR9(여기서, p는 0,1 또는 2이고, R9는 탄소원자수가 1내지 12개인 임의 치환된 알킬임)인 화합물.
  4. 제3항에 있어서, R4가 -ZR5(여기서, R5는 저급 알킬 카르복실산기임)인 화합물.
  5. 제4항에 있어서, R4가 -SCH2C(CH2)2COOH, -S(O)CH2C(CH3)2CO2H 또는 -SO2CH2C(CH2)CO2H인 화합물.
  6. 제1항에 있어서, R4가 오르토 또는 파라위치의 -SCH3인 화합물.
  7. 제1항에 있어서, R4가 파라 위치에 존재하는 화합물.
  8. 제1항에 있어서, R1및 R2가 키랄이 될수 있도록 상이한 화합물.
  9. 제1항에 있어서, R1및 R2가 모두 메틸 또는 에틸이거나 또는 함께 시클로알킬 고리를 형성하는 화합물.
  10. 제1항에 있어서, R1이 CH3이고, R2가 CH3이며, R3이 3위치의 CH5및 4위치의 C2H5이고, R4가 페닐 고리의 4번 위치에 연결된 -SCH2C(CH3)2CO2H인 화합물.
  11. 제1항에 있어서, R1이 CH3이고 R2가 CH3이며, R3이 페닐고리의 3번 위치의 C2H5및 페닐고리의 4위치의 C2H5이고, R4가 페닐 고리의 4번 위치에 연결된 -S(O)CH2C(CH3)2CO2H인 화합물.
  12. 제1항에 있어서, R1이 CH3이고, R2가 CH3이며, R3이 페닐고리의 3번 위치의 C2H5및 페닐고리의 4번위치의 C2H5이고, R4가 페닐 고리의 4번 위치에 연결된 S(O2)CH2C(CH3)2CO2H인 화합물.
  13. 제1항에 있어서, R1및 R2가 함께 메틸렌기 -(CH2)3-를 나타내고, R3이 페닐 고리의 3 및 4번 위치에 연결된 식 -(CH2)4-의 카프보시클릭 고리이고, R4가 페닐 고리의 4번 위치에 연결된 -SCH2C(CH3)2CO2H인 화합물.
  14. 제1항에 있어서, R1및 R2가 함께 메틸렌기 -(CH2)3-를 나타내고, R3이 페닐 고리의 3 및 4번 위치에 연결된 식 -(CH2)4-의 카프보시클릭 고리이고, R4가 페닐 고리의 4번 위치에 연결된 -S(O)CH2C(CH3)2CO2H인 화합물.
  15. 제1항에 있어서, R1및 R2가 함께 메틸렌기 -(CH2)3-를 나타내고, R3이 페닐 고리의 3 및 4번 위치에 연결된 식 -(CH2)4-의 카르보시클릭 고리이고, R4가 페닐 고리의 4번 위치에 연결된 -S(O2)CH2C(CH3)2CH2H인 화합물.
  16. 제1항에 따른 화합물 유효량과 담체로 이루어진, 바람직하지 못한 엘라스타제작용의 억제용 제약 조성물.
  17. 의약으로 사용하기 위한 제1항 내지 15항중 어느 한 항에 따르는 화합물.
  18. 개체에 있어서 엘라스타제 작용의 억제용 의약을 제조하기 위한 제1항 내지 15항중 어느 한 항에 따른 화합물의 용도.
  19. 급성호흡기 증후군의 치료용 의약을 제조하기 위한 제1항 내지 15항중 어느 한 항에 따른 화합물의 용도.
  20. 심근경색증을 치료하기 위한 제1항 내지 15항중 어느 한 항에 따르는 화합물의 용도.
  21. 치근막 질병을 치료하기 위한 제1항 내지 15항중 어느 한 항에 따르는 화합물의 용도.
  22. 엘라스타제 작용의 억제가 필요한 개체에서 제1항에 따르는 화합물을 투여하는 것으로 되는 엘라스타체 억제방법.
  23. 급성 호흡기 증후근의 치료가 필요한 개체에서 제1항에 따르는 화합물을 투여하는 것으로 되는 급성 호흡기 증후근의 치료방법.
  24. 심근 경색증의 치료가 필요한 개체에서 제1항에 따흐는 화합물을 투여하는 것으로 되는 심근 경증의 치료방법.
  25. 치근박 질병의 치료가 필요한 개체에서 제1항에 따르는 화합물을 투여하는 것으로 되는 치근막 질병의 치료방법.
