WO1982001551A1

WO1982001551A1 - Beta-lactamase-inhibiting composition

Info

Publication number: WO1982001551A1
Application number: PCT/JP1980/000255
Authority: WO
Inventors: Chemical Ind Ltd Takeda; Taisuke Matsuo; Mitsuzo Kuno; Kenji Okonogi
Original assignee: Takeda Chemical Industries Ltd
Priority date: 1980-10-23
Filing date: 1980-10-23
Publication date: 1982-05-13
Also published as: JPS5798258A

Abstract

Compounds having 1 to 2 substituents in the 3-position, represented by the following general formula: (FORMULA) (wherein R<u1>u represents an amino group which may be acylated or protected, and X represents a hydrogen atom or a methoxy group), show an excellent ss-lactamase-inhibiting action when used independently or in combination with other ss-lactam series antibiotics, thus being used as medicines for humans and for domestic animals.

Description

Specification

β-lactamase inhibiting composition

Technical field

The present invention is novel ¾ 1 over scan Ho ² - relates antimicrobial compositions ^ containing it and one rata Tamaze inhibitors Okisoazechijin compound.

Background art

In recent years, research on semi-synthetic antibiotics has made remarkable contributions to the treatment of infectious diseases. However, the problem of the development of resistant or resistant bacteria to these semi-synthetic antibiotics is one of the important issues. Recently, it has been proposed to treat β-lactamase-resistant bacteria with β-lactamase inhibitors. For example, a new ^ -lactamase inhibitor such as klavranic acid [Antimicrovia's Agent ♦ and. Chemoteraby, 丄丄, 852 (19777)] has been found. The inhibitory effect is sufficient for some bacteria and may be ineffective.

Invention opening ^ _

The invention relates to the formula

X

Ri

L

0 S0 ₃ H

[In the formula, Rl may be an acylated or protected amino group, and X represents hydrogen or methoxy. And a lactamase-inhibiting composition comprising a /?-Lactamase antibiotic.

The present inventors have found that the 1-sVho2-oxoxazetidine derivative of the general formula (I) has an excellent β-lactamase inhibitory action. As a result, the present invention was completed.

That is, the present invention

1. —General formula ''

[In the formula, Rl represents an amino group which may be acylated or protected, and X represents hydrogen or methoxy. Β-lactamase-inhibiting composition comprising a compound represented by the formula:

2. The present invention relates to the? -Lactamase inhibitory composition, which also contains a? -Lactam antibiotic.

In the above formula, Ri represents an amino group which has been converted into an amino group, and the amino group which has been converted into an amino group includes a known amino group at the 6-position amino group of a known silicon derivative. A substituted ash group, an ash group substituted for the 7-amino group of the cephalosporin derivative, and the like are used.

Examples of such acyl groups include, for example, the formula

R ₆ -CO—

[In the formula, R ₆ represents a phenyl or heterocyclic group which may have a substituent or a substituent. Group represented by], (≥) expression

R ₇ -NH-CH-C0- I

R ₉

{Wherein, R7 is hydrogen, a substituent an amino羧残group which may have a protective group of Amino group of the formula R8- (CE ₂₎ _n i- C0- wherein, R ₈ is a substituent Heterocyclic group which may be substituted, phenyl which may have a substituent, phenol which may have a substituent, phenol which may have a substituent Or Tei扱A key thio, nl is an integer of 0 Ruishi 4, respectively Wa table, _ (CE ₂₎ _n i group may have a substituent. ]

Formula (wherein 11 and g are the same or different hydrogen

Low Hi key, low handling A key force Rubamoiru, it may also have a substituent Hue - Ca ball - or sulpho the I each table na _0], or formula

R8 ^ -S0 ₂ - wherein represents a good Tei级A key may have a substituent. R9 represents hydrogen, a substituted or unsubstituted radical, a substituted or unsubstituted heterocyclic ring, a substituted or unsubstituted heterocyclic ring, Kenylene represents a heterocyclic carbamino which may have a substituent or may be via an alkylene chain. A group represented by}, (3) Formula 'RlO-RlICO- [wherein Rio is a formula-(wherein X represents an oxygen or yellow atom,

-x- Ri3

Rl2 represents a phenyl which may have a substituent or a heterocyclic group or a substituent; and R13 represents hydrogen, phenyl which may have a substituent, lower acyl, lower treatment. Alkyl or a group represented by the formula -R14 R15 (wherein R14 represents low alkylene or low phenylenylene, Ri5 represents carboxy, its ester or a heterocyclic group, respectively). Rii represents a single bond or a group represented by the formula -C0-NH-CH- (wherein R16 is a lower alkyl, even if it has a substituent)

■ 16

And represents a heterocyclic group which may have good substituents or substituents. ) Represents each group. A group represented by :)

Equation (4) ¾8

《^ CH- CO-

¾7.

[Wherein, R17 is hydroxy, sulfoxy, carboxyl, optionally substituted sphamoy, sulfo, optionally substituted phenolic Ajin, penziloxycarboni. , Homi / uoxy, and Rl8 represents hydrogen, low-accuracy aki, resistance aki, no, rogen, nitro, and hydroxy. A group represented by

Ho) expression

Rl9-Rg ₀ -GHg-CO-

[In the formula, R19 is a cyano, a phenyl which may have a substituent, a phenoxy which may have a substituent, a low phenol which may have a substituent, and a group which has a substituent. R20 represents a single bond or -S-, which represents a good alkylene or a heterocyclic group which may have a substituent. The group represented by] is used.

In the above formula, the lower group represented by R6 is preferably a group having 1 to 6 carbon atoms. The heterocyclic group in the heterocyclic group which may have a substituent is a 5- to 6-membered heterocyclic group containing 1 to 2 nitrogen atoms and containing 1 oxygen atom. : έ Examples of the heterocyclic group include, for example, i, noxazoly, biperazide, and imidazolin. Examples of the substituent of the ring group include low alkyl having 1 to 3 carbon atoms, low treatment of 1 to 3 carbon atoms, halogen, nitro, amino, oxo, thioxo and substituents. Moyo is used. Examples of the substituent in the phenyl which may have a substituent include, for example, low carbon atoms having 1 to 3 carbon atoms, and 1 to 3 carbon atoms. The lower aqoki ^, halogen, -toro, and amino roux are used.

In the above formula, the amino acid residue in the amino acid residue which may have a substituent represented by R ヮ includes, for example, glycine, ara-nore, paryl

, Zisil, Isoloisi 1, Seryl, Threonyl, Sisty-/! /, Cisti, methol, one or one aspati, one or one r-gutamyl, rigi, argi-U, fuarara, fueri grishi, tyro ij ^, histigi, tri Butofi, Broly Pido: used. Examples of the substituents which may be substituted on the amino acid residue include, for example, amino, low-valued amino, amino-protecting group, carbamoy, methylcanolepamoi, sulfamoyl, benzene, 4-ethyl-2,3- 11-year-old radio-carbo-boni, 41-jet, 2,3-dioxo-one-radio-carbino-amino is used. As the low-accuracy acqui in the low-acquisition amino, those having 1 to 3 carbon atoms are preferable. The protecting group of the Amino group, that used the same ones as protecting groups Amino groups below ₀

As the amino-protecting group represented by R ₇ , those similar to the amino-protecting group described below can be used.

Formula _{_{R8- (CH 2) n i -}} CO- , as the heterocyclic group in heterocyclic group which may have a substituent represented by R ₈ in the group represented, for example, one sulfur atom, a nitrogen atom Or a 5- to 6-membered heterocyclic group containing an oxygen atom, a 5- to 6-membered heterocyclic group containing 2 to 4 nitrogen atoms, 1 to 2 nitrogen atoms and ¹ to 5 containing a sulfur atom or an oxygen atom Examples include 6-membered heterocyclic groups, and these heterocyclic groups may be condensed with a 6-membered ring group containing 2 or less nitrogen atoms, a benzene ring or a 5-membered ring group containing one sulfur atom.

Specific examples of the heterocyclic group represented by R ₈ above include Viridi, 3-viridi, 4-biridi, bilimidi-, birazinil, bilidazi =, biperazi-, birazoli =, imidazolidi-, thiazoli, isothiazoli, oxazoli ^, isoxazoli, bidi [2,3-di Penzovillani / u, 1, 8 -Naphthyridini, 1, 5-Naphthyridini-, 1, 6 -Naphthyridii, 1, 7 -Naphthyridi-, 2,7-Naphthyridyl, 2,6 -Naphthyridi-Λ ^, Kinori, thieno [2,3-—] viridi, tetrazoli, thiadiazoli, oxadiazoli, triazi-, thie-, biloli, furi-rudo are used.

The substituent of the heterocyclic group which may have a substituent represented by R8 is, for example, an alkyl having 7 to 12 carbon atoms having a substituent.

Alkoxy with 1 to 3 carbon atoms, hydroxy, hydroxy, oxo, thioxo, aldehyde, trif / l, uamino, halogen, halogen with 1 to 3 carbon atoms =, 2, 6 -Jik mouth Feni, Coumarin- 31-carbo-, 4-Homo-111-biradil, Billau al-Dimino, Fran-A-Dimino, Coffen-a; u-Dimino, Messi, Substituted with a protecting group for the amino group, Halogen It can be used for ash with 2 to 4 carbon atoms. As the protective group for the amino group, the same as the protective group for the amino group of the backbone can be used. Examples of the group which may be substituted with an alkyl having 1 to 12 carbon atoms include, for example, phenyl, halogen, hydroxy, and di-vinylalkylamino. The space in the dialchiamino is a low-class structure with 1 to 3 carbon atoms.

The substituents in the phenyl which may have a substituent represented by R8 include, for example, low alkyl having 1 to 3 carbon atoms, low alkoxy having 1 to 3 carbon atoms, halogen, hydroxy and amino. Which is used,

CMPI g

The lower alkyl in the lower alkylthio represented by R8 is preferably a group having 1 to 3 carbon atoms.

Examples of the substituent in the phenyl which may have a substituent represented by R8 include a lower alkyl having 1 to 3 carbon atoms, a lower alkoxy having 1 to 3 carbon atoms, halogen, hydroxy ^, Amino or the like is used. Formula - (CH ₂₎ As a group which may be substituted by a group represented by _n i-, for example Amino, wherein one - R ₈ w wherein may have a Amino or location substituent Represents bipera ヅ-. And the like. Substituents have a good even Biberaji represented by R ₈ - The in substituents such as lower authors侄級alkylene _f having 1 to 3 carbon atoms having 1 to 3 carbon atoms:? Hydroxy, oxo, thixotropy, and halogen are used.

