GB1486578A - Process for preparing somatostatin and derivatives thereo - Google Patents

Process for preparing somatostatin and derivatives thereo

Info

Publication number
GB1486578A
GB1486578A GB52779/74A GB5277974A GB1486578A GB 1486578 A GB1486578 A GB 1486578A GB 52779/74 A GB52779/74 A GB 52779/74A GB 5277974 A GB5277974 A GB 5277974A GB 1486578 A GB1486578 A GB 1486578A
Authority
GB
United Kingdom
Prior art keywords
phe
boc
thr
lys
cys
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.)
Expired
Application number
GB52779/74A
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Wyeth Canada Inc
Original Assignee
Ayerst Mckenna and Harrison Inc
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
Priority claimed from US423352A external-priority patent/US3917578A/en
Priority claimed from US493595A external-priority patent/US3917581A/en
Application filed by Ayerst Mckenna and Harrison Inc filed Critical Ayerst Mckenna and Harrison Inc
Publication of GB1486578A publication Critical patent/GB1486578A/en
Expired legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/575—Hormones
    • C07K14/655—Somatostatins
    • C07K14/6555—Somatostatins at least 1 amino acid in D-form
    • 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
    • C07K5/10—Tetrapeptides
    • C07K5/1002—Tetrapeptides with the first amino acid being neutral
    • C07K5/1005—Tetrapeptides with the first amino acid being neutral and aliphatic
    • 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
    • C07K5/10—Tetrapeptides
    • C07K5/1019—Tetrapeptides with the first amino acid being basic
    • 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
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Molecular Biology (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Medicinal Chemistry (AREA)
  • Biophysics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biochemistry (AREA)
  • Endocrinology (AREA)
  • Toxicology (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