  26. (a)하기 일반식(XXⅧ)의 페닐아세트산을 산의 존재하에 알콜 ROH과 반응시켜 하기 일반식(XXIX)의 화합물을 얻는 단계, (b)R1또는 R2가 수소가 아닐 경우, 일반식(XXIX)의 화합물을 R1X및 (또는)R2X(여기서, X는 할로겐화물임)와 반응시켜 하기일반식(XXX)의 화합물을 얻는 단계, (c)하기 일반식(XXX)의 화합물을 알콜과 반응시켜 페닐알칸산 유도체를 생성시킨 다음, 페닐알칸산 유도체를 염소화시켜 하기 일반식(Ⅱ)의 산염화물 유도체를 생성시키는 단계, (d)하기 일반식(Ⅱ)의 화합물을 적합한 유기 염기의 존재하에 하기 일반식(Ⅲ)의 화합물과 반응시키는 단게, (e)임의로, Pg기를 제거하는 단계, (f)임의로, R′4이황 원자를 함유한 경우, 화합물을 설폭시드 또는 설폰 유도체로 산화시키는 단게, 및 (g)임의로, 제약상 허용되는 비독성 염을 형성시키는 단계로 이루어짐을 특징으로 하는 하기 일반식(Ⅵ)의 화합물 또는 그의 제약학상 허용되는 비독성 염의 제조방법.
    상기 식중, R1및 R2는 동일하거나 또는 상이한 것으로서, 수소원자, 탄소원자수가 1내지 6개인 알킬, 탄소원자수가 3내지 6개인 시클로알킬로 이루어진 군 중에서 선택되거나, 또는 R1및 R2는 함께 메틸렌기 -(CH2)n-(여기서, n은 1내지 6의 정수임)를 나타내고, R′3는 R3또는 R3Pg(여기서, PG는 적절한 보호기임)로서, R3은 수소원자, 할로겐, 탄소원자수가 1내지 12개인 할로알킬, 탄소원자수가 1내지 12개인 알킬, 탄소원자수가 1내지 12개인 알콕시, 탄소원자수가 2내지 12개인 알케닐, 탄소원자수가 3내지 12개인 시클로알킬, 일환식 또는 이환식 아릴, -ZR5(여기서, Z는 O, S,S(O) 또는 SO2이고 R5는 수소원자, 탄소원자수가 1내지 18개인 알킬, 탄소원자수가 3내지 12개인 시클로알킬이거나 또는 페닐임)-NR6R7[여기서, R6, R7은 동일하거나 또는 상이한 것으로서, 수소 원자, 탄소원자수가 1내지 12개인 알킬, 탄소원자수가 3내지 6개인 시클로알킬, 페닐, 탄소원자수가 1내지 12개인 알콕시, 식-C(O)R8(여기서, R8은 탄소원자수가 1내지 12개인 알킬, 탄소원자수가 3내지 12개인 시클로알킬, 페닐, CH3OC(O)CH2CH2-, HOOCCH2CH2, NaO3SCH2CH2NHC(O)CH2CH2-임)의 아실이거나 또는 R6및 R7은 함께 -C(O)CH2CH2C(O), -C(O)-C6H4-C(O)- 또는 -(CH2)x- (여기서, X는 2, 3, 4, 5 또는 6임)을 나타냄], 질소원자를 통해 페닐 고리에 연결된 모르폴리노, 이미다졸리노 또는 피페라지노로 이루어진 군중에서 선택된 1내지 5개의 치환체를 나타내거나 또는 R3은 인접한 고리 탄소원자들 사이에서 추가의 카르보시클릭고리를 완성하는데 필요한 1내지 6개의 탄소원자로된 원자들이거나 또는 하나 이상의 O, S 또는 N고리 원자들을 포함하는 5내지 6원 헤테로시클릭 고리를 나타내며, R′4는 R4이거나 또는 R4Pg(여기서, PG는 적절한 보호기임)로서, R4는 수소원자, 할로겐, 니트노, -C(O)CH3, S(O)CH3, S(O)pR9(여기서, p는 0,1 또는 2이고 R9는 히드록시, -ONa 또는 탄소원자수가 1내지 12개인 임의 치환된 알킬 또는 임의 치환된 시클로알킬임)중에서 선택된 1내지 5개의 치환체이다.
    ※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
KR1019910008164A 1990-05-22 1991-05-20 인체 호중구 엘라스타제의 억제제로서의 산화제 감수성 및 비감수성 방향족 에스테르 KR920005712A (ko)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US528967 1983-09-02
US07/528,967 US5214191A (en) 1990-05-22 1990-05-22 Oxidant sensitive and insensitive aromatic esters as inhibitors of human neutrophil elastase

