WO1982001872A1 - Derives azetidine et leur procede de preparation - Google Patents

Derives azetidine et leur procede de preparation Download PDF

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Publication number
WO1982001872A1
WO1982001872A1 PCT/JP1980/000296 JP8000296W WO8201872A1 WO 1982001872 A1 WO1982001872 A1 WO 1982001872A1 JP 8000296 W JP8000296 W JP 8000296W WO 8201872 A1 WO8201872 A1 WO 8201872A1
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Prior art keywords
group
amino
represented
acid
carbon atoms
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PCT/JP1980/000296
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English (en)
Japanese (ja)
Inventor
Chem Ind Ltd Takeda
Taisuke Matsuo
Noriyoshi Noguchi
Hirotomo Masuya
Michihiko Ochiai
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Takeda Chemical Industries Ltd
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Application filed by Takeda Chemical Industries Ltd filed Critical Takeda Chemical Industries Ltd
Priority to PCT/JP1980/000296 priority Critical patent/WO1982001872A1/fr
Priority to MX819801U priority patent/MX7096E/es
Priority to IL64314A priority patent/IL64314A/xx
Priority to HU813576A priority patent/HU189545B/hu
Priority to DK534381A priority patent/DK534381A/da
Priority to NO814113A priority patent/NO160297C/no
Priority to FI813851A priority patent/FI79528C/fi
Priority to US06/326,939 priority patent/US4822790A/en
Priority to SU813364650A priority patent/SU1662348A3/ru
Priority to AT81110154T priority patent/ATE13178T1/de
Priority to PT74087A priority patent/PT74087B/pt
Priority to ES507716A priority patent/ES507716A0/es
Priority to EP81110154A priority patent/EP0053815B1/fr
Priority to BE0/206751A priority patent/BE891365A/fr
Priority to NZ199168A priority patent/NZ199168A/en
Priority to GB8136617A priority patent/GB2091723B/en
Priority to LU83820A priority patent/LU83820A1/fr
Priority to FR8122774A priority patent/FR2495612A1/fr
Priority to AT0520781A priority patent/AT379800B/de
Priority to DE19813148020 priority patent/DE3148020A1/de
Priority to DE8181110154T priority patent/DE3170437D1/de
Priority to ZA818445A priority patent/ZA818445B/xx
Priority to CH7786/81A priority patent/CH656122A5/de
Priority to SE8107273A priority patent/SE8107273L/xx
Priority to IE2859/81A priority patent/IE53451B1/en
Priority to IT68585/81A priority patent/IT1146726B/it
Priority to JP56196078A priority patent/JPS57131759A/ja
Priority to NL8105468A priority patent/NL8105468A/nl
Priority to PCT/JP1981/000368 priority patent/WO1982002042A1/fr
Priority to KR1019810004759A priority patent/KR880001564B1/ko
Priority to AU78313/81A priority patent/AU551463B2/en
Publication of WO1982001872A1 publication Critical patent/WO1982001872A1/fr
Priority to ES513420A priority patent/ES513420A0/es
Priority to SU833547568A priority patent/SU1531852A3/ru
Priority to AT0170384A priority patent/AT380471B/de

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
    • C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
    • C07D205/06—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D205/08—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams
    • C07D205/085—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams with a nitrogen atom directly attached in position 3
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
    • C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
    • C07D205/06—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D205/08—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams
    • C07D205/09—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams with a sulfur atom directly attached in position 4
    • C07D205/095—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams with a sulfur atom directly attached in position 4 and with a nitrogen atom directly attached in position 3
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
    • C07F7/02—Silicon compounds
    • C07F7/08—Compounds having one or more C—Si linkages
    • C07F7/0803—Compounds with Si-C or Si-Si linkages
    • C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te
    • C07F7/0812—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te comprising a heterocyclic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
    • C07F7/02—Silicon compounds
    • C07F7/08—Compounds having one or more C—Si linkages
    • C07F7/10—Compounds having one or more C—Si linkages containing nitrogen having a Si-N linkage
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
    • C07F9/568—Four-membered rings

