KR830010063A - 엔케팔린아제 효소 억제 화합물의 제조방법 - Google Patents

엔케팔린아제 효소 억제 화합물의 제조방법 Download PDF

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KR830010063A
KR830010063A KR1019820002139A KR820002139A KR830010063A KR 830010063 A KR830010063 A KR 830010063A KR 1019820002139 A KR1019820002139 A KR 1019820002139A KR 820002139 A KR820002139 A KR 820002139A KR 830010063 A KR830010063 A KR 830010063A
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compound
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KR1019820002139A
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KR860001549B1 (ko
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싱그 빈드라 자스짓트
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윌리암 데이비스헌
화이자 인코포레이티드
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
    • C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
    • C07C319/20—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides by reactions not involving the formation of sulfide groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
    • C07C59/40—Unsaturated compounds
    • C07C59/58—Unsaturated compounds containing ether groups, groups, groups, or groups
    • C07C59/64—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings
    • 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
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • 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
    • C07C323/60—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 with the carbon atom of at least one of the carboxyl groups bound to nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C327/00—Thiocarboxylic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
    • C07C57/52—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing halogen
    • C07C57/58—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing halogen containing six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
    • C07C57/52—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing halogen
    • C07C57/58—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing halogen containing six-membered aromatic rings
    • C07C57/60—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing halogen containing six-membered aromatic rings having unsaturation outside the rings

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
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  • Biomedical Technology (AREA)
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  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
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  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)

Abstract

내용 없음

Description

엔케팔린아제 효소 억제 화합물의 제조방법
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음

Claims (10)

  1. (a) 하기 일반식(Ⅲ), (Ⅳ), (Ⅴ) 또는 (Ⅵ)로 표시되는 화합물을 가수분해시키고,
    (Ⅲ)
    (Ⅳ)
    (Ⅴ)
    또는
    (Ⅵ)
    (상기 일반식에서, X, R, n, m 및 R1은 앞서 정의한 바와 같고 P는 상기 가수분해에 의해 선택적으로 제거되는 황보호기이며, 또 R2는 상기 가수분해에 의해 선택적으로 제거되는 산 보호기이다.)
    (b) 하기 일반식(Ⅸ), (Ⅹ)로 표시되는 화합물의 디아스테레오머 혼합물 중에서 디아스테레오머들을 분리하여,
    (Ⅸ)
    또는
    (Ⅹ)
    (상기 일반식에서, X, R, n, m 및 R1은 앞서 정의한 바와 같다.)
    (c) 하기 일반식(ⅩⅠ), 또는 (ⅩⅡ)로 표시되는 화합물의 디아스테레오머 혼합물을 가수분해시키고,
    (ⅩⅠ)
    또는
    (ⅩⅡ)
    (상기 일반식에서, X, R, n, m, R1, P 및 R2는 앞서 정의한 바와 같다.) 이 결과 생성된 디아스테레오머 혼합물로부터 디아스테레오머들을 분리한 다음,
    (d) 일반식(ⅩⅠ) 또는 (ⅩⅡ)로 표시되는 화합물에서 디아스테레오머들을 분리하고 이 결과 분리된 디아스테레오머들을 가수분해하고,
    (e) 하기 일반식(ⅩⅢ)로 표시되는 화합물을 하기 일반식(ⅩⅣ) 또는 (ⅩⅤ)로 표시되는 화합물과 카플링 반응시켜서,
    (ⅩⅢ)
    (ⅩⅣ)
    또는
    (ⅩⅤ)
    (상기 일반식에서, X, R, n, m, R1, P 및 R2는 앞서 정의한 바와 같다.) 이 결과 생성된 디아스테레오머를 분리하여 가수분해하거나 생성된 디아스테레오머들을 가수분해하여 분리시켜서,
    (f) 하기 일반식으로 표시되는 화합무리 일반식(ⅩⅣ) 또는 (ⅩⅤ)로 표시되는 화합물과 카플링 반응시켜 이 결과 생성된 중간체를 가수분해시키고, 또 필요에 따라
    (g) 일반식(Ⅲ) 또는 (Ⅳ)로 표시되는 생성된 화합물을 약리학적으로 허용되는 양이온성염으로 전환시킴을 특징으로 하는 하기 일반식(Ⅰ), (Ⅱ), (Ⅲ), 또는 (Ⅳ)로 표시되는 엔케팔린아제 효소 억제 화합물의 제조방버.
    (Ⅳ)
    (Ⅳ)
    [상기 일반식에서, X는 수소원자, (C1-C3)알킬기, (C1-C3)알콕시기, 불소 ,염소, 브롬 또는 트리플루오토메틸기이고, R은 수소원자 또는 (C1-C3)알킬기, n은 1-4, m은 0.1 또는 2, R1은 (C1-C3)알킬기].
  2. 상기 제1항에 있어서, n이 2, m이 0 및 R1이 메틸기인 화합물의 제조방법.
  3. 상기 제2항 기재에 있어서, R이 수소인 화합물인 제조방법.
  4. 상기 제3항 기재에 있어서, X가 p-클로로기인 화합물의 제조방법.
  5. 상기 제3항 기재에 있어서, X가 p-메톡시기인 화합물의 제조방법.
  6. 상기 제3항 기재에 있어서, X가 수소인 화합물의 제조방법.
  7. 상기 제6항 기재에 있어서, 일반식(Ⅰ)인 화합물의 제조방법.
  8. 상기 제6항 기재에 있어서, 일반식(Ⅱ)의 화합물의 제조방법.
  9. 상기 제1항 기재에 있어서, 일반식(Ⅲ)인 화합물의 제조방법.
  10. 상기 제1항 기재에 있어서, 일반식(Ⅳ)인 화합물의 제조방법.
    ※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
KR8202139A 1981-05-18 1982-05-17 엔케팔린아제 효소 억제 화합물의 제조 방법 KR860001549B1 (ko)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US06/264,752 US4329495A (en) 1981-05-18 1981-05-18 Enkephalinase enzyme inhibiting compounds
US264,752 1981-05-18