Publications (1)

Publication Number Publication Date
KR920005712A true KR920005712A (ko) 1992-04-03

Family

ID=24107964

Family Applications (1)

Application Number Title Priority Date Filing Date
KR1019910008164A KR920005712A (ko) 1990-05-22 1991-05-20 인체 호중구 엘라스타제의 억제제로서의 산화제 감수성 및 비감수성 방향족 에스테르

Country Status (16)

Country Link
US (1) US5214191A (ko)
EP (1) EP0465802A1 (ko)
JP (1) JPH04226939A (ko)
KR (1) KR920005712A (ko)
CN (1) CN1056680A (ko)
AR (1) AR248128A1 (ko)
AU (1) AU640777B2 (ko)
CA (1) CA2042904A1 (ko)
FI (1) FI912468A (ko)
HU (1) HUT58265A (ko)
IE (1) IE911732A1 (ko)
IL (1) IL98202A0 (ko)
NO (1) NO175714C (ko)
NZ (1) NZ238168A (ko)
PT (1) PT97727A (ko)
ZA (1) ZA913727B (ko)

Families Citing this family (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU647838B2 (en) * 1990-11-07 1994-03-31 Cortech, Inc. Ester inhibitors
US5240956A (en) * 1990-11-07 1993-08-31 Cortech, Inc. Ester inhibitors
US5216022A (en) * 1991-12-19 1993-06-01 Cortech, Inc. Aromatic esters of phenylenedialkanoates as inhibitors of human neutrophil elastase
US5795890A (en) * 1995-09-27 1998-08-18 Ono Pharmaceutical Co., Ltd. Sulfonamide derivatives
KR20000022532A (ko) * 1996-06-27 2000-04-25 오노 야꾸힝 고교 가부시키가이샤 아릴(설파이드, 설폭시드 및 설폰)유도체 및 이를 활성 성분으로 함유하는 약물
FR2755015B1 (fr) * 1996-10-25 1998-12-24 Sod Conseils Rech Applic Utilisation d'un extrait flavonoidique de ginkgo biloba substantiellement depourvu de terpenes, dans le domaine buccodentaire, et composition contenant un tel extrait
US6300514B1 (en) 1997-06-25 2001-10-09 Ono Pharmaceutical Co., Ltd. Aryl (sulfide, sulfoxide and sulfone) derivatives and drugs containing the same as the active ingredient
WO2000051625A1 (en) * 1999-03-05 2000-09-08 The Trustees Of University Technology Corporation Inhibitors of serine protease activity, methods and compositions for treatment of herpes viruses
US6849605B1 (en) 1999-03-05 2005-02-01 The Trustees Of University Technology Corporation Inhibitors of serine protease activity, methods and compositions for treatment of viral infections
AU3511500A (en) 1999-03-05 2000-09-21 Trustees Of University Technology Corporation, The Inhibitors of serine protease activity, methods and compositions for treatment of nitric oxide-induced clinical conditions
US6355666B1 (en) 2000-06-23 2002-03-12 Medinox, Inc. Protected forms of pharmacologically active agents and uses therefor
