WO2005042523A1 - Nouveau derive d'oxazolidinone et son procede de production - Google Patents

Nouveau derive d'oxazolidinone et son procede de production Download PDF

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Publication number
WO2005042523A1
WO2005042523A1 PCT/KR2004/002805 KR2004002805W WO2005042523A1 WO 2005042523 A1 WO2005042523 A1 WO 2005042523A1 KR 2004002805 W KR2004002805 W KR 2004002805W WO 2005042523 A1 WO2005042523 A1 WO 2005042523A1
Authority
WO
WIPO (PCT)
Prior art keywords
formula
triazol
phenyl
fluoro
ylmethyl
Prior art date
Application number
PCT/KR2004/002805
Other languages
English (en)
Inventor
Jae-Hoon Kang
Chun-Ho Park
Jin-Sun Kwon
Original Assignee
Il-Dong Pharm. 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
Priority claimed from KR1020040082328A external-priority patent/KR20050042446A/ko
Application filed by Il-Dong Pharm. Co., Ltd. filed Critical Il-Dong Pharm. Co., Ltd.
Publication of WO2005042523A1 publication Critical patent/WO2005042523A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms

Definitions

  • the present invention relates to triazDlylmethyl oxazDlidinone derivatives of formula I with antibacterial activity, their pharmaceutically acceptable salts, pharmaceutical compositions comprising the same, a preparation method thereof. [2] [3] Formula I [4]
  • one object of the present invention is to provide oxazolidinone derivatives of formula I and pharmaceutically acceptable salt thereof which can be used as an antibiotic exhibiting higher activities against multi-drug resistant strains (MRSA).
  • MRSA multi-drug resistant strains
  • the other object of the present invention is to provide a process for preparing such an oxazolidinone derivatives of formula I or its pharmaceutically acceptable salt.
  • R is hydrogen atom, ethylcarboxylate, amide, diethoxymethyl, aldehyde, hydroxyoxime or nitrile;
  • X is each and independently carbon or nitrogen atom;
  • the resultant sulfonate derivative is then reacted with sodium azide in DMF to provide the azide (2-3) analogue, which is then cyclized by refluxing vinyl acetate. And then triazole was deprotected by hydrogenation to afford key intermediate aniline (2-4).
  • the aniline (2-4) was condensed with 2,5-dimethoxy-3-tetrahydro&rancarboxaldehyde to yield the formylpyrrole (formula 1-3) which was exploited for the preparation of oximepyrrole (formula 1-4) via standard transformations. Dehydration of the oxime with trichloroacetyl chloride in dichloromethane yielded the 3-cyano analogue (formula 1-5).
  • the compound of formula 1-1-14 may be used in its native form or as pharam- ceutically acceptable salt. In cases where forming a stable nontoxic acid or base salt is desired, administration of the compound as a pharmaceutically acceptable salt may be appropriate.
  • Pharmaceutically acceptable salts may be obtained using standard procedures well known in the art, alkali metal (for example, sodium or potassium) or alkaline earth metal (for example, calcium or magnesium) salts of carboxylic acids can be made. And reacting a sufficiently basic compound such as an amine with a suitable acid affording a physiologically acceptable anion (for example, ammonium, tri- ethylamine, pyridine and N,N-dimethylethanolamine salt).
  • Siitable inorganic salts are formed, including hydrochloride, hydrobromide, sulfate and nitrate salts.
  • Organic acid addition salts may also be formed with acids which form a physiological acceptable anion, for example, formic acid, acetic acid, tartaric acid, citric acid, methylsulfonic acid, lactic acid, succinic acid and benzenesulfonic acid.
  • the compound of formula 1-1-14 show inhibitory activity against a broad spectrum of bacteria, but its antibacterial activity is excellent in vivo.
  • the compound of the present invention can exert potent antibacterial activity versus various human and animal pathogens, including gram-positive bacteria such as Staphylococi, Enterococci and Streptococi, anaerobic microorganism, such as Bacteroides and Clostridia, and acid-resistant microorganism such as Mycobacterium tuberculosis and Mycobacterium avium.
  • the oxazolidinone antibacterial agents of the present invention have excellent activity against gram-positive bacterial infection, including MRS A strains.
  • the compounds are shown high stability as an antimicrobial medicament from LD 50 >4000mg/kg in oral routes. Accordingly, the compounds of the present invention can be used in the therapeutic treatment of human beings or animals infected with variety of gram-positive bacteria.
  • compositions comprising one or more of the compound I-l and their derivatives as active ingredients, in association with pharmaceutically acceptable carriers, excipients or other additives, if necessary.
  • the compositions may be formulated into various forms such as tablets, capsules, troche, suspension, solution, suppositories, ointment, cream, injection, which may contain conventional additives such as a dispersant, suspending agent, stabilizer and the like.
  • the compounds of formula I according to this invention are administered orally and parenterally, i.e., by injection, for example, by intravenous injection or by other parenteral routes of administration.
  • compositions for parenteral administration will generally contain a pharmaceutically acceptable amount of the compound according to formula I as a soluble salt (acid addition salt or base salt) dissolved in a pharmaceutically acceptable liquid carrier such as, for example, water-for-injection and a buffer to provide a suitably buffered isotonic solution.
  • a pharmaceutically acceptable liquid carrier such as, for example, water-for-injection
  • Suitable buffering agents include, for example, -(+)-lysine, -(+)-arginine, N-methylglucamine, sodium citrate, sodium bicarbonate and trisodium orthophosphate to name but a few representative buffering agents.
  • Citric acid (leq) was added to a solution of I-l (30mg, 0.09mmol) in isopropylalcohol (1ml) and was concentrated in vacuo afford a solid which was re- crystallized from boiling isopropylalcohol to afford title compound 31mg (65%).
  • Citric acid (leq) was added to a solution of 1-2 (30mg, 0.09mmol) in isopropylalcohol (1ml) and was concentrated in vacuo afford a solid which was re- crystallized from boiling isopropylalcohol to afford title compound 29mg (62%).
  • Citric acid (leq) was added to a solution of 1-5 (30mg, 0.08mmol) in isopropylalcohol (1ml) and was concentrated in vacuo afford a solid which was re- crystallized from boiling isopropylalcohol to afford title compound 29mg (62%).
  • the oxazolidinonoe derivatives of the general formula I have potent antibacterial activity against a broad spectrum of bacteria and their antibacterial activity is maintained high in vivo. Exerting potent antibacterial activity versus various human and animal pathogens, including gram-positive bacteria such as Staphylococi, Enterococci and Streptococi, anaerobic microorganism such as Bacteroides and Clostridia, and acid-resistant microorganism such as Mycobacterium, the compounds of the present invention are therefore use&l as antibiotics.
  • gram-positive bacteria such as Staphylococi, Enterococci and Streptococi
  • anaerobic microorganism such as Bacteroides and Clostridia
  • acid-resistant microorganism such as Mycobacterium

