WO1982001820A1 - Beta-lactamase-inhibiting composition - Google Patents

Abstract

Compounds having one or two substituents in the 3-position and represented by the following general formula: (FORMULA) (wherein R<u1>u represents an optionally acylated or protected amino group, and X represents a hydrogen atom or a methoxy group) show an excellent //c(ss-lactamase-inhibiting action when used alone or in combination with other ss-lactam series antibiotics, thus being utilized as medicines for humans and domestics animals.

Description

 Akira

 9-lactamase a harmful composition _

 Technical field

 Honsen Akira is a novel 1-suho 2-year-old oxoazetidinated ^ J / 9-lactamase inhibitor and an anti-blind product containing it.

 Background art

 In recent years, research on semi-synthetic antibiotics has greatly contributed to the cure of vigilant dysbiosis. However, the problem of the emergence of resistant and resistant bacteria to these semi-synthetic products is one of the important issues. Recently, it has been proposed to fight against S-lactamase-producing resistant bacteria with; 3-lactamase damage j. For example, new W / 9-ratha-se-inhibitors such as Kravlan (Antimicrovial 'Azide Azide Keterabi, 11, 52 (1977)) It has been found, however, that its β-lactamase S harmful effect is sufficient for some bacteria and may be impeached.

Disclosure of the invention

The invention relates to the formula

[In the formula, 1 ^ represents an amino group which may be acylated or optionally substituted, X represents hydrogen or methoxy. ] -Lactamase-inhibited S component having the compound represented by the formula [1] and the above-mentioned / 3-lactamase-inhibited S component also having a / 9-lactam-based product.

 The present inventors are one! 1 Formula (I) 1-sulfo-2-oxazetidine

c π The present inventors have found that the compound has an excellent 9-lactamase damage effect, and as a result of further studies, completed the present invention.

 That is, the present invention

L General formula

[In the formula, represents an amino group, X hydrogen or methoxy, which may be protected or protected. ^ -Lactamase containing a compound represented by the formula:

 ■ 2. The above S-lactamase inhibitory composition which also has a lactam antibiotic. ...

 In the above-mentioned killing formula, represents an amino group which has been added, and the amino group which has been converted into an amino group has been substituted by the amino group at the 6-position of a peniline phosphor which has been used in the past. And an amino group substituted for the amino group at the 7-position of the cephalesbolin derivative.

 As an example of such a group, for example, equation (1)

R ₆ -CO--[wherein, H ₆ may have a substituent or a substituent;-/, a heterocyclic group, a substituent; Express. And the formula (2)

 B „一; — CO—

 -I

{Wherein, is a hydrogen, an amino group which may have a substituent, a group for maintaining an amino group, a formula R ₈ -C¾) _{n] L} -CO- [where? ' ₈ has a substituent An optionally substituted heterocyclic group, a phenyl which may have a substituent, a low phenyl which may have a substituent, a phenyl or a low phenyl which may have a substituent N represents an integer of 0 or 4 and n represents an integer of 0 or 4, and the-(CH ₂ ) _nl -group may have a substituent. ].

Formula ^¾ > NC 0- [where: R ₈ 'and are the same or different ^

 , Lower aki, lower alkavamoy, which represents phenyl or sulfo which may have a substituent. ] Or expression

Eg- '-S0 ₂ - [. Wherein "is representative of a good Tei設A 〃 kill may have a substituent] a group represented by hydrogen, may grade have a substituent It has a substituent, a functional group, and a functional group.

 "^ Is a good heterocyclic ring, cyclo σ-alkene, ® substitution group 複 素 may have or may be through an alkylene chain. , (3)

^B 10— ^R ll— ^co

[ ^Wherein , 0 represents the formula ^R 12-¾-(wherein X represents

B ₁₂ represents a heterocyclic group which may have a substituent or a phenyl which may have a substituent, and 5ι _{; 5} may have a hydrogen atom or a baby group Feni / ^, low grade § shea, low grade A key or formula one: R ₁₄ -; R ₁₅ (wherein, the Tei级A

〃Kirylene or IS-Kenenylene,> _κ is carboxy, its esthetic

 Or a heterocyclic group そ れ ぞ れ, respectively. ;)), Respectively. } Is a simple bond or a formula-

-C0-NH-CH- (wherein the beta ₁₆ Tei经A key may Fe have a substituent -. Representing Le or optionally substituted heterocyclic group) in formula Represent the following groups. A group represented by

 (4) Equation 1--~,-"ヽ

(ί A ~:--. '\

 [Takenaka: R 1 * 7 is hydroxy, hydroxyloxy, carboxyl, spamoy, sulfo, or phenyl optionally substituted 置換: phenol that may be substituted Carbo, benzyl / oxycarbonyl, and imide-phthalamide, El8 is hydrogen, low-acid, low-oxy, low-oxy, halogen, azide, nitro, and hydroxy. The group represented,

 Equation (5)

：-H ₁₉ — B ₂₀ — C ¾ — CO-

[In the formula, E ₁₉ is a cyano, a phenyl which may have a substituent, a phenyl which may have a substituent, and a phenol which may have a substituent.

B20 represents a single bond or -S-, and L represents an alkenylene which may have a substituent or a heterocyclic group which may have a substituent. Are used.

In the above formula, as the alkyl represented by R6, those having 1 to 6 carbon atoms are preferable. The heterocyclic group in the optionally substituted nitrogen ring group is a 5- to 6-membered heterocyclic group having a nitrogen atom of 1 to 2 and containing one oxygen atom or Included are used. Specific examples of the nitrogen ring group include, for example, isoxazoli, biperazi-〃, and imidazoli: ¾. Examples of the substituent of the heterocyclic group include a low-alkyl having 1 to 3 carbon atoms, a low-alkoxy having 1 to 3 carbon atoms, a halogen, a thiol, an amino, an oxo, a thioxo, and a substituent. Fe, etc., which may have The substituents in the above-mentioned phenyl which may have a substituent include, for example, low carbon atoms of 1 to 3 carbon atoms, and prime numbers. The lower alkoxy, halogen, nitro and amino acids are used.

In the above formula, examples of the amino residue in the amino residue optionally having a substituent represented by R ₇ include, for example, glycine, aralar.

, Roy 5 / L, Isoleuci, Seri, Threoni, Sisti, Sisti / 1 /, Metio, a1 or / 9-asbachyl, a1 or 7 "-Gutami, Rigi ^, Argini, Feniarani Examples of the substituents which may be substituted on the amino-A residue include amino, low-alkamino, protecting groups for the amino group, and phenyl glycine, cis, histidine, tributy, and broly. Moy, sphamoy. Benzyl, eth2,3,3,2,3,4-diperoxy-carboni, lith-2,3,3 dioxo-1-bibaziradino cabamino . it is resistive element较alkylene 〃 Amino to ^kick:. the抵殺§ 〃 key, the protecting group is preferably the Amino group having 1 to 3 carbon atoms, speed similar to the bales Mamorumoto of Amino groups after Things used It is possible.

As the protecting group for the amino group represented by H ₇ , the same as the protecting group for the later amino group can be used.

Wherein _{B 8 - (CHg ^ i -} CO - in the heterocyclic group which may have a substituent represented by B ₈ groups represented: ^ Ru Examples of the heterocyclic group, For instance 1儇sulfur atom 5-6 membered heterocyclic group containing nitrogen or nitrogen atom, 5-6 membered cyclic group containing 2-4 nitrogen atoms, 1-2% nitrogen atom: ^ and 1% sulfur atom or A 5- to 6-membered bract ring group containing a nitrogen atom is used, and these heterocyclic groups include a 6-membered ring group containing two lower nitrogen atoms, a benzene ring or an even yellow atom. It may be combined with a 5-membered ring group.

As the component of the cyclic group represented by R ₈ above, for example, 2 ― Δ―

 Viridil. 3-Viridi, 4-Viridi, Bilimidini, Viradi-, Biridadi-〃, Biverazini, Birazolini, Imidazolidini, Thiazori, Isothiazoli ^, Saixazoli, Isoxazoli, Pyrid [2,3-d] Benzovirae, 1,8-naphthyridini-, 1,5-naphthyridini, 1,6-naphthyridini, 1,7-naphthyridini. 2.7-naphthyridini, 2, 6-naphthyridini, quinoli, thieno [2.3- "b] Viridini, tetrazo, thiadiazori, oxaziazioli, triazi, che, viroli, frida, etc.

And with the substituent of the heterocyclic group which may have a substituent represented by the B _8, for example A key good carbon 2 may have a substituent, low 1 to 3 carbon atoms Zirconoxy, hydroxy ^ 〃., O, xo, thioxo, ade odo, trifometi, amino, halogen, low aki / sulfo-, 2,6-dichlorobenzene-2 with 1-3 carbon atoms. , bear! 1-carbon, 1-hodium 1-biradizin, belo aldimino, brandimino, thiophenaldimino, mesi, amino-protecting group, carbon atom which may be substituted with halogen 2 The following amino groups may be used as the protecting group for the amino group. Examples of the group which may be substituted with a carbon atom of 1 to 12 carbon atoms include, for example, phenyl :, halogen, t-doxy, and diamino. The dialkylamino dialkylamino is preferably an S dialkyl having 1 to 3 carbon atoms.

Examples of the substituent in the phenyl which may have a substituent represented by R 8 include, for example, low alkyl having 1 to 3 carbon atoms, dihydroxy, halogen having 1 to 3 carbon atoms. , Hydroxy

As low级A key thio to kick A key 〃 represented Te said 11 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 a low alkyl having 1 to 3 carbon atoms, a low-alkoxy having 1 to 3 carbon atoms, halogen, and hydrogen. Used by de 13x and Amino.