Definitions

  • the present invention relates to a novel 1,3,4-K-substituted-2-oxozetidine derivative having an anti-activity or a / 3-lactamase i-inhibitory effect, and a method for producing the same.
  • the present inventors have conducted intensive studies for the purpose of obtaining a new and useful azetidine derivative-, and found that an azetidine derivative having a sulfo group at the 1-position satisfies the above-mentioned object. Completed the invention.
  • Ri is A Shinore reduction to or coercive ⁇ is also an amino 3 ⁇ 4 have, X Pas hydrogen or main butoxy, R4 is azido group or -OR 5, - _ R 5, (Where Rs is an organic residue, n is
  • R2 is T Shinore reduction to or Protected amino group,
  • X are as defined above are shown respectively] 2 represented by - given the Okisoazechijin derivative conductor to the scan / Reho emission reaction,
  • R 2 In the case of a protected amino group, 1-snolehoe-2-oxoathiine represented by the general formula (I) is characterized in that it is necessary to further remove a protecting group, if necessary. 'Derivative manufacturing methods, —
  • R4 and X have the same meanings as defined above, and a general formula characterized in that a 3-amino-1-snoleho- 2- oxazetidine adduct is attached to an acylated compound.
  • R 3 represents an amino-amino group
  • X and R 4 have the same meanings as described above].
  • the present invention relates to a method for manufacturing a conductor.
  • K 4 is OR 5 ,-? ⁇ 5 , in
  • the reliance represented by 5 means a hydrocarbon group, an acyl group, a heterocyclic group, or the like.
  • the hydrocarbon group is an aliphatic or branched chain, which may have a branched, branched, cyclic double bond or triple bond.
  • ⁇ means an aromatic group such as phenyl, naphthyl, etc.
  • ⁇ 'group' means such a hydrocarbon-converted carbonyl group.
  • a 5- to 6-membered heterocyclic group containing one sulfur atom and / or one to four nitrogen atoms is used as the heterocyclic group, and these complex ⁇ combine with benzene ⁇ . May be.
  • pyridile, tetrazoli / re, thiaziazolinole, thie-nore, thi'zolinole, isothiazolyl, benzothiazolyl and the like are mentioned.
  • Such a hydrogen hydride requisite, an ash / reaction, or a heterocyclic group is, for example, a lower alkanol having 1 to 3 carbon atoms, a lower alkoxy, a lower alkoxide, a lower alkoxycarbone, an oleoxycarbonyl group, a phenol group, and a phenol group.
  • H Chlorine »Halogen such as elemental, heterocyclic group such as phenoxy, phenyl, freenole, cheninole, carbon number 1 such as meth / rechi, ech / rechi
  • complex thio groups such as tetrazoly ⁇ thio, thiaziazolylthio, may be asinolated or exchanged with amino, cyano, etc.
  • Preferred among the acyl groups in the amino group which may be non-reacted are acetyl, propioni, and the like.
  • organic residues include, for example, e / reminore, acetinole, and propioni; les, isopropioninole, 2-hydroxyxanololeboninolearecetinole, sekinorenoboxisetyl, and methylthioa. ⁇ . (,,, 1 1 1 1 1 ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇
  • the amino group at the 6-position of the conventionally known base derivative is 1:
  • the ash that is ft-converted to the 7-position of the cephalosborin derivative is used.
  • R 7 is hydrogen, an amino residue which may have an IK lysine group, a protecting group for the amino group, a formula R8- (CH 2 ) nl-CO-[wherein, R 8 Is a heterocyclic group which may have a te exchange S, a phenyl group which may have a substituent group, and a phenyl group which may have a substituent group.
  • Xii may be 0 or 1 or a number of 4 or less, In the formula, the (Ci1 ⁇ 2) n i— group may have a substituted group.
  • Rl2 is 'good Hue have a group or substituent - an Honoré
  • R 13 is hydrogen,' heterocyclic ring which may have a substituent may have a substituent group Fueni, lower ⁇ Shi / R, lower alkyl or a group represented by the formula: R-Ri5 (wherein, Ru represents lower anolexylene or lower anorequeren, and Ri5 represents carboxyl, an ester thereof or a heterocyclic group, respectively).
  • R-Ri5 wherein, Ru represents lower anolexylene or lower anorequeren, and Ri5 represents carboxyl, an ester thereof or a heterocyclic group, respectively.
  • ⁇ , Rii is a mere bond or a formula
  • Ri6 represents a lower alkyl, a phenyl which may have a substituent or a heterocyclic group which may have a substituent.
  • Ri7 is hydroxynole, hydroxys , rehoninoleoxy, canoleboxinole, sunolefamoy 'which may have a substituent, sulfo, or phenoxycanolevo-nole, which may have a substituent.
  • Benzizoleoxycanolebol and honolemiloxyphthimide, Ris represents hydrogen, lower alkyl, lower alkoxy, no, logen, azide, nitro, and hydroxynole.
  • Ris is cyano, phenyl which may have a substituent, phenoxy which may have a substituent, phenol which may have a substituent, R20 represents an alkene which may have a group, a heterocyclic group which may have a cyclization group, and R20 represents -S-, which is a mere bond.
  • the lower quinole represented by R6 preferably has 1 to 6 carbon atoms.
  • the heterocyclic group in the heterocyclic group which may have a substituent is a 5- to 6-membered heterocyclic group containing 1 to 2 nitrogen atoms and containing or containing one oxygen atom. Things can be found.
  • Specific examples of the heterocyclic group include, for example, isoxazoly, biverazini, imidadolinole and the like.
  • substituent for the heterocyclic group examples include a lower phenol having 1 to 3 carbon atoms, a lower alkoxy group having 1 to 3 carbon atoms, a halogen atom, a halogen atom, an amino group, an oxo group, a oxo group, and a substituent.
  • feninore may be used.
  • substituent in the benzoinole which may have a substituent and the substituent in the phenyl which may have the above-mentioned substituent include, for example, lower phenol having 1 to 3 carbon atoms, 1 lower carbon atom, ⁇ 3 ⁇ Lower alkoxy, halogen, nitro, amino, etc. are used.
  • substituents which may be substituted on the amino acid residue include, for example, amino, lower ⁇ / lekylamino, amino-protecting group, canolebamoy / re, methanorebamoinole, s / refamoynole, Benzinole, 4-ethylenol 2, 3, 3-dioxane 1-pirazino-force-no-revo 2 / V, 4—eth / ray 2,3 dioxono 1-piradino-ino-carbo-noremino, etc. are used.
  • ⁇ / ⁇ / re in the lower phenol / rare those having 1 to 3 carbon atoms are preferable.
  • amino-protecting group those similar to the amino-protecting group described below can be used. -
  • heterocyclic group in the optionally substituted heterocyclic group represented by R 8 of the group represented by the formula I? 8-(CH2) nl -CO- is, for example, one sulfur atom
