KR920700221A - 극성 n-말단기들을 갖는 신규 리닌 억제인자 펩티드 - Google Patents
극성 n-말단기들을 갖는 신규 리닌 억제인자 펩티드Info
- Publication number
- KR920700221A KR920700221A KR1019900702636A KR900702636A KR920700221A KR 920700221 A KR920700221 A KR 920700221A KR 1019900702636 A KR1019900702636 A KR 1019900702636A KR 900702636 A KR900702636 A KR 900702636A KR 920700221 A KR920700221 A KR 920700221A
- Authority
- KR
- South Korea
- Prior art keywords
- methyl
- amino
- carbonyl
- phe
- hydroxy
- Prior art date
- Legal status (The legal status 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 status listed.)
- Withdrawn
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims 10
- 102000004196 processed proteins & peptides Human genes 0.000 title claims 2
- 239000003112 inhibitor Substances 0.000 title 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 52
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 47
- 150000003839 salts Chemical class 0.000 claims 31
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims 28
- -1 carboxy- Chemical class 0.000 claims 28
- UMMQVDUMUMBTAV-YFKPBYRVSA-N (2s)-2-amino-3-(1h-imidazol-5-yl)propanamide Chemical compound NC(=O)[C@@H](N)CC1=CN=CN1 UMMQVDUMUMBTAV-YFKPBYRVSA-N 0.000 claims 26
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 22
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 18
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims 18
- 239000007983 Tris buffer Substances 0.000 claims 17
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 claims 8
- 150000001204 N-oxides Chemical class 0.000 claims 8
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 8
- 229910052739 hydrogen Inorganic materials 0.000 claims 8
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims 8
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 claims 7
- RRHGJUQNOFWUDK-UHFFFAOYSA-N Isoprene Chemical compound CC(=C)C=C RRHGJUQNOFWUDK-UHFFFAOYSA-N 0.000 claims 6
- 239000001257 hydrogen Substances 0.000 claims 6
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 6
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims 5
- 150000002431 hydrogen Chemical class 0.000 claims 5
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 claims 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 4
- 125000003118 aryl group Chemical group 0.000 claims 4
- 229960001230 asparagine Drugs 0.000 claims 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims 4
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims 4
- 125000000217 alkyl group Chemical group 0.000 claims 3
- 150000001875 compounds Chemical class 0.000 claims 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 3
- WPLOVIFNBMNBPD-ATHMIXSHSA-N subtilin Chemical compound CC1SCC(NC2=O)C(=O)NC(CC(N)=O)C(=O)NC(C(=O)NC(CCCCN)C(=O)NC(C(C)CC)C(=O)NC(=C)C(=O)NC(CCCCN)C(O)=O)CSC(C)C2NC(=O)C(CC(C)C)NC(=O)C1NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C1NC(=O)C(=C/C)/NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)CNC(=O)C(NC(=O)C(NC(=O)C2NC(=O)CNC(=O)C3CCCN3C(=O)C(NC(=O)C3NC(=O)C(CC(C)C)NC(=O)C(=C)NC(=O)C(CCC(O)=O)NC(=O)C(NC(=O)C(CCCCN)NC(=O)C(N)CC=4C5=CC=CC=C5NC=4)CSC3)C(C)SC2)C(C)C)C(C)SC1)CC1=CC=CC=C1 WPLOVIFNBMNBPD-ATHMIXSHSA-N 0.000 claims 3
- 125000004455 (C1-C3) alkylthio group Chemical group 0.000 claims 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims 2
- 102000004881 Angiotensinogen Human genes 0.000 claims 2
- 108090001067 Angiotensinogen Proteins 0.000 claims 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 2
- 239000002253 acid Substances 0.000 claims 2
- 229910052736 halogen Inorganic materials 0.000 claims 2
- 150000002367 halogens Chemical class 0.000 claims 2
- 125000000623 heterocyclic group Chemical group 0.000 claims 2
- 229910052757 nitrogen Inorganic materials 0.000 claims 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 2
- 239000000758 substrate Substances 0.000 claims 2
- 230000007704 transition Effects 0.000 claims 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims 2
- 125000004042 4-aminobutyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])N([H])[H] 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- 125000000174 L-prolyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(*)=O 0.000 claims 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims 1
- 239000004472 Lysine Substances 0.000 claims 1
- 125000003746 N(6)-lysino group Chemical group [H]N([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(C(O[H])=O)N([H])[H] 0.000 claims 1
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical class O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims 1
- UKCXYGBXUWRGOJ-UHFFFAOYSA-N [CH-]1[ClH]C=CC1 Chemical compound [CH-]1[ClH]C=CC1 UKCXYGBXUWRGOJ-UHFFFAOYSA-N 0.000 claims 1
- 125000003670 adamantan-2-yl group Chemical group [H]C1([H])C(C2([H])[H])([H])C([H])([H])C3([H])C([*])([H])C1([H])C([H])([H])C2([H])C3([H])[H] 0.000 claims 1
- 125000002619 bicyclic group Chemical group 0.000 claims 1
- 239000008280 blood Substances 0.000 claims 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 125000005842 heteroatom Chemical group 0.000 claims 1
- 235000018977 lysine Nutrition 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 125000001624 naphthyl group Chemical group 0.000 claims 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 1
- 229910052760 oxygen Inorganic materials 0.000 claims 1
- 125000006513 pyridinyl methyl group Chemical group 0.000 claims 1
- 229910052717 sulfur Inorganic materials 0.000 claims 1
- 239000011593 sulfur Substances 0.000 claims 1
- 125000004434 sulfur atom Chemical group 0.000 claims 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
- C07K5/0227—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the (partial) peptide sequence -Phe-His-NH-(X)2-C(=0)-, e.g. Renin-inhibitors with n = 2 - 6; for n > 6 see C07K5/06 - C07K5/10
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- 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
-
- 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
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Oncology (AREA)
- Virology (AREA)
- Communicable Diseases (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
내용 없음
Description
내용없음
Claims (9)
- 리닌 기질(안지오텐시노겐(angiotensinogen))의 10,11위치에 상응하는 비－쪼개짐성 전이 상태 삽입물을 갖고 N－말단에 하기 일반식 L1부분을 갖는 펩티드:(상기식에서, X1은 a) H2N－, b) H2NC(CH3)2－, c) HO2C－, d) (H2N)(HO2C)CH－, 또는 e) (HO)2P(O)O－이고, n은 1－5이다.)