CA2420576C (en) * 2000-08-29 2005-06-14 Nobex Corporation Immunoregulatory compounds, derivatives thereof and their use
US6548099B1 (en) 2000-11-28 2003-04-15 Hershey Foods Corporation Process for crystallizing amorphous lactose in milk powder
US8048924B2 (en) 2001-08-29 2011-11-01 Biocon Limited Methods and compositions employing 4-aminophenylacetic acid compounds
US20040220242A1 (en) * 2003-05-02 2004-11-04 Leland Shapiro Inhibitors of serine protease activity, methods and compositions for treatment of nitric oxide induced clinical conditions
TWI328009B (en) 2003-05-21 2010-08-01 Glaxo Group Ltd Quinoline derivatives as phosphodiesterase inhibitors
PL1773767T3 (pl) 2004-07-07 2016-07-29 Biocon Ltd Synteza azowo związanych związków immunoregulacyjnych
US7741359B2 (en) * 2005-05-27 2010-06-22 Antibe Therapeutics Inc. Hydrogen sulfide derivatives of non-steroidal anti-inflammatory drugs
KR101495520B1 (ko) * 2006-07-18 2015-02-26 안티브 홀딩스 인크. 약제의 4-하이드록시티오벤즈아미드 유도체

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA949912A (en) * 1970-12-01 1974-06-25 Steven P. Cahill Carriage apparatus for serial printer
CH591437A5 (ko) * 1974-05-08 1977-09-15 Esteve Dr Lab Del Sa
US3954767A (en) * 1972-05-17 1976-05-04 Esteve Subirana Antonio Piperazine salts of 2,5-dihydroxy benzene sulfonic acid mono- and diesters
US4115648A (en) * 1974-09-13 1978-09-19 Laboratorios Del Dr. Esteve, S.A. 2,5-Dihydroxy benzene sulfonic acid mono esters
FR2508033A1 (fr) * 1981-06-23 1982-12-24 Fabre Sa Pierre Aryl-1 aminomethyl-2 cyclopropanes carboxylates (z), leur preparation et leur application en tant que medicaments utiles dans le traitement d'algies diverses
DE3443308A1 (de) * 1984-11-28 1986-05-28 Bayer Ag, 5090 Leverkusen 1-heteroaryl-4-aryl-pyrazolin-5-one zur verwendung als arzneimittel

Also Published As

Publication number Publication date
US5214191A (en) 1993-05-25
EP0465802A1 (en) 1992-01-15
JPH04226939A (ja) 1992-08-17
AR248128A1 (es) 1995-06-30
CN1056680A (zh) 1991-12-04
AU7707691A (en) 1991-11-28
HUT58265A (en) 1992-02-28
NO175714C (no) 1994-11-23
IE911732A1 (en) 1991-12-04
NO911956L (no) 1991-11-25
IL98202A0 (en) 1992-06-21
CA2042904A1 (en) 1991-11-23
FI912468A (fi) 1991-11-23
FI912468A0 (fi) 1991-05-21
AU640777B2 (en) 1993-09-02
PT97727A (pt) 1992-02-28
ZA913727B (en) 1992-02-26
NZ238168A (en) 1995-07-26
HU911703D0 (en) 1991-12-30
NO175714B (no) 1994-08-15
NO911956D0 (no) 1991-05-21