The lower alkyl represented by R and R or R ^ in the above formula preferably has 1 to 3 carbon atoms. As low-grade alkyls in low-grade aki-rubamoy, those with 1 to 3 carbon atoms are preferred. Examples of the substituents on the fern ball which may have a substituent include low-alkoxy having 1 to 3 carbon atoms, lower alkoxy having 1 to 3 carbon atoms, halogen, hydroxy, sulfoxy and the like. , Benzoxy etc. are used.

In the above formula, 11 ₈ "as low handling alkylene ^ is the optionally substituted lower A key may have a substituent represented by the group represented by -302-, preferably those having 1 to 6 carbon atoms, the substituent The group may be substituted at one or two positions, examples of which include amino, carboxy, pendant carbonyl, protected amino groups, and the like. As the protecting group in the above, the same as the protecting group for an amino group described below are used. As the low treatment alkyl for the low alkyl optionally having a substituent represented by R9, those having 1 to 3 carbon atoms are preferable. Examples of the substituents thereof include: Hue, Kapamoy, Metivamoy, Metchio, Che-Lacetamide, Ethoxyboe Mechikabamoy, N-methyltetrazolium, Halogen, and Sfamoy. .

The substituents in the phenyl which may have a substituent represented by R9 include, for example, low-strength irons having 1 to 3 carbon atoms, low-killing / u-koxy, halogens, and hydrides having 1 to 3 carbon atoms. Keys such as glyphos, sulfoxy, penzil, penziloxy, trimethylsilyl, and ashoxy having 2 to 10 carbon atoms are used.

The heterocyclic group which may have a substituent represented by Rg is, for example, a 5-membered heterocyclic group containing one sulfur atom, nitrogen atom or nitrogen atom, or 1 to 2 heterocyclic groups. 5- and 6-membered heterocyclic groups containing 2 to 4 nitrogen atoms and 5- or 6-membered heterocyclic groups containing 2 to 4 nitrogen atoms are used. Specific examples of the heterocyclic group include, for example, thiazolyl, isothiazolyl, oxazoli, isoxazoly, che- ^, furyl, virolyl-imidazoli, biradi-, bilimidyl, bilidazi, bipera-, triazi-, tetrazoli, and thiazoli. , Oxaziazoli and the like. The substituent is, for example, substituted with low alkyl of 1 to 3 carbon atoms, low alkoxide of 1 to 3 carbon atoms, halogen, hydroxyl, ト, sulfoxy, amino and halogen. Still further, acylamino fruct having 2 to 4 carbon atoms is used.

The cycloalkylene represented by R ₉ is preferably a 5- to 6-membered ring, for example, cyclohexene ^, cyclohexadene and the like. Can be.

As the heterocyclic group of carbo-amino which may have a substituent represented by R ₉ or may be via an alkylene chain, a 6-membered heterocyclic group having two nitrogen atoms is used. . As the heterocyclic group, for example, biperazyl and the like are used. Examples of the substituent include aki having 1 to 12 carbon atoms, lower alkoxy having 1 to 3 carbon atoms, oxo, thioxo, and amino. The alkylene chain preferably has 1 to 3 carbon atoms, and examples thereof include methylene, ethylene and n-propylene.

In the above formula, R12 of the group represented by the formula in Rio

. N-X-R13

The heterocyclic group in the heterocyclic group which may have a substituent represented is a 5-membered heterocyclic group containing one nitrogen atom, sulfur atom or oxygen atom and containing one nitrogen atom. Alternatively, those not included are used. Specific examples of the compound represented by the following formulas include 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 2-chloro, 3-che2yl, 2-fury, 3-furinol, and 2-pyrrolyl. , 3-biloli etc. are used. Examples of the substituent in the heterocyclic group represented by formula (1) include a low-ranked aki having 1 to 3 carbon atoms, a lower alkoxy having 1 to 3 carbon atoms, hydroxy, nodogen, amino, and zdogen. C2-4 arsenamino which may be used as * is used.

The substituent in the ferrule which may have a substituent represented by R12 includes, for example, lower ac having 1 to 3 carbon atoms, lower acoxy having 1 to 3 carbon atoms, halogen, -toro, and amino. , Hydroxyl or substituted hydroxy is used. Examples of the substituent in the substituted hydroxy include benzyl / pentzinole, and an acyl having 2 to 0 carbon atoms. One〗 0—

Tamil, 3-amino-3-carboxy lipone.

As the lower space represented by R13, those having 1 to 3 carbon atoms are preferable.

Examples of the substituent which may have a substituent represented by R13 include lower aki, lower ethoxy, and halogen.

As a low-killing compound which may have a substituent represented by Rl3, a compound having 2 to 4 carbon atoms is preferable as the low-killing compound, and for example, a halogen frit is used as the substituent. .

The low-treated alkylene represented by Rl4 in the group represented by the formula 1 Rl4 1 Rl5 in Rl3 is a group having 1 to 3 carbon atoms, such as methylene, ethylene, propylene, and isopyrylene. Used.

The lower alkylene represented by R14 is preferably a lower alkylene having 1 to 3 carbon atoms, and examples thereof include biylene and probenylene.

As the ester of carboxy represented by R15, for example, methylester, ethylester, and bubiester are used.

Examples of the heterocyclic group represented by R15 include a 6-membered heterocyclic group containing 窒素 nitrogen atoms and 駿 boron atom, and specific examples thereof include moholino.

The formula in Rll is represented by Ri ₆ of the group represented by CO lfH- H-

R16

As the low-kill, those having 3 to 3 carbon atoms are preferable.

Examples of the group in the phenyl which may have a substituent represented by Rl6 include, for example, a low-alkyl group having 1 to 3 carbon atoms and a low-alkyl group having 1 to 3 carbon atoms. Alkoxy 5, halogen, -toro, amino, C2 to C10 alkoxy, etc. are used.

Examples of the optionally substituted heterocyclic group represented by Rl6 include a 5-membered heterocyclic group containing one sulfur atom, nitrogen atom or oxygen atom, one or two nitrogen atoms and one strong atom. A 5-membered heterocyclic group containing a sulfur atom or an oxygen atom and a 5-membered extrinsic ring group containing 2 to 4 nitrogen atoms are used. Specific examples of the heterocyclic group include, for example, thiazolyl, isothiazolyl, oxazoli, isoxazolyl, ceni, furi, viloli, thiaziazoly, oxadiazoli, triazile, tetrazoli, imidazolyl, biradidini, birimidini-, bilimidazi-, bilimidibi-, bilimidazi- There are many things. The substituent is, for example, carbon number! Lower alkyl having 3 to 3 carbon atoms, lower alkoxy having 1 to 3 carbon atoms, halogen, hydroxy, amino, and amino acids having 2 to 4 carbon atoms which may have a substituent as substituents are used. .

As the substituent in sulfamoyl which may have a substituent represented by R17, for example, lower alkyl having 1 to 3 carbon atoms, amidino and the like are used.

As the substituent for phenoxycarbonyl which may have a substituent represented by R17, lower alkyl having 1 to 3 carbon atoms and lower alkoxy ruthenium having 1 to 3 carbon atoms are used. .

The low-ranking, low-ranking and hydrogen represented by Rl8 each preferably have 1 to 3 carbon atoms.

In the above formula, examples of the substituent of phenyl which may have a substituent represented by R 19 include lower alkyl having 1 to 3 carbon atoms, lower alkoxy having 3 to 3 carbon atoms, and halogen. , Nitro, amino, hydroxyl, Minomechi is used. Examples of the group in the substituted amino group include, but are not limited to, Pamoy, (2-oxo-13-benzylideneaminoimidazolidin-11-) carbo-, and (2-oxoimidazolidin-1-1-1) carbo-roto. Used.

The phenoxy substituents which may have a substituent represented by Rl9 include, for example, lower alkyl having 1 to 3 carbon atoms, lower alkyl having 1 to 3 carbon atoms, halogen, = to, amino , Hydroxy and aminomethyl are used. Examples thereof include the same substituents as those of the fue represented by Ri 9 of fW5. The lower radical which may have a substituent represented by Ri 9 is preferably a lower radical having 1 to 6 carbon atoms, and its g¾ group may be, for example, ぇぱ halogen, hydroxy ^ / u, cyano, trif. O τιMechi v¾do power S is used.

Examples of the alkene of alkenyl which may have a substituent represented by R19 include, for example, do-len and buguchi-benzene, and examples of the substituent include, Boxy, Ciano, etc. are used.

The heterocyclic group in the heterocyclic group which may have a substituent represented by Rl9 is a ^5- to ^6- membered heterocyclic group containing one sulfur atom or 1-4 nitrogen atoms, A 5- to 6-membered heterocyclic group containing one sulfur atom and one nitrogen atom or one sulfur atom is used. Specific examples of the heterocyclic group include, for example, 2-chee, penzocheninole, 3-ceni, 2-viridi, 3-biridyl, 4-biridyl, 2-thiazoli, 4-thiazoli, 5-thiazoli, isothiazolyl, 1 -Tetrazoli, 5-tetrazoli, vilolizy =, imidazolyl, 1,4-oxatin, etc. are used.

Examples of the substituent in the heterocyclic group which may have a substituent represented by Rl9 include a low alkyl having 1 to 3 carbon atoms and a low alkyl having 1 to 3 carbon atoms.

C? I Alkoxy nitrogen, nitro, hydropryl, amino, carboxy, oxo, or halogen having 2 to 4 carbon atoms may be used as a substituent, and acylamino having 2 to 4 carbon atoms and ash having 2 to 4 carbon atoms are used. .

In the above formula, specific examples of the aki having 12 to 12 carbon atoms include, for example, methyl, trifluromethyl, ethyl, n-provi, isobrobi, n-butyl, isobuchi, sec-butyl, Tert-butyl, ventil, isopench, hexyl, isohexyl hebuti, 3-heptyl, octyl, octyl, decyl, pendeci, dodecy, etc. In the above formula, as a specific example of a low-handled aki having from 6 to 6 carbon atoms, for example, ぱ methyl >> trimethyl-methyl, ethyl, n-propyl, isoprobi, n-butyl, isobutyl 'secc -But, tert-But, pliers Λ ', Isopen pliers, hex, is hex.

In the above formula, examples of the low-alkoxy having the number of carbon atoms of〗 to 3 include, for example, meth, trifluent meth, ethyl, η-probi, and isoprovir.

In the above formula, methoxy, ethoxy, η-propoxy, isopropoxy and the like are used as examples of the lower akoxy having 3 to 3 carbon atoms.

In the above formula, specific examples of halogen include chlorine, bromine, iodine, and fluorine.

In the above formula, examples of the lower alkyl sulfone having a carbon number of〗 to 3 include, for example, methyl sulfol, ethyl sulfol, η-provyls iso-isobrovis homo, and the like.