  • 5- to 6-membered heterocyclic groups are used, and these heterocyclic groups are fused with a 6-membered ring group containing two or less nitrogen atoms, benzene or a 5-membered ring group containing one sulfur atom. You can.
  • heterocyclic group represented by R8 include, for example, 2-biridinole, 31-pyridinole, 41-pyridi, pyrimidininole, virazini./le, bilidazinole, piberazinole, virazolinyl, i Midazolidinyl, Chia Zori, isotizazori / re, o-sazolyl, isokisori / re, bilido [23-d pyrimidini / re, benzopyrani ⁇ , 1,8-naphthyldininore,
  • the substituted strawberry of a heterocyclic group which may have a substituted group represented by R8
  • charcoal discards that may have a carbon exchange group.
  • Examples of the groups that may be used include phenyl, halogen, hydroxyxylene, and diphenyl.
  • a lower quinole having 1 to 3 carbon atoms for example, a lower quinole having 1 to 3 carbon atoms, a lower
  • the R 8 Te may phenylene which may have a substituent represented, as the kick substituents retinyl old, such as lower Azorekinore 1 to 3 carbon atoms, lower ⁇ of 1-3 carbon atoms. 7 records carboxymethyl , Halogen, hydroxyzole, amino, etc.
  • Formula - (CH 2) As a group which may be substituted by a group represented by nl-, for example Amino, wherein one NH- CO- R 8 z ", during [wherein, R8 is have a Amino or location Kiyoshimoto And represents a ⁇ group represented by :)
  • Examples of a substituent in piperazine which may have a substituent represented by R 8 , // For example, low-treated alkynole having 1 to 3 carbon atoms, lower alkoxy having 1 to 3 carbon atoms, hydroxyl, oxo, thioxo, zirogen and the like are used.
  • the lower alkyl represented by Rs and / or Rs in the above formula preferably has 1 to 3 carbon atoms.
  • As lower alkyl in lower alkyl. Lekanole bamoinole, one having 1 to 3 carbon atoms is preferable.
  • Examples of the substituent in the phenol group which may have a 'substituent' include, for example, lower alkoxy having 1 to 3 carbon atoms./re, lower anorecoxy having 1 to 3 carbon atoms, halogen, hydroxynole, and It is used for droxysinolephoninole, benzyl / reoxy, etc.
  • the lower A Kinore in R8 / -S 0 2 may be _ in have ft substituent represented by groups of represented lower ⁇ .
  • 'Rekinore preferably has from 1 to 6 carbon
  • the substituent may be substituted at one position or at two positions, and examples thereof include amino, urenoboxinole, benzyl carboxy, protected amino group and the like.
  • the protecting group in the protected namino group the same as the protecting group for the amino group described below are used.
  • the class alkynole is preferably one having 1 to 3 carbon atoms.
  • bases include feninole, moss, moss, mess, ss, ssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssss
  • N-methyltetrazolinoletchi N-methyltetrazolinoletchi, halogen, spamoy, etc. are used.
  • Examples of the substituent in the phenyl group which may have a substituent represented by Rg include lower quinole having 1 to 3 carbon atoms, lower anorecoxy having 1 to 3 carbon atoms, dizolene, hydroxy / 1 , Hydroxys .71 / Honi. / Oxy, Benzinoleoxy, Benzoxoxy, Trimethi, Resilinole, Carbonism 2 ⁇
  • the heterocyclic group of the heterocyclic group which may have a substituent represented by R 9 is, for example, a 5-membered, monocyclic group containing a sulfur atom, a nitrogen atom or an oxygen atom having a quality of 1 to 2 *
  • a 5-membered heterocyclic group containing one nitrogen atom and one sulfur atom or a nitrogen atom, and a 5- to 6-membered heterocyclic group containing 0.2 to 4 nitrogen atoms are used.
  • heterocyclic group examples include, for example, thiazoli ⁇ , isothiazolinole, oxazolinole, isoxazoli / le, cheninore, furi, biloli, imidazolinole, pyrazi-7le, pyrimidinini, bilidazinino and piperazinole. , Triazininole, tetrazori ⁇ , thiadiazori., Oxaziaziolinole, etc. are used.
  • the substituent is, for example, a lower carbon atom having 1 to 3 carbon atoms.
  • the cycloanolequene represented by Rg is preferably a 5- to 6-membered cyclone; for example, cyclohexanol / re and cyclohexahexene are used.
  • IrO --A heterocyclic group which may have a substituent represented by Rg and may be via alkylene ⁇ -a heterocyclic group of a nonolevonizoleamino group. ⁇ groups are used.
  • the heterocyclic group for example, piberazi / le is used.
  • the substituent for example, carbon atoms of 1 to 12 carbon atoms / reoxy, low carbon atoms of 1 to 3 carbon atoms, oxo, thio, oxo, amino and the like are used.
  • the anoalkylene chain preferably has 1 to 3 carbon atoms, and examples thereof include methylene, ethylene, ⁇ , and propylene.
  • the heterocyclic group in the heterocyclic group which may have a substituent represented is a 5-membered multiple-ring group containing one nitrogen atom, sulfur atom or oxygen atom and containing one nitrogen atom. Alternatively, those not included are used. Specific examples of this complex ring group include, for example, '2.-thiazolinole, 4-thiazolino, 5-thiazolinole, 2-che2 / re, 3-che2 / re, 2-free / re, 3-free. / Le, 2-pyrrolyl. Substituents in this heterocyclic group include, for example, lower carbon atoms of 1 to 3 carbon atoms and carbon atoms.
  • Examples thereof include lower phenols having 1 to 3 hydroxyls, hydroxylinole, mesoleic acid, zirogen, imino, amino, mesizoleamino, and cinoleamino having 2 to 4 carbon atoms which may have a halogen as a substituent. .
  • Examples of the substituent in the phenylene which may have a substituent represented by 3 ⁇ 42 include a lower phenol having 1 to 3 carbon atoms, a lower phenol having 1 to 3 carbon atoms, and a halogen.
  • (B) Amino, hydroxy A or substituted hydroxy is used. Examples of the substituent in the substituted hydroxy. I include, for example, benzinole, benzoinole, acyl having 2 to 10 carbon atoms, dig, / letamyl, 3-amino-3-force boxypropinole and the like.
  • ⁇ group of the phenyl group which may have an ft substitution group represented by Rl3, for example, a lower group, a lower group, a lower group, a halogen, and the like are suspended.
  • low-accuracy low-residue which may have a substituent represented by R13, those having 2 to 4 carbon atoms are preferable, and as the substituent, for example, halogen and the like are used.
  • R 13 l4 - as lower Anorekiren represented by Rl4 groups represented by RL5, preferably those having 1 to 3 carbon atoms, examples of such as methylene, ethylene, propylene, ⁇ physician like Lee Sopurobiren Can be
  • a low-rank alekenylene represented by Rl4 which has 1 to 3 carbon atoms, for example, ⁇ , bilen, probelenylene, etc. Is used.
  • esthetic of the carboxy represented by R15 for example, methinoleste 1 /, etinoleste, / le, propinoleste;