- 리닌 기질(안지오텐시노겐)의 10,11위치에 상응하는 비－쪼개짐성 전이 상태 삽입물을 갖는 펩티드에 있어서, N－말단에 하기 일반식 L1부분을 펩티드내 포함함을 개선점으로 하는 펩티드:(상기식에서, X1은 a) H2N－, b) H2NC(CH3)2－, c) HO2C－, d) (H2N)(HO2C)CH－, 또는 e) (HO)2P(O)O－이고, n은 1－5이다.)
- 제1항에 있어서, 하기 일반식(Ⅰ)의 펩티드 또는 그의 카르복시－, 아미노－, 또는 다른 반응성기 보호된 형태 또는 그의 제약학적으로 허용가능한 산 또는 염기 부가염:A6－B7－C8－D9－E10－F11－G12－H13(Ⅰ)상기식에서, A6은 하기 일반식 L1이 일가부분이고:B7은 부재하거나 하기 일반식 L2의 이가부분이고;C8은 하기 일반식 L3또는 L4의 이가 부분이고;D9은 하기 일반식 L4또는 L5의 이가 부분이고;E10－F11은 하기일반식 L6－L10중 임의의 것이 이가부분이거나 일반식 L11의 일가부분이고;H13은 a)－O－R5또는 b)－N(R1)(R5)이고; 식들에서 X1은 a) H2N－, b) H2NC(yCH3)2－, c) HO2C－, d) (H2N)(HO2C)CH－, 또는 e)이고, Q1은 a)－CH2－, －CH(OH)－, c)－O－, 또는 d)－S－이고 M1은 a)－C(O)－ 또는 b)－CH2이고; V1은 a)－O－또는 b)－N(R1)－이고; Y1은 a)－OH 또는 b)－NH2이고; P1은 a)－N3, b)－CN, C1－C6알킬, d)C1－C6시클로알킬, e)아릴, 또는 f)Het 이고 m은 1또는 2이고, n은 1－5이고, p는 0－5이고, 아릴은 하기중 0－3개로 치환된, 페닐 또는 나프틸이고; a)C1－C5알킬, b)히드록시, c)히드록시(C1－C5알킬), d)C1－C5알콕시, e) 아미노 f)아미노(C1－C5알킬), g)할로겐, h)－CHO, i)－CO2H, j)－CO2(C1－C5알킬), k)－CONH2, l)－CONH(C1－C5 알킬), m)니트로, n)머캅토, o)머캅토(C1－C5알킬), p)－SO3H, q)－SO2NH2, r)－CN;Het는 1－3개 이종원자(질소, 산, 황)를 함유하고, 임의의 비시클릭기를 포함하는 5－또는 6－원포화 또는 불포화고리이고, (이때, 상기 헤테로시클릭 고리중 임의의 것은 벤젠 고리 또는 다른 헤테로사이클로 융합되고, 화학적으로 가능하다면, 상기 질소 및 황 원자는 산화 형태일수 있다); 이는 하기중 0－3개로 치환되고 : a)C1－C5알킬, b)히드록시, c)히드록시(C1－C5알킬), d)C1－C5알콕시, e)아미노, f)아미노(C1－C5알킬), g)할로겐, h)－CHO, i)－CO2H, j)－CO2(C1－C5알킬), k)－CONH2, l)－CONH(C1－C5알킬), m)니트로, n)머캅토, o)머캅토(C1－C5알킬), p)－SO3H, q)－SO2NH2, r)－CN;R1은 a)수소 또는 b)C1－C5알킬이고; R2는 a)수소 b)C1－C5알킬, c)－(CH2)p－ 아릴, d)－(CH2)p－Het, e)－(CH2)p－CO2H, f)－(CH2)p－NH2, g)－(CH2)p－CH(NH2) (CO2H), h)C3－C7시클로알킬, 또는 i)1－또는 2－아다민틸이고;R3는 a)수소, b)C1－C5알킬, c)아릴, d)C3－C7시클로알킬, e)Het, f)C1－C3알콕시, 또는 g)C1－C3알킬티오이고;R4는 a)수소, b)C1－C8알킬, c)C3－C7시클로알킬, 또는 d)－CH(Ra)(R6)이고;R5는 R2는 a)수소 b)C1－C10알킬, c)－(CH2)p－ 알킬, d)－(CH2)p－Het, e)－(CH2)p－ 시클로알킬, f)－(CH2)p－CH(NH2)(CO2)H, g)－CR1((CH2)p NH2)C(O)－Het, 또는 h)－(CH2)n－R7이고;R6은 a)수소, b)히드록시, c)C1－C5알킬, d)C3－C7시클로알킬, e)아릴, f)Het, g)C1－C3알콕시, 또는 h)C1－C3알킬티오이고;R7은 a)히드록시, b)아미노, c)－CO2H, d)－SO3H, e)－SO2NH2, f)구아디닐, 또는 g)플리히드록시－치환－알킬 부분이며, 각각의 발생의 경우 정의된 변수 모두가 독립적으로 가변하고, 단, l)E10－F11이 L11일때, G12및 H13모두는 부재하고, 2)X1이 H2N－, H2NC(CH3)2－ 또는 HO2C－ 일때 E10－F11은 L11이 아니다.