In the above formula, specific examples of amino acids having 2 to 4 prime numbers include, for example, acetylamino, brobiolamino, η-butyrylamino, and isobutyrylamino. ζ

ο In the above formula, specific examples of the alkoxy having 2 to 10 carbon atoms include, for example, acetoxy, n-brobyoxy, n-butylyloxy, isobutyloxy, n-pentanooxy, n-hexanoy Oxygen, n-butanoyoki, n-octanoyoki, n-nonanoyloxy, n-decanoyloxy are used.

And you to § Le group of the formula R6-C0- (wherein, R ₆ is as defined above.) The ingredients佯例of Ashiru group represented by, for example, 3 -. (2 6 - Jikurorofue -) 1-Methylisoxazo-4-4-carbo-, ethyl-2,3-dioxo-11-biperazinocarbo-Λ ', 2-oxoimidazolidin-1-yl, etc. are used.

Specific examples of the ash group represented by the formula R ₇ — ΝΕ-9 Η—CO— (wherein, R ₇ and have the same meaning as described above:) include, for example, ぱ! Hue = Arani / u, a-Penge — N-force / u-Bonzoxy r-D-Glutami D-ara-nore, D-hue Glycy D-arani, N—cabobenzoxy-D—ニルダ fl fl D ー fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl fl. 1) Phenyl glyci, D—force Λο Moi 1 Tributy D—Hue = Glyci, Methylamidoasparaginyl-D-fueclicyl, Ν—kabopenzoximethyamidodoasnoragii D1-hue-Λ ^ Gri ^ , Ν1Carbobenzoxy D-7 ェ /! / Glycy D-fu- / ^ Glycyl, 2— (2,3-Diaminoprobiamide) 1-2-1 fu- /! ^ Acetyl, D-Irami ^^ D-Arani, 2- [2-Amino-3- (（-methylcarnomoy) probionamide] acetyl, 2- (2-Amino-3-sulfamoylprobionami C) 1 2 1 pheninoreaceti, 2 1 [2-amino-3 1 (4 1 1 2 Dioxo-1 11-biperazinocaboxamido) probionamide-1-2-furaceci, D-2 ((4-ethyl2,3 dioxo) 1-biperazinocarboxamido) 1-2- (4-methoxyphenoxy) , 4-Ethyl-2,3-Dioxo-one-biperazine carbodi, D—2 -— [2- (4-E-A / —2,3-Di-oxo-1-1-Biperazinocarboxamide) -1— (N-meth Power-lvamoy) p-bynamide] 1-2-phenylacetid, D-2-C2- (4-eth-2,3-dioxo-l-biperazinokaboxamido) acetamide] 1-2-fe-acet, D-2 — (3—Sulfamoyl) 1—2-phenylacetyl, D—21—2-Penzyloxycarboxamido 3— (4 · ^ Methoxyphenyl ^ xikaboxamido) Proviona Mid) 1-2 1-2-phenyl-2-1-2-pentacarboxylic carboxamide 3-(Ν-チ-ノノモ D D) 2-(Ν-carbopenzoid -Glycamino) 1-3-(Ν-Methyl carpamol) Bropiol, 1-Carbo penzoki ^-1-D-ara-, 2-(Benzyloxykaboxamide) 1-1 -Phenylacetyl, 2-Penzinoleoxycarboxamide 3—: Ν— Mechi Carpamoy Probio-, Ν-(41-ethyl-2,3-digitia-one-one-biperazino-carboninole) One! ) 1-fu-noreglysyl, 2- (2-amino-4,1-thiazolyl / 1-2- (4-ethyl-1,2,3-dioxo-11-biperazinocarboxamide) acetyl, 2- (2-hue: = Acetamido) propiole, 2— (4-ethyl-1,2,3-dioxo-l-biperazino-ylboxamide) -1 2-che-acetyl, D—2— (4-1-η 1-dodecyl-2,3-dioxo-1-11-biperazinocarboxamide) -1-2-phenylacetyl, D 2— (4,6-Jetyl-2,3-di-oxo)

One ο? .Ί? Ι _ 'one 1-11 Biperazinocaboxamide) 1-2-phenylacetyl, D 2-(4-hexhexyl 2,3-dioxor 1 -biperazino force boxamid) 1-2-ferrazacet, D 2-( 4-n-Ami-1-6 (S) -methyl-2,3-dioxo-11-biperazinocarboxamide-1-2-Che-luaceti, D-2 ((4-eth-5 (R) -meth-2, 3 1-oxo-1-1-biperazino force / u-boxamid) 1-2-Che

, D— 2— (4-eth-5 (S) —meth / ^-1,2,3-dioxo-piperazinocarboxamide) -1-2-thi-acet, 2 -— ((3-furidylendamine 2— Oxoimidazolidine-1 1) force bokamido] 1-2-chelasset, 2-(4-1, 2, 3-dioxor 1-piperazinoca-t /) 1 2-(4-me Toki fueni) acet, 2-(8-hydroxyl 1, 5-naphthyridine-l 7-carboxamide)-1-2-fuelacet / 1 /,, 2-(4-eth2,3-dioxo-l-l-l-biperazinokaboxami 1) 2-Hue-noreseti, 2— (4-n-octi / ^-1,2,3-dioxo) 1-biverazinokaboxamido) 1-2-Fue-noreseti, 2— (4-1-ethyl-2,3-di) Kiso 11-biperazinocarboxamide) 2- (4-hydroxyhexyl) acetyl, 2- (4-ethyl 2,3- 1-biperazinocaboxamide) 1—2 — (“4-chlorophene =) acet; 1,2— (4—n-octane2,3-dioxo-1—11-biperazino-forcebox) 1—2— ( 4-1-Sulfoxyphen-noreth) aceti, 2— (41- ^ 1,2,3-dioxo-111-biperazinocarboxamide) -1 2 -— (4-methoxyphen-2-) 2-, 3-dioxo-1-1-biperazinocaboxamide) 1-2- (4-trinothi-silice-) acet, 2— (4-1-2,3-dioxo-one-biperazino-force / u-boxamide) One 1- (3-Chloro-4-methoxyphenyl) acetyl, 2- (4-Ethyl-2,3-dioxo-one-biperazinocarboxamide) -1-2- (3-Chloro-4-1-sulfoxyfue = aceti, 2-— 4-1, 2-3 dioxone 1-biradino force / ^ boxamido)-1-2-(3-chloro-4-hydroxy =) acetyl, 2-(4-chill 2, 3-^ 1-1-biperazinocabo; =)-2-(1-penzi / li "xifeni) acetyl 1, 2-(4-1-n-octyl-2, 3-dioxo-1-biperazin-dicarboxamide) 1 2-(4-hydroxy-) Asechi, N- (4-ethyl-2,3-diluted-kisone-one-biperazinocarbo) -glutamine-,-(-(4-ethyl-1-2,3-dioxo-one-biradizinocarbol) -Fenilala = , 1ί-(4 1 ethyl 2, 3-dioxo 1 1 1 biperazino carboni / u) —!) Ara =, 2— (4 -Ethyl 2,3 1-dioxo- 1-biperazino force; 1-boxamide) 1 2— (4-hydroxy phenyl) acetyl, 2,2-bis (4-ethyl 2,3 -di-oxo) 1 1-biperazinocarboxamido) aceti, 2— (4-ethyl-1,2,3-dioxo-1-1-biperazinocarboxamido) -1 2 -— (1 to 1 mouth) x-acetyl-, 2-— 4 1 n-1-2,3-dioxo-1-biperazino carboxamide 1-2-cetyl, 2-(4-ethyl 2, 3-dioxo-1-biperazino carboxamide) 1 2— (2-Amino-4-thiazoli) aceti, 2— (4-Ethyl-2,3-dioxole 1-biperazinocaboxamide) 1—2— (2-Acetamido 4-4-thiazoli) acetyl, 2— (4 One ethyl two, three—two-year-old kiso one one biperazino force / boxamide) one two—choe-asechi , 2- (4 Echiru 2, 3 - Jiokiso one 1 one Biperajinoka Bokisami de) Single 2- (2-methyl-one-thiazolyl) Asechiru, 2- (4 one Echiru

(― Ci.iPI -2,3-Doxoxo 1-biperazinocaboxamide) 2- (2-Acetamido 4-Ithiazo) acetyl, 2-(-n-oct-1,2,3-Dioxo-1 Biperazinocarboxamide) 2- (2-amino-4-thiazoli) aceti, 2- (4-ethyl-1,2,3-dioxo-1,1-biperazinocaboxamide) -1 2-furiace, 2- (4-ethyl 2,3,3-dioxo) Biperazinocarboxamide) 1- 2- (2-virolyl) acetyl, 2- (4-technical 1-2, 3-dithyloxone 11-biperazinocaboxamide) 2- 2- (4-hydroxyphene- / u) ) Acetyl, 2-((4-n-octyl-1,2,3-dioxo-one-biperazinocaboxamide) -1-2- (2-chloroacetamido-4-thiazolyl) acetyl, N— (4-ethyl-1,2,3- Jokiso 1-piperazino force / u-boninore) One! ) メ, η, D-2-[4-1 (2-f-1)-2, 3-dioxo-1-biperazino force norevoxamide] 1 = acetyl, D-2-(4-1) -2,3-Dioxo-1-3-biperazinocarboxamide) 1-2- (4-benzynoleoxyphenyl) acetyl, 2,5-bis (4-ethyl / u-2, 3-dioxo-1 1-biperazinocaboxamide) pentanoyl, 2— (4-et / u-2,3-dioxo-1 1-biperazinocarboxamide) 1—3— (Ν-meth-acid Bamoy A Probio-, 2,3 1-bis (4-ethyl-2,3-dioxo) 1-biperazinokaboxamide Probi-, 2-((4-ethylino2,3-dioxo-1 1-piperazinocaboxamide) 1-3-clopropio-, 2- (4-1 2-, 3-dioxole 1-biperazino force boxamid) 1 2 -— (4-II-1 otatanoxy oxyfel) acetate , 2-(4-ethyl-2-, 3-dioxane-one-biperazinocarboxamide) -1-3-famoi bropiol, 3- [2- (4-ethyl-2,3-dioxo-one-biperazide)