Examples of the group which may be substituted with the group represented by the formula (CH ₂ ) _NL- include, for example, amino, and the formula: NH-CO-: wherein: may have an amino or a substituent.ぃ represents Viveradi-〃. ] Are listed. Substituents of biverazi-〃 which may have a substituent represented by the following are, for example, low carbon atoms having 1 to 3 carbon atoms. Alkoxy low alcohols having 1 to 3 carbon atoms ^, hydroxyyl, and oxo. , Thixo, halogen, etc. are used. In the above formula, alkyl fcL represented by H ₈ ′ and Z or E is preferably one having 1 to 3 carbon atoms. Low-priced iron A low-priced iron in Bamoi is preferably one with 1 to 3 carbon atoms. Examples of the substituents in the optionally substituted phenols include, but are not limited to, carbon atoms of 1 to 3 © low carbon atoms, carbon atoms of 1 to 3 carbon atoms, and τττ. Gen, hydroxy, hydroxy, and benzyl can be used.

In the above formula, BQ one - so ₂ - as low § key that takes a good Tadashi较§ keys may have a substituent group represented by B _s "of the groups represented by the number of carbon atoms

1 to 6 are preferable, and the substituent may be substituted at 1 m or at two positions, and examples thereof include, for example, amino, carboxy, benzyloxycarbonyl, and the above-mentioned amino group. And so on. The protecting group for the protected amino group is the same as the protecting group for the amino group described below. Is used.

 For the low-alkyl group which may have a substituent represented by Bg, the low-alkyl group preferably has 1 to 3 carbon atoms. Examples of the substituents thereof include fu-. Vaimoi, methylcarbamoy, methicone, che = acetamide, ethoxycaboni methicavamoy, N-meth / tetrasoraziothio, halogen, and spamoyl. It is required.

 Examples of the substituent in the phenyl which may have a substituent represented by Eg include 7 ^^-aki having 1 to 3 carbon atoms, 1-alkoxy having 1 to 3 carbon atoms, halogen, Hydroxy, hydroxysyloxy, benzoxy, benzodioxy, tomethysil, and 'oxy' having 2 to 10 carbon atoms are used.

 Represented by Bg. Examples of the heterocyclic group of the optionally substituted heterocyclic group include a 5-membered heterocyclic group containing 1 僙 real atom, nitrogen atom or nitrogen atom, 1 to A 5-membered heterocyclic group containing two nitrogen atoms and 1% wart or arsenic atom, and a 5-6 membered heterocyclic group containing 2-4% nitrogen atoms are used. Specific examples of the heterocyclic group include, for example, thiazoli, isothiazoli, oxazoli, isoxazoli V, che, frivilioli, imidazoli, biradi, bilimidie, biridazini, biverazini

 , Triazini, tetrazori, thiadiazori, oxaziazoli, etc. are used. The substituent may be, for example, substituted with low carbon having 1 to 3 carbon atoms, acetoxy having 1 to 3 carbon atoms, halogen, hydroxy, nitro, hydroxysoxy, oxy, amino or halogen. A carbon nanotube of 2 to 4 carbon atoms is used.

 The cycloalkylene represented by Rg has a 5- or 6-membered ring.

〇 PI Preference is given to using, for example, cyclohexenedicyclohexane, cyclohexadiene and the like.

Heterocyclic group which may have a substituent represented by H ₉ or may be via an alkylene chain-The carbo-amino heterocyclic group is a 6-membered heterocyclic group having two nitrogen atoms. Used. As the heterocyclic group, for example, biverazide and the like are used. The substituent is, for example, carbon number

1 to 12 aki, 1 to 3 alkoxy, oxo, thioxo, amino and the like are used. The alkylene chain preferably has 1 to 3 carbon atoms, for example, methylene 'ethylene' n-propylene.

In the above formula, B of the group represented by the formula ¾ ₂ -C- ′ in E ₁₀

 --R13

 The heterocyclic group in the heterocyclic group which may have a substituent represented by J is a 5-membered heterocyclic group containing one nitrogen atom, sulfur atom or oxygen atom. One or more nitrogen atoms can be found. Specific examples of the heterocyclic group represented by are, for example, 2-thiazoly, 4-thiazolyl, 5-thiazoly, 21-thier, 31-cheni, 2-bri, 3-frii, 2-biroli, and 3-biroli. Parudo is used. Examples of the substituent in this heterocyclic group include ^ 玆 aryl having 1 to 3 carbon atoms, low-acid-killing alkoxy having 1 to 3 carbon atoms, hydroxy, methyl, halogen, imino, amino, and the like. Mesamino and acetylamino having 2 to 4 carbon atoms which may have halogen as an immobilization group are used.

Examples of the substituent in the phenyl which may have a group represented by R ₁₂ include a lower alkyl having 1 to 3 carbons, a lower alkoxy having 1 to 3 carbons, halogen, nitro, amino, and amino. Droxy or substituted hydroxypoxy is used. Substituent i in substituted hydroxy For example, benzyl, benzoy, carbon with 2 to 10 carbon atoms, R-D—gutami, 3-amino-3—force, etc. are used.

The迗级A key represented by B _13, arbitrarily favored those carbon ¾ 1 to 3.

 Examples of the substituent of phenyl which may have a substituent represented by Ri3 include, for example, low-alkyl, low-alkoxy, and halogenated.

 The gg acyl having a substituent of 0 to 2 carbon atoms is preferable, and for example, a halogen frit is used as the substituent.

Takes the R ₁₃ wherein one Ei4 -: The low killing A Killen represented by groups represented by RL5, preferably those having 1 to 3 carbon atoms, examples of such as methylene, ethylene, propylene *, I Sopurobirenru The corner is sharp.

_Further , the low-bag _alkylene represented by _Β14ι is preferably one having 1 to 3 carbon atoms, and examples thereof include bi-lene and brobenylene.

The beauty / u mosquitoes Bokishi represented by beta _15, for example, methylcarbamoyl 〃 E stearate, E Ji Este 〃 is Providenciales Este Doga兒.

The heterocyclic group represented Te beta _15,. 1 6 membered heterocyclic group containing nitrogen atom spare one Shun atom of偎is used, as specific debt e.g. Mo Hori rests etc. are used.

Wherein one of R _n CO - NH - - with a group represented: The Tei铰A 〃 key represented Te R _16, Mashi纾those carbon 1-3.

 置換 Substituents in Fe2 which may have a substituent represented by 6

G rl For example, low carbon atoms having 1 to 3 carbon atoms are used, such as low carbon atoms having 1 to 3 carbon atoms, 1 koxy, halogen nitro, amino, and 2 to 10 carbon atoms. Can be

Examples of the optionally substituted substituent represented by B ₁₆ include a 1-membered sulfur atom, a nitrogen atom or a 5-membered heterocyclic group containing a nitrogen atom. A 5-membered heterocyclic group containing 1-valent or yellow atoms or a sulfur atom, or a 5-membered heterocyclic group containing 2 to 4 nitrogen atoms is used. Specific examples of the heterocyclic group include, for example, thiazoly, isothiazoly, oxazoli, isoxoxoli, che =, furyl, pylori, thiadiazoli, oxadiazoli, triazi =, tetrazoli, imidazoli.

, Villa., Bilimy, bildazini, biperaj; = · Λ. Examples of the substituent include low-acyl having 1 to 3 carbon atoms, low-alkoxy having 1 to 3 carbon atoms, halogen hydroxy, amino, and halogen. Four to four aluminos are used.

 As the substituent in spamoyl which may have a substituent represented by Rp, for example, low g-aki having 1 to 3 carbon atoms, amidino and the like are used. ···

As the substituents on the phenol carboxyl which may have a substituent represented by R ₁₇ , there are used, for example, aki having 1 to 3 carbon atoms, and low alkoxy having 1 to 3 carbon atoms.

Low扱A key and § 〃 Kokishi represented by B _18, respectively, preferably from 1 to 3 carbon atoms.

In the above formulas: The ¾ ₉ Te good Hue second location substituent may have a substituent group represented, for example, carbon ¾ 1 to 3 lower ^ A key, Low-proportioned acetoxy, halogen, nitro, amino, hydroxy, substituted aminomethyl, etc. are used. Examples of the substituent in the substituted aminomethyl group include, but are not limited to, bamoy, (2-oxo-3-benzylideneaminomidazolidin-1-11) cabo, (2-oxomidazolidine-1-11yl) A cab is available.

Examples of the phenoxy substituent which may have a substituent represented by R ₁₉ include a low aki having 1 to 3 carbon atoms, a low alkoxy having 1 to 3 carbon atoms, halogen, and nitrite. r, amino, hydroxy, and aminomethyl are used. The same groups as those described above for R = represented by R ₁₉ are used. B ₁₉ , which may have a substituent represented by B ₁₉ , is preferably a compound having 1 to 6 carbon atoms.

: For example, halogen, hydroxy, cyano, and tri-methyl are used.

Examples of the akenylene which may have a substituent represented by H and ₉ include bi-lene and b-butylene, and the substituents include, for example, Caboxy and cyano are used.