- 제3항에 있어서, A6은 일반식 L1(이때, X1은 (H2N) (HO2C)CH－이고, n은 2이다)의 일가 부분이고; B7은 부재하거나, Pro 또는 그의 유도체이고; C8은 Phe, (OCH3)Tyr 또는 그의 유도체이고; D9는 N－MeHis, His β－Asp 또는 그의 유도체이고; E10－F11은 LVA, CVA, CVG 또는 그의 유도체이고; G12는 부재하거나, Ile 또는 그의 유도체이고; H13은 AMP, AMP－NO, MBA 또는 NH(CH2)4CH(NH2)(COOH)인 펩티드.
- 제4항에 있어서, 하기로 구성되는 군으로 부터 선택된 펩티드;γ－Glu－Pro－Phe－N－MeHis－LVA－Ile－AMP 또는 L－ 히스티딘아미드, L－γ－글로타밀－L－프롤릴－L－페닐알라닐－N－〔2－히드록시－5－메틸－1－(2－메틸 프로필)－4－〔〔〔2－메틸－1－〔〔(2－피리디닐메틸)아미노〕카르보닐〕부틸〕아미노〕카르보닐〕헥실〕－Nα－메틸,〔1S－〔1R*, 2R*, 4R* (1R*,2R*)〕〕－, 트리스(트리플루오로아세테이트)(염);γ－Glu－Pro－Phe－N－MeHis－LVA－Ile－AMP－NO 또는 L－ 히스티딘아미드, L－γ－글루타밀－L－프롤릴－L－페닐알라닐－N－〔2－히드록시－5－메틸－1－(2－메틸프로필)－4－〔〔2－메틸－1－〔〔(2－피리디닐메틸)아미노〕카르보닐〕부틸〕아미노〕카르보닐〕헥실〕－Na－메틸, N－산화물〔1S－〔1R*, 2R*, 4R*(1R*,2R*)〕〕－, 트리스(트리플루오로아세테이트)(염); γ－Glu－Pro－Phe－N－MeHis－CVG 또는 L－히스티딘아미드, L－γ－글루타밀－L－프롤릴－L－페닐알라닐－N－〔1－시클로헥실메틸)－2,3－디히드록시－5－메틸헥실〕－Na－메틸－〔1S－(1R*, 2R*, 3R*)비스(트리플루오로아세테이트)(염); γ－Glu－Pro－(OCH3)Tyr－His－CVG 또는 L－히스티딘아미드, L－γ－글루타밀－L－프롤릴－0－메틸－L－티로실－N－〔1－시클로헥실메틸)－2,3－디히드록시－5－메틸헥실〕〔1R*, 2R*, 3R*〕－비스(트리플루오로아세테이트)(염); γ－Glu－Pro－Phe－N－MeHis－LVA－Ile－NH(CH2)4CH(COOH)(NH2) 또는 L－리신, N6－〔5－〔〔N－〔N－(1－D－γ－글루타밀－L－프롤릴)－L－페닐알라닐〕－N－메틸－L－히스티닐〕아미노〕－4－히드록시－7－메틸－2－(1－메틸에틸)－1－옥소옥틸〕－L－이소류실〕－〔2S－(2R*, 4R*, 5R*)〕－트리스(트리플루오로아세테이트)(염); γ－Glu－Pro－Phe－N－MeHis－CVA－Ile－NH(CH2)4CH(COOH)(NH2) 또는 L－리신, N6－〔N－〔6－시클로헥실－5－〔〔N－－(1－L－γ－글루타밀－L－프롤릴)－L－페닐알라닐)－N－메틸－L－히스티닐〕아미노〕－4－히드록시－2－(1－메틸에틸)－1－옥소헥실〕－L－이소류실〕－〔2S－(2R*, 4R*, 5R*)〕－, 트리스(트리플루오로아세테이트)(염);γ－Glu－Pro－Phe－N－MeHis－CVA－Ile－NH(CH2)4CH(COOH)(NH2) 또는 L－히스티딘아미드, L－γ－글루타밀－L－프롤릴－L－페닐알라닐－N－〔4－〔〔(5－아미노－5－카르목시펜틸)아미노〕카르보닐〕－1(시클로헥실 메틸)－2－히드록시－5－메틸헥실〕－N α－메틸－, 〔1S－(1R*, 2R*, 4R*(R*)〕〕－, 트리스(트리플루오로아세테이트)(염);γ－Glu－Pro－Phe－N－MeHis－CVA－MBA 또는 