WO1999033864A1 - Derives peptidiques - Google Patents

Derives peptidiques Download PDF

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Publication number
WO1999033864A1
WO1999033864A1 PCT/JP1998/005862 JP9805862W WO9933864A1 WO 1999033864 A1 WO1999033864 A1 WO 1999033864A1 JP 9805862 W JP9805862 W JP 9805862W WO 9933864 A1 WO9933864 A1 WO 9933864A1
Authority
WO
WIPO (PCT)
Prior art keywords
group
residue
alkyl group
compound
salt
Prior art date
Application number
PCT/JP1998/005862
Other languages
English (en)
Japanese (ja)
Inventor
Shinobu Sakurada
Masaki Hagiwara
Tetsuhisa Miyamae
Toru Okayama
Tadashi Ogawa
Tomomi Oya
Eriko Nukui
Masako Yagisawa
Original Assignee
Daiichi Pharmaceutical Co., Ltd.
Fuji Chemical Industries, Ltd.
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
Application filed by Daiichi Pharmaceutical Co., Ltd., Fuji Chemical Industries, Ltd. filed Critical Daiichi Pharmaceutical Co., Ltd.
Publication of WO1999033864A1 publication Critical patent/WO1999033864A1/fr

Links

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
    • C07K5/0202—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-X-X-C(=0)-, X being an optionally substituted carbon atom or a heteroatom, e.g. beta-amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Definitions

  • MS Contin increases to the gram unit, and it may be difficult to take it.In addition, it has to be discontinued due to the occurrence of side effects such as itch, which may be caused by histamine release. In some cases. Therefore, an orally administrable alternative drug that is safer and more effective than morphine is desired. Disclosure of the invention
  • R ri is an amino group, a mono C, _ 6 alkylamino group, - 6 Ashiruamino group, also Guanijino groups have a C IB ⁇ alkyl group, Bok Imino _ 6 alkyl group, C, _ fi al Kill also Urei de group have a group, C l 6 alkylthio group, C, _ 6 alkylsulfinyl Finiru group, C, alkylsulfonyl group, a C the IH Ashiru group, or Bokuhi Dorokishi C l ti alkyl group, n Represents an integer of 1-4) D- ⁇ -amino acid residue represented by:
  • alkoxy-substituted alkyl group examples include a methoxymethyl group, an ethoxymethyl group, a methoxethyl group, and an n -heptoxymethyl group.
  • alkoxy-substituted alkyl group examples include a methoxymethoxymethyl group, Examples include, but are not limited to, a toxetoxymethyl group.
  • the number of the amino groups substituted on the aminoalkyl group is preferably 1 or 2, particularly preferably 1.
  • the heterocyclic group represented by R 3 includes, for example, a 5- to 10-membered saturated ring containing one or more hetero atoms (eg, a nitrogen atom, an oxygen atom, a sulfur atom, etc.) as a ring-constituting atom. , Partially unsaturated, or aromatic heterocyclic groups can be used. When two or more heteroatoms are included, the types of the heteroatoms may be the same or different.
  • R 1 is a methyl group, AA ′ force; L-0-acetyltyrosine residue, force; D-methionine sulfoxide residue, AA 3 is L-phenylalanine residue A compound wherein A is a N-methyl--alanine residue and is a hydrogen atom;
  • R ' is a methyl group, ⁇ ' is a 2,6-dimethyl-di-tyrosine residue, AA ⁇ ; DN 5 -acetylorutin, AA : i is P-fluorophenyl A alanine residue, wherein AA 4 is an N-methyl- ⁇ -alanine residue and the force is-CH 2 CH 3
  • the peptide derivative of the present invention has an excellent analgesic effect and is useful as an active ingredient of a medicine, preferably an active ingredient of an analgesic.
  • the peptide derivative of the present invention has a relatively weak histamine releasing action and a lowering of heart rate associated with an analgesic action as compared with morphine, and has a low degree of cross-resistance with morphine, so that it is suitable for treating cancer pain. is expected.
  • all of the known analgesic peptide compounds have a problem that they cannot exert sufficient efficacy by oral administration, but the peptide derivatives of the present invention can exert an excellent analgesic effect by oral administration. It has characteristics and is expected to be as useful as MS Contin, a sustained-release oral preparation of morphine sulfate.
  • Example 51- Z-Tyr (Bzl) -D-HNLE-Phe-Me ⁇ Ala-0CH : i (12.0 g) obtained in (3) was dissolved in methylene chloride (20 ml), and PCC (1.94 g) Was added and stirred for 2 hours. The reaction solution was diluted with methylene chloride (30 ml), added with magnesium sulfate, stirred for a while and then filtered. The filtrate was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (eluted with chloroform: methanol 100: 1) to give 3.1 g of a colorless oil.