  • heterocyclic group represented by R15 a 6-membered heterocyclic group containing one nitrogen atom and 11 nitrogen atoms is used, and specific examples thereof include monoreholino.
  • the lower aki is preferably one having 1 to 3 carbon atoms.
  • Examples of the substituents in the phenol which may have a ⁇ ⁇ substituent include, for example, lower carbon atoms having 1 to 3 carbon atoms / requinole, lower carbon atoms having 1 to 3 carbon atoms, and lower alcohols having 1 to 3 carbon atoms.
  • xy, halogen, nitro, amino, and carbon / carbon 2 to 10 are used.
  • the optionally substituted ⁇ 1 element ⁇ group represented by R i6 is, for example, one 5-membered heterocyclic group containing a sulfur atom, nitrogen atom or oxygen atom, 1-2 nitrogen atoms And a 5-membered heterocyclic group containing 1 sulfur atom or 1 atom, or a 5-membered heterocyclic group containing 2 to 4 nitrogen atoms.
  • Specific examples of the heterocyclic group include, for example, thiazolinole, isothizazoli / re, oxazoli / re, isosekisazore./re, cheji / re, flinole ', pyrrolinole, thiadiazolinole, oxazidi.
  • Azolinole triazininole, tetraso * linole, imita'zolinole, birazinole, pyrimidinyl, pyridazini / le, piperazi-le, etc. are used.
  • substituents include lower ⁇ / req having 1 to 3 carbon atoms, lower ⁇ / rexy, 1 to 3 carbon atoms, nodogen, hydroxyxylene, amino, and halogen.
  • a carbon / rare mino having 2 to 4 carbon atoms which may be used is used. '
  • Snorrefamoinole which may have a substituent represented by R17, for example, lower alkyl having 1 to 3 carbon atoms, amidino and the like are used.
  • substituent in the phenoxycarbinole which may have a substituent represented by R17, lower alkynole having 1 to 3 carbon atoms, lower alkoxy having 1 to 3 carbon atoms and the like are used.
  • the lower aki and lower anoreoxy represented by R18 preferably have 1 to 3 carbon atoms, respectively.
  • the substituents of feninole which may have a K substituent represented by Ri9 include, for example, lower alkynoles having from 3 to 3 carbon atoms, lower anolexoxy having 1 to 3 carbon atoms, and halogens ,-Toro, amino, hydroxy, substituted amino, etc. are used.
  • the fi-substituent in the amino group include, for example, force / rebamoy. / Re, (2-oxo-one 3— ⁇ : ⁇ ⁇ 1 — — — — 1 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2.
  • Examples of the phosphine group of phenoxy which may have a 1-sliding group represented by Rl9 include, for example, lower alkyl having 1 to 3 carbon atoms, lower phenolic alkoxy having 1 to 3 carbon atoms, nodogen, nitrite. B, amino, hydroxyinole, aminomethinole and the like are used. The same substituents as those described above for the substituent of phenyl represented by R19 are used. As the lower radical which may have a substituent represented by 19, those having 1 to 6 carbon atoms are preferable, and examples of the substituent include halogen, hydroxynole, cyano, and trif. Leorometi ⁇ ⁇ is used.
  • Examples of the a / lekenylene which may have a substituted group represented by Rl9 include, for example, bi'-len and probenylene, and, j. Noreboxinole, cyano and the like are used. '
  • the heterocyclic group in the compound which may have a K-substituted group represented by Ri9 is a 5- to 6-membered cyclic group containing one sulfur atom or 1-4 nitrogen atoms, A 5- to 6-membered ring group containing a sulfur atom and one nitrogen atom or one oxygen atom is used.
  • Examples of the substituent in the heterocyclic group which may have a substituent represented by R19 include lower phenols having 1 to 3 carbon atoms, lower anolexoxy having 1 to 3 carbon atoms, halogen'nitro, and hydroxyl group. 'Protected amino' carboxy. Even if it has carboxylic acid, oxo or halogen as a direct group Good charcoal ⁇ ⁇ 2 to 4 ash ⁇ ⁇ rare mino, 2 to 4 charcoal ash paste etc. are used o
  • a / lequinole of charcoal ⁇ ⁇ ⁇ 2 are, for example, methinole, triflolomethinole, ethi ⁇ , n-f. Mouth Pisole 'sov. Mouth pinore, n-fuchi./re, isof * chinore, sec-butinore, tert-bout / re, pentinore, isopenit / re, hexinole, isohexinole, hefu.
  • Chinore, 3 Heptinore, octinole, noni / re, desinole, pedesire, dodecinore, cyclohexyl / rex.
  • specific examples of lower ⁇ -alkyl having 1 to 6 carbon atoms include, for example, methinole, trif / leolomethinole, etinole, and n-f. Lo Vinore, Isov. Ropi / re, n—butinore isofino, sec—butinore, tert—butinore, ventile, isopenchinore, hex / re, isohexore, etc. are used.
  • examples of lower alkene having 1 to 3 carbon atoms include: ⁇ i, for example, meth / re, trif'leorome / re, etinole, n-prohinole, isopropyl, redo, etc. Used.
  • examples of lower alkoxy having 1 to 3 carbon atoms include methoxy, ethoxy, n-proxy, and isopropoxy- 4- oxy.
  • chlorine, bromine, and fluorine are used as specific examples of the halogen.
  • the low-alkynoles lefonyl having 1 to 3 carbon atoms include methyls / lefole, ethyl / les'lefoni, n-propinoresolefoninole, and isopropinoles / lefonyl.
  • specific examples of asinoleamino having a carbon number of from 2 to 4 include, for example, acetinoleamino, propionia reamino, ⁇ -butyri. / Reaminino, and isobutyrylamino.
  • ash / reoxy having 2 to 10 carbon atoms include, for example, acetoxy, ⁇ -propionyloxy, ⁇ -butylinoleoxy, isobutili, ⁇ -pentanoinolexy, ⁇ — Hexanoy
  • acyl group represented by the formula R 6 —C ⁇ - (where,; has the same meaning as described above) include, for example, 3- (2,6 1-5 — Met / Rei Soxazono 1 41 1 Nore Canolepo-Nore, ⁇ etinore 2, 3 Gioxo 1 One-Pibelazino Power Norebo Nore, 2-Oxooi Midazori 1-Nonole, etc. Is used.
  • acylole group represented by the formula R 7 ⁇ NiH-H-C0- include, for example, ⁇ D-ara2nole, ⁇ 1 FCU / Learanninore, Nana Benji Rei ⁇ —Power Norebovenso * Kishi ⁇ -I D—Gnoreta Minore D—Varanie / Re, D-Fueii / Rec “Li Chinore D—Vara-Nore, ⁇ — Power Norevo Benzoxy!
  • Mouth pioninole 2-1 ( ⁇ etinole 2, 3 ⁇ oxorone 1 -piverazino force olevoxamide) 2 2-(4 — n —octanoy / reoxyphene) acet; 2,3—Ji-Ki-Sho 1-pi-z-radino-force-no-rexamido) -1
  • 3 Snorrefamoinole-propioninole, 3— [2-i- (4-ethyl-2,3-di-oxo-one-piperazino-canoleboxami) Do)
  • Mouth Pio-Nore 2 — (4-Echinore 1, 2, 3 ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ 3 —) 1 3 — (Che / Racetamido) (4-Echicle 2, 3 ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ 3 3 3 3)
  • Propio- Nore 2 — (4-1 Chinore 2, 3--dioxo 1-1-velazino force noreboxamide) 1-2-(1 H—te torazo ⁇ "nore 1-1 / acetinore, 2-1 ((3 —F / Ref. Li 2nd — Min. 2—F.
  • Kisamido] propion pioninole ! 1-3 ((2-oxo 3-snorehoy midazolidin 1-1 /) Force norevoxamide] 1-2-Cheninolacetinole, D-2-[(5- Methoxycanoleboninole 3 -methyl 2 -oxo-mita'-zolidine 1 -inole) force ./reboxamide] 1 -2 -pheninorea cetinole,! 1-2-[(5 1-benzinoleoxy One —