1486578 Somatostatin derivatives AYERST MCKENNA & HARRISON Ltd 6 Dec 1974 [10 Dec 1973 1 Aug 1974] 52779/74 Heading C3H [Also in Division C2] A process for the preparation of a peptide of formula or in which R<SP>1</SP> is H or NH 2 and R<SP>2</SP> is H or CO 2 H comprises treating a corresponding compound of formula or wherein R<SP>3</SP> is H or BOC-NH; R<SP>2</SP> is H or CO 2 H; α and # are either both hydrogen or independently represent Acm or Trt; γ,γ<SP>1</SP>,γ<SP>2</SP> are either all H or all But; to remove the protecting groups, and, optionally converting the compound to a pharmaceutically acceptable salt; wherein one of the Lys residues may be replaced by D-Lys. The preferred conditions to remove the protecting groups are anhydrous trifluoroacetic or 2-12N hydrochloric acid. Compound II may be obtained by removal of protecting groups α,# from II(a) (preferably with a mercuric or silver salt) followed by oxidation (preferably by hydrogen sulphide, iodine, oxygen, 1,2-diiodoethane or sodium or potassium ferricyanide), or by one-step conversion using iodine (preferably in a C 1-4 alkanol) or thiocyanogen. Compound (I) may be prepared by oxidation of compound (Ia). The peptides are claimed per se. Cyclic peptides prepared are Linear peptides prepared are: Boc - Ala - Gly - Cys(Acm) - Lys(Boc) - Asn- Phe - Phe - Trp - Lys(Boc) - Thr - Phe - Thr- Ser - Cys(Acm) - OH; Boc - Ala - Gly - Cys(Trt)- Lys(Boc) - Asn - Phe - Phe - Trp - Lys(Boc)- Thr - Phe - Thr - Ser - Cys(Trt) - OH; Boc - Ala- Gly - Cys(Acm) - Lys(Boc) - Asn - Phe - Phe- Trp - Lys(BOC) - Thr(But) - Phe - Thr(But)- Ser(But) - Cys(Acm - OH; Boc - Ala - Gly - Cys- (Trt) - Lys(Boc) - Asn - Phe - Phe - Trp - Lys- (Boc) - Thr(But) - Phe - Thr(But) - Ser(But)- Cys(Trt) - OH; H - Ala - Gly - Cys - Lys - Asn- Phe - Phe - Trp - Lys - Thr - Phe - Thr - Ser- Cys - OH; CH 3 CH 2 CO - Gly - Cys(Trt) - Lys- (Boc) - Asn - Phe - Phe - Trp - Lys(Boc) - Thr- (But) - Phe - Thr(But) - Ser(But) - Cys(Trt)- OH; Boc - Ala - Gly - Cys(Trt) - Lys(Boc) - Asn- Phe - Phe - Trp - Lys(Boc) - Thr(But) - Phe- Thr(But) - Ser(But) - NHCH 2 CH 2 S - Trt; CH 3 CH 2 CO - Gly - Cys(Trt) - Lys(Boc) - Asn- Phe - Phe - Trp - Lys(Boc) - Thr(But) - Phe- Thr(But) - Ser(But) - NHCH 2 CH 2 S - Trt; Boc- Ala - Gly - Cys(Trt) - D - Lys(Boc) - Asn - Phe- Phe - Trp - Lys(Boc) - Thr(But) - Phe - Thr- (But) - Ser(But) - Cys(Trt) - OH; Boc - Ala- Gly - Cys(Trt) - Lys(Boc) - Asn - Phe - Phe - DLys(Boc) - Thr(But) - Phe - Thr(But) - Ser(But)- Cys(Trt)-OH. Peptide intermediates isolated are: HEPTAPEPTIDES: Boc - Ala - Gly - Cys- (Acm) - Lys(Boc) - Asn - Phe - Phe - OCH3 and NHNH 2 ; Boc - Ala - Gly - Cys(Trt) - Lys(Boc)- Asn - Phe - Phe - OCH 3 and NHNH 2 ; H and Ddz - Trp - Lys(Boc) - Thr - Phe - Thr - Ser - Cys- (Acm) - OH; H and Ddz - Trp - Lys(Boc) - Thr- Phe - Thr - Ser - Cys(Trt) - OH; H and Ddz- Trp - Lys(Boc) - Thr(But) - Phe - Thr(But) - Ser- (But) - Cys(Acm) - OH; H and Ddz - Trp- Lys(Boc) - Thr(But) - Phe - Thr(But) - Ser(But)- Cys(Trt) - OH; Boc - Ala - Gly - Cys(Trt) - DLys(Boc) - Asn - Phe - Phe - OCH 3 and NHNH 2 ; H and Ddz - Trp - D - Lys(Boc) - Thr But)- Phe - Thr(But) - Ser(But) - Cys(Trt) - OH. HEXAPEPTIDES: Ddz - Trp - Lys(Boc) - Thr- Phe - Thr - Ser - OCH 3 and NHNH 2 ; Ddz- Trp - Lys(Boc) - Thr(But) - Phe - Thr(But) - Ser- (But) - OCH 3 and NHNH 2 ; CH 3 CH 2 CO - Gly- Cys(Trt) - Lys(Boc) - Asn - Phe - Phe - OCH 3 and NHNH 2 ; Ddz and H - Trp - Lys(Boc)- Thr(But) - Phe - Thr(But) - Ser(But) - NHCH 2 - CH 2 S - Trt; Ddz - Trp - D - Lys(Boc) - Thr(But)- Phe-Thr(But)-Ser(But)-OCH 3 and NHNH 2 . PENTAPEPTIDES: H and Chb - Cys(Acm)- Lys(Boc) - Asn - Phe - Phe - OCH 3 ; H and Trt- Cys(Trt) - Lys(Boc) - Asn - Phe - Phe - OCH 3 ; H and Z - Lys(Boc) - Thr - Phe - Thr - Ser - OCH 3 ; Z - Lys(Boc) - Thr(But) - Phe - Thr(But) - Ser- (But) - OCH 3 ; H and Trt - Cys(Trt) - D - Lys- (Boc) - Asn - Phe - Phe - OCH 3 ; Z - D - Lys(Boc)- Thr(But)-Phe-Thr(But)-Ser(But)-OCH 3 . TETRAPEPTIDES: Z and H - Lys(Boc)- Asn - Phe - Phe - OCH 3 ; Z and H - Thr - Phe- Thr - Ser - OCH 3 ; Z and H - Thr(But) - Phe- Thr(But) - Ser(But) - OCH 3 ; Z - D - Lys(Boc)- Phe-Phe-OCH 3 . TRIPEPTIDES: Boc and H - Asn - Phe - Phe- OCH 3 ; Z and H - Phe - Thr - Ser - OCH 3 ; z and H-Phe-Thr(But)-Ser(But)-OCH 3 . Dipeptide intermediates isolated are Boc-Ala- Gly-OCH 3 , OH and OTcp; Boc and H-Phe- Phe-OCH 3 ; Z and H-Thr-Ser-OCH 3 ; Z and H-Thr(But)-Ser(But)-OCH 3 . Pharmaceutical compositions comprise peptides I or Ia, optionally in unit dosage form, together with a pharmaceutically-acceptable carrier or diluent.
GB52779/74A 1973-12-10 1974-12-06 Process for preparing somatostatin and derivatives thereo Expired GB1486578A (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US423352A US3917578A (en) 1973-12-10 1973-12-10 Process for producing somatostatin and intermediates
US493595A US3917581A (en) 1974-08-01 1974-08-01 Derivatives of somatostatin and process therefor