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KR830010063A true KR830010063A (ko) 1983-12-24
KR860001549B1 KR860001549B1 (ko) 1986-10-04

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US (1) US4329495A (ko)
EP (1) EP0066956B1 (ko)
JP (1) JPS57193450A (ko)
KR (1) KR860001549B1 (ko)
AR (1) AR231279A1 (ko)
AT (1) ATE8881T1 (ko)
AU (1) AU529511B2 (ko)
CA (1) CA1179368A (ko)
DE (1) DE3260531D1 (ko)
DK (1) DK160711B (ko)
ES (2) ES512278A0 (ko)
FI (1) FI76555C (ko)
GR (1) GR75496B (ko)
HU (1) HU188058B (ko)
IE (1) IE53226B1 (ko)
IL (1) IL65799A (ko)
IN (1) IN158365B (ko)
NO (1) NO153768C (ko)
NZ (1) NZ200639A (ko)
PH (1) PH18206A (ko)
PL (1) PL138043B1 (ko)
PT (1) PT74913B (ko)
YU (1) YU42468B (ko)
ZA (1) ZA823386B (ko)

Families Citing this family (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4432972A (en) * 1981-08-03 1984-02-21 E. R. Squibb & Sons, Inc. Phosphonamidate compounds
US4474795A (en) * 1981-10-09 1984-10-02 E. R. Squibb & Sons, Inc. Enkephalinase inhibitors
US4401677A (en) * 1981-10-09 1983-08-30 E. R. Squibb & Sons, Inc. Enkephalinase inhibitors
US4474799A (en) * 1981-10-09 1984-10-02 E. R. Squibb & Sons, Inc. Enkephalinase inhibitors
JPS58140065A (ja) * 1982-02-10 1983-08-19 Meito Sangyo Kk メルカプトベンジル脂肪酸誘導体類及びその製法
FR2540495B1 (fr) * 1983-02-07 1986-02-14 Roussel Uclaf Nouveaux derives de o-mercaptopropanamide et de ses homologues, leur procede de preparation, leur application comme medicaments, les compositions les renfermant et les nouveaux intermediaires obtenus
FR2540498B1 (fr) * 1983-02-07 1986-02-14 Roussel Uclaf Nouveaux medicaments derives d'amides d'acide mercaptoacetique et de l'acide 3-mercaptopropionique et les compositions pharmaceutiques les renfermant
FR2556721B1 (fr) * 1983-12-14 1986-05-16 Roussel Uclaf Nouveaux derives de o-mercaptopropanamide d'o amino-acides, leur procede de preparation, leur application comme medicaments et les compositions les renfermant
FR2559770B1 (fr) * 1984-02-20 1986-10-24 Roussel Uclaf Nouveaux derives de n-alkyl-o-mercaptopropanamide, leurs procedes de preparation, leur application comme medicaments, les compositions les renfermant et les nouveaux intermediaires obtenus
EP0254032A3 (en) 1986-06-20 1990-09-05 Schering Corporation Neutral metalloendopeptidase inhibitors in the treatment of hypertension
EP0566157A1 (en) 1986-06-20 1993-10-20 Schering Corporation Neutral metalloendopeptidase inhibitors in the treatment of hypertension
US4801609B1 (en) * 1987-03-27 1993-11-09 Mercapto-acylamino acid antihypertensives
US4929641B1 (en) * 1988-05-11 1994-08-30 Schering Corp Mercapto-acylamino acid antihypertensives