  • acyl group represented by include, for example, nasnolephopheninoreacetinole, nadrodroxysinolehoninoleoxyphenynoresetinole, nadrodroxypheninorea cetinole, nanasoreno Famoinolefeninorease
  • Rl9 - R20 - CH 2 - CO- (. Wherein, with RL9 preliminary R20 are as defined above)
  • Specific examples of the reed ⁇ groups represented by, for example, Xia Noasechinore, Hue Nino Les acetylide Honoré, Fueno Kishiasechinore , Trif / Let's rometinorethioacetinole, Cyanometi thioacetyl, iH-tetrazole
  • amino-protecting group those similar to the “amino-protecting group” described below can be used.
  • the carboxyl / repoxy group includes all groups which can be used as / 5-lactam and organic chemistry in the field of organic chemistry, for example, the ester portion thereof. , For example, methine, ethinole, propinole, isopropinole, tertiary butinole, tertiary ami / re, benzinole, p—-trovenge / re, p—methoxybenzinole, benz hydrinole, fuenashinore, fuena ' , P-2 trofenile, methoximetinole, ethoxymechinore, benzinole cymechinore, acetoximetinole, pinotorainoreoxymechinore, ⁇ -methizoles rehonii / reetinoret, meth / rethiotine Nore, ⁇ , ⁇ , ⁇ 1 Trichloroeth
  • Dimethinorea Essences such as Minenoetinole, Pyridin-1-oxide 2—Methinole, Methinoles Nolefuininolemetinole, Bis (p-Methoxyphene / le) Methyle, 2—Cyanone 1, 1-Methysole
  • the present invention provides the novel single-el compound, and the selection of the protecting group is particularly limited. Although it is long, it is particularly preferable to use Benzinole, / 9, / 3, / 9 — trichloroethinole, p12 Trobenzinole 'p — methoxybenzinole * preferred.
  • the protecting groups for the amino group in the above general formula include / 3-lactam and --Those used for this purpose in the field of peptide synthesis are conveniently provided.
  • ⁇ Phthaloy , re, p-Trobenzoyl ', P-tert-Butinolevenzo / Re p-ter t-Butinorebenzensunorehoninore, Benzens melehoni, Re, Tonoreens / Rehonil, etc.
  • Tribe group such as horuminore, asechi, fu.
  • a group of aliphatic fatty acids such as methoxy, methoxycarbonyl, and graves, and, for example, tritinol .2--trophenylthio, benzylidene, 412 benzylidene, di or trialkyl.
  • Carrier groups for amino groups other than acyl groups such as silyl, benzyl /, p12-benzinole, are used.
  • the choice of the protecting group is not particularly limited, as in the case of the carboxy-protecting group. In particular, monoprotected acetyl, benzinoleoxy phenol, p-methoxypentinoleoxycaprate are preferred.
  • Reponinole and P-port benzoinoleoxycanolebol are preferred, among the amino groups which may be protected or protected, which are represented by Ri in the above general formula, have excellent antibacterial activity, More specifically, those exhibiting ⁇ -lactamase inhibitory action can be expressed by the formula:
  • WZ [wherein A is hydrogen, methyl, ethynyl, isobutynole and other lower anoalkyl groups, cyclohexyl, cyclohexyl and the like cyclic groups, and phenyl and other aryl groups.
  • Aranolecyl groups such as phenoxybenzinole, heterocyclic groups such as cheninole, benzocheninole, pyrrolinole, isoxazolinole, piperazino.thiazolinole, tetrazinole, and oxatiano, and A represents these heterocyclic groups.
  • the lower quinole group is preferably a chain or branched acryl group having 1 to 4 carbon atoms, and these are the above-mentioned N-methyl / reno-moinole, carbobenzyloxyamino. Taryazoi meleacetamide
  • Examples of the halogen that can be substituted for A include fluorine, salt, bromine and the like
  • examples of the lower acrecle group include methyl and ethyl
  • examples of the lower anoreoxy group include methoxy and ethoxy.
  • Examples of the amino group which may be retained and represented by W include chloroacetylenoleamino and a Laquinoleamino and aranolequinoleoxiana are used.
  • the complex ⁇ ⁇ ⁇ ⁇ in the complex cabosamide group represented by W is represented by phenyl, an alkenyl group having 1 to 12 carbon atoms, a SS lipoyl group, an arkeni having 2 to 8 carbon atoms: Lower phenolic groups which may have lower phenolic groups such as methoxy and ethoxy, phenolic phenolic phenolic groups, sulfonyl phenolic phenolic phenolic groups, Araslequinoleoxycanoleboni / re group or force / reboxy / re group may be used for tranquilization. Is preferably a chain or branched quinolyl group having 1 to 4 carbon atoms, and these are substituted with halogen such as chlorine, bromine and fluorine. It may be.
  • A are fenii / re, phenoxy, thiazoli / re, cheninole, and piperazino, and are further substituted with amino, lower areki, and lower anorecoxy. Those having a non- or ⁇ -amino methoxyimino group at the ⁇ - position are preferred.
  • compound (I) Since compound (I) has a phospho group, it can generally form a salt by acting with a base. Therefore, the compound ( ⁇ ) may be collected as a salt, and the compound obtained as a salt may be in a free form or as another salt. Further, the compound (I) obtained in a free form may be referred to as 3 ⁇ 4.
  • the above-mentioned base include inorganic bases such as lithium, potassium, sodium, canoledium, and ammonium, such as pyridine, collidine, and triethylamine. Organic substances such as triamine and triamine are used.
  • the compound (I) of the present invention is also encompassed by the present invention.
  • a method for releasing the compound obtained as a salt for example, a method using an acid or the like is used.
  • the type of stool used varies depending on the type of the protecting group and other conditions.
  • the acid include inorganic acids such as hydrochloric acid, sulfuric acid, and phosphoric acid, formic acid, and the like.
  • P — nucleus ⁇ such as ⁇ , ⁇ .
  • acid 'ion-exchange resin is used as the rot.
  • acetonitrile, tetrahydrofuran, methanol / le, ethanolol, dioxane, etc. a soluble solvent, water or a mixed solvent is often used.
  • the compound (() may have an isomer (eg, D-isomer, L-isomer).
  • an isomer eg, D-isomer, L-isomer.
  • their respective isomers and their compounds are also included in the description.
  • the compound (I) thus obtained is useful as a medicine, and has, for example, an effect on certain gram 'positive and gram negative ⁇ .
  • the acute toxicity of the compound (I :) of the present invention upon intravenous injection into mice is greater than 500 ⁇ /.
  • the compound (I) of the present invention is useful, for example, for treating mammals (eg, mice, rats, humans, etc.) that have been infected by the above-mentioned infection.
  • the compound ⁇ (I) of the present invention can be used as a therapeutic agent for small infectious diseases, for example, as a respiratory tract infection, urticaria, suppurative disease, biliary tract infection, field infection, obstetrics / gynecology infection, Can be used to treat surgical infections.
