WO1982003858A1 - Derives d'azetidine et procede de preparation - Google Patents

Derives d'azetidine et procede de preparation Download PDF

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Publication number
WO1982003858A1
WO1982003858A1 PCT/JP1981/000102 JP8100102W WO8203858A1 WO 1982003858 A1 WO1982003858 A1 WO 1982003858A1 JP 8100102 W JP8100102 W JP 8100102W WO 8203858 A1 WO8203858 A1 WO 8203858A1
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Prior art keywords
solution
group
add
ppm
acid
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PCT/JP1981/000102
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English (en)
Japanese (ja)
Inventor
Chem Ind Ltd Takeda
Taisuke Matsuo
Hirotomo Masuya
Noriyoshi Noguchi
Michihiko Ochiai
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Takeda Chemical Industries Ltd
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Priority to MX819801U priority Critical patent/MX7096E/es
Application filed by Takeda Chemical Industries Ltd filed Critical Takeda Chemical Industries Ltd
Priority to PCT/JP1981/000102 priority patent/WO1982003858A1/fr
Priority to IL64314A priority patent/IL64314A/xx
Priority to HU813576A priority patent/HU189545B/hu
Priority to DK534381A priority patent/DK534381A/da
Priority to FI813851A priority patent/FI79528C/fi
Priority to NO814113A priority patent/NO160297C/no
Priority to SU813364650A priority patent/SU1662348A3/ru
Priority to US06/326,939 priority patent/US4822790A/en
Priority to DE19813148020 priority patent/DE3148020A1/de
Priority to IE2859/81A priority patent/IE53451B1/en
Priority to DE8181110154T priority patent/DE3170437D1/de
Priority to FR8122774A priority patent/FR2495612A1/fr
Priority to ES507716A priority patent/ES507716A0/es
Priority to LU83820A priority patent/LU83820A1/fr
Priority to IT68585/81A priority patent/IT1146726B/it
Priority to EP81110154A priority patent/EP0053815B1/fr
Priority to AT81110154T priority patent/ATE13178T1/de
Priority to JP56196078A priority patent/JPS57131759A/ja
Priority to AT0520781A priority patent/AT379800B/de
Priority to CH7786/81A priority patent/CH656122A5/de
Priority to NL8105468A priority patent/NL8105468A/nl
Priority to PT74087A priority patent/PT74087B/pt
Priority to NZ199168A priority patent/NZ199168A/en
Priority to GB8136617A priority patent/GB2091723B/en
Priority to SE8107273A priority patent/SE8107273L/xx
Priority to KR1019810004759A priority patent/KR880001564B1/ko
Priority to PCT/JP1981/000368 priority patent/WO1982002042A1/fr
Priority to AU78313/81A priority patent/AU551463B2/en
Priority to ES513420A priority patent/ES8305325A1/es
Publication of WO1982003858A1 publication Critical patent/WO1982003858A1/fr
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
    • C07D205/09—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
    • 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
    • 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 is a novel antibacterial or anti-lactamase inhibitor
  • the present invention relates to 1-sulfo-3,4-monosubstituted-2-oxoazetidine derivatives and a method for producing the same.
  • the present inventors have conducted intensive studies with the aim of obtaining a new and useful azetidine derivative, and found that an azetidine derivative having a spho group at the 1-position meets the above-mentioned object, and further studied ⁇ : completed.
  • the present invention provides:
  • R4 is azide group, halogen or -0 B 5
  • the present invention relates to a method for producing a conductor having the following properties:
  • R 4 is an azide group, a halogen or — 0, —? — R 5,
  • Ting for example fluorine, chlorine, bromine, etc. iodine, organic Sezzanmoto represented by B 5 is a hydrocarbon group, Ashiru group means etc. heterocyclic group.
  • the hydrocarbon group means an aliphatic group which can have a straight-chain, branched, or cyclic double bond or triple bond, or an aromatic group such as fu- ⁇ or naphthyl. Thus, it means a hydrocarbon-substituted carboxy group.
  • the heterocyclic group for example, a 5- to 6-membered heterocyclic group containing one sulfur atom and / or 1 to 4 nitrogen atoms is used, and these heterocycles may be condensed with a benzene ring. .
  • pyridinole, tetrazoli, thiaziazolyl, che, thiazoly, isotizazoly, benzothiazoly and the like are used.
  • the hydrocarbon group, the acyl group and the heterocyclic group are, for example, lower alkoxy having 1 to 3 carbon atoms, such as halogen, phenoxy, and phenyl, such as lower alkoxy, carboxy, futan, element and bromine. /, Such as free chael 3 ⁇ 4 heterocyclic group, methiothio, ⁇ chinolechio 3 ⁇ 4 lower alkynoleci group having 1 to 3 carbon atoms, heterocyclic thio group such as tetrazolylthio, thiadiazolylthio,
  • the amino group may be substituted with an amino group, cyano, or the like.
  • Hi in Amino groups that are ⁇ assimilation represented by B 2 and R3, as the Nru group, conventionally known behenate - silicon emissions induced, in the 6-position Amino groups of the conductor
  • an aryl group or an ⁇ group substituted for the 7-amino group of the cephalosporin derivative 15 may be used.
  • H 6 represents lower phenol or a substituted or unsubstituted phenol, a heterocyclic group or a substituted or unsubstituted benzoyl.
  • H 7 is hydrogen, yo Amino acid residues which may have a substituent, a protecting group of the Amino group of the formula R 8 - (CH 2) nl -C0- wherein, R 8 substituent A heterocyclic group which may have 25; a phenyl which may have a substituent; A lower quinolene or a phenyl or an lower alkylthio which may have a substituent, and nl represents an integer of 0 or 1.4, and 1 (CH 2 )
  • the n i -group may have a substituent.
  • the term refers to hydrogen, low-alkyl, low-alkyl rubamoyl, and optionally substituted phenyl or sulfo. ':), or expression
  • R 8 ′ -S 0 2- wherein, in the formula, represents a lower alkyl which may have a substituent.
  • R 9 may be hydrogen or a substituent.
