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WO1999021867A1 - Derives d'erythromycine a - Google Patents

Derives d'erythromycine a Download PDF

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Publication number
WO1999021867A1
WO1999021867A1 PCT/JP1998/004779 JP9804779W WO9921867A1 WO 1999021867 A1 WO1999021867 A1 WO 1999021867A1 JP 9804779 W JP9804779 W JP 9804779W WO 9921867 A1 WO9921867 A1 WO 9921867A1
Authority
WO
WIPO (PCT)
Prior art keywords
group
formula
carbon atoms
acid
erythromycin
Prior art date
Application number
PCT/JP1998/004779
Other languages
English (en)
Japanese (ja)
Inventor
Toshifumi Asaka
Masato Kashimura
Tetsuya Tanikawa
Takaaki Ishii
Akiko Matsuura
Tomohiro Sugimoto
Original Assignee
Taisho Pharmaceutical Co., 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 Taisho Pharmaceutical Co., Ltd. filed Critical Taisho Pharmaceutical Co., Ltd.
Priority to AU96459/98A priority Critical patent/AU9645998A/en
Publication of WO1999021867A1 publication Critical patent/WO1999021867A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
    • C07H17/04—Heterocyclic radicals containing only oxygen as ring hetero atoms
    • C07H17/08—Hetero rings containing eight or more ring members, e.g. erythromycins

Definitions

  • the present invention relates to a novel derivative of the antibiotic erythromycin A.
  • Erythromycin A is an antibiotic that is widely used as a treatment for infectious diseases caused by gram-positive bacteria, mycoplasmas, and the like. Erythromycin A, however, has the disadvantage that it is degraded by acid in the stomach because it is unstable to acids, and its pharmacokinetics is not constant. Many erythromycin A derivatives have been produced to date to improve such biological or pharmacological properties. For example, a 6-0-methylerythromycin A derivative (U.S. Pat. No. 4,331,803) has improved stability to acids, and has better in vivo antibacterial activity upon oral administration than erythromycin A. It has been reported.
  • An object of the present invention is to provide a next-generation macrolide antibiotic having a strong antibacterial activity against not only conventional erythromycin-sensitive bacteria but also erythromycin-resistant bacteria, which have been increasing in recent years. To do that. Disclosure of the invention
  • the present inventors have found a compound having antibacterial activity not only against susceptible bacteria but also against resistant bacteria by converting the carboxy group at the 9-position of erythromycin A to a certain substituent.
  • the present invention has been completed.
  • the present invention provides a compound represented by the formula (I):
  • R 1 represents a hydrogen atom or an alkyl group having 1 to 6 carbon atoms.
  • R 2 represents a cladino siloxy group, and a formula — OCO-CH 2 -R 4
  • R 4 is a phenyl group, a pyridyl group, a quinolyl group, or an alkyl group having 1 to 3 carbon atoms, a cyano group, an amino group, a dimethylamino group, a nitro group, a carbon atom.
  • X is an oxygen atom
  • n represents an integer of 1 to 5
  • R 5 and R 6 are the same or different.
  • R 7 is of the formula N—R 9
  • R 8 represents a hydrogen atom, an alkyl group having 1 to 6 carbon atoms or an alkanol group having 2 to 7 carbon atoms
  • R 9 represents a phenyl group, a benzyl group, a pyridyl group, a pyridylmethyl group.
  • R s and R 9 above are the same as) a group represented by or wherein one S0 2 - N-R 9
  • Erythromycin A derivative represented by the formula or a pharmaceutically acceptable salt thereof.
  • an alkyl group having 1 to 6 carbon atoms means a methyl group, an ethyl group, a propyl group, a butyl group, a pentyl group, a hexyl group, an isopropyl group, an isopropyl group, a tert-butyl group.
  • An isopentyl group, a cyclohexyl group, etc., and an alkanoyl group having 2 to 7 carbon atoms refers to an acetyl group, a propionyl group, an isopropionyl group, a butylyl group, etc., and a halogen atom and Is fluorine, chlorine, bromine Indicates an atom or iodine atom.
  • Pharmaceutically acceptable salts refer to salts used in the chemotherapy and prevention of bacterial infections. They include, for example, acetic acid, propionic acid, butyric acid, formic acid, trifluoroacetic acid, maleic acid, tartaric acid, citric acid, stearic acid, succinic acid, ethyl succinic acid, lactobionic acid, dalconic acid, Darcoheptonic acid, benzoic acid, methansulphonic acid, benzoic sulphonic acid, 2-hydroxyethanesulphonic acid, benzenesulphonic acid, para-toluenesulphonic acid, lauryl sulphate, lingoic acid, aspartic acid, glutamin Acids, adipic acid, cystine, N-acetyl cystine, hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, hydroiodic acid, dicotinic acid, oxalic acid, picric acid, thiocyanic acid, pende
  • the compound of the present invention can be produced according to Examples described later.
  • the compounds of the present invention can be administered orally or parenterally.
  • the dosage forms are tablets, capsules, powders, lozenges, ointments, suspensions, suppositories, injections, etc., which can be manufactured by common formulation techniques.
  • the dosage is 100-1. OOOmg daily for treatment of adults, which can be administered in 2-3 divided doses a day. This dosage may be adjusted as appropriate according to the age, weight and condition of the patient.
  • Example 3 9—Doxo 9—Aminoerythromycin A 9, 11—Cyclic power—Bamate 3 g (4.0 mmol) of 9-deoxo-19-aminoinothromycin A synthesized by the method described in the literature (Tetrahedoron Le 11., p. 29, 1972) was prepared in the same manner as in Example 1 by using a method similar to that of Example 1. To give 0.6 g (yield 193 ⁇ 4) of the title compound.
  • the compounds of the present invention have antibacterial activity not only against erythromycin-sensitive bacteria but also against resistant bacteria. Therefore, the compounds of the present invention are useful as antibacterial agents for treating bacterial infections in humans and animals (including farm animals).