  • the daily administration is about 20 to about 200 ⁇ / 3 ⁇ 4 ⁇ as compound (I), and it is divided into 2 to 4 times daily and once about 5 to about 10 ⁇ ' ⁇ ⁇ ⁇ A direct dose is appropriate.
  • the compound ⁇ (I) or a physiologically acceptable salt can be administered by conventional means, for example, in the form of tablets, capsules, drops, or the like, or can be administered by conventional means.
  • It can be formed into a propellant, mixed with a degradable carrier usually produced by S means, and administered parenterally.
  • compound (I) has a / 5-lactamase inhibitory action and is useful as a ⁇ -lactamase inhibitor.
  • the compound (I) of the present invention is used to administer? -Lactam antibiotics for the treatment and prevention of bacterial infections in livestock or livestock.
  • the compound (I) of the present invention is formulated in a unique manner, it is used before or after the administration of the ⁇ -lactam antibiotic, or is used by mixing at the time of use. It can also be formulated as a mixture with lactam antibiotics.
  • the compound of the present invention ( ⁇ ) Can be used in an amount (weight) of 1Z10 to 10 per 1 / 9-lactam antibiotic, but in a ratio of 1 to 1/3, for example, a ratio of 1 / '5 or 1-6.
  • the compounds of the present invention are generally 50 to 100 per day, and usually 20 to 100 per day.
  • 150 is emitted, for example, 1 to 6 times, and usually 2 to 4 times.
  • the 1-snorrehoe 2-oxozetidine ⁇ -form (I) of the present invention can be produced, for example, by subjecting the compound ( ⁇ ) to a snorehonation reaction.
  • This snorephonation reaction refers to a reaction in which a phospho group is introduced, and can be performed by subjecting the compound (II) to, for example, a reactive derivative of anhydrous ft ⁇ or sulfuric anhydride to undergo anti-IS.
  • Examples of the reactive conductors of the above-mentioned sulfuric anhydride include, but are not limited to, sulfuric anhydride-pyridin ⁇ anhydrous sulphide sulfide / dioxane, sulfuric anhydride / trimethinoleamine, sulfur / anhydrous sulfuric acid / resorolefone, etc. Is used.
  • the reaction temperature is about 0 to about 80, and more preferably about 10 to about 40 !.
  • a solvent may be used.
  • the solvent include dioxane, tetrahydrofuran, and ethenoleatenore.
  • the compound (I) can be obtained as an arbitrary compound by subjecting the anti-) core compound to a purification / separation means known per se such as solvent extraction, recrystallization and chromatography.
  • the starting compound ( ⁇ 1)) can be subjected to the reaction as a salt, an ester, a silinole derivative or the like.
  • the 11-snorrejo-2-oxoxetidine derivative (IV) of the present invention can be produced, for example, by subjecting compound (I :) to an acylation reaction.
  • This acylation is carried out by reacting the compound (I) with an acylating agent.
  • the acylating agent used in this reaction may be organic levonic acid bearing an acyl group represented by R 3 , or a reactive amino acid derivative of these acids.
  • examples of the reactive ⁇ form of the above-mentioned organic acid include ⁇ anhydride, active ad, active estenole, and the like. Specific examples of the reactive derivative of such an acid are given below. It is as follows.
  • the acid anhydride examples include, for example, mixed acid anhydrides of hydrohalic acid (for example, hydrochloric acid, hydrated water, etc.), monocarboxylic acid anhydrides, and aliphatic oleonic acids (for example, vinegar, Acid, valeric acid, iso-bentanoic acid, tricarboxylic acid, etc.) mixed anhydride, aromatic / levonic acid (eg, benzoic acid, etc.) mixed anhydride, nominal type An anhydride or the like is used.
  • hydrohalic acid for example, hydrochloric acid, hydrated water, etc.
  • monocarboxylic acid anhydrides for example, monocarboxylic acid anhydrides
  • aliphatic oleonic acids for example, vinegar, Acid, valeric acid, iso-bentanoic acid, tricarboxylic acid, etc.
  • aromatic / levonic acid eg, benzoic acid, etc.
  • the active amide for example, an amide with virazole, imidazole, 4-substituted imidazole, dimethylvirazole, benzotriazole and the like is used.
  • examples of the active ester include methyl ester, ethyl ester, methoxymethyl ester, bromine, ruginoleestenol, 4-trofenolenoester, 2,4-jetrophenyl ester, trichlorophenol ester,
  • esters such as pentachlorophenylinoleester and mesinolephenylester, 1-hydroxyl 1H-2-pyridone, N-hydroxysuccinimide, N-hydroxyphthalimid and the like and the carboxylic acids and the like
  • An ester with an acid or the like is used.
  • ⁇ ⁇ -derived derivative of such a nucleic acid having a nucleic acid is appropriately selected depending on the kind of the acid to be used, and when a free acid is used as the acylating agent, the reaction is carried out in the presence of a condensing agent.
  • such condensing agents include, for example, , ⁇ dicyclohexynolecarbodimide, ⁇ -cyclohexyl N'-morpholino-noethyl canolejo 'dimide, ⁇ -cyclohexylene N'-(4- Dimethylaminocyclohexyl) carbodiimide, ⁇ -ethyl ⁇ ⁇ "(3-dimethylaminobutyrate) carbodimid, etc. are used ⁇
  • the acylation reaction is usually performed in a solvent.
  • Solvents include water, acetone, dioxane, toluene-tolyl, dimethylene chloride, chloroform, dichloromethane, tetrahydrofuran, ethinole sulphate, dimethylformamide, pyridine or other reactions.
  • a common organic solvent is used, and among them, an aqueous solvent can be used by mixing with water.
  • the acylation reaction is, for example, sodium hydroxide, sodium carbonate, or ⁇ .
  • _-Inorganic bases such as potassium carbonate, sodium hydrogencarbonate, etc., trialkylamines such as trimethylamine, triethynoleamine-tributinereamin, N-methinolemosolefolin, N-methylbiveridine, N, N-dialkylaline, N , N dialkylbenzylamine, pyridine, bicholine, lutidine, organic tertiary amine, 1,5-diazabicyclo [4'3,0] non-5-ene, 1,4-diazabicyclo [22,2] octane, 1'8 —Diazabicyclo [5,4,4] can be carried out in the presence of an organic base such as pendene 7, and a liquid of the base or the above-mentioned condensing agent can also be used as a solvent.
  • the reaction temperature is not particularly limited, but is usually performed at room temperature with
  • the reactive derivative at the amino group in the starting compound ( ⁇ ) or salts thereof and the acylating agent may have only one stereoisomer when the compound has a non-carbon. It can be used in any form or in a mixture. In the case where these isomers are mixedly produced in this reaction, each of the isomers can be singulated by a conventional method such as column chromatography or recrystallization if necessary.