  • R 10 is a group represented by the formula R 12 _S— ′, wherein X is an oxygen or sulfur atom.
  • Rl2 is good Hue have a good heterocyclic group or a substituted group which may have a substituent - Le
  • R 13 is hydrogen, which may have a S3 ⁇ 4 group Feni ⁇ , low killing ⁇ Shi
  • a lower alkyl or a formula Hl4-Rl5 (wherein, Ei4 represents a lower alkylene or a lower alkylene, and .5 represents a carboxyl, an ester or a complex thereof).
  • a group represented by ⁇ , bond or the formula E n is Ru single 3 ⁇ 4
  • R 16 represents a lower alkyl, a substituted or unsubstituted heterocyclic group which may be substituted).
  • the groups represent each.
  • B 17 is hydroxy, hydroxysoxy, carboxyl, sphamoyl, sho 'which may have a substituent, or a phenoxy force ball which may have a substituent.
  • benzyl; 1 Okishikanoreboni / 1 the host mill old Kishifuta imide, 3 ⁇ 4 8 is hydrogen, lower ⁇ ⁇ kill, low handling a co alkoxy, halogen, azido, - Toro, hydroxy, I respectively table ⁇ ; represented by] Group,
  • R 19 represents cyano, a substituted or unsubstituted phenyl group, a substituted or unsubstituted phenyl group, a substituted or unsubstituted lower alkyl group, A substituted or unsubstituted heterocyclic group; B 20 a single bond or -s-; a group represented by Table cD, etc. .
  • the lower aki represented by B 6 is preferably a lower aki having 1 to 6 carbon atoms.
  • the heterocyclic group in the optionally substituted heterocyclic group is a 5- to 6-membered heterocyclic group containing 1 to 2 nitrogen atoms and containing one element atom. Those not included are used.
  • the heterocyclic group for example, isoxazoly, piperazyl, imidazoly and the like are used.
  • Examples of the heterocyclic group include, but are not limited to, C 1 -C 3 -alkyl, C 1 -C 3 -a-koxy, halogen, two-to-one, amino, oxo, toxo, and Oki groups.
  • substituent in the substituted or unsubstituted benzoic acid and the substituent in the substituted or unsubstituted phenyl include, for example, a low-said alkyl having 1 to 3 carbon atoms and a 1 to 3 carbon atoms. Lower alkoxy, halogen, nitro, amino and the like are used.
  • Substituents which may be substituted with amino acid residues include, for example, amino, lower ⁇ / U quilamino, amino group protection, carpamoy, meth!
  • amino-protecting group represented by R 7 those similar to the amino-protecting group described below can be used.
  • the heterocyclic group which may be a substituent represented by R 8 of the group represented by the formula Eg-(CHg) !!! -CO- includes, for example, 1 even sulfur atom, nitrogen 5-6 membered heterocyclic group containing atoms or oxygen atoms, 5-6 membered heterocyclic group containing 2-4 nitrogen atoms, containing 1-2 nitrogen atoms and one sulfur or nitrogen atom
  • a 5- to 6-membered heterocyclic group is used, and the heterocyclic group is a 6-membered ring group containing two or less nitrogen atoms, a benzene ring or a 1-membered ring. It may be condensed with a 5-membered ring group containing i sulfur atoms.
  • R 8 Specific examples of the compound ring group represented by R 8 include, for example, 2-biridyl, 3-pyridyl, 4-pyridyl, bilimidinyl, birazinyl, biridazyl, biperazinyl, birazolinyl, imidazolidinyl, thiadiyl
  • Examples of the substituent of the heterocyclic group which may have a substituent represented by R 8 include alkyl having 1 to 12 carbons and 1 to 12 carbons which may have a substituent. 3 lower alkoxy, hydroxyl, oxo thioxo, — aldehyde, trifluoromethyl, amino, halogen, 1 to 3 carbon atoms
  • the 25 groups include, for example, lower alkyl having 1 to 3 carbon atoms and 1 ⁇ 1 / Coxy, Halogen, Hydroxylene, Amino Rude are used.
  • the lower A Kill in lower A key thio represented by the B 8 preferably from 1 to 3 carbon atoms.
  • Examples of the substituent in the phenyl which may have a substituent represented by R 8 include lower alkyl having 1 to 3 carbon atoms, lower alkoxy having 1 to 3 carbon atoms, halogen, hydroxy /, Used for amino.
  • Examples of the substituent in piperazyl include low-alkyl having 1 to 8 carbon atoms, lower alkoxy having 1 to 3 carbon atoms, and hydroxy. , Oxo, Choki, No, and Harogen Rudo are used.
  • the lower aki represented by H 8 ′ and / or R preferably has 1 to 3 carbon atoms.
  • Low Alkita-Power The lower alky which can be used in Bamoy is preferably a lower alkyd having 1 to 3 carbon atoms.
  • Examples of the substituent in the carboxy which may have a substituent include lower alkyl having 1 to 3 carbon atoms, lower alkoxy having 1 to 3 carbon atoms, halogen, hydroxy, and hydroxysoxy. , Penziloxy etc. are used.
  • U s - S 0 2 - as lower A key to kick the goodness lower alkylene which may have a substituent group represented by group B 'represented by is preferably one having a carbon number of 1-6, The substituent may be substituted at one or two positions, and examples thereof include amino, carboxy, pendoxycarbonyl, and protected amino groups.
  • Security As the protecting group in the obtained amino group, the same as the protecting group for the amino group described below can be used.
  • the lower group in the lower anoalkyl which may have a substituent represented by R 9 , those having 1 to 3 carbon atoms are preferable.
  • the substituents include, for example, fu-, molybdenum, methacrylic acid / ⁇ balmoy, methy / Uchio, cho- / Uacetamide, ethoxycarbo-methicapamoy, N-methytetrazolylthio, halogen, and Famoi is used.