L－히스티딘아미드, L－γ－글루타밀－L－프롤릴－L－페닐알라닐－N－시클로헥실메틸－2－디히드록시－5－메틸－4－〔〔(2－메틸부틸)아미노〕카르보닐〕헥실〕Nα－메틸,〔1S－(1R*, 2R*, 4R*－(R*)〕〕－, 비스(트리플루오로아세테이트)(염);γ－Glu－Pro－Phe－N－MeHis－CVA－AMP 또는 L－히스티딘아미드, L－γ－글루타밀－L－프롤릴－L－페닐알라닐－N－〔1－(시클로헥실 메틸)－2－히드록시－5－메틸－4－〔〔〔(2－메틸－1－〔〔(2－피리디니리메틸)아미노〕카르보닐〕부틸〕－아미노〕헥실〕－N－메틸, 〔1S－(1R*, 2R*, 4R*(1R*,2R*)〕－, 트리스(트리플루오로아세테이트)(염);γ－Glu－Pro－Phe－N－MeHis－CVA－Ile－MBA－NO 또는 L－히스티딘아미드, L－γ－글루타밀－L－프롤릴－L－페닐알라닐－N－〔1－(시클로헥실메틸)－2－디히드록시－5－메틸－4－〔〔〔(2－메틸－1－〔〔(2－피리디니리메틸)아미노〕카르보닐〕부틸〕－아미노〕카르보닐〕헥실〕－N α－메틸, N－산화물, 〔1S－(1R*, 2R*, 4R*(1R*,2R*)〕－,트리스(트리플루오로아세테이트)(염);γ－Glu－Pro－Phe－N－MeHis－LVA－AMP－MBA 또는 L－히스티딘아미드, L－γ－글루타밀－L－프롤릴－L－페닐알라닐－N－〔2－히드록시－5－메틸－4－〔〔(2－메틸부틸)－아미노〕카르보닐〕－1－(2－메틸 프로필)헥실〕－N－메틸,〔1S－(1R*, 2R*, 4R*－(R*)〕〕－, 비스(트리플루오로아세테이트)(염);γ－Glu－Phe－－Asp－LVA－MBA 또는 L－아스파라진, N2－(N－L－γ－글루타밀－L－페닐알라닐)－N－〔2－히드록시－5－메틸－4－〔〔(2－메틸부틸)아미노〕카르보닐〕－1－(2－메킬프로필)헥실〕, 〔1S－(1R*, 2R*, 4R*－(R*)〕〕－, 비스(트리플루오로아세테이트)(염);γ－Glu－Phe－N－MeHis－LVA－Ile－AMP또는 L－히스티딘아미드,L－γ－글루타밀－L－페닐알라닐－N－〔2－히드록시－5－메틸－1－(2－메틸프로필)－4－〔〔〔(2－메틸〕－〔〔(2－피리디닐메틸)아미노〕카르보닐〕부틸〕아미노〕카르보닐〕헥실〕－Nα－메틸, 〔1S－(1R*, 2R*, 4R*(1R*,2R*)〕－,트리스(트리플루오로아세테이트)(염);－Glu－Phe－N－MeHis－LVA－MBA 또는 L－히스티딘아미드, L－γ－글루타밀－L－페닐알라닐－N－〔2－히드록시－5－메틸－4－〔〔〔(2－메틸부틸)아미노〕카르보닐〕－1－(2－메틸프로필)헥실〕－Nα－메틸,〔1S－(1R*, 2R*, 4R*(R*)〕〕－, 비스(트리플루오로아세테이트)(염);γ－Glu－Phe－N－MeHis－CVA－MBA또는 L－히스티딘아미드,L－γ－글루타밀－L－페닐알라닐－N－〔1(시클로헥실메틸)－2－히드록시－5－메틸－4－〔〔(2－메틸부틸)아미노〕카르보닐〕헥실〕－Nα－메틸, 〔1S－(1R*, 2R*, 4R*(R*)〕〕－, 비스(트리플루오로아세테이트)(염);γ－Glu－Phe－N－MeHis－LVA－AMP－NO 또는 L－히스티딘아미드, L－γ－글루타밀－L－프롤릴－L－페닐알라닐－N－〔2－히드록시－5－메틸－1－(2－메틸프로필)－4－〔〔(2－메틸－1－〔〔(2－피리디닐메틸)아미노〕카르보닐〕－2－메틸부틸)아미노〕－카르보닐〕헥실〕－N－메틸, N－산화물, 〔1S－(1R*, 2R*, 4R*(1R*,2R*)〕〕－,트리스(트리플루오로아세테이트)(염); 또는γ－Glu－Phe－N－MeHis－CVA－Ile－AMP－NO 또는 L－히스티딘아미드, L－γ－글루타밀－L－페닐알라닐－N－〔1－(시클로헥실메틸)－2－히드록시－5－메틸－4－〔〔(2－부틸－1－〔〔(2－피리디닐메틸)아미노〕카르보닐〕부틸)아미노－카르보닐〕헥실〕－N－메틸, N－산화물, 〕－〔1S－(1R*, 2R*, 4R*(1R*,2R*)〕〕－,트리스(트리플루오로아세테이트)(염);