The heterocyclic group in the heterocyclic group which may have a substituent represented Te H _19, 1僵of琉賁屎子or 1-4 lie <nitrogen atom-free 5-6-membered heterocyclic group, 1 A 5- to 6-membered heterocyclic group containing a hydrogen atom of Li and a nitrogen atom of 1 Levi or one oxygen atom is used. Examples of the elementary groups include, for example, 2-Che, Benzoche, 31Che, 2-Billie, 3-Bridge, 4-Bridge, 2-Thiazoli, 4-Thiazoli, 5Thiazoli ^ , Isothiazoli Λ ^, 1-tetrazoli, 5-tetrazoli, pyrrolidini, 'imidazoli, 1,4-oxatin, etc. are used.

A substituent on the heterocyclic group optionally having an S group represented by R _1S Examples thereof include low alkyl having 1 to 3 carbon atoms, low alkoxy having 1 to 3 carbon atoms, halogen, -to-T3, hydroxy, optionally retained amino, carboxy, and oxo. For example, amino having 2 to 4 carbon atoms and halogen having 2 to 4 carbon atoms which may have a halogen as a substituent are used.

 In the above formula, specific examples of the C 1 to C 12 anoreki include, for example, meth ^ ^, trifluoromethyl. Ethyl. N-1 7 "guchi bill, isoprovir, n-butyl ^, isobuchi, sec-1. Buchi, tert-buchi, bench, isopench / u, hex, isohexyl, hept, 3 へ, ク, ニ, noni, deshi; V, デ, ド, 口Helix is used.

 In the above formula, as an example of the capture of low-carbon charcoal with carbon t16, t. Toemechi, triforomechi 'echi' n-one-provi, iso-provi, n-one-buchi, iso-buchi, sec- Buty, tert-butyl, pliers A ', isobench, hex, and isohexyl.

 In the above formula, examples of low carbon atoms having 1 to 3 carbon atoms include, for example, methyl, triforme, ethyl, II-probi, and isoprobi.

 In the above formula, examples of the lower alkoxy having 1 to 3 carbon atoms include methoxy, ethoxy, n-propoxy ', and iso-propoxy'. In the above formula, as the halogen component, iodine, bromine, iodine and fluorine are used.

In the above formula, examples of C1-C3 low-axes / honi include, for example, methys-ho, ethyshoni, n-provisulhoni, and isoprovishoni. . In the above formula, specific examples of the alkamino having 2 to 4 carbon atoms include, for example, acetylamino, propio- / amino, n-butylimino.isobutyridamino, and the like.

 In the above formula, specific examples of the alkoxy having 2 to 10 carbon atoms include, for example, acetoxy, n-brobyoxy, n-butyryloxy, isobutyryloxy, n-ventanoyloxy, n ^ xanoyloxy , N-Hetanoy, II-Octanoyoki, 31-Nonanoy, η-decanoyoxy.

 In the above acyl group, examples of the acyl group represented by the formula -CO-(wherein, E6 has the same meaning as described above:) include, for example, ぱ 3- (2,6-dichlorofe = ) One 5 —Medium soxazoose 4-1-A One; 1 / boni / u, -one-one / — 2, 3 —Dioxo-1 1-one-biperazizoka-bo 2, 2 —One-year-old ^ Which is used.

Specific examples of the ash group represented by the formula: R ₇ -H-CH-C 0-(wherein, B ₇ and R _n have the same meanings as described above) are, for example, D-ara- , D-fe-/ ^ ara-, na-benji-N-force ^ bobenzoki-ha-D-gutami- D-ara-, D-fu-e-glycy D-araranil, N D-Phenigly, D-Araninole D-Fen-Glysi, D-G ^ Tami-D-Dara 2 / u, D-Fen-Gri, D-Fen: = Glysi / V, D. Bamoy; ^ Tributy D—Hue = Leguri 5 /, Methamido asparaginyl-1 D—Fenidaryl, N Hue-Glyci ^, N-K-Boben-Zoki-D-Hue- / U-Gri-D-Fe-n / v-Glyci / ✓, 2— (2,3-Diamino-Brobianamide) 1 2 — Hue-Aseti, D—Aranyi ^ D - § La Second, 2- [2

. 1-Amino-3- (N-methylazomoxy) brobionamide] aceti, 21- (2-Amino-3-sulfamoi ^ probionamide) 1-2-1phenylase, 2- [2-amino-3-(4-ethyl) /-2, 3 -dioxo 1-l-vinylazino-force) boxyamide) 1- 2-ferrasse, D ■ 2-(4-l-l2,3-dioxo 1-l-lazinokaboxamide ) 1-2-(4-methoxy-2 /) aceti, 1-ethyl-2, 3-dioxo-1-11-biverazinocarbo-, D-2-[2-(4-1-1-2-3-dioxo-1-1-biverazinoca Boxamide) 1-3 (N-Metica / Zumoi;) Bropion-Mid)-1-2-Fu-acetyl, D-2-[2-(4-1 2, 3-3- Bibez azinoka boxamido) acetamide] -1-2-phenylase, D-1 2- (3-source Amoy / ー 21 〃 力 力 力 ボ ボ ボ ボ 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 Samido) Probionamide] 1-Fe / Aceti, 21- [2-Benzyloxycarboxamido] 3- (N-Methylcarbamoyl) -m-Bionamide] Acetyl, 2- (N-Carbobenzoxy-D-phenylglycylamino ) 1-3-(N-methica vamoy) Probionyl, N-carbenezoxy-D-arae 2-(Benzi-sikakaboxamido)-1-1-fu: = rusacetyl, 2-benzyloxykaboxamido 3-: K "-Mechika Bamoy Proboni, 2T- (Beechi-2,3-dithioxo-one-11-veraverinocarboni) -D-Feniglycyl, 2- (2-Aminothiazol-4-1- ) 1-2 (1-1, 2-3-dioxo-1-1-biradino diboxamide) acet, 2-(2-phenylacetamide)

) Probi, 2-(4 チ .1 2, 3 -Dioxo 1 1 Zinokaboxamide) 1—2—Ce2 aceti /, 2— (4—11—2,3—dioxo) 1—Biberazinokaboxamide) 1—2—fe = Acet, D—2— (4, 6 —Jet 2,3—Di ^ “Kiso 1 1 Biberazinokaboxamide) 1—2-Fuacetchi D—2— (4 1-Hex 2,3, Jixabox 1 1 Biberazinokaboxamide) 1 2-phenylene, D-2- (4-hexoxy-2,3-dioxo-1-1-bipera-n-carboxamide) -1-2-cheniaceti, D-1-2 (4-n-ami-1-6 CS) 1-Methyl ^ 1,2,3-Dioxo1-1 1 Biberazinocaboxamide) 1-12-Chenylacetyl, D—2— (4-1,5-CB1) -Methyl-2,3-Dioxo1-1 1-Biperazinocarboxamide 2—Che-Sech, D—2— (4-1 5 (S) 1-Mem 2.3. Kisamide) 1 2—Chaseasechi, 2 — ((3-Fri V-denaminow 2-Oxomidazinidine 1-11) Carboxamido] 1-2-Chaselace, 2— (41-1E) // ^ 12,3-Dioki y-1-11Biberazinocabonii) -1 2- (4-Methoxyxy-) acetyl, 2- (8-Hydroxy-1,5-Naphthyridine-1 7-Power Boxamide) -1 2—Hue-Acetich, 2—1 (4—2, 3—Ji-Kizo 1—Biradino Power Bosamid) 1—2—Hue = Acetil, 2— (4—1 n—2, 3— Dioxo-1-1-biperazino / u-boxamin) 2-Fe = aceti, 2-(4-ethyl-2,3-dioxo-1-1-biperazinokaboxamido) -1-2- (4-hydroxysoxyphene / No.) Acet, 2-1 (4-ethyl / ^-1,2,3-dioxo- 1-biberazinocarboxamide) 2-1— (4 D) aceti /, 2- (4--octa-2,3-dioxo-one-biberazinoca boxamid) -1 2- (4-hi-dros-honi キ ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ Chi-2,3-dioxo-one-biperazinocarboxamide-1-1- (4-trimethylsilyl-) acetyl, 2- (4-1-ethyl-2,3-di-sixiso-1) -biverazinocarboxami 1) 2-(3-4-meth) ^ acechi, 2-(2-3, 2-才 ビ ビ ビ ビ) 1 2-(3-chloro-4 κ) Droxys honoki feni) Aceti, 2— (4-et-2,3-di) ^ 1-11-bipera dinocaboxamide-1) 2- (3-Chloro-4-hydroxide ^ fe-) acetyl, 2 — (4 一 1 一 2,3 一 1 キ 1 ソ 1 一 1 一 1 ペ 2 ペ 4 ペ 2 ペ 3 44 ペ 1 ー 2 ペ 3 44 キ 2 キ 3 ビ 1 キ 2 キ 3 ビ 1 キ 2 キ 3 キ 1 キ 2 キ 3 ビ 1 キ 2 キ 3 ビ 4 ビ 2 キ 3 ビ 2 キ 3 ビ 4 キ 2 キ 3 ビ 4 キ 2 キ 3 キ 4 ジ 2 キ 3 ビ 4 キ 4 キ 2 ー 3 Cut; —2,3-Dioxo. 1-Biberazinocaboxamide) 1—2- (4-Hydroxypheny) acetium, N— (4-Hetoxy2,3-Dioxo-1—11-Biperazinocarbo2, N -(4-ech, 3-dioxor 1-radino force)-n / = = =, N-C-echyl-2, 3-dioxo-1-1 velazinoka-/)-D-ara =, 2- (4-ethyl-2-2.3-dioxo-11-biverazinocaboxamide) -1-2- (4-1hydroxy ^ phenyl) aceti, 2,2-bis (4-ethyl-2,3-dioxo-1-11biverazinocarbox Samido) Asechi, 2- (4-ethyl-2-3, 3-diene-butane-one) 2, 3 才 一 ソ 一 一 一 一 ビ 一 一 — — — — — — — — — — — Chi-2, 3 - Jiokiso 1 one Biberajino force Boki Sami de) - 2 - (2-Aminochiazo - 4 - I 〃) Asechi, 2-C.4

