FI89058B - Foerfarande foer framstaellning av som remin-inhibitorer anvaenda 2-(l-alanyl-l-histidylamino)-butanol-derivat - Google Patents

Foerfarande foer framstaellning av som remin-inhibitorer anvaenda 2-(l-alanyl-l-histidylamino)-butanol-derivat Download PDF

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Publication number
FI89058B
FI89058B FI880734A FI880734A FI89058B FI 89058 B FI89058 B FI 89058B FI 880734 A FI880734 A FI 880734A FI 880734 A FI880734 A FI 880734A FI 89058 B FI89058 B FI 89058B
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FI
Finland
Prior art keywords
cyclohexyl
amino
conh
histidyl
naphthylmethyl
Prior art date
Application number
FI880734A
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English (en)
Finnish (fi)
Other versions
FI89058C (sv
FI880734A (fi
FI880734A0 (fi
Inventor
Kohji Nakano
Takashi Fujikura
Ryuichiro Hara
Masato Ichihara
Yukiko Fukunaga
Masayuki Shibasaki
Original Assignee
Yamanouchi Pharma Co Ltd
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Application filed by Yamanouchi Pharma Co Ltd filed Critical Yamanouchi Pharma Co Ltd
Publication of FI880734A0 publication Critical patent/FI880734A0/fi
Publication of FI880734A publication Critical patent/FI880734A/fi
Application granted granted Critical
Publication of FI89058B publication Critical patent/FI89058B/fi
Publication of FI89058C publication Critical patent/FI89058C/sv

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    • 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
    • C07D233/64—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 substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • 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
    • 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
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • C07K5/06078—Dipeptides with the first amino acid being neutral and aromatic or cycloaliphatic
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S530/00—Chemistry: natural resins or derivatives; peptides or proteins; lignins or reaction products thereof
    • Y10S530/86—Renin inhibitors

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)

Claims (4)

1. Förfarande för framställning av som renin-inhibitorer använda 2-(L-alanyl-L-histidylamino)-butanol-derivat med formeln I CH2R2 CH2-R3 (I) r1-ch-conh-ch-con-ch-ch-r4 OH Rs där R^ är ^yo-(CH2)n- (n = 1 eller 2); halogen —/ ^N-CO-(CH2)n- (n = 1 eller 2); <^r^~(CH2)n- (n = 1 eller 2); 4. rakkedjad eller förgrenad C^-Cg alkoxikarbonylamino; 5) (CH2)n- 6. rakkedjad eller förgrenad C^-Cg alkoxikarbonyl; 7) -CONH- rakkedjad eller förgrenad C^-Cg alkylen-OH; 74 89058
8. I-1 I -H-CO-(CH2)n- (n = 1 eller 2); 9) O N-NHCO-; v_y 10. rakkedjad eller förgrenad C^-Cg alkylkarbonyl~(CH2)n-(n = 1 eller 2); 11. f~°\ V (CH2)n- (n = 1 eller 2); — 0 / 12) /~~°\ (CH2)n- (n = 1 eller 2); CO-(CH2)n- (n = 1 eller 2); ·- 14) N -pi (CH2)_- (n = 1 eller 2); ,,λΤ
15. C^-Cg alkyny1 -(CH2)n- (n = 1 eller 2);
16. NC-(CH2)n- (n = 1 eller 2);
17. C3-C7 cykloalkyl-CO-(CH2)n- (n = 1 eller 2); . 1B) / \ J-CO-(CH2)n- (n = 1 eller 2); “ Q. (CH2)n-NHC°- (n = 1 eller 2); 75 89058 20. r—-. NHCO- \_J
21. C3-C7 cykloalkyliden-C^-Cg alkynyl;
22. C3-C7 cykloalkyl-C^-Cg alkylen, som kan vara substituerad med hydroxi; eller 23) O V— C^-Cg alkylen, som kan vara substituerad \-/ med hydroxi ; R2 är 1. feny1; eller 2. naftyl R3 är 1. rakkedjad eller förgrenad C^-Cg alkyl; 2. cyklohexyl; eller 3. fenyl ; R4 är t V 1) nitrometyl; * # » 2) -COORc (Rc är rakkedjad eller förgrenad C^-Cg alkyl); 76 89058 3) -(CH2)-S-Rd (0)n (n = 0, 1 eller 2); är tetrazolyl, soin kan vara substituerad med en lägre alkyl, karbamoyl-lägre alkyl, eller avser en heterosyklisk grupp a) b) N—π -4J- -4J— Cj^-Cg alkyl; σ) N N * -’H" -4)—C^-Cg d) V~T Ci-Cg alkyl; ·’ t) As—
9. N^j ; el 1 er h) -N -v 77 89058 R5 är 1. väte; eller 2. ci_c6 alkyl , kännetecknat därav, att a) en förening med formeln II j-NH ck2A„^ CHoRo (II) R1-CH-CONH-CH-COOH där Rl och R2 är ovan definierade, omsätts med en förening eller dess C-terminalt aktiva ester, med formeln III CHoR-s NH-CH-CH-R4 (III) I I r5 oh där R3, R4 och R5 är ovan definierade, b) en förening med formeln IV CH2R2 I (IV) Rj^-CH-COOH • där Ri ja R2 är ovan definierade, omsätts med en föreningen eller dess C-terminalt aktiva ester, med formeln V 78 89058 j- NH ΟΗ2Λν^ ch2-r3 (V) H2N-CH-CON-Ah-CH-R4 I I r5 oh där R3, R4 och R5 är ovan definierade, c) en förening med formeln VI j NH ch2-An^ ch2r2 ch2-r3 (VI) R-ι -Ah-CONH-CH-CON-Ah-CH-CH R5 0 där R·^, r2, R3 och R5 är ovan definierade, omsätts med en förening med formeln VII Rd-SM (VII) där Rd är ovan definierad och M är väte eller en alkalimetallatom och varvid ur en enligt ovan nämnda förfaranden erhällen förening vid behov avlägsnas skyddsgruppen.
2. Förfarande enligt patentkravet 1, kännetecknat . ; därav, att (2RS,3S)-3-[N-[2-(1-naftylmetyl)-3-(morfolinokar-bonyl)propionyl]-L-histidyl]-amino-2-hydroxi-4-cyklohexyl-voisyra-isopropyl ester framstälIs. 79 89058
3. Förfarande enligt patentkravet 1, kännetecknat därav, att (2RS,3S)-3-[N-[2-(1,4-dioxo-4-morfolino-2-(1-naf-tylmetyl)-3-( butyl)-L-histidyl amino)]-4-cyklohexyl-1-(1-metyl- 5-tetrazolyltio]-2-butanol framställs.
4. Förfarande enligt patentkravet 1, kännetecknat därav, att (2RS,3S)-3-[N-t-butoxikarbonyl-L-fenylalanyl-L-histidyl amino)-4-cyklohexyl-l-(1-metyl-5-tetrazolyltio]-2-butanol framställs. t i · < %
FI880734A 1987-02-27 1988-02-17 Förfarande för framställning av som remin-inhibitorer använda 2-(L-ala nyl-L-histidylamino)-butanol-derivat FI89058C (sv)