- 제3항에 있어서, A6은 일반식 L1(이때, X1은 H2NC(CH3)2－이고, n은 1이다)의 일가부분이고; C7은 부재하고; C8은 Phe 또는 그의 유도체이고; D9는 N－MeHis, β－Asp 또는 그의 유도체이고; E10－F11은 LVA, CVA, 또는 그의 유도체이고; C12는 부재하거나, Ile 또는 그의 유도체이고; H13은 AMP, AMP－NO, MBA NH(CH2)4CH(NH2)(COOH), Ampip 또는 NH－CH((CH2)4(NH2)C(O)－Ampip 인 펩티드.
- 제6항에 있어서, 하기로 구성되는 군으로 부터 선택된 펩티드:β－Val－Phe－N－MeHis－LVA－Ile－AMP－NO 또는 L－히스티딘아미드, N－(3－아미노－3－메틸－1－옥소부틸)－L－페닐알라닐－N－2－히드록시－5－메틸－1－(2－메틸프로필)－4－〔〔〔2－메틸－1－〔〔(2－피리디닐메틸)아니모〕카르보닐〕－부틸〕아미노〕카르보닐〕헥실〕－N α－메틸, N－산화물, 〔1S－(1R*, 2R*, 4R*(1R*,2R*)〕〕－비스(트리플루오로아세테이트)(염);β－Val－Phe－N－MeHis－CAV－Ile－AMP 또는 L－히스티딘아미드, N－(3－아미노－3－메틸－1－옥소부틸)－L－페닐알라닐－N－〔1－(시클로헥실메틸)－2－히드록시－5－메틸－4－〔〔2－메틸부틸)아미노〕카르보닐〕헥실〕－－N α－메틸,〔1S－(1R*, 2R*, 4R*(R*)〕〕－,비스(트리플루오로아세테이트)(염);β－Val－Phe－N－MeHis－CAV－Ile－AMP 또는 L－히스티딘아미드, N－(3－아미노－3－메틸－1－옥소부틸)－L－페닐알라닐－N－〔1－(시클로헥실메틸)－2－히드록시－5－메틸－4－〔〔〔2－메틸－1－〔〔(2－피리디닐메틸)아미노〕카르보닐〕－부틸〕아미노〕카르보닐〕헥실〕－N α－메틸, N－산화물, 〔1S－(1R*, 2R*, 4R*(1R*,2R*)〕〕－트리스(트리플루오로아세테이트)(염);－Val－Phe－N－MeHis－CVA－Ile－AMP－NO 또는 L－히스티딘아미드, N－(3－아미노－3－메틸－1－옥소부틸)－L－페닐알라닐－N－〔1－(시클로헥실메틸)－2－히드록시－5－메틸－4－〔〔〔2－메틸－1－〔〔(2－피리디닐메틸)아미노〕카르보닐〕－부틸〕아미노〕카르보닐〕헥실〕－N α－메틸, 〔1S－(1R*, 2R*, 4R*(1R*,2R*)〕〕－트리스(트리플루오로아세테이트)(염);β－Val－Phe－－Asp－LVA－MBA 또는 L－아스파라진, N2－〔N－(3－아미노－3－메틸－1－옥소부틸)－L－페닐알라닐－N－〔2－히드록시－5－메틸－4－〔〔(2－메틸부틸〕아미노〕카르보닐〕－1－(2－메틸프로필)헥실〕－〔1S－(1R*,2R*, 4R*(R*)〕〕－모노(트리플루오로아세테이트)(염);β－Val－Phe－β－Asp－LVA－Ile－AMP 또는 L－아스파라진, N2－〔N－(3－아미노－3－메틸－1－옥소부틸)－L－페닐알라닐－N－〔2－히드록시－5－메틸－1－(2－메틸프로필)4－〔〔〔2－메틸－1－〔〔(2－피리디닐메틸)아미노〕카르보닐〕부틸〕아미노〕카르보닐〕헥실〕－,〔1S－(1R*, 2R*, 4R*(1R*,2R*)〕〕－비스(트리플루오로아세테이트)(염);－Val－Phe－N－MeHis－LVA－MBA 