 ―One: '

.one 2-, 3-Dioxo- 1-Biberazinocaboxamide) 2- (2-Chloroacetamidothiazole-1-4) Acet, 2-(4-1-C2,3-Jisinoquino-1-11-Biberazinokaboxamide) 1) 2-Chacet, 2- (4-C23-dioxo-11-biverazinocaboxamide) 1-2- (2-Methithiazol-41) Case-2.-C4-C1-2 3-dioxo-1 1-biperazizocaboxamide 1) 2- (2-acetamidothiazol-1-4-aceti, 2- (4-n-octyl2,3-dioxo-1 1-biverazinocarboxamide) 1 2 — (2-Aminothiazo-1 / ^-1-) acetyl, 2-(4-ethyl2,3-dioxole 1-biperazinocaboxamide) -1 2-furacetyl, 2-(ethylethyl2,3 dioxor1) One biverazino force boxa amide) One 2- (2-viroli) acetyl , 2-(-V V-2, 3 dioxoxo 1 ΰ ペ ペ ペ ラ ラ ラ ラ ラ ペ '一 一 2 — — — — — ペ ペ ペ ペ ペ ラ ラ ラ ペ ペ ラ ペ ペ ペ ペ ペ ペ ペ1-Biberazino force boxamid) 1- 2- (2-Chloroacetamidothiazole-4-1) aceti, Κ- (4-et 2.3-dioxole 1-biverazinoka bo2! /) -1 D-methioni, D — 2— [4-1 (2-1 fu): 2,3-dioxo 1-biverazinoka bokisamido] -fe-acetyl, D-2-(4-2, 3-zoki y- 1-Biberazinokaboxamide) 1 2— (4 Benzoxy phenyl) aceti, 2, 5 -bis (4 〃 2, 3-Dioxo 1 1 Biperazino carboxamido) Bentanoy / ✓ , 2-C 4-2,3-dioxo- 1-1-biperazinocarboxamide) 1-3-(N-methinoreca vamoy) probio , 2, 3 - bis (4 one - Ji - 2, 3 - di O Kiso 1 one Biperajinoka Bokisami de) Burobioni, 2 - ^ 4 Echi — IS—

A'- 2, 3—Di-kisoxone 1-bipera dinoca-boxamide) -1 3-Black mouth brovionil, 2- 4-1-n-ク タ ク タ ノ ノ セ セ セ チ, 2 2, 2-(4-2 2, 3 キ キ キ 一 一 一 一 ビ 3 3 — — — — — — — — — — — モ モ — — 1 (4 1 2 1, 2-3 years old Kiso 1 1 bevelazino power / ^ boxamide) -3-[(1 1 1 1 1 H-tetrazo 5-) チ years old] 2 — (-Echi-1,2,3-dioxo-1-1-biverazino power boxamido) acet, D—2 -— [4-1-1 (2-hydroxyxetil) -2.3-Ji-kiso-1-1. Dinocarboxamide] 1-2-phenylacetium, D-2-[4- (2-chloroethene)-1, 2, 3-dioxo-1-1 Biperazinocaboxamide]-1-2-Fenaceti, 2-(1 Kochi — 2,3 Goxoxo 1-biperazinocarboxamide) 1 3— (Ethoxy ^ cabo2 ^ methylcarbamoy) Probi n, 2-(4-Ethyru2,3-Dioxo-11) Bibera dizoca boxamido) 1-3- (thi-acetamide) propio

, 2— (4-ethyl-2,3-dimethyl oxo-1-1-biverazino carboxamide) -1-3- [2- (1E-tetrazol-1-1i) acetamide] povoni, 2— (4-1-2-1,3-dioxo-11-piberazinoca boxamide) -1—2- (1H-tetrazo-1-y) acetyl, 2-1 ((3-phenylideneminamino 2-oxo) Midazolidin-1 1-yl) r-Lupoxamide] -1 2-Fenacetid, 2-[(3-furideneamino-2-oxomidazolidine 1-11) Power ruboxamide]-2-( 4 -Hydroxyfue;) aceti, 2— [(

3-Funolefurylideneamino-2-oxomidazolidin-1-11) Power boxamid] -1 2- (4-Hydroxyphene / ^) aceti /, 2— [(

^{R≤A ··?} Ι 3-Febrillidenamino-2-force-boxymid) -2-1 (4-hydroxy-doxys-ho-xif-e-le) a-set ^^, 21-[[2-oxo-l-31 (Ciophene 2-a / ^ domino) i-midazolidin 11-i-kaboxamido) -1 2-fe-a-s-chi Λί 21-((3-if-free-ridinamino 2-oxo-midazolidin-1-1-i) ka Boxamid] -1 2—Che = Aceti, 2-(31-Meth / 1 / 2-oxo-midazolidin-1 11a) Carboxamido] -2-Fa-Aceti, 21-((3-F ^ Fridyanamino 2-oxo-midazolidin-1-force boxamid] -1 2- (2-amino-azo; V-yl) aceti, 2-(3-furido-redidamino-1- Oxoyid midazolidin-1- (force) 〃boxamido] -1-2- (2-chrome Acetamidothiazo1-1-4ace), acetyl, 2-((3-cy2-oxomidazolidin-1-1-1) carbokimid] -1-2-fe-aceti, 2-[[2才 才 キ — — （— — 才 才 才 才 カ 才 才 才 才 才 才 才 才 才 才 才 才 才 才 才 才 才 才 才 才 — 才 才 才 才 才 才 才1 1) Carboxamido] 1-2-Chenaceti, D-2-((3-Fridyanamide 2-2-year-old midazolidin 1-1) Carboxamide) Probio-, 2-1 (4- (Hydroxy 6-methynicotinamide) -1 2-Fe-Acet, 2- (4-Hydroxy-6-methoxynicotinamide) 1-2- (4-Hydroxyphene; V) acetyl, 2-C5. 8—Jihi Draw 2— (4-Homo 1 1 Beverage =)-1 5—Oxo Bill [2, 3—d Birimidine-1 6-force boxamid) -1 2-phenynolacet, 2- (3,5-dioki V-1, 2,4, -triazine-6-force boxamid) 1 2- (4-hydroxyphene) Asechi, D-2 ~ (3-Flyridenamino-2-oxomidazolidin-1-1-force-boxamido) Brobin-bi-2, D-3-[(2-year-old xo3-su-homidazolidin-1-1-I) carboxamide ] 1-2- acetic acid,-2-((5-methoxy-force / u-;--3-methyl-2-oxo-midazolidin 1-1) force) 2-Acet, D—2 — ((5-benzil-adhesive ^ bon-2-3-meth—2—year-old midazolidin-1 1-) carboxamide) -1-2-Fa-acet, D- 2- (5-carboxy-3-methyl-2-oximidazolidin-1-11) carboxamide] -1-2-fe-noraseci, 2-(\ coumarin-1-3-force-boxamido) 1-2-phenyl / aceti , 2— (4 1-2.3-dioxo-1-1-biperazinocaboxamide) 1—2- (2-chloro 1-port一 一 1), — チ D D, D— 2 D D n n 4 4 4 4 4 4 4 D D D D D D D D D 1-6 (B) -Meth-2,3-di-oxo 1-11-biperazinokaboxamido-1—Che = Acet, 2— (4-Hydroxy 7—Methyl 1,8,1-Naphthyzine 1— (Carboxamide) 1-2-phenylacetium, 2-(4-hydroxy 7-trifluoromecinoquinone-3-force boxamide) 1-2-/ 2 /: acechi, Ν-[2-( 2—Aminothiazo 1 4-A) Acet J 1 D-Fen-n-gri, 2 1 (6-Bromo- 1-ethyl 1, 4-Jihi-Draw 4 1-year-old xothieno [2, 3—'o] Viridin 1 3—force boxamide) 1—2—fe = ■ acetyl, 2— [2— (2-aminothiazo-4-1y) acetamide] —1—2-Fe2, 2— [2- (2-Chloroacetamidothiazonolay 41-yl) acetamido] -1-Fenaceti, 2- (2,5-di-oxo-1,2-, 4-triazono 6- Carboxamid) 1 2-Che / Aceti, 2— (2,4-Dioxobirimidino-5-force / ^ Boxamido) -1 2-Che / Acet, 2— (6—Hydroxy ί / -1 1 , 5-Naphthyl dinicaboxamide) 1-2-phenylacetido, 2- [2- (4-ethyl-2,3-dimethyl oxo-1-1-bipera dinocaboxamide) 1-2-Chenacetamide] 1-2 One-way, two-one (two-one-one-two-acetamid) one two-way, two- (two-one-side-two-chee / wasetamide) one two- 4-1-Hydroxysulfoni-/-) aceti; ^, 21- (2-perimeter-1-1-acetamid) 1 2-- (4-hydroxy-sulfoni-A-aceti'nore, 2-(1-kabobenzoki) Broliamino) 1-2-furirasechi, 1 (Che-Mechikabo) Arani, 2-4 Benzoureido 1) 2 Choe-Lasetyl, 2-. (21-Che; ^ Acetamido) Aceti, N-Benzykaboxamido D-ARA--, N- (4-hydroxybenzoylur D-ara- , 2-1 (4-1-mouth benz amide) Probi-2, 2-(4-aminobenzamide) aceti ^, N-1 (4-ethyl-2, 3-ji-1-1-velazinoca-/ ^) 2-D-Ferglyci, D-2-([2- (2,6-dichlorophenyl) acetamide] -1 2-Fe-acetyl, D-2— [[3- (2, 6- Diclo-mouth)-1-Methyl isoxazo 4) Carboxamide] 2-1-Ch2 / ^ Acet 2-, 2- (force Pamoy) ami No 2-C-ace, N-force Vamoy D-Fue Glyci, 2-(3-meth / u carpamoy / no 3-methinole 1-ゥ raid) 1-2-セ チ チ 2, 2-(3-methavamoy 3-methyl 1 ゥ) Raid) 1-2-(4-Hydroxyfie-) acetyl, 2-(3-Methyl carbamoy 3-Methyl-1 ureido) 1-2-Che2; 2 -— (3- (2-hydroxybenzoic) -1--1 Raid) -1 2-Fe-N-Achi-S 2- (3-1 (2-benzoxypenzoi) -1 1- ゥ Raid) -1 2-1-1 (4-Head Droxys Honi Sekisui 2 / V) Aceti, 2- [3- (2-hydroxybenzoic) -11-Ureido] 1-121 (4-Hydroxybenzoe: = R) Aceti, 21- (3-Meticavamoy) 3 1-Met 1--1 Raid) 1-2-1 (4-Hydroxyfever 2) Aseti