c:; n Nocarboxamido) 1-3-[(1-Methyl-1H-tetrazole-5-i) thio] propio-, 2- (4-eth-1,2,3-dioxo-1-1-biperazinocarboxamide) acet V, D-- 2- [4- (2-hydroxy 5 / ethy) -2,3-dioxo-1-1-bis-dinocarboxamide] -1 -2-phenylacetyl, D-2-C- (2-chloro Methyl) -2,3 1-doxoxo 1-biperazinocarboxamide] -1 5 »-Feninoleacetyl, 2— (4-ethyl2,3-dioxo-1 1-biperazinocarboxamide) 1 3— ( Ethoki ^ carbo-methica pamoyl) brovi er, 2-(4-1,2-dioxo- 1-1-biperazinoca boxamid)-1-3-(Chenacetamide) brovio, 2-(4 1-ethyl 2,3-dioxole 1-biradino force boxamid) 1 3 -— [2— (1H-tetrazo 1-11 Le) acetamido] probiol, 2- (4-ethyl-1,2,3-dioxo-one-biperazinocarboxamide) -1-2- (1H-tetrazole-11-) acetyl, 2- [ (3-butylideneamino 2-quinoline midazolidin 1-1) power boxamido] 1-2-1-acetylacetyl, 2-1 ((3-butylideneamino 2-1-year old quinoimidazolidin-1-1) carboxamide) 1 2— (4-Hydroxyphenyl) acet, 2 — ((3-Fluorideneamine) 2-oxoimidazolidin-1-yl) Rubixamide] 1-2— (4-sulfoxyphenyl) acet, 2 — [[2-oxo-1-3- (thiophene-2-adimino) imidazolidine-11-yl] force-reboxamido] -1 2--Fu-l-acet //, 2-C (3-furfurideneamino-2- 2-oxomidazolidine 1-inole) -force-boxamido] -1 2-che-acetyl, 2 -— ((3-methylsulfol- 2--2-oxoimidazolidin-1-yl) carboxamide] 1-2-fe-acetyl, 2— [(3— Furi Fri Denamino-2-oximidazolidin-1-yl) force boxamid] 1 2- (2-amino-4-thiazolyl acetyl, 2- [(3-fluoroimidazomin 2-oxoimidazolidin-1-1-1) Λ (carboxamide) -1 2 (2-chloroacetamido 4-thiazolyl) acetyl, 2-[(3-me-2-oxoimidazolidin-1 1 ィカル carboxamide) 1-2-fe = ruaceti , 2-[[2-oxo-l3- (thiophene-l-aldimino) imidazolidin-l-l-yl] carboxamide] -l2-cheniacetyl, 2-((3-meso-2-oxo-imidazolidin-l 1) Carboxamide] —2—Che-Lacetyl, D—2 — ((3-Fridylaminomin-2-oxomidazolidin-1-1-1) Carboxamido] Provyl; 2- (4-Hydroxy-6— Mechiniko Chinamide) 1—2—Hue = Russeti, 2— (4-Hydroxy 6—methylnicotinamide) —1—1 (4—Hydroxyphenyl) acetyl, 2—C 5, 8—Dihydro 1— (4) 1-biperazi-/ — 5-oxobilide [2,3-d] birimidine-1 6-force boxamid] -1 21-hue-luasetti, 2— (3,5-dioxo-1,2,4 — Triazine-1 6—carboxamide) 1—2— (4-Hydroxyphene) acetyl, D—2 — [(3—furfurideneamine 2—oxoimidazolidin-1-yl) carboxamide] Brobionbio =, D—3 — ((2-oxo-3-—Shoimidazolidin-1-1-) carboxamide) —1-2-Chenylacetyl, D—2 -— (5-Methoxyca / u—3— main Chiru 2 Okisoi Midazorijin one] Ichii) Karubokisami de] one ₂ one Hue-le Aceti, D—2 — [(5-benzilic acid / u-3-1-methyl-2-oxoimidazolidine-11-yl) power boxamid] -12-phenylacetyl, D-2-C (5 -Carboxy-3-Meth ^ one 21

Οί.Γ7Ι キ力イ 1 1 / / / / / / / 2 — / 2/2 2 2 2 2 2 2 2 2 2 2 2 2 — 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 Dioxo-1 11-biperazinocarboxamide 1) 2- (2-chloro- 1-cyclohexene 1-11) acetyl, D— 2— (4-n-amyl 2,3 1-biperazino dicarboxylic acid) 1- 2-acetyl-, D- 2- (4-n-ami-6 (R) -methyl-2,3-dioxo- 1-biperazinocarboxamide) 1 2- : = Acetyl, 2— (4-hydroxyoxymethyl-1,8-naphthyridine-13-force boxamid) -1 2-fe = / aceti, 2— (4-hydroxy-4-7-trifluoromethylquinoline 1- 3-carboxamide) 1- 2-phenyl-2- (2- (2-amino-4-thiazolyl) acetyl 1) D-phenylglyci-2,1- (6-hydroxy-1,4-dioxothieno2.3-b) biridin-3-carboxamide 1-2-fuerasechi, 2 — [2-((2-amino 4-thiazolyl) acetamide] -1-2-phenylacetyl, 2 -— (2- (2-chloroacetamido 4-thiazolyl) acetamide] -1-2-phenylacetyl, 2- (2,5 —Jisho Kiso 1,2,4-Triazinone 6-carboxamide) 1—2—Che = Aceti, 2— (2,4—Dioxobilimidino 1—5—force / ^ boxamid) 1—2—Che n Acet 2-(6-hydroxy 1,5-naphthyridi-recarboxamide)-1-2-phenylacetyl, 2--[2--(4-ethyl-2,3-dioxo-1 -bipera dinocarboxamide)-1-ceni / uacetamide One two-feet Chinore, two one (twoー 2—Cheninoreacetamide) 1—2-phenylacetidium, 2— (2-peridone 2—Chenylacetamide) 1—2—1 (4-sulfoxyfever /) acetid, 2 1 {.

3 \-" ^{c Λ} ―

. I Acetamide) 1-2-(4-hydroxy: 7 acetyl, 2-(N-carbopenzoxy brollyamino)-1-2-furaceti, β-(Chenylmethicarbo)-, 2-(.4-chloropenzoy) (Raid) 1-Cha-Acechi, 2- (2-Cha-Racetamido) Aceti A ', —Penzilka Boxamido!) One-Ral, N— (4-Heady ^ Penzoy D-One) La i / u, 2— (4—black mouth penzamido) pvioni, 2— (4—aminobenzamide) asechi, N- (4 41ethyl 1 2,3— ジ 1 キ 1 ソ 1 D) Fe-Grill, D- 2- [2- (2,6-Diclo-Fe = Thio) acetamide] -1 2-Fe = / uAcet, D-2 -[[[3- (2,6-dichlorophene) -1-5-methylisixazo-4-4] carboxamide] -1-2-d-d-acetyl, 2-(carpamo A) Amino-2-Cacetyl, N-capamoy D-Fe-Glyll, 2— (3-Metica-Bamoy 3-Methyl-110-Raid) 1-2-Fe-acetyl, 2— ( 3—Metica / Moie 3—Methyl 1-Raid) 1 2— (4-Hydroxy) -Fa-acetyl, 2— (3-Metika Bamo 3—Met 1-Raid) 1 2— Chenyl acetyl, 2- [3- (2-hydroxybenzoyl) -1-11 ureido] -1 2-1-acetyl, 2- [3- (2-benzyloxybenzoyl) -1 -1-peroxide] 1 2— (4-hydroxyphenoxy) acetyl, 2— [3— (2-hydroxypentyl) -1 1-peroxide] 1 2— (4-hydroxypheny) acetyl, 2— (3-methynoleca) 3-Methyl-1 1-Raid) 1-2- (4-Hydroxy) phenylacetyl, 2- [3-benzio Shibenzoi) Single 1 Urei de] one 2 Hue - Ruasechinore, 2 one [3 i (2-pen Jill O carboxymethyl pen zo I le) one 1 one Ulei de] one 2- (4 "arsenate

? Doxyphen-) aceti, D-1 2— (Penzi A i * ki carboxamide) -1 2— (Penzoxyka) ethanes honamido) 1-2-Ferassetti, Pameshid D

The rules are used.

Specific examples of the acyl group represented by the formula R ₁₀ -CO-(wherein, Rio * and Rii have the same meanings as described above) include, for example, N— [2- (2-amino-4-1) Thiazoli) 1-methoxyi minoaceti] 1! ) Ara =, N-[2-(2-amino-4-thiazoli)-1-2-methoxy-minacetyl]! ) 1-n-Gly, 2- (2-amino- 4-thiazolyl) -1-2- [2- (2-amino- 4-thiazolyl) -l- 2-methoxyiminoacetamido] acetyl, 2- (2-chloroacetamide 4-thiazol) -1 2- [2- (2-chloroacetamido 4-thiazoli) -12-methoxyminoacetamido] aceti, 2- (2-chloroacetamide 1-4-thiazoli) 1-2-methoxyminacetyl , 2— (2-Amino-1-4-thiazolyl) -1 2-methoxyminoacetinole, 2- (2-Amino-1-4thiazolyl) -1 2-oxyminoacetyl, 2—Chelu 2-Methoxyiminoacetyl, 2, F Lee 2-Methoxy Iminoacetyl, 2- (4-Hydroxyphenyl) -1-2-Methoxyiminoacetyl, 2-Fe-I-2-I-Methoxyiminoacetyl, 2-Fy-2-aminoxy-acetyl , 2-Che-2-2-Amino Acetate, 2-Che-Lu 2-Ci-L-Acetyloxymino Acetate, 2-C- (r-D-Glutamic Moxy) phenyl)-2-Amino Acetate, 2- (4- (3-amino-3-potenoleoxypropoxy) phenyl) -1-2-oxominoacetyl, 2-one-two-two- (3-moholinoproboxyminino) acetyl, 2- -2- f 2—amino-4 monothiazolyl) 1 2

C '. 2-methylaminoacetamide] -1-2-acetyl-, 2- (5-chloro-2-aminochloro-4-aminothiazolyl) -12-methoxyaminoacetyl, 2- (5-cyclo2- Amino-4-thiazolyl) 1-2-methoxyminoacetyl, 2- (2-amino-4-thiazolyl 212-isobromoboxyminaceti · 2— [11- (t-butoxycarbo-

ソ isobroboximino] 1 2 ~ 2 /! ^ Amino-4'-thiazolyl) acetyl, 2- [1- (1; butoxycabonyl) isopropoxyminino] 1-2 '(2-triphenylmethyi) Aminow 4-thiazolyl acetyl, 2- (2-chloroacetamide 4- thiazolyl) -1,2-isobropoxy minoacetyl, 2-methoxyimimino 2-C2-saminoamino 4- thiazoli A acetyl, 2-[ 2- (2-chloroacetamide 4-monothiazoli) -1-2-methoxyminoacetamide-1-2-phenylacetyl, 2-phen ^ -1 2-ρ-trithioiminoacetyl, 2- [2-

(2-Amino-4-thiazolyl) —2-Methoxyiminoacetamide] cetyl is used.

Rl8

Formula ~? ^E — ^C0- (wherein, R17 and Rl8 are as defined above.