  • Compound 02) used as a starting compound in the acylation reaction may be in the form of a salt or a silyl derivative.
  • the salt those similar to the examples of the salt of the compound (I) can be used.o
  • the starting compound is used in the form of a salt in the acylation reaction, it can be produced.
  • Compound (IV) may also be obtained as a salt. When it is obtained as a salt, it can be collected as another salt in the same manner as in the exchange of the salt of compound (I).
  • compound (IV) obtained in the form of a salt can be collected as a free form.
  • the salt of the compound (I) is converted into the free form. A method similar to the above method is used.
  • compound (I) has a protecting group and can be used as a compound.
  • the method for removing the protecting group of the zetidine derivative (I) may be a method using ⁇ , a method using a base, a method using reduction, a method using hydrazine, thiourea or N
  • a conventional method such as a method using sodium methyldithiate lupamate can be appropriately selected and carried out.
  • the acid in the case of the method using an acid, the acid varies depending on the kind of the protecting group and other conditions. Examples of the acid include inorganic acids such as hydrochloric acid, sulfuric acid, phosphorus shun, gishun, and acetic acid.
  • Trifluo-drought acid Trifluo-drought acid, brobionic acid, benzene sulfonic acid, p Organic acids such as toluene ⁇ fonic acid and others, and acid / ion exchange resins are used.
  • a base for example, alkali metal such as sodium and potassium or alkali earth metal such as calcium and magnesium is used as a base.
  • organic bases such as alkoxides, organic amines, quaternary ammonium salts, etc., basic ion exchange resins, etc. are used.
  • a hydrophilic organic solvent When a solvent is used in the above-mentioned method using a metal or a base, a hydrophilic organic solvent, water or a mixed solvent is often used.
  • the reduction method it depends on the type of the protecting group and other conditions.
  • metals such as tin and sodium or gold compounds such as chromium dichloride and chromium acetate, and acetic acid, brobionic acid, and hydrochloric acid
  • a method of conveniently using an acid such as an organic or inorganic acid such as a catalyst, a method of reducing in the presence of a metal catalyzing agent for catalytic reduction, and the like are used.
  • Platinum wire platinum sponge, platinum black, platinum oxide, platinum catalyst such as platinum colloid, palladium sponge, palladium black, palladium oxide, palladium sulfate, palladium carbonate, palladium carbon, palladium silica gel, colloid Palladium catalysts such as palladium, reduction nickel oxide, nickel oxide, Raney nickel, Urushibara nickel, etc. 0
  • a metal compound such as iron and chromium, an inorganic acid such as hydrochloric acid, and an organic acid such as formic acid, acetic acid, and tramonic acid are used.
  • the reduction method is usually carried out in a solvent.
  • alcohols such as methanol, ethanol, bromo alcohol, and isopropyl alcohol, and ethyl thiocyanate are frequently used.
  • water, acetone, etc. are used.
  • the acid is a liquid, the acid itself can be used as a solvent.
  • the reaction is usually carried out under cooling or heating.
  • the protecting group is a residue of an organic carboxylic acid and there is a substituent such as a free amino group, a hydroxy group, a mercapto group, a carboxy group, a sulfo group, etc. on the carbon adjacent to the carboxyl group.
  • a substituent such as a free amino group, a hydroxy group, a mercapto group, a carboxy group, a sulfo group, etc.
  • it is preferable to remove the protecting group which is advantageous.
  • the free amino group is converted to a thiolate group.
  • a method of removing a protecting group by using a known method used for a method of decomposing a butadi bond is used.
  • the temperature of this reaction is not particularly limited and is appropriately selected depending on the type of the protecting group, the type of the elimination method, and the like, but it is preferable to carry out the reaction under mild conditions such as cooling and heating.
  • ⁇ C:.! FI In this reaction, when Ri is a compound having a carboxy group, the carboxy group may be changed to a carboxy group in some cases, but such a case is also included in the scope of the present invention.
  • the thus-obtained compound (I) from which the protecting group has been removed is prepared by a conventional method.
  • the starting compound ( ⁇ ) (in) of the present invention can be produced, for example, by the following method.
  • the starting compound (H) of the present invention can be prepared by the method described in JP-A-54-76570, when R4 is an acyloxy group, for example, tetrahedron letters (Tetrahedron Letters) 4059 CI 978). If 3 ⁇ 4 is a substitution group (one S—S—R 5 ), for example, the method described in Chemical's Communication (845) (1971) or a method similar thereto Yo]? In the above formula, when 3 ⁇ 4 is an acyloxy or a non-dichloro compound, for example, the following method is used according to the method described in Anna 1 en der Chemie 1974, 539. It can be synthesized by the ⁇ , 2) route.
  • R2, R3, R, and x have the same meaning as described above, and R8 represents a retained amino group.
  • the MR spectrum is measured with a Varian HA 100 (10 Giz), EM390 (90 MHz) or T60 (6 OMHz), and the three values are expressed in ppm based on tetramethylsilane.
  • S is a singlet, br. S is a wide singlet, d is a doublet, dd is a doublet, t is a trilett, q is a quartet, m is a multilett, and ABq is a quartet of AB type.
  • J is the binding constant
  • HF is tetrahydrofuran
  • DMF is dimethyl sulfonamide
  • DMSO dimethyl sulfoxide
  • IR w cra- 1 3290, 1798, 1670, 1525,
  • 21- (2-chloroacetamidothiazole-4-yl) -1-21-methoxyiminoacetic acid (syn isomer) 2 was added to 20 ⁇ of methylene chloride, and the mixture was added under ice and triethylamine 0.87. Add 1.5 parts of phosphorus chloride and stir for 5 minutes. After stirring at room temperature for 30 minutes, the mixture is concentrated under reduced pressure, and the residue is washed with hexane. To this is added THF 10 to remove insolubles. This solution is added dropwise to a mixed solution of the previously prepared solution and propylene oxide 3 under ice cooling.
  • Resin manufactured by ROHM 'And' Haas
  • I icw— 1 3420, 3270, 1780, 1760, 16
  • IR 3420-3325, 1785, 1665, 1615, 1515, .1280, 1240, 1068, 1040
  • the present compound 2-oxazetidine * isomer (I) is a bacterium, which can be used as a harmful agent in the human or household; for the prevention of bacterial infection Used.