US5262436A (en) * 1987-03-27 1993-11-16 Schering Corporation Acylamino acid antihypertensives in the treatment of congestive heart failure
EP0355784A1 (en) * 1988-08-24 1990-02-28 Schering Corporation Mercapto-acylamino acid antihypertensives
US4879309A (en) * 1988-09-27 1989-11-07 Schering Corporation Mercapto-acylamino acids as antihypertensives
ZA902661B (en) * 1989-04-10 1991-01-30 Schering Corp Mercapto-acyl amino acids
FR2652087B1 (fr) * 1989-09-15 1993-10-15 Bioprojet Ste Civile Derives d'amino-acides, leur procede de preparation et leurs applications therapeutiques.
US5599951A (en) * 1989-09-15 1997-02-04 Societe Civile Bioprojet Amino acid derivatives, the process for their preparation and their applications to therapy
US5407960A (en) * 1989-12-22 1995-04-18 Schering Corporation Mercaptocycloacyl aminoacid endopeptidase inhibitors
AU7957291A (en) * 1990-05-17 1991-12-10 Schering Corporation Disulfide derivatives of mercaptoacylamino acids

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US4046889A (en) * 1976-02-13 1977-09-06 E. R. Squibb & Sons, Inc. Azetidine-2-carboxylic acid derivatives
US4053651A (en) * 1976-05-10 1977-10-11 E. R. Squibb & Sons, Inc. Compounds and method for alleviating angiotensin related hypertension
GB2074571B (en) * 1980-04-11 1984-02-15 Wellcome Found Alpha-benzyl-substituted amides
FR2480747A1 (fr) * 1980-04-17 1981-10-23 Roques Bernard Derives d'acides amines et leur application therapeutique

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GR75496B (ko) 1984-07-24
FI76555C (fi) 1988-11-10
NO153768C (no) 1986-05-21
IL65799A0 (en) 1982-08-31
IE821168L (en) 1982-11-18
DK221182A (da) 1982-11-19
ATE8881T1 (de) 1984-08-15
ES8306719A1 (es) 1983-06-01
DK160711B (da) 1991-04-08
NZ200639A (en) 1985-08-30
IE53226B1 (en) 1988-09-14
KR860001549B1 (ko) 1986-10-04
JPS57193450A (en) 1982-11-27
EP0066956B1 (en) 1984-08-08
JPS637542B2 (ko) 1988-02-17
YU42468B (en) 1988-08-31
PH18206A (en) 1985-04-25
AU8375982A (en) 1982-11-25
US4329495A (en) 1982-05-11
PT74913B (en) 1985-05-16
FI76555B (fi) 1988-07-29
ES512278A0 (es) 1983-06-01
EP0066956A1 (en) 1982-12-15
CA1179368A (en) 1984-12-11
PL236425A1 (en) 1983-08-01
ES519668A0 (es) 1984-03-01
IL65799A (en) 1985-12-31
YU104282A (en) 1985-06-30
DE3260531D1 (en) 1984-09-13
IN158365B (ko) 1986-11-01
PT74913A (en) 1982-06-01
NO821595L (no) 1982-11-19
AU529511B2 (en) 1983-06-09
AR231279A1 (es) 1984-10-31
NO153768B (no) 1986-02-10
PL138043B1 (en) 1986-08-30
HU188058B (en) 1986-03-28
ZA823386B (en) 1983-03-30
ES8403107A1 (es) 1984-03-01
FI821736A0 (fi) 1982-05-17

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