  • heterocyclic grave are also good heterocyclic group having a substituent represented by E 9, for example, 5-membered double heterocyclic group containing one sulfur atom, a nitrogen atom or an oxygen atom, 1-2 A 5-membered heterocyclic group containing one nitrogen atom and one sulfur or oxygen atom, and a 5- to 6-membered heterocyclic group containing 2 to 4 nitrogen atoms are used.
  • heterocyclic group examples include, for example, thiazoli, isothiazoli, oxazoli, isoxazoli, ceni, fury, viloli, imidazoli, biradi-, pyrimidi-, pyridazini, biperazi-, triazini, tetrazoliz, thiadiazoli, thiadiazoli, thiadiazoli, thiadiazori
  • substituents include lower alkyl having 1 to 3 carbon atoms, lower alkoxy having 1 to 3 carbon atoms, halogen, hydroxy 1, -toro, and hydroxys! Asoxyleamino having 2 to 4 carbon atoms, which may be substituted with ethoxy, amino, or halogen, is used.
  • the cycloanolekelene represented by is preferably a 5- to 6-membered ring, and examples thereof include cyclohexyl and cyclohexeninole.
  • Heterocyclic group which may have a substituent represented by R9 or may be via an alkylene chain
  • a 6-membered heterocyclic group having two nitrogen atoms is used.
  • the heterocyclic group for example, biladide is used.
  • the substituent for example, an alkyl having 1 to 12 carbons, a lower alkoxy having 1 to 3 carbons, oxo, thioxo, aminoamino, etc. are used.
  • the alkylene group those having 1 to 3 carbon atoms are preferred, and examples thereof include methylene, ethylene, and n-brovirene.
  • a 5-membered heterocyclic group containing one nitrogen atom, sulfur atom or oxygen atom and containing or containing one nitrogen atom is used.
  • this complex ring group include, for example, 2-thiazolyl, -thiazolyl, 5-thiazolyl, 2-dithiol, 3-chloro, 2-free, 3-free, 2-pyrroli, 3-pyrroli, and the like. Is used.
  • substituent in this heterocyclic group include lower alkyl having 1 to 8 carbon atoms, lower alkoxy having 1 to 3 carbon atoms, hydroxy, mesyl, halogen, imino, amino, mesylamino, and halogen.
  • An amino acid having 2 to 4 carbon atoms which may be used is used.
  • the substituent in the phenol which may have a substituent represented by Ri2 includes, for example, lower ac having 1 to 3 carbon atoms, lower acoxy having 1 to 3 carbon atoms, halogen, -toro, amino , Hydroxy or substituted hydr A mouth kiss is used.
  • a substituent in the substituted hydroxy for example, benzyl, benzoy, ash having 2 to 10 carbon atoms, rD-gutami, 3-amino-3-force boxybrobi!
  • phenyl-0 substituent which may have a substituent represented by B13, for example, lower alkynole, low alkoxy, halogen and the like are used.
  • a lower bond having a substituent represented by R13 a lower bond preferably has 2 to 4 carbon atoms.
  • substituent for example, halogen frit is used.
  • the kylene preferably has 1 to 3 carbon atoms, and examples thereof include methylene, ethylene, brovirene, and Oral billets are used.
  • the lower alkylene represented by Ri4 is preferably a lower alkylene having 1 to 3 carbon atoms.
  • Examples of the lower alkylene include bilen and ⁇ -belene.
  • heterocyclic group represented by H 15 6-membered heterocyclic group containing one nitrogen atom and one oxygen radicals is use, as its ingredients ⁇ be use for example motor Norehorinoru etc. is.
  • Rll-C0-NH- As the lower alkyl represented by Ri 6 in the group represented by H-, those having 1 to 3 carbon atoms are preferable.
  • substituent in the phenyl which may have a substituent represented by B16 include a lower alkyl having 1 to 8 carbons and a lower alkyl having 1 to 3 carbons.
  • the heterocyclic group which may have a substituent represented by is, for example, one 5-membered heterocyclic group containing a sulfur atom, a nitrogen atom or an oxygen atom, 1-2 nitrogen atoms and 1
  • a 5-membered heterocyclic group containing a sulfur or oxygen atom and a 5-membered heterocyclic group containing 2 to 4 nitrogen atoms are used.
  • ring group examples include, for example, thiazoli, isothiazoli / ⁇ , oxazoli, isosoxazoli, thie-, furyl, vilolyl, thiaziazoli ⁇ , oxaziazo! /, Triazyl, tetrazoli, imidazolyl, virazi-l, pyrimidizyl. It is used for brieflyazi, biperazin, and so on.
  • substituent include a lower ac having 1 to 3 carbon atoms, a lower acoxy having 1 to 8 carbon atoms, halogen, hydroxy, amino, and halogen, which may have 2 to 4 carbon atoms. Ascidino is used.
  • substituent in the sulfamoyl which may have a substituent represented by B17, for example, lower anolex having 1 to 3 carbon atoms, amidino and the like are used.
  • Examples of the substituent in the phenoxycarbo which may have a substituent represented by Ri «? include a lower ac having 1 to 3 carbon atoms and a lower ac having 1 to 3 carbon atoms.
  • the low suisuki alky and lower alkoxy represented by R18 each preferably have 1 to 3 carbon atoms.
  • C PI As the greeting group, for example, lower carbon atoms having 1 to 3 carbon atoms, lower alkoxy having 1 to 3 carbon atoms, halogen, -toro, amino, hydroxyl, substituted aminomethyl, and the like are used. Substituents in the substituted aminomethyl include, for example, carpamoy, (2-oxo-13-benzylidaminoaminoimidazolidin-11-yl) carbo-/ ⁇ , and (2-oxoimidazolidin-1-1- / t-force). Pod is used.
  • Hue is represented by the above H 19 - the same as the group of Honoré is use.
  • the lower group optionally having a substituent represented by 9 is preferably a lower group having 1 to 6 carbon atoms. Examples of the substituent include Haguchigen, hydroxy »cyano, and trif. ⁇ ⁇ chi 3 ⁇ 4 3 ⁇ 4 3 ⁇ 4 :: Used for.