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Saccharide Compounds (AREA)

Abstract

Dérivés d'érythromycine A représentés par la formule générale suivante (I) ou leurs sels acceptables sur le plan pharmaceutique.
PCT/JP1998/004779 1997-10-29 1998-10-22 Derives d'erythromycine a WO1999021867A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU96459/98A AU9645998A (en) 1997-10-29 1998-10-22 Erythromycin a derivatives

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP29682497 1997-10-29
JP9/296824 1997-10-29

Publications (1)

Publication Number Publication Date
WO1999021867A1 true WO1999021867A1 (fr) 1999-05-06

Family

ID=17838639

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP1998/004779 WO1999021867A1 (fr) 1997-10-29 1998-10-22 Derives d'erythromycine a

Country Status (2)

Country Link
AU (1) AU9645998A (fr)
WO (1) WO1999021867A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6946482B2 (en) 2002-08-29 2005-09-20 Kosan Biosciences, Inc. Motilide compounds

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS62158B2 (fr) * 1975-04-07 1987-01-06 Thomae Gmbh Dr K
WO1993013116A1 (fr) * 1991-12-27 1993-07-08 Taisho Pharmaceutical Co., Ltd. Derive de 5-o-desosaminylerythronolide

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS62158B2 (fr) * 1975-04-07 1987-01-06 Thomae Gmbh Dr K
WO1993013116A1 (fr) * 1991-12-27 1993-07-08 Taisho Pharmaceutical Co., Ltd. Derive de 5-o-desosaminylerythronolide
WO1993013115A1 (fr) * 1991-12-27 1993-07-08 Taisho Pharmaceutical Co., Ltd. Derive de 5-o-desosaminylerythronolide

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
HUNT E., ET AL.: "9,11-CYCLIC ACETAL DERIVATIVES OF (9S)-9-DIHYDROERYTHROMYCIN A.", THE JOURNAL OF ANTIBIOTICS, NATURE PUBLISHING GROUP, GB, vol. 42., no. 02., 1 January 1989 (1989-01-01), GB, pages 293 - 298., XP002915959, ISSN: 0021-8820 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6946482B2 (en) 2002-08-29 2005-09-20 Kosan Biosciences, Inc. Motilide compounds

Also Published As

Publication number Publication date
AU9645998A (en) 1999-05-17

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