KR930004280A - 경구 활성 엘라스타제 억제제 - Google Patents

경구 활성 엘라스타제 억제제 Download PDF

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KR930004280A
KR930004280A KR1019920015028A KR920015028A KR930004280A KR 930004280 A KR930004280 A KR 930004280A KR 1019920015028 A KR1019920015028 A KR 1019920015028A KR 920015028 A KR920015028 A KR 920015028A KR 930004280 A KR930004280 A KR 930004280A
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alkyl
val
cycloalkyl
ala
group
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폴 피트 노톤
리차드 안젤라스트로 마이클
폴 버크하트 조셉
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스티븐 엘. 네스비트
메렐 다우 파마슈티칼스 인크.
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
    • C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
    • C07D265/30—1,4-Oxazines; Hydrogenated 1,4-oxazines not condensed with other rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/08—Tripeptides
    • C07K5/0827—Tripeptides containing heteroatoms different from O, S, or N
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06191—Dipeptides containing heteroatoms different from O, S, or N
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
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  • Bioinformatics & Cheminformatics (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Pyridine Compounds (AREA)

Abstract

내용 없음.

Description

경구 활성 엘라스타제 억제제
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음

Claims (5)

  1. 하기일반식(1)의 화합물, 그의 수화물, 동배체 또는 제약적으로 허용가능한 염.
    식 중, P1은 Ala, bAla, Leu, Ⅰle, Val, Nva, bVal, Met, Nle, Gly 또는 N-메틸 유도체이고, P2는 알파-아미노기의 질소가 R기[여기서, R은 (C1-6)알킬, (C3-12)시킬로알킬, (C3-12)시클로알킬(C1-6)알킬, (C3-7)비시클로알킬, (C4-11)비시클로알킬(C1-6)알킬, (C6-10)아릴, (C6-10)아릴(C1-6)알킬, (C3-7)헤테로시클로알킬, (C3-7)헤테로시클로알킬(C1-6), (C5-9)헤테로아릴, (C5-9)헤테로아릴(C1-6)알킬, 융합 (C6-10)아릴(C3-12)시클로알킬, 융합 (C1-6)아릴(C3-12)시클로알킬, (C1-6)알킬, 융합 (C5-9)헤테로아릴(C3-12)시클로알킬, 또는 융합 (C5-9)헤테로아킬(C3-12)시클로알킬, (C1-6)알킬임]로 치환될 수 있는 Ala, bAla, Leu, Ⅰle, Val, Nva, bVal, Met, Nle, Gly, Tyr, Trp 또는 Nal(1)이거나, 또는 P2는 Pro, 1,2,3,4-테트라히드로-3-이소퀴놀린 카르복실산(Tic)티아졸리딘-4-카르복실산(Tca) 또는 Ind이고; P3는 Ala, bAla, Leu, Ⅰle, Val, Nva, bVal, Met 또는 Nle 또는 N-메틸 유도체, Pro, Ind, Tic 또는 Tca, 또는 각각 오메가 아미노기가 모르폴리노-B-기로 치환된 Lys 또는 Orn이고; P4는 Ala, bAla, Leu, Ⅰle, Val, Nva, bVal, Met 또는 Nle 또는N-메틸 유도체 또는 단일 결합이고; B는 하기 일반식의 기또는 -SO2-이고; R′은 수소 또는 C1-6알킬기이고; X는 N 또는 CH이다.
  2. 제1항에 있어서, B가및중 하나의 기이고, P1이 노르발린 또는 발린이고, P2가 프롤린이고, P3가 이소로이신, 발린 또는 알라닌이고, P4가 알라닌 또는 단dor합이고, X가 N인 화합물.
  3. 제2항에 있어서, MC-Ala-Ala-Pro-Val-C2F5(SEQ. ⅠD 2) 및 MC-Val-Pro-Val-C2F5, MCBz-Ala-Ala-Pro-Val-C2F5(SEQ. ⅠD 3) 및 MCBz-Val-Pro-Val-C2F5중에서 선택된 화합물.
  4. 하기 일반식(5)의 펜타플루오로에틸 펩타이드 유도체를 하기 일반식(6) 또는 일반식(7)의 화합물과 반응시킴을 특징으로 하는 하기 일반식(1)의 화합물, 그의 수화물, 동배체 또는 제약적으로 허용 가능한 염의 제조방법.
    식 중, P1은 Ala, bAla, Leu, Ⅰle, Val, Nva, bVal, Met, Nle, Gly 또는 N-메틸 유도체이고, P2는 알파-아미노기의 질소가 R기[여기서, R은 (C1-6)알킬, (C3-12)시킬로알킬, (C3-12)시클로알킬(C1-6)알킬, (C4-11)비시클로알킬, (C4-11)비시클로알킬(C1-6)알킬, (C6-10)아릴, (C6-10)아릴(C1-6)알킬, (C3-7)헤테로시클로알킬, (C3-7)헤테로시클로알킬(C1-6), (C5-9)헤테로아릴, (C5-9)헤테로아릴(C1-6)알킬, 융합 (C6-10)아릴(C3-12)시클로알킬, 융합 (C1-6)아릴(C3-12)시클로알킬(C1-6)알킬, 융합 (C5-9)헤테로아릴(C3-12)시클로알킬, 또는 융합 (C5-9)헤테로아릴(C3-12)시클로알킬, (C1-6)알킬임]로 치환될 수 있는 Ala, bAla, Leu, Ⅰle, Val, Nva, bVal, Met, Nle, Gly, Tyr, Trp 또는 Nal(1)이거나, 또는 P2는 Pro, 1,2,3,4-헤트라히드로-3-이소퀴놀린 카르복실산(Tic) 티아졸리딘-4-카르복실산(Tca) 또는 Ind이고; P3는 Ala, bAla, Leu, Ⅰle, Val, Nva, bVal, Met 또는 Nle 또는 N-메틸 유도체, Pro, Ind, Tic 또는 Tca 또는 각각 오메가 아미노기가 모르폴리노-B-기로 치환된 Lys 또는 Orn이고; P4는 Ala, bAla, Leu, Ⅰle, Val, Nva, nVal, Met 또는 Nle 또는 N-메틸 유도체 또는 단일 결합이고; B는 하기 일반식의 기또는 -SO2-이고; R′은 수소 또는 C1-6알킬기이고, X는 N또는 CH이다.
  5. 하기 일반식(1)의 화합물, 그의 수화물, 동배체 또는 제약학적으로 허용 가능 한 염으로 이루어지는, 염증성질환 및 기종의 치료용 제약 조성물.
    식 중, P1은 Ala, bAla, Leu, Ⅰle, Val, Nva, bVal, Met, Nle, Gly 또는 N-메틸 유도체이고, P2는 알과-아미노기의 질소가 R기[여기서, R은 (C1-6)알킬, (C3-12)시킬로알킬, (C3-12)시클로알킬(C1-6)알킬, (C4-11)비시클로알킬, (C4-11)비시클로알킬(C1-6)알킬, (C6-10)아릴, (C6-10)아릴(C1-6)알킬, (C3-7)헤테로시클로알킬, (C3-7)헤테로시클로알킬(C1-6), (C5-9)헤테로아릴, (C5-9)헤테로아릴(C1-6)알킬, 융합 (C6-10)아릴(C3-12)시클로알킬, 융합 (C1-6)아릴(C3-12)시클로알킬(C1-6)알킬, 융합 (C5-9)헤테로아릴(C3-12)시클로알킬, 또는 융합 (C5-9)헤테로아릴(C3-12)시클로알킬, (C1-6)알킬임]로 치환될 수 있는 Ala, bAla, Leu, Ⅰle, Val, Nva, bVal, Met, Nle, Gly, Tyr, Trp 또는 Nal(1)이거나, 또는 P2는 Pro, 1,2,3,4-헤트라히드로-3-이소퀴놀린 카르복실산(Tic) 티아졸리딘-4-카르복실산(Tca) 또는 Ind이고; P3는 Ala, bAla, Leu, Ⅰle, Val, Nva, bVal, Met 또는 Nle 또는 N-메틸 유도체, Pro, Ind, Tic 또는 Tca 또는 각각 오메가 아미노기가 모르폴리노-B-기로 치환된 Lys 또는 Orn이고; P4는 Ala, bAla, Leu, Ⅰle, Val, Nva, nVal, Met 또는 Nle 또는 N-메틸 유도체 또는 단일 결합이고; B는 하기 일반식의 기또는 -SO2-이고; R′은 수소 또는 C1-6알킬기이고, X는 N또는 CH이다.
    ※ 참고사항 : 최초출원 내용에 의하여 공개되는 것임.
KR1019920015028A 1991-08-22 1992-08-21 경구 활성 엘라스타제 억제제 KR100242046B1 (ko)