  • alkylene which may have a substituent represented by Ri 9 examples include biylene and probelene, and the substituents include, for example, Boxyl, Siano, etc. are used.
  • heterocyclic groups include 2-Chenyl, Benzoche:, 3-Ithi-, 2-Pyridyl, 3-Pyridyl, 4-Pyridyl, 2-Thiazolinole, 4-Thiazolin, 5-Thiazoli, Isothiazoli, 1-tetrazoli, 5-tetrazoli, pyrro-1-di-, imidazoli, 1,4-oxatin, etc. are used.
  • a substituent in the heterocyclic group which may have a substituent represented by R 19 for example, a lower alkyl group having 1 to 3 carbon atoms, a lower alkoxy group having 1 to 3 carbon atoms, nodogen, nitro group , Hydroxy / 1 /, optionally protected amino, carboxy, oxo, halogen having 2 to 4 carbon atoms which may have a substituent, and acyl having 2 to 4 carbon atoms. Used.
  • alkyl having 1 to 12 carbon atoms include, for example, methyl, trifluoromethyl, ethyl, n-probi, isob ⁇ bi /, n-butyl, U, tert-bubble; u, tert-bubble / ⁇ , pliers, isopeni, hex, isohexi, heptyl, 8-hepti, saibu, no-, de, pendesi, dodeci, cyclohex 3 ⁇ 4 is used.
  • lower alkyl having 1 to 6 carbon atoms include, for example, meth, butyl, eth, n-propyl, iso-probi, n-petit, isopti, sec-butyl / 1, tert-butyl, bench, Isopentic, hexyl and isohexyl are used.
  • lower alkyl having 1 to 3 carbon atoms include, for example, methyl, trifluoromethyl »ethyl, n-propy, isobrobi and the like.
  • lower alkoxy having 1 to 3 carbon atoms include methoxy, ethoxy, n-buboxy and isopho. Can be used for key
  • halogen examples include chlorine, bromine, iodine, and fluorine.
  • lower axonyl having 1 to 3 carbon atoms examples include methysole, ethysulfo, and n-probis / 1/2 /! , Isopropyl sulpho-rudose is used.
  • acetylamino having 2 to 4 carbon atoms include acetylamino, Used for propio-noleamino, n-butylamino, isobutylamino, etc.
  • oxy having 2 to 10 carbon atoms include, for example, acetoxy, n-propio-oxo ⁇ , n-butyrioxy, isobutyroxy, n-ventanoyloxy, II-hexanoyloxy, For n-butanoyloxy, n-octanooxy, n-nonanooxy, n-decanooxy, etc.
  • Carboxamido-2--Che Acet, 0-2-[(5 —Methoxy bonni ⁇ 3—Methyl ⁇ -2—oxomidazolidine-11-yl) carboxamide] 2-0 F ⁇ -acetyl, D—2 — [(5-benzyloxycarb-3-1-methyl 2 Oxoimidazolidin-1 1) carboxamide 1-2 phenylacetyl, D—2 — [(5-carboxy-3r-methyl- 2-oxoimidazolidin-1 1; carboxamide] 2-phenylacetium, 2— (coumarin-3—carboxamide) -1 2-phenyl-2-, 2-C-2,3,3-oxo1 .1 Piperazinocarboxa
  • acyl group represented by the formula H 10 —R 1; CO— (wherein R 10 and have the same meaning as described above :) include, for example, N- [2- (2-aminothiazole-4 1-yl) 1- 2-Methoxyiminoacetyl] 1-D-ral, ⁇ - [2- (2-amithiazol-4-1y) 1- 2-methoxyminoacetyl], D-Fehlglyci , 2- 02 Maminothiazo-1-4-A — '2— [2 (2-aminothiazo-1-4-yl)
  • Examples of the ash group represented by)) include, for example, "1-hydroxy-acetyl, ⁇ hydroxy-hydroxy-acetyl, hydroxy-fluor-acetate / U, na-famo-yl-acetyl, Na, phenoxycarba-feracetyl, na, (p-tolyloxykaboe) fuerasset, a-home: ⁇ kisif-ruacetyl, ⁇ -carboxyphen-acetyl, a-penzi 21- (N, N-dimethysfamoyl) -2-1 phenol- /, 2-bromo-21-phenylacetyl, 2-azide l 2-phenylacetium, 2-phthalimide 2-chloroacetium, 2-azide 2- (3-chlorophenyl) acetyl, and the like are used.
  • acyl group represented by the formula 9-1 R20—CH2—CO— (wherein: 3 ⁇ 49 and 3 ⁇ 40 have the same meanings as described above) include, for example, 'for example, cyanoacetyl, phenylacetyl, and phenoxya.
  • the amino group and the ⁇ or carboxy group in the above-mentioned ash groups include those having a protecting group.
  • amino-protecting group those similar to the "amino-protecting group" described later are used.
  • the protecting group for the carboxy group includes / 3-lactam and organic chemistry.
  • C PI It includes all groups that can normally be used in the field as protecting groups for carboxyl groups, for example, where the ester moiety is, for example, methyl, ethyl, propyl, isopropyl, tertiary phthalic acid 1, tertiary amine, benzyl, / U, p--Tropenedi, P-methoxybenzil, Penzhidri, fenasi, phenyl, p--Tropfenii; /, Methoxymethyl, ethoxymethyl, pendioximeci-, acetoximethi, vinoloioximechi, -methisho-vech 1, methic meth meth, trit, ⁇ , ⁇ , / 3-trichloroe., ⁇ - 3 - Doechiru f trithiadiaza ⁇ Li; ", Jimechirushiri, ⁇ cetirizine methylcarbamoyl, p Torobendi methyl
  • the selection of the protecting group is not particularly limited, and particularly, is benzene, ⁇ , ⁇ , ⁇ -tricholine / U, ⁇ - ⁇ trovenge / U, ⁇ -methodine. Is preferred.
  • those used for the purpose of iS lactam and peptide synthesis in the field of synthesis are conveniently adopted.