Landscapes

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

Abstract

Composés représentés par la formule générale: HN=C(R?1)-AA1-AA2-AA3-AA4-OR2¿, dans laquelle R1 représente alkyle C¿1?-C6, amino, etc.; R?2¿ représente hydrogène, alkyle C¿1?-C6, etc.; AA?1¿ représente un résidu O-acyl-L-tyrosine éventuellement substitué, etc.; AA2 représente un résidu D-5-oxonorleucine ou D-5-hydroxynorleucine, etc.; AA3 représente un résidu L-phénylalanine éventuellement substitué, etc.; et AA4 représente un résidu β-aminoacide de formule: -N(R?8)-CH(R9)-CH(R10¿)-CO (où R?8, R9 et R10¿ représentent hydrogène, alkyle C¿1?-C6, alcényle C2-C6, etc.). Ces composés, ainsi que leurs sels, sont utiles pour la prévention et le traitement de la douleur.
PCT/JP1998/005862 1997-12-26 1998-12-24 Derives peptidiques WO1999033864A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP35996597 1997-12-26
JP9/359965 1997-12-26

Publications (1)

Publication Number Publication Date
WO1999033864A1 true WO1999033864A1 (fr) 1999-07-08

Family

ID=18467211

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP1998/005862 WO1999033864A1 (fr) 1997-12-26 1998-12-24 Derives peptidiques

Country Status (2)

Country Link
TW (1) TW474945B (fr)
WO (1) WO1999033864A1 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000012539A1 (fr) * 1998-08-31 2000-03-09 Fuji Chemical Industries, Ltd. Composes de peptides
WO2001013938A1 (fr) * 1999-08-25 2001-03-01 Daiichi Fine Chemical Co., Ltd. Composition therapeutique pouvant etre administree par voie percutanee ou par les muqueuses
WO2007144979A1 (fr) * 2006-06-12 2007-12-21 Vexon, Inc. Dérivé de peptide
WO2007145208A1 (fr) 2006-06-12 2007-12-21 Vexon, Inc. Dérivé peptidique
WO2010119864A1 (fr) * 2009-04-17 2010-10-21 株式会社ヴェクソン Dérivé peptidique

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995024411A1 (fr) * 1994-03-08 1995-09-14 Human Genome Sciences, Inc. Proteines des corpuscules de stannius, la stanniocalcine
WO1997010261A1 (fr) * 1995-09-11 1997-03-20 Daiichi Pharmaceutical Co., Ltd. Derives peptidiques
WO1997010262A1 (fr) * 1995-09-11 1997-03-20 Daiichi Pharmaceutical Co., Ltd. Derives peptidiques

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995024411A1 (fr) * 1994-03-08 1995-09-14 Human Genome Sciences, Inc. Proteines des corpuscules de stannius, la stanniocalcine
WO1997010261A1 (fr) * 1995-09-11 1997-03-20 Daiichi Pharmaceutical Co., Ltd. Derives peptidiques
WO1997010262A1 (fr) * 1995-09-11 1997-03-20 Daiichi Pharmaceutical Co., Ltd. Derives peptidiques

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000012539A1 (fr) * 1998-08-31 2000-03-09 Fuji Chemical Industries, Ltd. Composes de peptides
WO2001013938A1 (fr) * 1999-08-25 2001-03-01 Daiichi Fine Chemical Co., Ltd. Composition therapeutique pouvant etre administree par voie percutanee ou par les muqueuses
WO2007144979A1 (fr) * 2006-06-12 2007-12-21 Vexon, Inc. Dérivé de peptide
WO2007145208A1 (fr) 2006-06-12 2007-12-21 Vexon, Inc. Dérivé peptidique
JPWO2007145208A1 (ja) * 2006-06-12 2009-10-29 忍 櫻田 ペプチド誘導体
WO2010119864A1 (fr) * 2009-04-17 2010-10-21 株式会社ヴェクソン Dérivé peptidique

Also Published As

Publication number Publication date
TW474945B (en) 2002-02-01

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