Applications Claiming Priority (8)

Application Number Priority Date Filing Date Title
JP4645487 1987-02-27
JP4645487 1987-02-27
JP11514487 1987-05-12
JP11514487 1987-05-12
JP20614687 1987-08-18
JP20614687 1987-08-18
JP28901787 1987-11-16
JP28901787 1987-11-16

Publications (4)

Publication Number Publication Date
FI880734A0 FI880734A0 (fi) 1988-02-17
FI880734A FI880734A (fi) 1988-08-28
FI89058B true FI89058B (fi) 1993-04-30
FI89058C FI89058C (sv) 1993-08-10

Family

ID=27461876

Family Applications (1)

Application Number Title Priority Date Filing Date
FI880734A FI89058C (sv) 1987-02-27 1988-02-17 Förfarande för framställning av som remin-inhibitorer använda 2-(L-ala nyl-L-histidylamino)-butanol-derivat

Country Status (6)

Country Link
US (1) US4904660A (sv)
EP (1) EP0281316A3 (sv)
AU (1) AU612626B2 (sv)
CA (1) CA1325497C (sv)
FI (1) FI89058C (sv)
NO (1) NO880851L (sv)

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FI870474A (fi) * 1986-02-07 1987-08-08 Ciba Geigy Ag Med svavelhaltiga grupper substituerade 5-amino-4-hydroxivalerylderivat.
EP0244083A3 (en) * 1986-04-01 1989-11-15 Kissei Pharmaceutical Co. Ltd. Amino acid derivatives
US4895834A (en) * 1986-12-15 1990-01-23 Warner-Lambert Company Renin inhibitors III
ATE107658T1 (de) * 1988-01-26 1994-07-15 Sankyo Co Renin inhibierende polypeptide, ihre herstellung und anwendung.
ZA897514B (en) * 1988-10-07 1990-06-27 Merrell Dow Pharma Novel peptidase inhibitors
US5736520A (en) * 1988-10-07 1998-04-07 Merrell Pharmaceuticals Inc. Peptidase inhibitors
CA2012306A1 (en) * 1989-03-28 1990-09-28 Werner Neidhart Amino acid derivatives
US5098924A (en) * 1989-09-15 1992-03-24 E. R. Squibb & Sons, Inc. Diol sulfonamide and sulfinyl renin inhibitors
EP0427939A3 (en) * 1989-10-11 1991-11-06 American Cyanamid Company Renin inhibitors
TW225540B (sv) * 1990-06-28 1994-06-21 Shionogi & Co
US6008372A (en) * 1996-01-16 1999-12-28 Warner-Lambert Company Substituted dinaphthylmethyl and diheteroarylmethylacetyl histidine inhibitors of protein farnesyltransferase

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS52111572A (en) * 1976-03-16 1977-09-19 Santen Pharmaceutical Co Ltd Nn*mercapto substituted acyl**hystidine
AU1643283A (en) * 1982-07-19 1984-01-26 E.R. Squibb & Sons, Inc. Substituted peptides
JPS61236770A (ja) * 1985-04-15 1986-10-22 Kissei Pharmaceut Co Ltd 新規なアミノ酸誘導体
EP0244083A3 (en) * 1986-04-01 1989-11-15 Kissei Pharmaceutical Co. Ltd. Amino acid derivatives
US4921855A (en) * 1987-06-22 1990-05-01 Fujisawa Pharmaceutical Co., Ltd. New Histidyl amino acid derivatives, and pharmaceutical composition comprising the same

Also Published As

Publication number Publication date
US4904660A (en) 1990-02-27
FI89058C (sv) 1993-08-10
AU612626B2 (en) 1991-07-18
NO880851D0 (no) 1988-02-26
AU1250288A (en) 1988-09-01
NO880851L (no) 1988-08-29
EP0281316A2 (en) 1988-09-07
EP0281316A3 (en) 1990-08-16
FI880734A (fi) 1988-08-28
FI880734A0 (fi) 1988-02-17
CA1325497C (en) 1993-12-21

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Owner name: YAMANOUCHI PHARMACEUTICAL CO., LTD.