또는 L－히스티딘아미드, N－(3－아미노－3－메틸－1－옥소부틸)－L－페닐알라닐－N－〔2－히드록시－5－메틸－4－〔〔(2－메틸부메틸)아미노〕카르보닐〕－1－(2－메틸프로필)헥실〕－N α－메틸,〔1S－(1R*,2R*, 4R*(R*)〕〕－비스(트리플루오로아세테이트)(염);β－Val－Phe－N－MeHis－LVA－Ile－AMP 또는 L－히스티딘아미드, N－(3－아미노－3－메틸－1－옥소부틸)－L－페닐알라닐－N－〔2－히드록시－5－메틸－1－(2－메틸프로필)－4－〔〔〔2－메틸－1－〔〔(2－피리디닐메틸)아미노〕카르보닐〕부틸〕아미노〕카르보닐〕헥실〕－N α－메틸,〔1S－(1R*, 2R*, 4R*(1R*,2R*)〕〕－트리스(트리플루오로아세테이트)(염);β－Val－Phe－NC(CH3)His－LVA－Ile－NC(CH2)4CH(COOH)(NH2) 또는 L－리신, N6－〔N－〔5－〔〔N－〔N－(3－아미노－3－메틸－1－옥소부틸)－L－페닐알라닐〕－N－메틸－L－히스티딜〕아미노〕－4－히드록시－7－메틸－2－(1－메틸에틸)－1－옥소부틸〕－L－이소류실〕－,〔2S－〔2R*, 4R*, 5R*)〕－트리스(트리플루오로아세테이트)(염);β－Val－Phe－NC(CH3)His－CVA－Ile－NC(CH2)4CH(COOH)(NH2) 또는 L－리신, N6－〔N－〔5－〔〔N－〔N－(3－아미노－3－메틸－1－옥소부틸)－L－페닐알라닐〕－N－메틸－L－히스티딜〕아미노〕－6－4－히드록시－2－(1－메틸에틸)－1－옥소부틸〕－L－이소류실〕－,〔2S－〔2R*, 4R*, 5R*)〕－트리스(트리플루오로아세테이트)(염);β－Val－Phe－NC(CH3)His－CVA－Ile－NC(CH2)4CH(COOH)(NH2) 또는 L－히스티딘아미드, N－(3－아미노－3－메틸－1－옥소부틸)－L－페닐알라닐〕－N－메틸－〔4－〔〔(5－아미노－5－카르복시펜틸)아미노〕카르보닐〕－1－(시클로헥실메틸)－2－히드록시－5－메틸헥신〕－Nα－,〔1S－(1R*,2R*,(1R*)〕〕－트리스(트리플루오로아세테이트)(염);－Val－Phe－NC(CH3)His－LVA－Ile－AmPip 또는 L－히스티딘아미드,N－(3－아미노－3－메틸－1－옥소부틸)－L－페닐알라닐－N－〔2－히드록시－5－메틸－1－(2－메틸프로필)－〔4－〔〔〔2－메틸－1－〔〔(4－피페리딜메틸)아미노〕카르보닐〕부틸〕아미노〕카르보닐〕헥실〕－N α－메틸, 〔1S－〔1R*, 2R*, 4R*(1R*,2R*)〕〕－, 트리스(트리플루오로아세테이트)(염); β－Val－Phe－NC(CH3)His－LVA－NH－CH((CH2)4)C(O)－AmPip 또는 L－히스티딘아미드,N－(3－아미노－3－메틸－1－옥소부틸)－L－페닐알라닐－N－〔2－히드록시－5－메틸－1－(4－아미노부틸)－4－〔〔〔2－메틸－1－〔〔(4－피페리딜메틸)아미노〕카르보닐〕부틸〕아미노〕카르보닐〕헥실〕－N α－메틸, 〔1S－〔1R*, 2R*, 4R*(1R*,2R*)〕〕－, 테트라비스(트리플루오로아세테이트)(염);
- 제3항에 있어서, A6은 일반식 L1(이때, X1은 (HO)2P(O,O－이고, n은 1 또는 3이다)의 일가부분이고; C7은 부재하거나; Pro 또는 그의 유도체이고; C8은 Phe, 또는 그의 유도체이고; D9는 β－Asp, N－MeHis 또는 그의 유도체이고; E10－F11은 LVA, CVG 또는 그의 유도체이고; G12는 부재하거나, Ile 또는 그의 유도체이고; H13은 부재하거나 AMP, AMP－NO 또는 MBA인 펩티드.