Abstract

La présente invention concerne un nouveau composé d'oxazolidinone représenté par la formule générale (1) ou les sels pharmaceutiquement acceptables de ce composé, ainsi que son procédé de préparation. Ce composé présente un large spectre antibactérien et une activité antibactérienne supérieure. Ainsi, ce composé peut être utilisé comme agent antibactérien.
PCT/KR2004/002805 2003-11-03 2004-11-03 Nouveau derive d'oxazolidinone et son procede de production WO2005042523A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
KR10-2003-0077372 2003-11-03
KR20030077372 2003-11-03
KR1020040082328A KR20050042446A (ko) 2003-11-03 2004-10-14 신규 옥사졸리디논 유도체 및 그 제조방법
KR10-2004-0082328 2004-10-14

Publications (1)

Publication Number Publication Date
WO2005042523A1 true WO2005042523A1 (fr) 2005-05-12

Family

ID=34554990

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2004/002805 WO2005042523A1 (fr) 2003-11-03 2004-11-03 Nouveau derive d'oxazolidinone et son procede de production

Country Status (1)

Country Link
WO (1) WO2005042523A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008143649A2 (fr) * 2006-12-04 2008-11-27 Dr. Reddy's Laboratories Limited Nouveaux composés oxazolidinones comme agents anti-infectieux
CN113661163A (zh) * 2019-02-28 2021-11-16 国立大学法人大阪大学 用于修饰蛋白质和/或肽的分子

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001081350A1 (fr) * 2000-04-25 2001-11-01 Astrazeneca Ab Derives d'oxazolidinone ayant une activite antibiotique
WO2003006447A2 (fr) * 2001-07-09 2003-01-23 Pharmacia Italia Spa Inhibiteurs d'interaction de tcf-4 avec de la beta-catenine
WO2003072575A1 (fr) * 2002-02-28 2003-09-04 Astrazeneca Ab Composes chimiques
WO2003072576A2 (fr) * 2002-02-28 2003-09-04 Astrazeneca Ab Composes chimiques

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001081350A1 (fr) * 2000-04-25 2001-11-01 Astrazeneca Ab Derives d'oxazolidinone ayant une activite antibiotique
WO2003006447A2 (fr) * 2001-07-09 2003-01-23 Pharmacia Italia Spa Inhibiteurs d'interaction de tcf-4 avec de la beta-catenine
WO2003072575A1 (fr) * 2002-02-28 2003-09-04 Astrazeneca Ab Composes chimiques
WO2003072576A2 (fr) * 2002-02-28 2003-09-04 Astrazeneca Ab Composes chimiques

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008143649A2 (fr) * 2006-12-04 2008-11-27 Dr. Reddy's Laboratories Limited Nouveaux composés oxazolidinones comme agents anti-infectieux
WO2008143649A3 (fr) * 2006-12-04 2009-01-15 Reddys Lab Ltd Dr Nouveaux composés oxazolidinones comme agents anti-infectieux
CN113661163A (zh) * 2019-02-28 2021-11-16 国立大学法人大阪大学 用于修饰蛋白质和/或肽的分子
EP3932912A4 (fr) * 2019-02-28 2022-09-07 Osaka University Molécule pour modification par une protéine et/ou un peptide

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