 2- (3-benzoloxy benzoy)-1-raid) 1-2-f-acetyl / u, 2--(3-(2-benziloxy benzoyl)-1-1 u-ray)-1-1 ( 4-Hydroxyphen-) aceti, D—2— (21- (benzoxykaboxani)) 1-12-1 (benzoxykaboni) ethanes-honamido) 1-2-Fenacechi, N—Mesiru D-fe D;

Formula Elo- Bn - CO- (wherein, R _10:. ^ Pre B _u is that having a same meaning as蓟記) Specific钶of Ashiru groups represented by, for example, N [2 - (2 - Aminothiazole (1-4-1) -1-2-methyimide / acetinol) -1-D-ara-, N- [2- (2-aminothiazo-1-4-1) -1-2-methoxyminoacetyl-] 1-D-fe-〃 Glycidid, 2- (2-aminothiazol-4-y) -1-2- [2- (2-aminothiazoni-1-y) -1-2-methyxinominoacetamide] aceti, 2- (2-acetamidothiazol-) 4- (yl) -1-2- [2- (2-chloroacetamidothiazole-4-)-1-2-methoxyminoacetamide] acetyl 21- (2-chloroacetamidothiazole-4-ii) 1-2-methoxyminaceti, 2— (2-Aminothiazol-4-4-)-1 2-Isopropho'xymino Aceti, 2- (2-aminothiazo-1-4-)-1 2-Methoxyiminoacetyl, 2- (2-aminothiazo-1; ^ 1-A I 2-methoxyminoacetyl, 2-chemino 2-methoxyminoacetyl, 2-fu]; Α '-2-methoxyminoacetyl, 2-1-(4-hydroxyminoacetyl)-2-methoxyminoacetyl , 2-1-2 methinoaminoacetic acid, 2-1-2 quinoaminoacetic acid, 2-1 chloro-2-amino acetic acid, 2-1 chloro-2-aminodiaminoacetic acid, 2- [4-(0 0-Gutami Aci "xy) = / 一 ォ ォ 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 2 1 2 1 2-(3-1-aminothiazo- 1-4-A 1-2-methoxymino acetamido 3-2-phenylacet /, 2 — (5—crown Toamidothiazoi 4 i) 1-2-methoxythiocyanate, .2-(5-clochio 1-aminothiazolo / ^ i4-1) 1-2-methoxyaminoacetio, 21 (2-aminothiazolo) 4-1-)-1 2-Isopropoxy minoacetyl / u, 2- [1- (1; butoxycabo-) i-sopropoxymino] -1 2- (2-Saminoaminothiazo / ^ 14-) aceti, 2- [1ー (; butoxyca bonii /) sobrovokimino)-2-(2-trifluoro-〃meth / 1 ^ aminothiazole 4-1) aceti, 2-(2-chloroacetamide dothiazo-ru 4) 1-) 1-2-isobutyl s / iminoacetyl, 2-methoxyminnow 2- (2-saminoaminothiazo-141-) aceti, 2- [2- (2-chloroacetamide dothiazo- 1-4-) One 2—Methoxy Minoacetam) 2-Phenylacetium, 2-Fe-221-r-Trithiominaminoacetyl, 2- [2- (2-Aminothiazol-1-4-//)-2-2-Methoxyiminoacetamide] acetino, 2- (2—Mesami notchiazo / ^ 1 4

· ΗΆ ^) 1-1-isoproho-xyminosine, 2- (2-imino-3-me5 / 11-thiazoline-4-y) -12-isobroboxyminoacet, rudo is used.

^Ε 18

Formula cH i ± -—C then · Oυ -_ (Formula: Α <Central,,: RCV ₁ j ₇ f ?: έ, :: RΠ ₁₁₈₈ is the same as SU in SCi and C * J意, T 義 -¾

\ I / I. Examples of the ash group represented by) are: -Shofe-Luaseti, a-Hydroxys / Nohoni, Xifenylacetil, -Hydroxyfenacet, a Famoi ^ Fenacechi一, フ ノ ノ = な p p p p p p = = = = = = = = ^ = ァ ^ ^ = ^ = ^ ^ = ^ ァ = ^ = = = ^ = = -Hue-; ^ Aceti, 21 (: N, N—Dimethyls 7amoi) -1 2—Feniacet, 2-bro '-2—Feniasset, 21-Azido

2-Fe: ^ acetinole, 2-phthalimido 2-cheniaceti, 21-azido 2- (3-cloth feninole) acechi, etc. Equation ₉ one B ₂₀ - C¾ one CO - (. Wherein, ¾ ₉ preliminary ¾ ₀ is having the same meaning as defined above) as ingredients ^ Examples of § shea 〃 group represented Te, for example, § Roh Asechiru, phenylene / Acetyl, fenoki 5 acetyl, triff '3 "rometinolethioacetyl, ^ anomethiothioaceti, 1H-tetrazoirue 1 aceti / V, 2 ichie = aceti. 2-(2-aminotiazo 1-4-1) ) Aceti, 2-(2-chloroacetamidothiazole-1-4-acetyl, 4-1-thioacetyl, 2-1-thioacetyl, 3, 5-dichloro-1, 4-jihi-draw 4, 1-year-old quinobilin A ', β-carboxybithioacetin, 2- (2-aminomethyphen

-) Acetyl, 21 (2-1

 5Τ2

_C:. '. FI ) Acechi, 2-(2-lay meth / ^ fu-) acechi / 1 /, 2-[2-(2-oxomidazolidin 1-) carbonyl amino-) acechi, 2-[2-( 3-benzylideneamino 2-oxoimidazolidin 11-yl) kaboki ^ aminomethyi 2) acetate, 2-(5, 6-dihydro 1, 4-oxatin 1 2-) acetyl , 2— (2,5—dioxovirolidine-1—3) /) acetyl,, 2—1 succinyl acetic, 2— (1—1 acetic 1, 2,4-dioxomidazolidine—3- ィ / ν I can put it.

 The amino group and the Z or carboxy group in the above-mentioned amino group may have a protecting group.

 Examples of the protecting group for the amino group include the same as those described below for "Namino group for amino group".

Examples of the protecting group for the carboxy group include 3-latatam and all the groups which can be usually used as a protecting group for a hydroxyl group in the field of attached chemistry, for example, when the ester moiety is, for example, methyl,チ, ビ, ビ, プ ロ, プ ロ, 第三, 第三, ベ ン,-,-, ツ, エ, —, ト, ト, Ethoxymethyl, Penzi-Siximeth, Acetoximethi / U, Vivaloy-Siximethyl, β-Methylshonieci, Methithiomethi / ^, Trichi, β, β-Trichloroeth, Rhodoethi / u, Trimethisil / ✓ , Dimethylsilyl, acetylmethy, ρ-: = 1 trobenzoy meth, ρ-methybenzoymeth, phthalimidmethy, probioxy-methy, 1, 1-dimethypropylu, 3-methyl 3-buty-, succinimide, 3-, 5-di-tert-butyl 4-hydrodonesibenzi, methyl methyl, benzene Suoni / U-methyl, phenylthiomethi, dimethylaminomethi, viridin-one-one-year-old chisaido 2—methi, meth ^ sulfinylmethyl, bis

(p-methoxybenzene) 1000] ^, 2-cyano 1, 1-dimethylethyl, etc. Esters and silicides are shown. The present invention provides the novel monocyclic compound, and the choice of the protecting group is determined by the fact that it is difficult to determine the protective group, particularly, benzene / 1 /, β, β-tricycloethyl, p-Trobenzene;, p-Methoxybenzy is preferred.