Rl7

You. Specific examples of the ash group represented by) are, for example, a-sulfo-noreaceti / u, a-s-V-fox-acetate, a-hydroxy-phenylacetate, na-s-famoi-phenylacetate-a-phenoxycarbo- Rufus-aceti, a— (p-trinoreo s / caboni) huacetil, naichi-formomixifuze-ruasechi, naichiru /! / Boxyfuaceti, a 2- (N, N-dimethylsulfamoy) 1-2-1 acetyl chloride is used.

？? I-I ---- Wherein _{Rl 9 - R20 - CH 2 -} CO - (. Wherein, with the same meaning as Ri 9 ^ pre Rg0f ± above) Specific examples of A ^ Le group represented by, for example, Shiano Asechi, Hue - Ruasechiru , Phenoxytesetil, trimethyl thiol-acetylacetyl, ^ anomethylthioacetyl, 1E-tetrazo-1-1-acetyl-2-thi-acetyl, 2-(2-amino-4-thiazolyacetyl, 2-(2 —Chloroacetamido 4-Ithiazoli) aceti, 4—Biridiothioacetyl, 21-Chithioaceti, 3,5-Dichloro-1,4-Dihydro 4- 4-oxoviridine-1-Acetyl, β-Carboxybi = Thioacetyl, 2— 2-Aminomethylphenyl) acetyl, 2- (2- 2-carbopenzoxyaminomethiphenyl) -acetyl, 2— (2- ゥ leidomethyphenyl) acetyl, 2-—2- (2oxo) Mida Resin-1 11) Cabon /! Aminometh] \ / Fue: Nore] acechi 2— [2— (3-Penzylideneamino2 2-oxoimidazoline 1 1) Carboxaminoaminophen Acetyl), 2- (5, 6-dihydro-1,4, one-year-old xatin-1-2-yl) acetyl, 2- (2,5-di-year-old quinobilo lysine-1-3-yl) acetyl, 2-succi 2-Imidoacetyl, 2- (1-Acetyl-2,4-diethyl thiocyanate) is used.

The amino group and the Ζ or carboxy group in the above-mentioned acyl group include those having a protecting group.

As the amino-protecting group, those similar to the "amino-protecting group" described later are used.

The protecting group for the carboxy group includes β-lactam and all groups which can be usually used as a protecting group for a hepoxyl group in the field of organic chemistry, for example, when the ester moiety is, for example, methyl, ethyl, propyl, etc. Provir, Third Treatment Buti, Third Jamil, Pendant, p-trobenzil, P-Metro ^ Penzi, Penzhi-Hori, Fenashi Hue, p--Fou Echi, Metoki Meh, Etoki ^ Methi, Penzoki ^ Methi, Acetoki ^ Methi, Vivaloydiokimethi, β-Methisholeti, Methylthiomethyl, Tritchi,, 5, / 3-Triclomouth etil, β-Iodoetyl, Trimethyli dimethylsilyl, acetylmethyl, ρ--topenzomethy, ρ-melupenzomethy, phthalimidomechi, bubby-okimethyl, 1,,] dimethybi, 3-methyl-3 — Bute, Saksimimi Domechi ^, 3, 5 — Di-third Butyl 4-Hydroxy ^ Benzi, Mesi Mechi, Ben Zensulhoni Methi, Hue n / i / Chiomechi, Dimethi Aminoeth, Viridin 1-1 Oxide 2-methylcarbamoyl, methylcarbamoyl V Surubui two methylate, bis (.rho. main Tokishifue =) methylcarbamoyl, 2 one Shiano 1, 1 is an dimethylcarbamoyl E Ji like Este, etc. Nri b if ¾ are exemplified. The present invention provides the novel monocyclic compound. The selection of the protecting group is not particularly limited: ¾: ^, in particular, pendyl, β, β, β-, J-chloro, p Pendant with 12 mouth, p-Methoxyponica S 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 3-lactam and peptide synthesis are conveniently employed. For example, aromatic sacyl groups such as phthaloyl, p- ■ = ■ benzoyl, p-tert-butylbenzoyl, P-tert-butylbenzenesulfonyl, penzensho /, toenshol, etc., for example, formyl, acetyl, Probio n / u, monochloroacetyl, dichloroaceti, trichloroacetyl, methanesulfonyl, ethansjoer, trifluroylacetyl, maloy, succinic, etc., aliphatic radicals such as methoxy Boni, ethoxycarbonyl, t-butoxycarb, isopropoxycarb, 21-cyanoethoxycarbonyl n, β * β, β-J p—-tropendi-loxykaboni, p-methoxydioxykaboel, diphen-methyloxykabol, methoxymethyi-carbon, acechi-methyi-xicarboni, isobodioxycarboni, fue-carbo Esterified carboxyl groups such as phenyl, methylene groups such as (hexahydryl 1-azebine-1-yl) methylene, etc. sulfulfo groups such as 2-amino-2-carboxyethyl sulfo-, and, for example, trityl , 212 phenylphenyl, benzylidene, 412 benzylidene, di- or tri-A, pendyl, p-, trobenzyl, etc. A protecting group for an amino group other than the group is used.

In the general formula, among the acylated or protected amino groups represented by Ri, those preferred as ^ -lactamase inhibitors are more specifically shown by the formula:

A— C— C0NH-/ \

W Z

[In the formula, A is a lower alkyl group such as hydrogen, methyl, ethyl, or isobutyl, an alicyclic group such as hexyl hexyl or hexyl, an aryl group such as phenyl, etc.] Racyl group, cho-, benzozonyl, heterocyclyl group such as bicolyl, isoxazolyl, biperazino, thiazoly, tetrazoi, oxathiano, etc., where A is amino, lower alkyl, low-grade aquo ^ , Hydroxy, halogen, or chloroacetamide. W is hydrogen when Z is hydrogen, an optionally esterified carboxy group, sulfo group, sulfamoi

<'One One One: iTI Groups, hydroxys / u-holoxy 5 groups, protected amino groups, phenyl groups such as phenolic carboxamides, amide groups such as lower carboxamides, lower acryloboxamides, etc. , 2-di-Zo-Zo, (2,3-dioxo-1-1-biperazino) carboxamide, imidazolidino-force-boxamide, oki; / imidazolidino-carboxamide, (1,2-diazo) caboxamide, Isoxazo 1-1-4-carboxamide, (2-aminothiazol-141-yl) meth-boxboxamide, 2, 3-dioxo-11-biperazinocarboxamide) -1-2-carbobenzozoxyami nobrobion Heterocyclic carboxamide groups such as amides, and W and Z are combined to form the formula NX-G (where X is an oxygen, sulfur or sulfoxide group, G is a lower aki group,, —dimethyl-one-force / ^ Power of boxymethyl etc. Alkyl groups such as xy-substituted low-alkyl groups, ferry-like groups, and acetyl-like groups

, A hydrogen group. :), and — A— may represent a bond. .

In the above equation, the low key / u key represented by A is the number of carbon atoms! Chain- and branched-chain alkyl groups of up to 4 are preferably N-methyl carbamoyl! /, Cabobenge / oxyamino, for example, a fary-like aryl group, tetrazoacetamide, 4 1,2,3-dioxo-11-biperazinocarboxamide, which may have phenyl, methyl, or ethyl at the 3-position; may be substituted with a heterocyclic group such as 2-diazo Good.

Examples of the halogen that can be mentioned in A include fluorine, nitrogen, bromine and the like, low alkyl groups such as methyl and ethyl, and low alkoxy groups such as methoxy and ethoxy.

Examples of the optionally protected amino group represented by W include chloroacetylamino, arachiamino, arachiroxyamino and the like. It is.

The heterocyclic ring in the heterocyclic carboxamide group represented by w is phenyl, an alkyl group having 1 to 12 carbon atoms, a saturated alicyclic group, an alkyl group having 2 to 8 carbon atoms, such as methoxy. , Ethoxy, etc. てもァ扱扱よいよいよい · · · · · · · · · · · · リ · リリリアルコキシアルコキシリアルコキシアルコキシェェェOr a carboxy group.

The lower alkyl in the low-alkyl carboxamide group represented by W is preferably a linear or branched alkyl group having 1 to 4 carbon atoms, and these may be substituted with a halogen such as chlorine, bromine or fluorine. Good.

A compound in which R i is amino in compound (I) is, for example, acylated.], A compound in which Ri is an amino group in which Ri is acylated in compound (I) can be produced. it can.

The compound having a protecting group in the compound (I) of the present invention is obtained by removing the protecting group], leading to a compound having no protecting group in the compound (I). Can be. Compound (I :) can form ¾ with して group or acid. Therefore, compound (I) is collected as 揎]? The substance obtained as 樘 may be in free form or may be used as another 氇. Further, the compound (I) obtained in a free form may be referred to as ¾. Examples of the above base include inorganic bases such as lithium, potassium, sodium, potassium, ammonia, and the like; organic bases such as pyridine, collidine, triethylamine, and triethanamine; and acids such as hun, sulfate, and the like. , Phosphoric acid or inorganic acids such as Rokushun, succinic acid, Probion II, mandelic acid, cunic acid, or organic acids such as tartaric acid are all used as stable powders, almost tasteless and toxic. rare,

c .vi (On rat LD 50 2 g i¾) ₀

Compound (I) may have optical isomers (eg, D-isomer, L-isomer). In that case, each isomer thereof and a mixture thereof are also included in the present invention.

The inhibitor of the present invention is used when administering a lactam antibiotic for the treatment or prevention of bacterial infections in humans or livestock.

When the inhibitor of the present invention is formulated alone, it is used before or after administration of the i9-lactam antibiotic, or is used as a mixture at the time of use. It can also be formulated as a mixture with a 3-lactam antibiotic. For example, as a? -Lactam antibiotic, there may be mentioned, for example, pendibe-^-lin, phenoxymethi / benicillin, su / benicillin, capenicillin, ambicilin, amoxicillin, mesilinam, kuxixicillin, Dicloxacillin, viraxillin, abacillin, ticasilin, cephalolizine, cephalothin, cefazolin, cephalexin, cefacetri, cefamandho / u naphite, cefuroxime, cefocitam, cefoxitin, cefoxitin Cefsulodin, cefataro, cephatrizine, cefataxime, cefmenoxime, ceftazidine, ceftezoxime, and other known ぺ -silines and cephalosbolins; and hetamine, meta-ambicillin, tarambicillin, dihydrocarcinidine ^ Li down, Bibume cylinder is use, injections, dry syrups, granules, tablets, prepared according to a conventional method to force blanking cell agent. Preferably, it is used in the form of ¾ or hydrate as an injection.

The compound (I) of the present invention has a weight ratio of 10 to the β-lactam antibiotic:

1 to 1: 10 can be used. Also, a ratio of 1: 1 to 1: 8, for example, 1: 2, 1: 3, 1: 4, ί: 5 or 1: 6 is advantageous.