  • Probioni Monochloroacetyl, Dichroacetyl, Trichloroa Cet, methanesulfol, ethane sulfonyl, trifluoroacet, maloy; 1, aliphatic sucrose groups such as succinyl;
  • Amino groups other than acyl groups such as, for example, trityl 2-triethyl phenyl, benzylidene, 4-trobenzylidene di- or trialkyl ⁇ ryl, benzene, p- trobenzyl, etc.
  • Protecting groups are used.
  • WZ (where A is hydrogen, methyl, isobutyl, etc., a low radical group such as cyclohexyl, cyclohexyl, etc., alicyclic group, phenyl group, phenoxybenzy, etc. ⁇ represents a double-ringed ring group such as a lacyl group, cho, bezoche, viloli, isoxazolyl, biperazi, thiazolyl, tetrazoi, oxachiano, etc., where A is ami, low aki, gradea; It may have 12 substituents such as enoxy, oxo, hydroxyl, /, gen or chloroacetamide.
  • And; may represent a bond or a bond.
  • the low-alkyl group is preferably a linear or branched alkyl group having 1 to 4 carbon atoms, and these groups are the above-mentioned ⁇ N-methyl-bamoyl, carbopendoxyamino, for example, an aryl group such as phenyl, and tetrazoacetoamide.
  • Ethyl-2r3-dioxol 11-piverazinocaboxamide which may have phenyl, methyl, or ethyl at the 3-position, or may be substituted by a 1,2-diazo-1 heterocyclic group.
  • AK9M includes halogens such as fluorine, chlorine, and bromine, low-acid-killing groups include methyl and ethyl, and low-alkoxy groups include methoxy and ethoxy.
  • Examples of the protected amino group represented by W include chloroacetylamino and aryl.
  • the heterocyclic ring in the heterocyclic carboxamide group represented by W is phenyl, an alkyl group having 1 to 12 carbon atoms, a saturated aliphatic group, an alkyl group having 2 to 8 carbon atoms, such as methoxy and ethoxy. Even if it has a low cis-acidoxy group, it can be a carbonyl group, a furf V-redenamino group, a sulfo group,
  • G-viPI It may be substituted with a carbonyl group, an aralkyloxycarbyl group or a carboxy group.
  • the lower alkyl in the low alkylcidic carboxamide group represented by W is preferably a linear or branched alkyl group having 1 to 4 carbon atoms, which may be substituted with a halogen such as chlorine, bromine or fluorine.
  • A is phenyl, phenoxy, thiazolyl, chel, biperazino, and further substituted with amino, lower alkyl, or lower alkoxy, and is unsubstituted at the a position.
  • the compound (I) Since the compound (I has a phosphine group, it can form ⁇ 1: by the action of a substituent at the exclusion. * Therefore, the compound 3 ⁇ 4 (I) can be detected as ⁇ .
  • the compound 4 obtained as a salt may be in free form or as another salt, and the compound (I) ⁇ may be obtained in free form.
  • Inorganic groups such as phenol and ammonia are used, for example, organic pyridine groups such as pyridine, collidine, lytylamine, and triethanolamine.
  • Compounds of the present invention (I) are also included in the present invention.
  • a method for releasing a compound obtained as a salt into a free form for example, a method using an acid and the like are used.
  • the acid to be used depends on the protecting group and other conditions. Examples of the acid include inorganic acids such as hydrochloric acid, sulfuric acid, and phosphoric acid, and organic acids such as formic acid, severe acid, and P-toluenesulfonic acid. Used. ⁇ Other than that, ion exchange resins are used.
  • a hydrophilic aqueous organic solvent such as eaceton, tetrahydrofuran, methano, le, ethano, dioxa, etc., water or a mixed solvent is often used.
  • Compound (I) has a stereoisomer (eg, D-isomer, L-isomer).
  • the compound obtained in this way is useful as a medicament]. For example, it has antibacterial activity against certain Gram-positive and Gram-negative bacteria.
  • the acute toxicity of the compound (I) of the present invention by intravenous administration to mice is as follows:
  • the compound (I) of the present invention is useful, for example, for the treatment of mammals (eg, mice, lads, humans) infected with the above-mentioned bacteria.
  • the present invention I is used as a therapeutic agent for bacterial abrasion, for example, as described in the above-mentioned mammals, ⁇ respiratory infection, urinary tract infection, genital illness, biliary tract infection, intestinal infection, and Feeling, surgical storage Can be used for any treatment. So
  • the daily dose is about 20 to about 200 ⁇ ⁇ ⁇ as compound (I)], and the dose is about 5 to about 10 ⁇ ⁇ ⁇ divided into 2 to 4 times daily. It is appropriate to do so.
  • the compound (I) or a physiologically acceptable substance can be given orally by a conventional means, for example, in the form of a tablet, a case, a drop, and the like, or a Q form, or For example, it can be molded into an injection, then mixed with a fungal carrier produced by conventional means, and administered parenterally.
  • chemical formula (1) has a ratatamase inhibitory activity and is useful as a ⁇ -lactamase inhibitor.
  • Compound (I) of the present invention is useful for the treatment and prevention of bacterial infections in humans and livestock.
  • the compound (I.) of the present invention is formulated alone, it is used before or after administration of the / 9-latatam antibiotic, or is used in combination at the time of use. It can also be formulated by mixing with 9-lactam antibiotics.
  • the compound (I) of the present invention has a ratio of 1 ⁇ 10 to the 3′-lactam antibiotic 1 ′.
  • 1 to 0 times (weight) can be used, but a ratio of 1 to ⁇ 8, for example, 1Z5 or 1Z6, is advantageous.
  • ⁇ / ⁇ Is administered for example, 16 times, and more usually 2 to 4 times.
  • the 1S1-2-oxoxetidine derivative (I) of the present invention can be produced, for example, by subjecting a compound (IT) to a sulphonation reaction. This sulfonation reaction introduces a sulfo group ⁇ :
  • O PI WI?- (H) for example, by reversing sulfuric anhydride or sulfuric anhydride reactivity induction ⁇ ).