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US748,607 1976-12-08
US74860791A 1991-08-22 1991-08-22

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EP (1) EP0529568B1 (ko)
JP (1) JP3311392B2 (ko)
KR (1) KR100242046B1 (ko)
AT (1) ATE147756T1 (ko)
AU (1) AU655831B2 (ko)
CA (1) CA2076307C (ko)
DE (1) DE69216713T2 (ko)
DK (1) DK0529568T3 (ko)
ES (1) ES2099186T3 (ko)
FI (1) FI923787A (ko)
GR (1) GR3022915T3 (ko)
HU (1) HU208703B (ko)
IL (1) IL102858A (ko)
NO (1) NO308999B1 (ko)
NZ (1) NZ243998A (ko)
ZA (1) ZA926185B (ko)

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AU655831B2 (en) 1995-01-12
IL102858A (en) 1998-12-27
JPH05213991A (ja) 1993-08-24
NO923280L (no) 1993-02-23
AU2106592A (en) 1993-02-25
CA2076307A1 (en) 1993-02-23
ATE147756T1 (de) 1997-02-15
DE69216713T2 (de) 1997-05-28
FI923787A0 (fi) 1992-08-21
EP0529568A1 (en) 1993-03-03
HU208703B (en) 1993-12-28
EP0529568B1 (en) 1997-01-15
FI923787A (fi) 1993-02-23
DK0529568T3 (da) 1997-02-03
GR3022915T3 (en) 1997-06-30
ZA926185B (en) 1993-03-01
CA2076307C (en) 2003-01-07
ES2099186T3 (es) 1997-05-16
IL102858A0 (en) 1993-01-31
JP3311392B2 (ja) 2002-08-05
HUT62014A (en) 1993-03-29
NO923280D0 (no) 1992-08-21
NZ243998A (en) 1994-11-25
DE69216713D1 (de) 1997-02-27
KR100242046B1 (ko) 2000-03-02
NO308999B1 (no) 2000-11-27

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