IT O

The compound of the present invention is administered at a rate of 50 to 100 OOg per day, and usually 100 to 75 Offig per day, for example, 1 to 6 times, more usually 2 to 4 times. Is administered.

The 3-lactam antibiotic in the composition having a synergistic effect of the invention is usually used in an amount that is convenient to use it or less.

Test example:

Measurement of inhibitor concentration required to inhibit enzyme activity by 50%

A typical example of cephalosbolinase is Enterobacter luciferase, IF 0 1937, and a typical example of ぺ -silinase is Staphylococcus. 05 mol, PH 7]) Incubate with an appropriate dilution of the inhibitor product in a phosphate buffer for 30 minutes at 30 t, add cephalotin at a final concentration of 0.1 mM, and allow the enzyme reaction to proceed for 10 minutes. You. The enzymatic activity is measured using the microiodine method [Journa 'ob. Generalola', Mikuguchi Biology, Vol. 33, page 121 (1963)]. Hereinafter, the inhibitor concentration required to inhibit enzyme activity by 50% is abbreviated as 150. Table 1 shows the 150 values for Enteropatar's Chlore force, and Table 2 shows the 50 values for Staphylococcus oreus. Rl X

2- (4-n-octyl 2,3 dioxor 1-hydrogen 2.8 radinoka dexamide) 2-Chenetamide

2— (4 n—year-old 2 3 year-old kisso 1-by-method ^ 0. 046 radinocarboxamide)

D—2 — [(2-year old quinoline 3 furidmino methoxy 0.333 midazolidine 1 yl) power oxamide] 2-fe

Two T setamito *

2 Penciloxy Power ^ 2 Roo 2 Hua-Luaseta Metoki ^ 0.04 5 '

2 Carboxy-2 phenyl cetamide methoxy 0.

2-Pendyloxycarpoxamide 3- (2ί-methymethoxy1.1-yl) y-B; T-Mido

D--1 Piperamethoxy 1.1 Dino

D—N force A ji ぺ nzoki S ^ T La -Λ ^ Τmino methoxy 3.2-

[3— (26 dichloromouth phenyl) 5 methyliso

Oxazoly] force oxamide hydrogen 0.068

2— (4,2,3-dioxor 1 biperazino hydrogen 2.3 power oxamide)

Nore) acetamide

Ν— 2— (4-ethyl-2,3-dioxo-1-bipera methoxy; 0.26 dino power Λ ^ 'oxamide) 2-fecetamide

2- (2-amino-4 thiazolyl) 2-methoxymethoxy hydrogen; 1.4 minoacetamide

2- (2 amino-4 thiazoly) 2 methoxy methoxide 0.27 minoacetamide

2- (2-chloroacetamide-4 thiazolyl) 2methoxy 0.3-methoxyiminoacetamide

2-hydroxysulfonyl-2-oxy-2-phenylacetate hydrogen; 3.6 amide *

2 Methoxyimino 2 phenylacetamide hydrogen; 5.0

2,6 Dimethoxy benzoylamino hydrogen i 2.5

2, 6 dimethoxybenzoylamino methoxy 1.8 Chemical ⁷ Ri X 150 «^)

19 2-C5 Chloro-2 chloroacetamido-4 thia water 0.3 zori) 2-Methoxyiminoacetamide

20 2-((2-amino-5-clo-4 thiazoly)) 2 Water 1.2-methodiminoa

21 2 Hue-2p Torino iminoacetamide Water 0.55

22 2- (4,2,3 dioxor 1 biperazino water 3.0

Power oxamide) 2— (2—crow 1—black chrome

Sen 1

23 2— (2 amino-4 thiazoli A — 2 iso-T

24 2-[[3- (N-Sphamoyl) 1-Methoxy 0.76 Penzoxy Minoff * π-Bionamide] F * αΐί-Onmid!

I

25 2— [3 C 6-Cyclo mouth phen-2-5-methyl water thread I 3.6

Isoxazolu 4-yl) power / ^ 'xamido 2—che

i

Cetamide

26 2- 1- (t butoki frog), noboxy hydrogen ₅ 0.0055 imino] 2- (2-amino-4-thiazoli)

Acetamide

27 2— [1 (t butoxy power / ^ iso: A3 poxy water 0.050 imino :) 2 1 (2 triffee-methine / minnow 4

Thiazolyl) acetoamide

I

28 2— (2 chloroacetamido-4 thiazolyl) 2 water ¾! 1.10 Isopropyl oximinoacetamide 1

29 2 Methoxyimino 2— (2-Sulfamino-4-Hot thread! 0.07 AZOL セ acetoamide Ϊ

Two

Rl X

D—2— (4,5 (S) -methyl 1,2,3 di-water 1.2-kilo y—1-biperazinocaxamide) 2-—di-acetoamide

D—2 — [[3- (2,6-dichlorophen =〉 -5—water 0.4 methyl isoxazo 1-4 4- / J-force oxamide] 2

Cheni Setamid

D—2 — [(2-oxoimidazolidine 1-A Hydrogen 2.4

Oxamide] 2-thisetamide

Β— 2— Γ 6 6 w 々ロロロ画画画 * * * ΛΓ ΛΓ Μ

D-2- 2-Amino-4 thiazolyl) acetami water 5.0 d) 2-phenicetamide

2 Carbopentoxy amino-2 Penzilokica Water 1.7 Bo-ethyls Λ ^ ι ^ Τmid

Test example2

Surplus action with cefotiam

Cefotiam is added according to the cefotiam concentration gradient to a ^ medium containing 1 Hs nl of each of compound Nos. 3, 9, 12, 26, 27, and 29, and the test bacteria are inoculated thereon. After 18 hours, the minimum inhibitory concentration (hereinafter abbreviated as MIC) is measured. Use was inoculum concentration 1 0 ^8, culture area DOO Ripuchikesu ® Soiaga [Bae-click ton 'Dickinson' and 'Kampa - I over (: Becton Dickinson & Companey), manufactured by the United States] was use to.

Table 3 shows the obtained results. Table 3

Cef compound number (coexistence) Test bacterium alone 3 9〗 2 26 27 29

7 * n Teus Mogar ΊΝ 387 200. 39 39 02 02 25 <02 100 (Proteus morganii) ^ tar dr j IFO 12937 100 3.13 0.39 02 0.39 0.39 0.78

(Enterotacter cloacae) Sitter TP yr TfT 512 625 0.39 0.39 C 02 0.39 CX39 039 (Citrobaoter freundii)

TlW 75 ¾ίΠ 5 297 400 400 100 25 ku 02 <0J≥ 200 (Proteus vulgaris)

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

DF: Dimethylformamide DMS 0: Dimethyl soxide s: Grenette d: Doublet t Triplet q Quatet Multilett dd Dub Dublet ddd Sixt quintet: Quintet broad: Broad Reference example z

3-amino-2-oxoazetidine 0.14 g of DMF 4 W solution in DMF (3-furidene aminor 22-oxo-1-1-imidazolidinocarbonyl) arane 0 · 354 g and dichloromethane Add Luka Bozimid 0 · 269 S and stir for 8 hours at room temperature. After removing the precipitated crystals, the solution is concentrated, and the residue is added with sulfuric acid to remove the insolubles. After washing thoroughly with severe acid, the residue is purified by silica gel column chromatography. 0.373 g of 3- [D-2-([3-furf !; redenamine 2-oxooxomidazolidine-11-yl) carboxamide] bionamide] -12-oxoazetidine is obtained.

IR

cm "¹; 3275, 1760, 1725, 1660, 1415 Reference Example << 2-

3-Amino-3-methoxy-2-oxazetidine 0.16 g¾Dissolved in methylene trioxide 2 and cooled under cooling with propylenoxide. Add D-N— (3- Furfuridenaminoh 2-oxo-l-imidazolidinocarbol) alan 1.0 Add a solution of acid chloride obtained from 1.065 in methylene dioxide 2. After stirring at the same temperature for 5 minutes, add 0, 7 and 12 g of pyridine and further stir for 1 hour. Concentrate the reaction mixture under low pressure, add ice water to the residue, and extract with a black hole hood. The extract was washed with water, concentrated under reduced pressure, and the residue was purified by silica gel column chromatography 'to give 3- [1> -l-[(3-furfurylidene aminow 2-oxoimidazolidin-l. 1-yl) canoleboxamide] brobionamide-1-3 (S) -methox-2-oxoxazetidine [I] and 3- [! > One 2 — [(3—furfuridenamimino 2—one year old

) Force boxamide] probionamide-1-3 (R) -methoxy 2-

CMPI Xosezetidine [I] is obtained.

o CD I R

cm "'; 3230. 1755, 1725, 1655, 1520. 1415, 1230.

NUR (DMSO-d ₆ , ppm); 1.30 (d, J = 7Hz, CH ₃ ) _f

. 3.35 (s, OCH3) 3.47 (q J = 6,8Hz, C 4 -H.), 3.80 (s, one CHg -), 4.46 (quintet, J = 7Hz f - (j: E-), 6.5 ~ 7.9 (m, furyl H), 7.73 (s, -CE-N-), 8.29 (s, NH), 8.44 (d, J = 7Hz.NH), 9.23 (s, HH).

o [I] IR cnf ¹ ; 3230, 1755, 1725, 1655,

1520, 1415, 1230.

_{NMR (DMS0-d 6, ppm} ); 1 .32 (d, J "= 7Hz, CH 3),

3.36 (s, -0CH3), 3 , 50 (q, J = 6, 12Ez, C 4 -H), 3 · 80 (ε, - CHs -), 4.46 (quintet, J = 7Hz, -CJH-), 6.5-7.9 (m, furyl H), 7 73 (s, CH = N-), 8.32 (s, NH), 8.45 (d, J = 7Ez, NH) _f 9 29 (s, NH) Example 0:

3Amino-2 oxazetidine is reacted with an acylating agent in the same manner as in Reference Example / -A and Reference Example 2 = Β, and the compound shown below is obtained. In the following,) represents the product, to) represents the corresponding method, and (c) represents the physicochemical constant of the product.

(Dfa.) 3— [D— 2— (4 n-octyl 1, 2,3-di-oxo 1-bi-perazinocarboxamide) 1 2-che-acetamide] 1 2— Xisozetidine

(b) A

(c) IR cn ~ ¹ ϊ 3280. 2925, 2855, 1755, 17〗 0, 1675, 1505, 1190.

(2) feJ 3 — [D—2— (4-n—doderu 2,3-dioxo-1,1-biperazinocarboxamide) -1-2-Fe-R-acetamide] -1-2-oxoazetidine

fo) A

{c} IR ^ max ^{1 J} 3280, 2920. 2850, 1755, 1710,

1675, 1505, 1085.