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Abstract

Derives 1-sulfo-2-oxoazetidine representes par la formule generale suivante I: (FORMULE) (ou R1 represente un groupe amino eventuellement acyle ou protege, X represente un atome d'hydrogene ou un groupe methoxy, et R4 represente un groupe azido ou un groupe represente par (FORMULE) (ou) R5 represente un reste organique, et n represente 0,1 ou 2)), et leur procede de preparation illustre ci-dessous:) (FORMULE) sera faite dans la formule (ou R2 represente un groupe amino acyle ou protege, R3 represente un groupe amino acyle et R1 et R4 sont tels qu'ils sont definis ci-dessus).
PCT/JP1980/000296 1980-12-05 1980-12-05 Derives azetidine et leur procede de preparation WO1982001872A1 (fr)

Priority Applications (34)

Application Number Priority Date Filing Date Title
PCT/JP1980/000296 WO1982001872A1 (fr) 1980-12-05 1980-12-05 Derives azetidine et leur procede de preparation
MX819801U MX7096E (es) 1980-12-05 1980-12-05 Metodo para preparacion de derivados de 2-oxoazetidina
IL64314A IL64314A (en) 1980-12-05 1981-11-19 2-oxoazetidine derivatives,their production and antimicrobial and beta-lactamase inhibitory compositions containing them
HU813576A HU189545B (en) 1980-12-05 1981-11-26 Process for producing 2-oxo-azetidine derivatives
DK534381A DK534381A (da) 1980-12-05 1981-12-02 Fremgangsmaade til fremstilling af 2-oxoazetidinderivater
NO814113A NO160297C (no) 1980-12-05 1981-12-02 Analogifremgangsmaate for fremstilling av terapeutisk virksomme 2-oksoazetidinderivater
FI813851A FI79528C (fi) 1980-12-05 1981-12-02 Foerfarande foer framstaellning av farmaceutiskt verksamma 2-oxoazetidinderivat.
US06/326,939 US4822790A (en) 1980-12-05 1981-12-03 1-Sulfo-2-oxoazetidine derivatives and their production
SU813364650A SU1662348A3 (ru) 1980-12-05 1981-12-03 Способ получени призводных 2-оксоазетидина
FR8122774A FR2495612A1 (fr) 1980-12-05 1981-12-04 Derives de la 2-oxoazetidine, leur preparation et leur utilisation
CH7786/81A CH656122A5 (de) 1980-12-05 1981-12-04 2-oxoazetidin-derivate, verfahren zu ihrer herstellung und diese enthaltende praeparate mit pharmazeutischer wirksamkeit.
ES507716A ES507716A0 (es) 1980-12-05 1981-12-04 Procedimiento para preparar derivados de 2-oxoazetidina .
EP81110154A EP0053815B1 (fr) 1980-12-05 1981-12-04 Dérivés de 2-oxoazétidine, leur préparation et leur application
BE0/206751A BE891365A (fr) 1980-12-05 1981-12-04 Derives de la 2-oxoazetidine, leur preparation et leur utilisation
NZ199168A NZ199168A (en) 1980-12-05 1981-12-04 2-oxoazetidine derivatives and pharmaceutical compositions
GB8136617A GB2091723B (en) 1980-12-05 1981-12-04 Derivatives of 2-oxoazetidine-1-sulphonic acid
LU83820A LU83820A1 (fr) 1980-12-05 1981-12-04 Derives de la 2-oxoazetidine,leur preparation et leur utilisation
AT81110154T ATE13178T1 (de) 1980-12-05 1981-12-04 2-oxoazetidin-derivate, ihre herstellung und verwendung.
AT0520781A AT379800B (de) 1980-12-05 1981-12-04 Verfahren zur herstellung von neuen 2-oxazetidin-derivaten
DE19813148020 DE3148020A1 (de) 1980-12-05 1981-12-04 2-oxoazetidin-derivate, ihre herstellung und ihre verwendung
DE8181110154T DE3170437D1 (en) 1980-12-05 1981-12-04 2-oxoazetidine derivatives, their production and use
ZA818445A ZA818445B (en) 1980-12-05 1981-12-04 2-oxoazetidine derivatives,their production and use
PT74087A PT74087B (en) 1980-12-05 1981-12-04 2-oxoazetidine derivatives their production and use
SE8107273A SE8107273L (sv) 1980-12-05 1981-12-04 2-oxoazetidinderivat, sett att framstella democh anvendning derav
IE2859/81A IE53451B1 (en) 1980-12-05 1981-12-04 2-oxoazetidine derivatives,their production and use
IT68585/81A IT1146726B (it) 1980-12-05 1981-12-04 Derivati della 2 ossoazetidina loro produzione ed impiego
JP56196078A JPS57131759A (en) 1980-12-05 1981-12-04 2-oxoazetidine derivative, its preparation and use
NL8105468A NL8105468A (nl) 1980-12-05 1981-12-04 2-oxoazetidinederivaten, werkwijze ter bereiding hiervan en preparaten die deze derivaten bevatten.
PCT/JP1981/000368 WO1982002042A1 (fr) 1980-12-05 1981-12-05 Derives d'azetidine et leur procede de preparation
KR1019810004759A KR880001564B1 (ko) 1980-12-05 1981-12-05 2-옥소아제티딘 유도체의 제법
AU78313/81A AU551463B2 (en) 1980-12-05 1981-12-07 2-oxoazetidine derivatives
ES513420A ES513420A0 (es) 1980-12-05 1982-06-25 "procedimiento para preparar derivados de 2-oxoazetidina".
SU833547568A SU1531852A3 (ru) 1980-12-05 1983-02-02 Способ получени производных 2-оксоазетидина или их солей с основани ми
AT0170384A AT380471B (de) 1980-12-05 1984-05-23 Verfahren zur herstellung von neuen 2-oxoazetidin-derivate

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
WOJP80/00296801205 1980-12-05
PCT/JP1980/000296 WO1982001872A1 (fr) 1980-12-05 1980-12-05 Derives azetidine et leur procede de preparation

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WO1982001872A1 true WO1982001872A1 (fr) 1982-06-10

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PCT/JP1980/000296 WO1982001872A1 (fr) 1980-12-05 1980-12-05 Derives azetidine et leur procede de preparation

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BE (1) BE891365A (fr)
WO (1) WO1982001872A1 (fr)
ZA (1) ZA818445B (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3225619A1 (de) * 1981-07-16 1983-02-10 Von Heyden GmbH, 8000 München 4-substituierte derivate von 2-oxo-1-azetidinsulfonsaeuren und ihre salze
US4771045A (en) * 1982-05-31 1988-09-13 Takeda Chemical Industries, Ltd. 2-oxozetidinone derivatives, their production and use

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
No relevant documents have been disclosed. *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3225619A1 (de) * 1981-07-16 1983-02-10 Von Heyden GmbH, 8000 München 4-substituierte derivate von 2-oxo-1-azetidinsulfonsaeuren und ihre salze
US4771045A (en) * 1982-05-31 1988-09-13 Takeda Chemical Industries, Ltd. 2-oxozetidinone derivatives, their production and use

Also Published As

Publication number Publication date
BE891365A (fr) 1982-06-04
ZA818445B (en) 1982-10-27

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