- 제8항에 있어서, 하기로 구성되는 군으로 부터 선택된 펩티드;(HO)2P(O)OCH2C(O)－Phe－β－Asp－LVA－Ile－AMP 또는 L－아스파라진, N－〔2－히드록시－5－메틸－1－(2－메틸프로필)－4－〔〔〔2－메틸－1〔〔2－피리디닐메틸)아미노〕카르보닐〕부틸〕아미노〕카르보닐〕헥실－N2－〔N－〔(포스포녹시)아세틸〕－L－페닐알라닐〕－, 모노히드로클로라이드, 〔1S－(1R*, 2R*, 4R*－(1R*,2R*)〕〕－;(HO)2P(O)OCH2C(O)－Phe－N－MeHis－LVA－Ile－AMP 또는 L－히스티딘아미드, N－〔(포스포노옥시)아세틸〕－L－페닐아라닐－N－〔2－히드록시－5－메틸－1－(2－메틸프로필)－4－〔〔〔2－메틸－1〔〔2－피리디닐메틸)아미노〕카르보닐〕부틸〕아미노〕카르보닐〕헥실－N α－메틸－, 디히드로클로로라이드〔1S－(1R*,2R*,4R*－(1R*,2R*)〕〕－;(HO)2P(O)OCH2C(O)－Pro－Phe－N－MeHis－LVA－Ile－AMP 또는 L－히스티딘아미드, N－〔N－1－〔(포스포노옥시)아세틸〕－N－프롤릴〕－L－페닐알라닐－N－〔2－히드록시－5－메틸－1－(2－메틸프로필)－4－〔〔〔2－메틸－1〔〔2－피리디닐메틸)아미노〕카르보닐〕부틸〕아미노〕카르보닐〕헥실－Nα－메틸－,디히드로클로로라이드〔1S－(1R*,2R*,4R*－(1R*,2R*)〕〕－;(HO)2P(O)OCH2C(O)－Pro－Phe－N－MeHis－LVA－Ile－AMP－NO 또는 L－히스티딘아미노, 1－〔(포스포노옥시)아세틸〕－N－프롤릴〕－L－페닐알라닐－N－〔2－히드록시－5－메틸－1－(2－메틸프로필)－4－〔〔〔2－메틸－1〔〔2－피리디닐메틸)아미노〕카르보닐〕부틸〕아미노〕카르보닐〕헥실－Nα－메틸, N－산화물, 디히드로클로라이드 〔1S－(1R*,2R*,4R*－(1R*,2R*)〕〕－;(HO)2P(O)OCH2C(O)－Pro－Phe－N－MeHis－LVA－Ile－AMP－NO 또는 L－히스티딘아미노, N－〔(1－〔1－옥소－4－(포스포노옥시)부틸〕－3－피롤리디닐〕카르보닐〕－L－페닐알라닐－N－〔2－히드록시－5－메틸－1－(2－메틸프로필)－4－〔〔〔2－메틸－1〔〔2－2－피리디닐메틸)아미노〕카르보닐〕부틸〕아미노〕카르보닐〕헥실－Nα－메틸,디히드로클로라이드〔1S－(1R*,(SR*),2R*,4R*(1R*)〕〕－(HO)2P(O)OCH2C(O)－Pro－Phe－N－MeHis－LVA－Ile－AMP 또는 L－히스티딘아미드 N－〔(1－〔1－옥소－4－(포스포노옥시)부틸〕－3－피롤리디닐〕카르보닐〕－L－페닐알라닐－N－〔2－히드록시－5－메틸－1－(2－메틸프로필)－4－〔〔〔2－메틸－1〔〔2－2－피리디닐메틸)아미노〕－카르보닐〕부틸〕아미노〕카르보닐〕헥실－N－메틸,N－산화물,모노히드로클로라이드,〔1S－(1R*,－(SR*),2R*,4R*(1R*2R*)〕〕－;또는(HO)2P(O)OCH2C(O)－Pro－Phe－N－MeHis－CVG 또는 L－히스티딘아미노, 1－〔(포스포노옥시)아세틸〕－L－프롤릴－L－페닐알라닐－N－〔1－(시클로헥실메틸)－2,3－디히드록시－5－메틸헥실〕－N－메틸－,모노히드로클로로라이드,〔1S－〔1R*,2S*,3R*)〕－※ 참고사항 : 최초출원 내용에 의하여 공개되는 것임.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US33975089A | 1989-04-18 | 1989-04-18 | |
| US07/339750 | 1989-04-18 | ||
| PCT/US1990/001764 WO1990012804A2 (en) | 1989-04-18 | 1990-04-05 | Peptides having novel polar n-terminal groups |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR920700221A true KR920700221A (ko) | 1992-02-19 |
Family
ID=23330419
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1019900702636A Withdrawn KR920700221A (ko) | 1989-04-18 | 1990-04-05 | 극성 n-말단기들을 갖는 신규 리닌 억제인자 펩티드 |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP0468998A1 (ko) |
| JP (1) | JPH04504716A (ko) |
| KR (1) | KR920700221A (ko) |
| AU (1) | AU5407190A (ko) |
| WO (1) | WO1990012804A2 (ko) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5554728A (en) * | 1991-07-23 | 1996-09-10 | Nexstar Pharmaceuticals, Inc. | Lipid conjugates of therapeutic peptides and protease inhibitors |
| DE4126485A1 (de) * | 1991-08-10 | 1993-02-11 | Bayer Ag | Trifluormethyl-haltige pseudopeptide |
| WO1993006127A1 (en) * | 1991-09-17 | 1993-04-01 | Warner-Lambert Company | Novel amino acid prodrug renin inhibitors |
| BR9306058A (pt) * | 1992-03-11 | 1997-11-18 | Narhex Ltd | Derivados de amina de hidrocarbonetos oxo- e hidroxi- substituidos |
| DE69333270T2 (de) | 1992-03-11 | 2004-08-05 | Narhex Ltd. | Aminderivate von oxo- und hydroxy- substituierten kohlenwasserstoffen |
| US5888992A (en) * | 1992-03-11 | 1999-03-30 | Narhex Limited | Polar substituted hydrocarbons |
| US6071895A (en) * | 1992-03-11 | 2000-06-06 | Narhex Limited | Polar-substituted hydrocarbons |
| AU3748393A (en) * | 1992-03-25 | 1993-10-21 | Pfizer Inc. | Antiviral peptides |
| DE4215874A1 (de) * | 1992-05-14 | 1993-11-18 | Bayer Ag | Dithiolanylglycinhaltige HIV-Proteaseinhibitoren vom Hydroxyethylenisostertyp |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0104041B1 (en) * | 1982-09-15 | 1988-07-27 | Aktiebolaget Hässle | Enzyme inhibitors |