  • Examples of the reactive derivatives of the above-mentioned sulfuric anhydride include, for example, Sulfuric anhydride, viridine, sulfuric anhydride, dioxane, sulfuric anhydride, 1-trimethylamine, sulfuric anhydride, cros. Is used.
  • the above reaction is carried out by reacting about 1 to about 5 ⁇ of sulfuric anhydride- or sulfuric anhydride with respect to 1 mole of the compound ('I), and more preferably about 1 1
  • the reaction temperature is about 0 to about 03 ⁇ 4, more preferably about 1 to about 403 ⁇ 4, and a solvent may be used for the reaction.
  • the solvent include ⁇ ⁇ , tetrahydrofuran, and jet / ⁇ Ethers such as ether, severe acid, formic acid, etc.
  • the 1-phospho-12-oxozetidine-derived fold (17) of the present invention can be produced, for example, by subjecting a compound (I) to a chemical reaction.
  • This acylation can be carried out by reacting an acylating agent with the chemical compound 3IE).
  • the carboxylic agent used in this reaction may be a bonded carboxylic acid containing an amino group represented by R 3 , or a reactive derivative of these acids.
  • examples of the reactive derivative of the organic acid include an acid anhydride, an active amide, and an active ester.
  • the reactive derivative of such an organic acid is specifically described. is there.
  • the acid anhydride examples include, for example, hydrohalic acid (eg, hydrochloric acid, hydrobromic acid, etc.) ® acid anhydride, monocarboxylic acid mixed acid anhydride, aliphatic acid carboxylic acid (eg, acetic acid, Acids, valeric acid, isopentanoic acid, trichloroacetic acid, etc.) mixed acid anhydrides, aromatic carboxylic acids (eg, benzoate) mixed acid anhydrides, symmetrical acid anhydrides, etc. are used.
  • hydrohalic acid eg, hydrochloric acid, hydrobromic acid, etc.
  • monocarboxylic acid mixed acid anhydride aliphatic acid carboxylic acid (eg, acetic acid, Acids, valeric acid, isopentanoic acid, trichloroacetic acid, etc.) mixed acid anhydrides
  • aromatic carboxylic acids eg, benzoate
  • active amide for example, amides with virazo, imidazo-1, 4-substituted imidazole, dimethyl virazo, benzotriazole and the like are used.
  • examples of the active esthetics include methieste, ethieste, methoxymethyl esthe, propargyl ester, 4-trofe-esthe, 2,4-dinitrophenyl esthe, trichloro phenyl, pentachloro phen (2)
  • esthetics such as esters and mesophylesters, etc., as well as 1-hydroxy-1-H--2-pyridone, .N-hydroxysuccinimide, N-.hydroxyphthalimide, etc. ⁇ Esthetics are used.
  • the reactive derivative of such organic humor is appropriately selected depending on the type of acid used. Further, when a free acid is used as the acylating agent, the reaction is carried out in the presence of a condensing agent.
  • condensing agents include, for example, Moholinethyl carbodiimide, N cyclohexyl N (4-diethyl; Uaminocyclohexyl) carbodiimide, and N-ethyl N- (3-dimethylaminopropyl) carbodiimide are used.
  • the acylation reaction is usually performed in a solvent.
  • a solvent water, acetone, dioxane, acetonitrile, methylene chloride, chlorophonolem, dichloroethane, tetrahydrofuran, ethyl alcohol, dimethylformamide, pyridine or any other organic solvent used for the reaction can be used.
  • the ⁇ water ⁇ solvent can be mixed with water.
  • the acylation reaction includes, for example, sodium hydroxide, charcoal sodium, potassium carbonate, sodium hydrogencarbonate, etc.
  • the reaction can be carried out in the presence of any of the above-mentioned groups or the above-mentioned condensing agents which can be used as a solvent, and the reaction temperature is not particularly limited, but is usually cooled or cooled. It is often done at
  • a reactive conductor or an amino acid and an acylating agent for an amino group in a raw material (3 ⁇ 4) have an asymmetric carbon in their compounding.
  • the three-dimensional plug ⁇ can be used alone or in a mixed rescue climb.
  • each of them can be isolated by a conventional method such as column chromatography, recrystallization or the like, if necessary.
  • Compound HI) used as a starting material compound in the acylation reaction may be in the form of a salt or a silyl derivative.
  • the salt those similar to those mentioned in the example of the above-mentioned compound (I) are used.
  • the compound (17) to be produced may be obtained as ⁇ .
  • it can be collected as another salt in the same manner as in the exchange of the salt of compound (I).
  • the compound (W) obtained in a salt form can be collected as a free form.
  • a method similar to the above-mentioned method of converting the salt of compound (I) into a free form is used.
  • the compound having a protecting group in compound CI) can be led to a compound by removing the protecting group.
  • a method for removing the protecting group of the azetidine derivative (I) depending on the type of the protecting group, a method using an acid, a method using a 3 ⁇ 4 group, a method using reduction, a method using hydrazine, thiourea or N-methyi; A conventional method such as a method using sodium diammonium bamate can be appropriately selected and performed. Therefore, in the case of the method using a shade, 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 and phosphoric acid, formic acid, m,, trifluoroacetic acid, and probiotic acid.
  • acidic ion exchange resins are used.
  • examples of the base include alkali metals such as sodium and potassium, as well as alkaline earth metals such as magnesium and magnesium.
  • Organic bases such as contacting bases, metal acoxyides, amines, and tandem ammonium salts, as well as base ion exchange resins are used.
  • metal such as chromium or metal compound such as chromium disulfonate> chromium oxyphosphate and an acid such as static, pubionic acid, and sulfuric acid, and an acid such as non-contact acid, etc.
  • platinum catalysts such as platinum wire, platinum sponge, black and white, platinum oxide, colloidal platinum, etc. may be used in the contact method. .
  • palladium catalysts such as radium sponge, palladium black, palladium oxide, palladium sulfate, palladium sulfate, radium carbonate, palladium carbon, palladium lizard, loydario, etc.
  • a metal compound such as iron and chromium, an inorganic acid such as hydrochloric acid, and an organic acid such as gishun, drusic acid and propionic acid are used.