 As the protecting group for the amino group in the above-mentioned killing formula, those used for this purpose in the field of -lactam and peptide synthesis are conveniently used. For example, aromatic radicals such as phthaloy, p-nitrobenzoy, p-ΐβ-Γ-butylbenzoyl, ρ-tert-butylbenzenesulfonate, benzenesulfo-butenes, etc. Aliphatic ash groups such as, for example, methoxycarbonitriol, triacetate, triacetate, methanesulfonate, ethaneshonie, trifossacemalloy, succinyl, etc .; U, ethoxycarbonyl, nitrobutoxybon, isobrofoxicaboni, 21-hydroxycarbonyl, β, β, trichloroethoxycarbonyl / bonyl, benji / toshikibonoji, ρ— Nitrobenzoxykaboni /, ρ—Methoxybenzoxykaboni / ✓, diphenyimethoxycarbonyl, methoxymethyoxycarbonyl, aceti Vmethyoki Esthetized carboxy groups such as carbo-, isobo / u-kis-ki-boni, and fu-e-oxo-boles, and methylene groups such as (hexahydro 1H-azebine-1-1-) methylene groups' 2 — 1 2 1-strength boki ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^-Thio, benzylidene, 412 tröbenj

; A T

_ οί. ·:? ι 一 Protecting groups for amino groups other than acyl groups such as lidene, di- or triaxyl, benzyl, and p-trobenzy are used.

 In the above killing formula, among the amino groups which may be protected or protected, represented by: Rl, those which are preferable as β-lactamase inhibitors are more specifically described, and Rl is represented by the formula

 A-C-C 0NH—

 / \

 W Z

[In the formula, A is a lower alkyl group such as hydrogen, methyl, ethyl, and isopuchi; a g-cyclic group such as cyclohexyl, cyclohexeninole; an aryl group such as phenyl; and an aryl such as benzyl. Groups, ceni, benzocheni, viloli, isoxazoli, piberazino, thiazoli, tetrazoi, oxoxathiano, etc., and these symbols represent amino, low-acyl, low-alkoxy, fu- / u, 2, 6 It may have one or two substituents such as phenol, oxo, hydroxy, halogen or chloroacetamide. W is hydrogen when Z is hydrogen, an optionally esterified group, a sulfo group, a spamoy group, a hydroxysoxy group, an amino group which may be protected, Amido groups such as carboxamides, such as 1,2-diazo, (2,3-dioxo-one-bi-belazi 7;) Boxamid, imidazolidino power Boxamid, liquoride midazolidino power / ^ boxamido, (1,2, -diazo-1) force Boxamid, isoxazoline-type force Boxamid, (2-aminothiazoline 4-ii) ) Metica boxa amide, 2,3-dioxo-11-biverazinoca boxa amide) 1—2—force; ^ A heterocyclic carboxamide group such as bobenzoxyaminoprobionamide, and W and S are combined. And the formula NX-G (where X is aragonic, S or sulfur group, G may be protected by lower radical or carboxy group, such as a, a-dimethyla-carboxymethyl, etc. ^ Substituted lower radical, phenyl A library like 〃, case

A group such as. ^ Represents a group ^ ").

 May represent a bond or -C-.

 In the above formula, the lower aki represented by A is preferably a chain or branched alk group having 1 to 4 carbon atoms, and these are the above-mentioned N-methyl / force vamoy.一 ¾ セ ， ， テ ト ラ ， テ ト ラ テ ト ラ テ ト ラ ， テ ト ラ ， リ ， リ リ ¾ リ リ リ リ ¾ ¾ よ い リ ¾ よ い ¾ リ ¾ よ い ¾ よ い ¾ ¾. It may be substituted with a heterocyclic group such as 1,2-diazole.

 Examples of the halogen which can be substituted for A include fluorine,: ^ element, and bromine. Examples of the low alcohol group include methyl and ethyl A ^, and examples of the low alcohol group include methoxy and ethoxy.

 Examples of the optionally protected amino group represented by W include chloroacetylamino, arachamino, and aralkylamino.

 The heterocyclic ring in the heterocyclic carboxamide group represented by w is phenyl, an aryl group having 1 to 12 carbon atoms, a cyclic group, an ak / u group having 2 to 8 carbon atoms, for example, a methoxy group. , Ethoxy, etc., which may have an alkoxy group, a carboxy group, a fluoridamino group, a suho group, an axoxy bononi group, an araki / oxy group, Group, carboxylic acid group, etc., which may have 1-2 儇

 The ^ | 扱 alkyl in low treated akirka boxamide S represented by W is preferably a ^^, C 1 -C 4 ^ -branched aky group, which is a cliff,

(OV.ll It may be substituted with halogen, sulfamoi group, optionally linked amino group such as iodine, bromine or fluorine, and the spamoy group may be substituted with diphospho group.

 The compound (I) of the present invention is, for example,

 X

 ¾

 I c I)

₀ ^

 (Wherein, and X have the same meanings as described above) and, for example, a reaction of sulfuric anhydride or sulfuric anhydride—by reacting with a conductor.

 \ The above-mentioned conductors of the reaction of pyrosulfuric acid include, for example, ^ water-pyridin, anhydrous sulfur-dioxane, ^ water phosphate methamine, ^ water sulfate-crofreth. Additional codes are used. ·

 In the above reaction, about 1 to about 5 moles, and more preferably about 1 to about 2 moles, of the reactive compound of water and sulfuric acid are added to 1 mole of the compound (I).

 Reaction temperatures are from about 0 to about 80, more preferably from about 10 to about 40. In the above reaction, a solvent may be used as the solvent, and the solvent may be water, dioxane, tetrahydrofuran, jet-type, water-soluble, and water-soluble. Which ester, phthalocyanine, methylene chloride, halogenated carbonized; ^ hydrocarbons, benzene, toene, η-hexane hydrocarbon, dimethyformamide, dimethyacetamide Tight organic solvents can be used alone or mixed. After the completion of the reaction, the reaction mixture is subjected to a purification method known per se, such as solvent extraction, recrystallization, chromatography, etc.), and the compound I) can be obtained as an arbitrary degree.

one Compounds Among the raw compounds (I) for synthesizing J (I), compounds having X or a hydrogen atom are described in JP-A-51-125061-51-125064 and the like. Some compounds are methoxy, for example, the general formula

Is converted to tetrahydrofuran, dioxane 'N, N-dimethylformamide, N, N-dimethylacetamide, benzene, aceton, billin, methanol, ethanol, propano, butanol. In water, water, chloroform, dichloromethane, carbon tetrachloride or a mixture thereof, for example, ozone, alkali metal permanganate (eg, suitable manganic acid potassium, permanganese sodium) ), Can be manufactured by oxidizing with earth metal permanganate (eg, permanganese balium), osmium tetraphosphate, and sulphite. In the above-mentioned (Association), a compound in which X is methoxy is, for example, lithium, sodium and potassium in methanol in the presence of a compound in which the corresponding X is a hydrogen atom and methanol. Halogens such as nitrogen and bromine, N- / N-roymids such as N-closcinimide, N-bromosuccinimide, haloamides such as N-chloroacetamide and N-glomoacetamide , N-co-pentene sulfone amides, · -chloro-p-phen-sulfonamides, etc., ハ ロ -halosphonamides, 1-ha benzototriazoles, ΐ-butyl hippoc amides, etc. Alkaline chlorides such as tetrahydrofuran, dioxane, methylene chloride, chloropho / nmm, acetonitol, methanol, Ν, Ν-dimethylformamide , Ν, 2ί— It can be manufactured by reacting in amide or a mixture of these. Alternatively, compound (I :) may react with various g or ¾ groups as ¾, este, silicon conductor, or the like.

 In the compound (I), the compound i¾J in which Ei is an amino is i¾J by the ^ method], and in the compound (I), Hi is an amino group. Can lead to compounds.

 In the compound of the present invention, the compound having a protecting group is removed by removing the protecting group. However, it is possible to lead to a compound that does not have a bale protective group in Compound I (I :). Compound I) can form a salt with ^ group or ¾. Therefore, chemical compound (I) may be searched for as ¾], and the one obtained as a border may be converted to 藍 or the salt of ¾. Further, a chemical obtained in the form of a tongue may be used as a chemical. The above groups include, for example, pyrrole groups such as lithium, potassium ', sodium, calcium, and ammonium, such as pyridine, collidine, trithiamine, and triethanolamine. Amin, which is used as a base, for example, Shiojun,., Rinpuru, etc., such as sulphonic acid, amberjack, probion, mandeic acid, quen, and tokuishiku Are used, each of which is a stable powder and almost smells of pearl.]?

(On the rat L ¾ ₀ 2 data).

 In addition, compound (I) may have an optical component (eg, D-heterogene, isomer). In this case, those components and mixtures thereof are also included in the present invention.

 The inhibitor of the present invention is used to administer a β-lactam antibiotic κ for the treatment and prophylaxis of box infection in humans or livestock.

The harmful agent of the present invention, when formulated alone / 9-lactam antibiotic ^ r ^ Use for administration ΐϋ or administration 混合, or mix at the time of use. It can also be formulated by mixing with; 9-latatams. In this case, 9-lactam antibiotics may be purchased, for example, as benzylbenicillin, phenoxymethibenilin, subenirin, potenecilin, ambicilin, amoxicillin, mesilinam, and kuxixa'silin. , Dikoxa, sibera, bivera sylline, ano <siline, chica; ^ siline, cephalolysine, cephalotin, .cephazoline, cephalexin, cephacetri, sebuamando naphtoate, ceph oxime, ceph Tiam, cefoxitin, cefmetazo-, cefsulodin, cefaclor, cephatolysin, cefataxime, cefmenoxime, ceftazidine, ceftezoxime and other known benicillins and cephalosbolins; Nashi Emissions, mosquito Feshi phosphorus Bibume silicon down is used, injection j, 'dry syrup. Granulocyte agents, 锭剤 be called ¾ usual manner in capsules, and the like. Preferably, it is in the form of 氇 or hydrate II as an injection.