NR (DMS0-d ₆ , ppm) ί 0.86 (t, CH ₃ ), 2.95 (dd, J = 3, 6 Hz, 3, 38 (t, J = 6 Hz, C4 is H), 3 * 4-4 1 (m, -CH _2- ), 4.87 (ddd, J = 3, 6,8Hz, C3-H), 5.46 (d, J = 7Hz,-(j! H-), 7.2-7.5 (m, phenyl H), 7.99 (s, NH), 9.12 (d, J = 8Hz, ΝΗ), 9.81 (d J = 7Hz, NH). I3) (a.) 3 — [D— 2— (4—n—ami / — 2, 3-Dioxo-one 1-radio-carboxamide) 1- 2-Fe-acetamide] 1- 2-year-old xoazetidine

(b) A

(0) IR cm " ¹

3280, 1755, 1710, 1675, 1510.

NMR (DliS0-d ₆ , Ppm); 0.87 (t, CE ₃ ), 2.95 (dd, J = 3.6 Hz, C ₄ -3H) _f 3.39 (t, J = 6 Hz _f C ₄ -aH), 3.4- 4.1 (m, -CH _2- ), 4.88 (ddd, J = 3, 6, 8 Hz, C3-H), 5,46 (d, J = 7Ez,-(fH-), 7.2-7.5 (m, phenyl H), 8.00 (s, NH), 9.12 (d, J = 8Hz, liH), 9.82 (d, J = 7

(4} {a) 3— [D—2— (4-n-amido2,3-dioxo-one-dibidinocarboxamide) -1 2 ”chased amide I Sozetidine

(b) A

(c) IR v ¾ on "¹; 3280, 1755, 1710, 1675, 1505. NR (DMS0-d6, ppm); 0.87 (t, CH ₃ ), 3.01 (dd, J =

_{3, 6Hz, C 4 -?} H), 3.42 (t, J = 6Hz, C 4 ~ aE), 3 · 4 - 4.1 (m, - CHg), 4.88 (ddd, J = 3, 6, 8Hz, C ₃ -H), 5.73 (d, J = 7Hz,-(j; H-) _f 6.9-7.3 (m, thienyl E), '8.01 (B, ΝΗ), 9.16 (d _f J = 8Hz, NH), 9.74 (d, J = 7

(5) (a) 3 — [2- (5-chloro-2-chloroacetylamine 4-thiazolidine) -1-2-methoxyiminoacetamide] -2-oxoxazetidine (b) B

(c) IR απ- '; 3260 , 1740, 1665, 1555, 1040. NMR (LMS0-d6, Ppm) ϊ 3.08 (? dd, J = 3, 6Hz, C 4 - H), 3.49 (, J "= 6Hz, C ₄ -aH), 3.94 (s, OCH3), 4.39 (s, -CH2-), 5.00 (ddd, J = 3, 6, 8Ηζ, C3-H), 8.02 (s, ΝΗ), 9.23 (d _f J = 8Hz, ΝΗ), 13.0 (broad s, ΝΗ). (6) (a) 3-CD-2-(4, 6 (R)-Jetyl—2,3-Dioxo-1 (Radinoxylboxamide) 1- 2-acetamide 1- 2-oxoazetidine

(b) A

(c) IR cnT ¹ ; 3270, 1750,〗 7Ό5, 1670, 1500,

1090.

Μ Μ R (DMS0-d ₆ , Ppm) ί 0.89 (t, J = 7Hz, CH ₃ ), to οι.? Ι V'ir (t, J = 7Hz, CH3), 1, 58 ((luintet _f J = 7Hz, -CH2-),

2.94 (dd, J = 3, 6Ez, C 4 -y3H), 3 · 38 (t, J = 6Hz, C 4 one αΗ), 4.87 (ddd, JT = 3,6, 8H2, C3-H), 5.41 (d, J = 7Hz,-<-), 7.2-7.5 Cm, phenyl H), 7.97 (s, NH), 9.08 (d, J = 8Hz, NH) _t 9.85 (d, J = 7Ez, NH).

(7) ia) 3-CD- 2- (4, 6 (S) ~ Jetyloo 2, 3-Dioxo

1-biperazinokaboxamide) 1- 2-phenylacetamide] 1 2-oxoazetidine

() A

fo) I R v | r ^ -1. 3270, 1750, 1705, 1670, 1500,

1090.

NR (D S0-d ₆ , Ppm); 0.81 (t, J = 7Ez, CH ₃ ), 1.10 Ct, J = 7 Hz, CH ₃ ), 1.3-1.7 (m, -CH _2- ). 2.95 (dd, _{J = 3, 6Hz, C 4} -iSH), 3.39 (1 1 J = 6Hz, C 4 - / 3S), 4.87 (ddd, J = 3, 6,8Hz, C3 "-H), 5.41 (d, J = 7Hz,-^ Η-),

7.2-7.3 (m, phenyl E), 7.99 (s, ΝΗ), 9.14 (d, J = 8Hz, NH), 9.84 (d, J = 7Ez _f NH).

(8) (a) 3— (2-hue = ■ 1 2-p-tolylthioiminoacetamide)

() A

(c) IR cm "¹; 3250, 1755, 1725, 1645.

_{NMR (DMS0-d 6, ppm} ) J 2.33 (s, CH 3), 3.28 (dd, J = 3, 6Ez, C4 ~ i9E) f 3.55 (t f J = 6Hz, C4-aH), 4.8- 5.2 ( m, C3-E) _t 7.2-7.8 (m, phenyl E), 7.96, 8.06 (s, NH), 8.88 (d, J = 8Hz, NH), 9.46 (d _f J = 8 Hz .NH).

(9) (a) 3— [D— 2— (4-1,3-dioxo-1,2-dipazono 11-biperazinocarboxamide) 1-2-F: acetamide] 1-2-oxoazetidine

(b) A

(c) IR

cnT ¹ ; 3280, 2930, 1755, 1710, 1670,

1505, 1180.

NR (D S0-d6, ppm); 2.94 (dd, J = 3, 6Ez _f C-3H), 3.38 (t.J = 6Hz, C ₄ -aH), 3.4-3.9 (m, -CH _2- ) , 4.86 (ddd, J = 3,6,8Hz _t C3-H), 5, 44 (d.J = 7H2,-(jJH-), 7.2-7.5 (m, phenyl H), 7.97 (s, lTH) , 909 (d, J = 8Hz, NH), 9.78 (d, J = 7Hz, NH).

(10) (a) 3— (2,6-dimethoxypentazamide) -1-2-oxazetidine

(b) A

(c) IR £ cin- ¹ ; 3370, 1760, 1725, 1648, 1593,

1470.1250, 1110.

KMR (D S0-d6 »ppm); 3.08 (dd, J = 3, 6Hz, C ₄ -H),

3.48 (t. J = 6Hz, C -E), 3.76 (s, CH 3), 5.01 (ddd, J = 3, 6,9Hz, C3-H), 6.67 (d, J = 9Hz, phenyl H), 7.30 (t, J = 9Ez.phenyl H), 7,91 (8, NH), 8.62 (d, J = 9Hz, NH).

(11) (a) 3 — [D—2— (4-n-ami-6- (R) -methyl-2,3-dioxo-11-biperazinocarboxamide) 1-2-Chenacetam De] 1-oxazozetidine

O! IPI (b) A

(c) IE

en "¹; 3280, 1762, 1710. 1680, 1500,

1192. '

NMR (DMS0-d ₆ , ppm) i 0.88 (t, J = 7Hz, CEs), 1.25

(d, J = 6Hz, CH3) .3.01 (dd _f J = 2,6Hz, C -E), 3.41

(t, J = 6Hz, C 4 -H), 4.66 (m, - (j; H-), .88Cddd f J = 2 t 6,8Hz, C 3 -E), 5.69 (d, J = 7Hz. ^{"§ H"). 6.9- 7.2} (m f thienyl E), 7, 42Cm, t ienyl H), 9.15 (d, J = 8Ez, NE). 9.80 (d, J = 7Hz, NH).

(12) (a) 3-[I> 1-2-(4-n-amino-6 (S)-methyl-2,

3-Dioxo- 1-biperazinokaboxamide) 2- 2-Che-Vacetamide]-2- 2-oxoazetidine () A

fc) IR-

cm ""¹; 3275, 1760, 1710, 1670, 1500,

1190.

NR (DMS0-d ₆ , ppm); 0.88 (t, J = 7Hz _t CH ₃ ), 1.22 Cd, J = 6Ez, CE3) .3.03 (dd, J = 2, 6E2, C4-H), 3.41 (t , J = 6Hz, C ₄ -H), 4.68 (m, ~ (jlH-), 4.88 (ddd, J = 2,6,8Ez, C ₃ -H), 5.72 (d, J = 7Hz »~ § ^E 6,9- 7.2 (m, thienyl H), 7.43 (m, thienyl E), 9.21

(d, J = 8Hz, 2iE) _f 9.80 (d, J = 7Ez, NH).

(13) (a) 3— [D—2— (4-n-ami-6-methyl-2,3-doxo-1-1-biperazinocarboxamide) -1—3-cloth brobion amide] -1 2 —Tokisozetidine to) A

^

'''■ ·, (c) IR

CBT ¹ ; 3300, 1750, 1713, 1675, 1510,

1200.

N ii R (DMSO-de.PPm); 0.88 Ct, J = 6HiZ, CH ₃ ), 1.24 (d, J = 6 Hz, CH ₃ ), 2.80 (dd, J = 2.6 Hz, C ₄ -H) , 4.28Cm .- (j; H-), 4.65 (m,-ー), 4.86 Cm, C3-H), 7.96 (broad s ^ NH), 8.72 (d, J = 8Hz, NH) _f 9.35 (d, J = 7Hz, NH).

(14) fe,) 3— [I> -1 2 — [[3— (2,6-dichroic filler) 1-5 1-Methylisoxazo 4-4-1] carboxamide] 1 2-Chenase Toamid] 1-year-old xoazetidine

(b) A

(c) IR CBT ¹ ; 3270, 1755, 1653.- Nli R (D SO-d 6, ppm); 2.71 (s _f CH ₃ ), 2.96 (dd,

_{J = 3, 6Hz, C 4} -H) »3.37 (. T, J = 6Hz, C4-H) 4.80 (m, C3-H), 5.70 (d, J = 8Hz, - (H-), 6.97 ( _{m f t ienyl E). 7.39} (m, thienyl E), 7.55 (s t phenyl E), 7.9 (d, J = 7Hz, NH), 7.91 (broad B, NE), 9.01 (d, J = 8Ez, NH).

(15) fa.) 3- [D-2- (4-ethyl-5 (R) -methyl-2,3-dioxo-1-1-biperazinocaboxamide) -1-2-acetamido] 1-2-year-old xoazetidine

(b) A

(c) IR ^ max ^s 3270. 1755. 1702, 1665, 1500,

1 180.