  • the reduction method is usually carried out in a solvent.
  • alcohols such as methanol, ethanol A ⁇ bromo alcohol, isopropyl alcohol, u alcohol, ethyl acetate, u, etc. are commonly used. Is done.
  • water, acetone and the like are frequently used, but when the acid is a liquid, the acid itself can be used as a solvent.
  • the reaction is usually carried out under cooling or heating.
  • Ri is a compound having a carboxy group
  • the derivative at the carboxyl group may be converted to a carboxyl group, but this case is, of course, included in the scope of the original description.
  • the thus-obtained compound () from which the protecting group has been eliminated can be converted into a desired compound by a conventional method.
  • the raw material 3 ⁇ 4 ( ⁇ ) () of the present invention can be produced, for example, by the following method.
  • the starting compound (E :) according to the present invention is a compound of the present invention wherein, when R4 is an acyloxy group, for example, to tetra] ⁇ Lon Letters (Te traiiedron Letters)
  • R 2 , R 3 , ⁇ 4 , and X have the same meanings as described above, and ⁇ 8 represents a protected amino group 3 ⁇ 4T ⁇ L.
  • NMB spectrum is Parian: BA 100 type Cl Of O MHz) Measured with EM 390 (90 Ha) or T 60 (60 MHz), and based on tetramethylsilane, values in ppm You. S is a singlet, t> r.s is! ! Wide singlet, ⁇ is doublet, dd is doublet, t is triplet * q is force test, m is gusset, ABq is AB plastic force test, J is coupling constant, and T HF is Tet.lahydrofuran, DMF means dimethinolephonoremamide, DMSO means dimethylsulfoxide, ⁇ 3 ⁇ or broad means broad arom is aromatic.
  • IR ⁇ eiT 1 3290, 1770, 1675, 1525, 1290, 1275,
  • 1 E 3300, 1800, 1695, 1530, 1300,
  • IB i 'KBT c 1 3370 , 3270, 1790, 1680, 1540
  • IB 3380, 3250, 1790, 1680, 1540
  • NMB (DMSO, -ds, ppm) 2.97 (s, CH3), 3,95 (s, CH3).
  • NiiR (DMSQ-de, ppm) 2.12 (.s, CH S), 3.70, (s,, C.)
  • (3S, 4S) 4-acetoxy 3-[D-2-1 (41-et / ⁇ 1-2] 3-dioxo-one-biverazinokaboxamide) -1-2-fe-aceto amide] -1-2-y
  • (3S, 4S) -4-azide 3 -— [D—2— (4-ethyl 2r 3-Doxoxo 1-biperazino power; boxamid) —2-phenylacetamide] 1-2-oxozetidine 1.6%.
  • IB v g3 ⁇ 4caf 1 1765, 1705, 1670, 1510
  • IB 3330, 2950, 2930, 1750, 1720,
  • IR fSH- 1 3375, 3325, 2950, 2930, 1750,
  • NME (CDC1 3 »ppm): 0.24 (s, CH 3 ), 0.26 (s, CHs), 0.97 (s, tB); l * 82 (broad s, 3 ⁇ 4), 2.13 (s, CH3).
  • IR 1 3270, 2110, 1775, 1720, 1670,
  • NMB (CDC1 3, ppm): 2 -30 (s, C3 ⁇ 4) 3.05 (broad s, W]
  • IB KBr cm 1 3270, 3210 , 1772, 1725, 1097
  • NM B (DMS0-d6, ppm): 3.90 (s, OC), 4.35 (s, -C3 ⁇ 41),
  • IR fg3 ⁇ 4 cw 1 1760, 1660, 1545, 1050
  • NMB (d6 ⁇ DMS0, ppm) : 2-06 (s, CH 3), 3.87 (s, CH 3).
  • IR or 1 8370.1785, 1685, 1290, 1250,
  • N MB (d ⁇ -DliSO.ppm): S.16 (s, C3 ⁇ 4), 4.53, one C one
  • the oily substance to be separated by addition of GE Ether 3 is crystallized by jetting with ethyl ether, and the oil is separated by distillation. Kisika boxomido 4-methoxy-2-oxazetidine 1-sulfonate 0.226 da is obtained.
  • IR cm 1 3500-3400, 1780, 1665, 1520,
  • IB / KBr of 1 3450, 3260, 1778, 1660, 1512,
  • ⁇ ' ⁇ ⁇ / ⁇ 1 3400, 3250, 1775, 1660, 1522,
  • IR csT 1 1760, 1700, 1665, 1505, 1240,
  • IR ⁇ KBr era- 1 3380, 1782, 1760, 1710, 1512,
  • 3-(2-1-2-Fe: acetamide) 1-2-oxoazetidin 0.156 in DF solution 2 LMF, DMF complex 0.105 f DMF solution 0.7 Is at 70 e C Then, react at 15-5'C for 2 days. Adding 0.055 f of viridine and treating in the same manner as in Example 1, sodium (3S, 4S) —4-acetoxy 3 -— (2-bromo-21-Fe-acetamide) —2— Oxozetidine-l-lose phosphate 0.06 is obtained.
  • IR w 1 : 3400, 3275, 1780, 1750, 1670, 1540, 1278, 1250, 1042
  • IR ⁇ ⁇ - 1 3460, 3280, 1772, 1708, 1675,
  • Example 34 Sodium (3R, 4S), 4macetylthio-3- (2- (2-chloroacetamide thiazolyl) 4-yl) -1-methoxyiminoacetamide-amide] -2-oxazetidine-1 1
  • sodium sulfonate 0.11 in water 5 EI add sodium phosphate monohydrate barium 0.036 to the solution under permanent cooling and stir at room temperature for 2 hours.
  • 4 S 4-Acetylthio 31-1 [2- (2-Aminothiazol-4-1) -1 2-Methoxy 5-aminocetamide-]-1 2-oxo5azetidine 1 1 V 0.0 3 2 is obtained.