 The compound of the present invention (I :) can be used in a weight ratio of 10: 1 to 1:10 with respect to the / 9-lactam antibiotic. In addition, a ratio of 1: 1 to 1: S, for example, 1: 2, 1: 3, 1: 4, 1: 5 or 1: 6 is advantageous.

 The compound of the present invention is given at a daily rate of 50 to: I 000, more usually at a daily rate of 100 to 0.75 «y, for example 1 to 6 times, more usually Is administered 2-4 times.

 The amount of the ^ -lactam antibiotic in the compound having a synergistic effect of the present invention is usually used in an amount suitable for use or less.

Test example

—? 】 、 ノ ノ. 一 Measurement of the degree of harm required for inhibiting 505δ of enzyme activity

Typical of Cephalosho Linaise ^! As typical examples of enteropatricor * clore force, IF 012937 and bacillinase, Staphylococcus * aureus, 1840-added / 9-lactamase, 0.05 mol, ρΗ 7] Incubate with an appropriate diluent of the harmful agent product at 30 ° C for 10 minutes, add cephalothin or ambilicin at a final concentration of 0.1 mM, and let the solution react for 10 minutes. The enzymatic activity is determined by the microiodine method [Journal of Geneva, Microbiology, Vol. 33, page 121 (1963)]. An inhibitor of requiring a subsequent enzyme Katsu拴to $ 50 inhibition 1 ₅₀ to ½ serial. Enteropakuta Table 1 - E for Kuroaka ₅₀惶, against the Staph Gray Lactococcus' old Ureusu in Table 2: ₀ indicating the值.

Table 2

Test example 2

 : Surplus with Sefo-tiam ^^

Cefotium is added to the agar containing each compound according to the S. sotium concentration, and the test bacteria are inoculated on the agar, and the minimum inhibitory concentration is determined 18 hours after inoculation. Measure as MIC ^). Contact inoculum瀆度used was 1 0 ⁸ / si, ¾¾ DOO Ripuchikesu ® Soiaga [Bae click t-Dikinso down - Anne de force Npanii one (Bec¾on Dictinson & Companey), manufactured by the US anonymous] had to.

 Table 3 shows the obtained results.

― C? I v.:roichi

Hereinafter, the contents of the present invention will be described in detail with reference to Reference Examples, Synthesis Examples, and Practical Examples. The symbols used in these synthesis examples have the following meanings:

 D M P

 D M S 0

 s single let

 d doublet

 リ Triblet

 q Quartet

c:.: n m;

 d d; dub doublet

 d d d j sick state

 quintet; quintet

 h e t e t; heptet

 broad; broad

 arom.; Manyo

 Reference example 1

 3-Amino-2-oxoazetidine 0.1 04 / ODMF 4 D-N- (3-furfurylideneamino-2-y-y-midazolidino power) 4-alanine 0,3549 and hexica bodimid Add 0.2691 and stir for 8 hours in the room. After removing the 'precipitated' crystals, remove the liquid and remove the insolubles from the residue. (It may be purified by chromatography.) 3- [D-2-[(3-furidylamino-2'-oxomidazolidine-11 / force) / ^ boxamide] brobionamide] -12-oxozetidine 0.3 to 29 is obtained. Can be

IR macsT ¹ ; 3275. 1760, 1725. 1660, 1415 Reference example 2

3-Amino-3-methoxy-2-oxazetidine 0.1 16 is dissolved in methylene dioxide 20 W, and under cooling 15-15, brovirenoxide 15 is added, and then D—N— (3— Add the solution of methylene oxide 20 0 ^ in the mouth lid obtained from the free lidamine minnow 2-oxo-1-dimidazolidinanol = 1.06, and stir for 5 minutes at the same time. Add 0.7 1 2 f and stir for an additional hour. —33—

 Shrink, add ice water to the residue, and extract with black hole form. The extract was washed with water, concentrated under reduced pressure, and the residue was purified by silica gel chromatography to obtain 3- [D-2-([(3-phenylideneamino-2-oxo). Midazolidin-1 11) carboxamide] brobionamide] 1-3 (S:)-methoxy 2-oxozetidine [I] and 3- [D-2! : (3-butylidaminomin-2-oxomidazolidin-1-1-) power-boxamido] propionamide] -13 (R) -methoxy-2-oxoazetidine [I] is obtained.

0 CD B ί / KBr cgf ¹ ; 3230, 1755, 1725. 1655,

 max

 1520, 1415.1230.

_{NB (D S0-d 6,} ppm); 1.30 (d, J = 7Hz, CH 3), 3 - 35 (s, OCE 3), 3.47 (q ^ J = 6.8Hz, C 4 -H), '3.80 (s, -CH _2- ), 4 -46 (quintet, J = 7Hz,

 -CH-), 6.5-7.9 (111, free (furyl) E), 7-73 (s, -CH-N-), 8.29 (s, NH), 8.44 (d, J = 7Hz, NH), 9 -23 (s, NH).

o [I] IB v ^ fj csT ¹ ϊ 3230, 1755, 1725, 1655,

 1520, 1415, 1230-"*

_{NMR (D SO-d 6,} ppm); 1.32 (Q, J = 7Hz, CH 3), 3.36 (s, -0CH 3), 3.50 (q, J = 6, 12Hz, C 4 -E), 3 · 80 (s, 1 C¾1), 4 -46 (q inte, J = 7Hz, -CH-), 6-5-7.9 (m, free (furyl 7.73 (s, ^ CH = N-), 8.32 (s -NH), 8.45 (d, J = 7Hz, NH), 9-29 (s, NH).

Reference example 3

D ^ 3-Amino-2-oxazetidine is reacted with acylation 考 in the same manner as in Reference Example 1 = A and Reference Example 2 = B. . : ^, Below: ^, where (a) is the product, fo) is the corresponding method, and) is the physicochemical function of the product.

 (23) (a) 3- (2-oxo-one 2-Fe-acetamide) -one 2-oxoazetidine

 ib) B

(cj IE

οτΓ ¹ ; 3280. 1745, 1720, 1660-

_{NB (DMS0-d 6, ppm} ); 3 - 31 (dd, J = 3, 5Hz, C one H), 3. 9 (t, J = 5Hz, C -H), 5.OOCddd, J = 3, 5.8Hz, C ₃ -H),

): H), 8.01

 (s, NH), 9.55 (d, J = 8Hz, NH). (24) (a) 3- [2- (2-Mesylaminothiazo--4-1-)-2--2-sopropoxyminoacetamide] 1-2-year-old oxoazetidine

(b) B

(c) IR

CT ¹ ; 3275, 1750, 1660, 1535, 1120.

R (DMS0-d ₆ , ppr.); 1.27 (d, J = 6 Hz, _ ° ¾), 2.96

(s, C¾), 3 - 14 (dd, J = 3, 5Hz, C 4 -H), 3.48 (t,

J = 5Hz, C ₄ one H), 4.36 (iiepte t, J = 6Hz, -CH-),

4.95 (m, C ₃ -H), 6.88 (s, γ ^), 8.01 (s, NH),

 9.20 (d, J = 8Hz, KE)-(25) (a) 3- (2-Bromo-2-Fe / Noacetamido) -1 2-year-old zeoazetidine

 (b) A

(c) IE i'lli en- ¹ ; 3280, 1755, 1730, 1660- NM R (DMS0 ~ d ₆ , ppm); 3-03-3.73 (m, C ₄ -H), 3.47,

3.52 (each t, J == 5Hz, C4-H), 4 -94 (m, C ₃ -H), 5-63 (s,-CjJH-), 7.30-7-90 (E, ^^ ( phenyl) E), 8.07 (s, NH), 9.28 (d, J = 9Hz, NH).

 (26) (a) 3— (2-Azido 2—Fenacetamide) 1—2 years old

 (b) A

 (c) I R cffl; 3300, 2103, 1752, 1670.

 NMR (DMSO-de, ppm); 3.47 (, J = 6Hz, C4-H), 3

-(t, J = 6Hz, C4-H), 5.00 (n, C ₃ -H), δ -09Cs,-(p-) _f

 7-52 (s. Phenyl) E, 8.07 (broad s, NH), 9,12 (d, J = 8Hz, NH).

 (27) (a) 3— Toshi amino-2 oxoazetidine

 (b) B

(c) IB f ^ Br cT ¹ ; 3265. 3080, 1745, 1330, 1155.

 max

_{NMR (DMS0-d 6, ppa} ); 2.49 (s, C), 2.98Cdd, J-

(28)

 One-year-old xozetidine

fb) A

ic) IB

cm ¹ ; 3280, 1760, 1710, 1660, 1520,

1380, 1100, 720

NR (D SO-de, pps); 2.99, 3.20 (d, d, J = _{-4,1- 4.2Hz, C 4 -. /} 9H), 3.40 3 · 43 ( each t, J = Hz,

C ₄ in a flat H), 4.70-5- 15 (m, C 3 -H), 6-20. 6.23 s,

 H H

-(fH-), 6.90 to 7-25 (m, ¾), 7.49, 7-50 (each d,, 7.97, 8.00 (each s, arom.≡), 8.83.

 8.93 (each d, J = 6Hz,-各)-

(29) (a) 3— [2-Azido 2— (3-chlorophene /) acetamide] -1-2-oxoazetidine

(h) A

(c) IRJ c ^ r ¹ ; 3250, 2100, 1750, 1660

_{NM H (DMSO - d 6,} ppm); 3.20 ~ 3.70 (m, C -H), 5-08:. (S, -CH-), 4- 90-5.20 (E, C 3 H) 6-93 (S, NH), 7.40 (s, 7: -i> Jien3rl) H), 8.03 (m, Ξ).