Similar Documents

Publication Publication Date Title
KR920005712A (ko) 인체 호중구 엘라스타제의 억제제로서의 산화제 감수성 및 비감수성 방향족 에스테르
HUP0204147A2 (hu) [(RR,SS)-3-(2-dimetilaminoetil-1-hidroxiciklohexil)fenil]-2-hidroxibenzoátból származtatott új észterek, eljárás az előállításukra, ezeket tartalmazó gyógyszerkészítmények és alkalmazásuk
RU95108329A (ru) Замещенные производные тиазолидиндиона, способ их получения, фармкомпозиция
KR970703346A (ko) [a]-어닐레이트된 피롤 유도체와 이들의 약리학적 용도([a]-Annelated Pyrrole Derivatives and Pharmaceutical Use Thereof)
ATE52498T1 (de) Amidderivate.
ATA260587A (de) Verfahren zur herstellung von 4h-1-benzopyran-4-on-derivaten, neue 4h-1-benzopyran-4-on-derivate und ihre verwendung als arzneimittel
KR920009815A (ko) 아미노코우마란 유도체, 그들의 제조방법 및 용도
ES2059069T3 (es) Nuevos derivados de 1-alcoxi-(2-acilamino-etil)-naftalenos y su procedimiento de preparacion.
DK490288D0 (da) Hidtil ukendte forbindelser
HUP9700126A2 (hu) 2-Oxo- és 2-tio-1,2-dihidrokinolinil-oxazolidinon-származékok és ezeket tartalmazó gyógyszerkészítmények, eljárás előállításukra és intermedierjeik
KR950704294A (ko) 축합 벤조화합물(fused benzo compounds)
KR970703345A (ko) [a]-어닐레이트된 피롤 유도체와 이들의 약리학적 용도([a]-Annelated Pyrrole Derivatives and Pharmaceutical Use Thereof)
ATE202702T1 (de) Verwendung von oestrogenagonisten und - antagonisten zur herstellung eines medikaments zur behandlung von atherosklerose, unabhängig von lipidsenkung
KR910006241A (ko) 피리미딘-4,6-디카복실산 디아미드, 이의 제조방법, 이의 용도 및 이들 화합물을 기초로 하는 약제
SE9601110D0 (sv) Substituted 1,2,3,4-tetrahydronaphthalene derivatives
HUP9900567A2 (hu) Neutrofil-elasztáz gátló hatású pirrolo-pirrolonszármazékok, intermedierjeik, előállításuk és alkalmazásuk, a vegyületeket tartalmazó gyógyászati készítmények
ATE165600T1 (de) Diphenylpiperazinderivat und dieses enthaltendes arzneimittel für kreislauforgane
DE69434198D1 (de) Verfahren zur senkung des serumcholesterinspiegels mit 2,6-dialkyl-4 silyl-phenol derivaten
HUP9802393A2 (hu) Benzotiazolonszármazékok, alkalmazásuk, az ezeket tartalmazó gyógyszerkészítmények, eljárás a vegyületek előállítására és intermedierjeik
KR950704727A (ko) 4-클로로-2-티오펜카복실산의 위치선택적 제조 방법(regioselective synthesis of 4-chloro-2-thiophenecarboxylic acid)
LV10235A (lv) Jauni esteri to iegusanas panemiens farmaceitiska kompozicija arstesanas metode
KR970706826A (ko) 포스포디에스테라제 IV 억제제로서의 디아제피노-인돌(Diazepino-Indoles as Phosphodiesterase Ⅳ Inhibitors)
DE69214784D1 (de) Verfahren zur herstellung von cephalosporinzwischenverbindungen
DE69005974D1 (de) Heteroaryl-3-oxo-propannitril-derivate, nützlich zur behandlung von rheumatoider arthritis und anderen autoimmunkrankheiten.
DE69103630D1 (de) Oxazolederivate, ihre herstellung und diese enthaltende pharmazeutischen zubereitungen.

Legal Events

Date Code Title Description
WITN Application deemed withdrawn, e.g. because no request for examination was filed or no examination fee was paid