| DE3830825A1 (de) * | 1987-09-15 | 1989-03-23 | Sandoz Ag | Hydrophile reninhemmer, ihre herstellung und verwendung |
| EP0312157A3 (en) * | 1987-10-13 | 1990-07-25 | Merck & Co. Inc. | Tetrapeptide renin inhibitors having a novel c-terminal amino acid |
-
1990
- 1990-04-05 JP JP2505724A patent/JPH04504716A/ja active Pending
- 1990-04-05 WO PCT/US1990/001764 patent/WO1990012804A2/en not_active Application Discontinuation
- 1990-04-05 KR KR1019900702636A patent/KR920700221A/ko not_active Withdrawn
- 1990-04-05 AU AU54071/90A patent/AU5407190A/en not_active Abandoned
- 1990-04-05 EP EP90905979A patent/EP0468998A1/en not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| JPH04504716A (ja) | 1992-08-20 |
| EP0468998A1 (en) | 1992-02-05 |
| WO1990012804A3 (en) | 1990-11-29 |
| WO1990012804A2 (en) | 1990-11-01 |
| AU5407190A (en) | 1990-11-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US5496805A (en) | Inhibitors of neutral endopeptidase | |
| CA1271596A (en) | Hypotensive peptides, their preparation and their use | |
| ES2272763T3 (es) | Derivados de dolastatina 10. | |
| KR920700221A (ko) | 극성 n-말단기들을 갖는 신규 리닌 억제인자 펩티드 | |
| EP0231919B1 (en) | N-heterocyclic alcohol renin inhibitors | |
| CA2146059A1 (en) | Imidazole-containing inhibitors of farnesyl protein transferase | |
| AU715765B2 (en) | Serine protease inhibitors | |
| Roderick et al. | Thiorphan and retro-thiorphan display equivalent interactions when bound to crystalline thermolysin | |
| JPH03500772A (ja) | （１‐アミノ‐２‐ヒドロキシ‐２‐ヘテロサイクリック）エチル基を含有するレニン抑制物質類 | |
| KR19990022395A (ko) | 가역성 시스테인 프로테아제 억제제 | |
| KR910004661A (ko) | Lhrh 동족체 | |
| WO1997008193A1 (en) | Acylated oligopeptide derivatives having cell signal inhibiting activity | |
| KR910006224A (ko) | 아미노산 유도체 | |
| KR880000103A (ko) | 중성 메탈로엔도펩티다제 억제제 | |
| KR890005148A (ko) | N-아실아미노산 유도체 및 그의 용도 | |
| NO20000231L (no) | Dolastatin-15-derivater | |
| KR890006572A (ko) | 아미노산 유도체 | |
| US20060160749A1 (en) | Tripeptide and tetrapeptide thioethers | |
| US6265382B1 (en) | Dipeptide inhibitors of protein farnesyltransferase | |
| WO1997007131A1 (en) | Acylated oligopeptides containing phosphotyrosine as inhibitors of protein tyrosine kinases | |
| US6307090B1 (en) | Acylated oligopeptide derivatives having cell signal inhibiting activity | |
| KR950701935A (ko) | 항혈소판제로서의 입체배좌적으로 억제된 펩타이드 동족체(Conformationally restrained peptide analogs as antiplatelet agents) | |
| Dean | Structure, function and subcellular localization of a human platelet Ca2+-ATPase | |
| ES2141849T3 (es) | Composicion transdermica de n-(n-(5-(4-(aminoiminometil)fenil)-1-oxopentil)-l-alfa-aspartil)-l-fenilalanina o sus esteres y sus sales farmaceuticamente aceptables. | |
| GB2123834A (en) | Substituted peptide compounds |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0109 | Patent application |
Patent event code: PA01091R01D Comment text: Patent Application Patent event date: 19901218 |
|
| PG1501 | Laying open of application | ||
| PC1202 | Submission of document of withdrawal before decision of registration |
Comment text: [Withdrawal of Procedure relating to Patent, etc.] Withdrawal (Abandonment) Patent event code: PC12021R01D Patent event date: 19921116 |
|
| WITB | Written withdrawal of application |