(30) (a) 3- (2-Azido 2-phenidase amide 5—3-Met pheasant 21-year-old; xoazetidine fb) B

(c) I R V KBr; 3260, 2100, 1755, 1682.

 m z

 NMB (CDC1 „, ppm); 3.36, 3 · 43 (each s, one C), 3.75 (dd, J = 6Hz, C ^ -H), 5-15 (s, -CH-), 6.95 (s , Η), 7.50 (s, エ 2) S., 8.08 (s, 2m). Synthesis example 1

3-CD-2-C (3-butylideneamino-2-quinimidazolidin-1-i /) Power boxamido] propionamide] 1-2-oxoazetidine 0.36 DMF solution of da, viridin-water 5 Inject the drum complex 0.15 and invert the room for 2 days. On the other hand, add a jetie and divide it to Dc ez 507 Ν _& ^: £ ' The eluate was purified with an Emberlight XA DI (Portland Haas Co., USA) column.

 -2-(3-furidene amino-2-year old quinone midazolidin-1-1) carboxamide] probion amide] 1-2-year old oxoazetidine 11-sulfonate 0.37 f is obtained.

IR vSlJ of ¹ ; 3300, 1755, 1725, 1415, 1270,

 1235, 1050.

 NMR (DMS0-d5, pps); 1.29 (d, J = 7Hz, CH3), 3-26

. (dd, J = 3.6Hz, C 4 -9S) 3.68 (t, J = 6Hz, C 4 - a H),

3.81 (s, -CH ₂ ~-), 4.33 (quintet, J = 7Hz, -CH-),

 1

 4.86 (ddd, J = 3,6,8Hz, C ^ -H), 6.5-7.9 (m, free

 (f ryl) H), 7-74 (s, -CE = 2-'), 8 -43 (d, J = 7Hz), 8 * '87 (d, J = 8Hz-,).'

 The following compound was produced by sulfonating the corresponding 2-oxoazetidine derivative in substantially the same manner as in Synthesis Example 1.

Synthesis Example 28

 Sodium 3-Benzyloxy Power / Ethylamide 3-Methoxy 2-Oxazetidine

IB cm ¹ ; 1760, 1720

, 1625, 1505, 1260,

1050.

NM B (DMS0-d ₆ , ρρζι); 3.36 (s, -0C¾), 3.56, 3.76

(Each <i, J = 6Hz, C -CH 2), 5.13 (s, one C I), 7.40

 (s, arom-H), 8.90 (croad s, NH).

Synthesis Example 29

 Sodium 3-[2-(2-aminothiazoe-4-) ^ g = r

, -Sobroch 'minoacetamide'-2-oxoazetidine-1-source

IR ^KBr em "¹; 1760, 1660, 1620, 1525, 1250, max

 1050-

, .CH3

NMR (DMSO-d ₆ , ppm); 1 -22 d, J = 6 Hz, „ ₃ ;

3.66 (t, J = 6Hz, C 4 - H), 4.33 (s, one CH ₂ -), 4-33

(quintet, J = 6Hz, one CE rather), 4 · 96 (m, C 3 -H), 7.36

^{. (s, y H) .9.23} (. d J = 8Hz, 2iH) Synthesis Example 30 'diisocyanato Li um 3 - (2-Okiso one 2-phenylene ^ § Se Toami de) Single 2- Okisoazechijin one 1 over scan Honey

IR ^ ^KBr c ^ ¹ ; 3375, 1760. 1668. 1510, 1272,

 max..-

♦ 1238, 1180, 1050.

_{NMR (D SO-d 6,} ppm); 3.45 (dd, J = 3, 6Hz, C 4 -H), 3.70 (t, J = 6Hz, C 4 -H), 5.01 (ddd, J == 3, _{6, 9Hz, C 3 - H} ), 7.50-8.10 (m, Hue - (phenyl) E), 9.65 (d, J = 9Ez, NH).

Synthesis Example 31 "* isocyanatomethyl Li Umm 3 - [2-. (2 - eyes were Aminochiazo one over I) one 2-Isopuroho Kishii Minoase Toami de] one 2 - year old Kisoazechijin one 1 over the scan Hone door IE ^ CT7 ¹ 3450, 3275, 1760, 1660, 1532,

1470, 1240, 1115, 1050

NMR (DMSO-d ^, pus "); 1.23 {d, J = 6Ez, 2.73

 ° then 3

(s, CH3), 3.33 ( άά, J = 3, 6Ξζ, C 4 -E), 3.63 (t, J = 6Hz, C ₄ -H), 4.33 (hepte, J = 6Kz, one? H-) '

4.91 (m, C ₃ -H), 6.67 (s, ^H ), 9 · 12 (, J = 9Hz, NH).

 Synthesis Example 32

 Sodium 3— [2— (2-imino-3—meso-41-thiazoline

-41-) 2-isopropoxyminoacetamide-1-2-oxoazetidine-1-1 phosphonate

IRV KBr esT ¹ ? 3 3 ^ 0. 3300, 1768, 1650, 1538,

 max

 , 1270, 1245, 1120, 1058. 1040.

■ 'NMRCD SO-d _fi , upm); 1.24 (ά, J = 6Hz,-), 2.91

 "

(s, CH ₃ ), 3.30 (dd, J = 3, 6 Hz, C ₄ -H), 3.65 (t, J = 6 Hz, C-H), 4.36 (Heptet, J == 6 Hz, -CH-), 4.93 (m, C3-H), 6 -86 (s, "^), 9.32 (d, J = 9Hz, NH). 'Synthesis example 33-Sodium 3— (2-Bromo-2-phenylacetamide C)-21 oxoazetidine

 I R V g j carl; 3325, 1760, 1670, 1533, _1240, 1055

_{NM R (DMSO- d 6, ppm} ); 3.20 (s, C 4 one H), 3-58 (t, J = 5Hz, C 4 -H), 3.64 (t, J = 6Hz, C 4 -H) , 4.83 (m,

C ₃ -H), 5.58 (s, -CH-), 7.30-7.70 (E, feninole

 (phenrl): 5), 9.28 (d, J = 9Hz, NH).

—Synthesis example 34

Sodium 3- (2-azido-2-phenylacetamide) -1 2-oxozetidine-11-sulfonate, IR ^ KBr of ¹ ; 3460, 2110, 1755, 1670. 1240, max

 1053.

NM HC DMSO-d, ppm) 3.28, 3.35 ( each dd, J = 3, 6Hz, C 4 one H), 3.60.3.63 (each _{t, J = 6Hz, C 4} - H), 4.87

(m, C ₃ -H), 5.00 (s, -CH-), 7 -45 (s, arom.H),

9.17 (d, J = 9 Hz, -NH-),

 Synthesis Example 35

 Sodium 3—tosamino 2—oxazetidine 11 / ^

IRV ^BT c ^ ¹ ; 3265, 3175. 1745, 1332, 1280,

 max

1245, 1115, 1050 - NM R (. DMsO-de, ρριτ); 2.42 (s, one _{CH 3), 2.76 (dd,} J = 3, 6Hz, C 4 -H), 3.30 (t, J = 6Ez, C4-H), 4.47 (dd,

_{. J = 3.6Hz, C 3 -H} ), 7.58 (ABq, J = 9, 29Hz, aron H), 8 - 51 (broad s, - NE -).

Synthesis Example 36

 Sodium 3— (2-phthanolamide 2—thienylacetamide) 1—2 years old

^{IRV KBr c l; 3345, 3070} , 1753, 1710, 1520,

 max

 1380, 1240, 1195, 1100, 1045, 720

Synthesis Example 37

 Sodium 3— [2-Azido 2— (3-cloth fueni /) acetamide) 1—2—Xosezetidine 1-1—Sulfonate

IR ^ KBr ca ¹ ; 3400, 2110, 1755, 1670, 1240,

 max

1050- —45—

_{NM E (DMSO - d 5,} ppm); 3.31,3.33 ( each dd, J = 3, 6Hz,

_{. C 4 -H), 3 ·} 60,3.63 ( each t J = 6Hz, C ₄ one H), 4.86 (m, C 3 -H), 5 - 13 (s, -CH-), 7.28-7.55 ( m, Hueni

 (phenyl) H), 9.15 (d, J = 9Hz, H).

 Synthesis Example 38

 Sodium 3— (2-Azido 2-Fe / Acetamide) -1 3-Methoxy 2-Oxazetidine 1-1 Sulfonate

IB 2? ^B ^ es

max ¹ ; 3400, 2110, 1765, 1685. 1248,

_{1055- NMR (DMSO - d 6,} ppm); 3.13, 3.36 ( each s, -CH ₃₎ .3.40

~ 3.80 (m, C ₄ one E), 5-08 (s, -CH- ), 7.44 (s, arom H.), 9.63,9.66 ( each s, -NH -) -.. . · Real旌例9 ''

 Fill the inoculum vial with a volume of 12 with ^^.

Example 10

 Fill Compound No. 44 500 into a 17-volume paia and seal.

Jeongjeong 11 ·

 Cefotium 250 and Kago Kago 32 35.5f are mixed in an old fashion, and the mixture is filled with 250 ^ (force i) in a 12 W internal volume rooster vial, and vacuum sealed at 50 ^ Hg.

Claims

l Range of billing S

 1. —killing ceremony

 X

 R,-

.ヽ S O H

[In the formula, B 1 is an amino group which may be acylated or protected, and X represents hydrogen or methoxy. ]

 3-Lactamase inhibiting composition.

 2. The composition according to claim S1, which also contains a 3-latatam antibiotic.

, V-