  • Example 37 (3 R, 4 S) -4-methylthio-13 ——2- (2-methyl Cetamido thiazole 4- 1) 1- 2-Methoxyiminoacetamide] 1 2 1-year-old oxoazetidine 0.3 4 1 To a DMF 2W solution of 1 MF complex 0.4 0 0 Add ODF 2.7 solution at 170 ° C ⁇ After reacting for 2 days at O'C, add pyridine 0.206 and treat in the same manner as in Example 1 to obtain sodium (3R, 4 (S) 4-Methylthio 3 -C 2-(2-methyl 1 oacetamide thiazolone 4 4 / V) — 2-methyl, quinoacetamide 1 ⁇ 2-year-old oxoazetidine 1 1 sulfone 0.2 4 6 is obtained.
  • IR 3 ⁇ 4 ( ⁇ 1 : 3480, 3280, 2105, 1772, 1708, 1670, 1505, 1275, 1242, 1185, 1045
  • IB ⁇ — 1 3480, 3275, 2115, 1775, 1710, max
  • IB f ⁇ ⁇ 1 1760, 1705, 1670, 1500, 1240, 1145
  • I i ca 1 1765, 1670, 1540, 1260, 1045
  • IR / 1 1760, 1665, 1615, 1525, 1260,

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Abstract

Derives de 1-sulfo-2-oxoazetidine representes par la formule generale (I) suivante: (FORMULE) (dans laquelle R1 represente un groupe amino eventuellement acyle ou protege, X represente l'hydrogene ou un groupe methoxy, R4 represente un groupe azido, un atome d'halogene, ou un groupe represente par (FORMULE) (ou R5 represente un reste organique et n represente 0,1 ou 2)), et procede de preparation illustre par le schema (FORMULE) (dans lequel R2 represente un groupe amino acyle ou protege, R3 un groupe amino acyle, et R1 et R4 sont comme definis precedemment).
PCT/JP1981/000102 1980-12-05 1981-04-30 Derives d'azetidine et procede de preparation WO1982003858A1 (fr)

Priority Applications (32)

Application Number Priority Date Filing Date Title
MX819801U MX7096E (es) 1980-12-05 1980-12-05 Metodo para preparacion de derivados de 2-oxoazetidina
PCT/JP1981/000102 WO1982003858A1 (fr) 1981-04-30 1981-04-30 Derives d'azetidine et procede de preparation
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
FI813851A FI79528C (fi) 1980-12-05 1981-12-02 Foerfarande foer framstaellning av farmaceutiskt verksamma 2-oxoazetidinderivat.
NO814113A NO160297C (no) 1980-12-05 1981-12-02 Analogifremgangsmaate for fremstilling av terapeutisk virksomme 2-oksoazetidinderivater
SU813364650A SU1662348A3 (ru) 1980-12-05 1981-12-03 Способ получени призводных 2-оксоазетидина
US06/326,939 US4822790A (en) 1980-12-05 1981-12-03 1-Sulfo-2-oxoazetidine derivatives and their production
IT68585/81A IT1146726B (it) 1980-12-05 1981-12-04 Derivati della 2 ossoazetidina loro produzione ed impiego
CH7786/81A CH656122A5 (de) 1980-12-05 1981-12-04 2-oxoazetidin-derivate, verfahren zu ihrer herstellung und diese enthaltende praeparate mit pharmazeutischer wirksamkeit.
DE8181110154T DE3170437D1 (en) 1980-12-05 1981-12-04 2-oxoazetidine derivatives, their production and use
FR8122774A FR2495612A1 (fr) 1980-12-05 1981-12-04 Derives de la 2-oxoazetidine, leur preparation et leur utilisation
ES507716A ES507716A0 (es) 1980-12-05 1981-12-04 Procedimiento para preparar derivados de 2-oxoazetidina .
LU83820A LU83820A1 (fr) 1980-12-05 1981-12-04 Derives de la 2-oxoazetidine,leur preparation et leur utilisation
DE19813148020 DE3148020A1 (de) 1980-12-05 1981-12-04 2-oxoazetidin-derivate, ihre herstellung und ihre verwendung
EP81110154A EP0053815B1 (fr) 1980-12-05 1981-12-04 Dérivés de 2-oxoazétidine, leur préparation et leur application
AT81110154T ATE13178T1 (de) 1980-12-05 1981-12-04 2-oxoazetidin-derivate, ihre herstellung und verwendung.
JP56196078A JPS57131759A (en) 1980-12-05 1981-12-04 2-oxoazetidine derivative, its preparation and use
AT0520781A AT379800B (de) 1980-12-05 1981-12-04 Verfahren zur herstellung von neuen 2-oxazetidin-derivaten
IE2859/81A IE53451B1 (en) 1980-12-05 1981-12-04 2-oxoazetidine derivatives,their production and use
NL8105468A NL8105468A (nl) 1980-12-05 1981-12-04 2-oxoazetidinederivaten, werkwijze ter bereiding hiervan en preparaten die deze derivaten bevatten.
PT74087A PT74087B (en) 1980-12-05 1981-12-04 2-oxoazetidine derivatives their production and use
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
SE8107273A SE8107273L (sv) 1980-12-05 1981-12-04 2-oxoazetidinderivat, sett att framstella democh anvendning derav
KR1019810004759A KR880001564B1 (ko) 1980-12-05 1981-12-05 2-옥소아제티딘 유도체의 제법
PCT/JP1981/000368 WO1982002042A1 (fr) 1980-12-05 1981-12-05 Derives d'azetidine et leur procede de preparation
AU78313/81A AU551463B2 (en) 1980-12-05 1981-12-07 2-oxoazetidine derivatives
ES513420A ES8305325A1 (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
WOJP81/00102810430 1981-04-30
PCT/JP1981/000102 WO1982003858A1 (fr) 1981-04-30 1981-04-30 Derives d'azetidine et procede de preparation

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WO1982003858A1 true WO1982003858A1 (fr) 1982-11-11

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Cited By (1)

* 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

Non-Patent Citations (1)

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

Cited By (1)

* 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

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