Publications (1)

Publication Number Publication Date
GB1486578A true GB1486578A (en) 1977-09-21

Family

ID=27025966

Family Applications (3)

Application Number Title Priority Date Filing Date
GB52779/74A Expired GB1486578A (en) 1973-12-10 1974-12-06 Process for preparing somatostatin and derivatives thereo
GB50493/76A Expired GB1486579A (en) 1973-12-10 1974-12-06 Heptapeptides
GB50494/76A Expired GB1486580A (en) 1973-12-10 1974-12-06 Heptapeptides

Family Applications After (2)

Application Number Title Priority Date Filing Date
GB50493/76A Expired GB1486579A (en) 1973-12-10 1974-12-06 Heptapeptides
GB50494/76A Expired GB1486580A (en) 1973-12-10 1974-12-06 Heptapeptides

Country Status (10)

Country Link
JP (1) JPS5088064A (en)
CA (1) CA1034116A (en)
CH (1) CH605680A5 (en)
CS (1) CS191922B2 (en)
DE (1) DE2458135A1 (en)
FR (1) FR2253532A1 (en)
GB (3) GB1486578A (en)
IL (1) IL46065A (en)
NL (1) NL7415916A (en)
SE (1) SE7415414L (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5712417A (en) * 1989-09-28 1998-01-27 Abbott Laboratories Inhibitors of retroviral proteases

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5712417A (en) * 1989-09-28 1998-01-27 Abbott Laboratories Inhibitors of retroviral proteases

Also Published As

Publication number Publication date
CS191922B2 (en) 1979-07-31
DE2458135A1 (en) 1975-06-12
CH605680A5 (en) 1978-10-13
CA1034116A (en) 1978-07-04
NL7415916A (en) 1975-06-12
IL46065A (en) 1978-07-31
FR2253532A1 (en) 1975-07-04
GB1486580A (en) 1977-09-21
IL46065A0 (en) 1975-02-10
GB1486579A (en) 1977-09-21
JPS5088064A (en) 1975-07-15
SE7415414L (en) 1975-06-11

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Legal Events

Date Code Title Description
PS Patent sealed [section 19, patents act 1949]
476 Application for correction of clerical errors now open to opposition (sect. 76/1949)
PCNP Patent ceased through non-payment of renewal fee