NR (DMSO-de.ppm); 1 .14 (t, J = 7Hz, CH 3), 1 .20 c.:.?i (d.J = 7Hz, CH3) .3.02 (dd, J = 3.6Hz.C4-H),

3.43 (t, J = 6Hz.C4-H), 4.88 (m, C3-H), 5.73 (d, J-7Ez,-(fH-) .8-01 (s.NHX, 9 , J-8HZ, NH), 9.72 (d, J = 7Hz, NH). (16) (a) 3— [D—2— (4-ethyl-5 (S) —meth-1-2,3-dioxo-one-biperazino Force boxamid) 1- 2-Chenacet amide] 1- 2-oxozetidine fb) A

(c) IR v |? £ cm "¹; 3270, 1755, 1705, 1665, 1500, 1180.

_{NMR (DMS0-d 6, ppm} ) i 1.12 (t. J = 7Hz, CH3), 1.22 (d, J = »6Ez, CH 3), 3.OO dd, J = 3 f 6Hz. C4-H),

3.42 (t .J = 6Hz, C4-H), 4.90 (m, C3-H), 5.70 (d,, 6.9-7.2 (m, thienyl H), 7.4-

7.5 (m, thienyl H), 8.00 (s, NH) _f 9.〗 6 (d, J = 8

Hz.NH), 9.70 (d, J = 7Hz, NH). (17) (a) 3— [D—2 — [(2-oxoimidazolidin-1-1-1) carboxamide] -1-2-chassis Toamide] 1-oxazotidine (b) A

(c) IR

cm " ¹ i 3270, 1750, 1725, 1658.

NMR (DMS0-d ₆ , ppm) i 2.90-4.00 (m, -CH ₂ ~ .C4-H), 4.83 (m, C3 ~ H) _f 5 68 (d, J-8Hz,-( -), 7.10- 7.37 (m, thienyl H), 7.45 (s, NH), 7.87 (s, NE), 9.00 (d _f J = 8 Hz, NE).

ί ': One I,,, (18) (a) 3— [D—2 — [(5-Methoxycapo-3-methyl-2-oxomidazolidine 1-1-) carboxamide] 1-2-phaseamide] 1-2 years Kisoa

(b) A

(o) IR ν ^ ϊ. cm " ¹ i 3280, 1750» 1720. 1660.

NMR (D S0 ~ d6, ppm) ϊ 2,76 (s, CH3), 2.95 (dd _t J = 3.6Hz, C ₄ -H), 3.34 (dd, J = 4, 10Hz. ~ CE2 ~), 3.38

• 10Ηζ ·-(jJH-), 4.85 (m _f C ₃ -H), 5.40 (d, J = 8Hz, 1 (fH-), 7 · 33 (s, phenyl H). 7.98 (s, NH), 9.07

(d, J = 8Hz, NH), 9.11 (d, J = 8Hz _t H).

(19) £ a) 3— [D— 2— ((5-Penzyloxy ^ carbo-2-3-methinolyl 2-oxomidazolidine 1-11) Power revoxamide] 1-2-Facetamide] One two-year-old xoazetidine

(b) A

(c) IR

^cnr " ¹ 3310, 1750, 1740, 1712, 1688,

1660.

NMR (DMSO-d6, ppm) J 2.74 (s _f CH ₃ ), 2.92 (dd, J = 3, 5HZ.C4-H), 3.20-3.47 (m, C ₄ -H, -CH2-). 3.68 ( , J = 10Hz, -CH2 ~), 4.65 (dd, J = 4,) 0Hz,-(jJH-), 4.83 (m, C ₃ -H), 5.15 (s _f -CH _2- ) _f 5.39 (d , J = 8Hz,-(jJH-), 7.34 (s, henyl H), 7.96 (s, NE), 9.08 (d, J = 8Hz, NH), 9.12 (d, J = 8Hz, NE).

3--(4-2.3-dioxo- 1-1-biperazinocarboxamide) 1-2-(2-chloro-1-hexone-1

o. 1) acetamide] 1—2-year-old xoazetidine to) A

(c) IR v ¾ on "¹; 1760. 17] 5, 1670, 1510. (21 3— [2— (5-triamino-4 4-thiazoli)) 1 2—CC 1-t-butoki Isobroboxy) amino] acetamide] 1-2-year-old xoazetidine Cb) A fc) IR

ca ""¹; 1760, 1725, 1675, 1520, 1140.

NMR (DMSO-de, ppm) i 1.33Cs, CH 3), 3.03 (dd f J = 2,6Hz.C 4 -?. H), 3.20 (s, CH2) 3.36 (t, J = 6Hz,

C ₄ -aH), 4.86 (m, C ₃ -E), 6.66 (s, Y ^E ), 7.15- 7.40 (m, phenyl H) .7.90 (broad s.NH), 8.66 (s.NH), 8.70 (d, J = 8Hz, NH). (22) fe.) 3— [2— (δ-croroacetamino 4- 4-thiazoli) -1-2-isopropoxyiminoacetamide] 1-2-oxoazetidine N

(b) A

(c) IR cm " ¹ ί 3250, 1740. 1655, 1540.

NMR (DMSO-de, ppm) i ] · 22 (d, J = 6Hz , - CH <^ 3), teeth ± L3 3.13 (dd, J = 2, 6Hz t C 4 -? E), 3.46 (t, J = 6Hz, C ₄ -aH), 4.33 (s, CH2), 4.33 (quintet, J = 6Hz, -CK ^ _{) t} 5.o (m _f C ₃ -H), 7-36 (s, f ^E ) · 8.0 (broad s _f KH), 9.10 (d, J = 8Ez, NH). Synthesis example Z

3— [D— 2— [(3-Fluoridamine 2 Lysine-11-yl) carboxamide] propionamide] -1-oxoazetidine 0.36 g <DMF 2 «Add viridine monoanhydride sulfate complex 0.15 g to the solution and react at room temperature for 2 days. . The oily substance to be separated by adding diethyl ether to the reaction solution was passed through a Dowex 50 W Na type resin, and the eluate was purified with Amperlite [Rohm & Haas Co. (USA)]. [D—2 — [(3-Fr / Fridyanamidino-2-oxomidazolidine-1) -yl) caboxamide] brobionamide] -1-2-oxoazetidine-11-sulfonate 0.37 g is obtained. .

IR ^ max ^1; 3300, 1755, 1725. 1415, 1270,

1235, 1050.

NMR (DMS0-d ₆ , ppm); 1.29 (d, J = 7 Hz, CH ₃ ), 3,26 (dd, J = 3, 6H2.C4-3H), 3.68 (t, J = 6 Hz, C ₄ ~ aH) _f 3.81 (s, ~ CH _2- ), 4.33 (qulntet, J = 7Hz,-(j; H ~), 4.86 (ddd, J = 3, 6.8Hz, C ₃ -H), 6.5-7.9 ( m _f iuryl H). 7.74 (s, ~ CH = N-). 8.43 (d, J = 7Hz). 8.87 (d, J = 8Hz _t NH).

The following compounds (Synthesis Examples < ^{2 to} <27>) were produced by sulfonating the corresponding ^2- oxoazidine derivative in substantially the same manner as in Synthesis Example :.

Synthesis example << 2

Sodium 3— [1> 1-21 [(3-furideneamino-2-oxoisomidazolidine-11-yl) -boxylamide] brovionamide] 1-3 (S) -Methoxy 2-oxoxazetidine-1] Monosulfonate

IR νξξζ. Cm " ¹ J 1768, 1722, 1670. 1520, 1480,

1420.1270, 1240, 1050.

Vvli O NMR (D SO-de .ppm); 1.32 (d. J = 7 Hz, CE ₃ ). 3.35 (s,

0CH ₃ ), 3.63 (q. J = 7.13 Hz, C4-H), 380 (s, 11), 4.46 ((iTiintet, J-a; Bz, 1 (j! H—), .6.5- 7 «9 (m, furyl E), 7.73 (s, -CH = N-). 8.43 (d. J = 7Hz, NH), 9-38 (s.NH).

Sodium 3— [D—2 — [(3-fluoridaminemino 2-oxoimidazolidin-1 11) carboxamide] Probiamide] 13- (R) —Methoxy 2—age Xosezetidine-1-1 sulfonate IR v¾ cm "« i 1768, 1722, 1670, 1520, 1480,

1420, 270, 1240, 1050.

NMR (DMSO-d.6, ppm) ;. 1 .30 (d, J = 7Hz, CH 3), 3.34 (s, CH3) 3.59 (qJ = 6, 12Hz, C4-H), 3 · 80 (s , One CE _2- ), 4.45 (quintet, J = 7Hz, 6.5-7.9 (m, furyl H),

7.73 (s, -CE = N ~) _f 8.42 (d, J = 7Hz, NH), 9.35 (s, MH). Synthesis example

Sodium 3— [D—2— (4-n-octyl-1,3-dioxo-11-biperazino force / boxamide) -1 2-cheacetamide] -1 2-year-old xoazetidine 1-1-sulfonate

IR * Ί¾ ^cm ~ ¹ 3280, 2925, 2855, 1760, 1710,

1675, 1505, 1270-1240, 1190, 1050.

KMR (LMS0-d _6. ppm); 0.86 (t, J = 7 Hz, CH ₃ ), 1.1.7 (m, -CHg-), 3.17 (dd, J = 3,6 Hz _f C ₄ -3H), 3.3 ~ 4.1 (m.-CH2-), 3.62 (t, J = 6Hz, C4-aE), 4.87 (ddd, J = 3,6,8Hz, C ₃ -E) _f 5.72 Cd, J = 7Hz,-( fH-), 6.9-7.6 (m, thienyl H), 9.30 (d, J = 8Ez, H), 9.73 (d, J =

C:.:? I- 7HZ.NH) .- Synthesis example

Sodium 3— [D—2— (4-n—dodeci-1,2,3-dioxo-11-biperazinocarboxamide) -1—2-phenylacetamide] -1 2-oxoazetidine-1 1 sulphonate

IR

cnT ¹ ϊ 3280, 2920.2850, 1760, 1710,

1675.1505, 1270-1240.Π 90.

. Ν Μ R (. DMS0- d 6 ppm) 5 0.85 (t, J = 7Hz, CH 3) 3.11 (. Dd J = 3, 6Ηζ, 0 4 -? / Η). 3, 57 (t, J = 6Hz, C -aH), 3.4-4.1 (m, -CH _2- ), 4,85 (ddd, r = 3,6,8H2;, C ₃ -H), 5.44 (d, J == 7Hz (j! H-), 7.2-7-.5 (m, phenyl H), 9.24 (d, J = 8H2.NE), 9.79 (d, J = 7H2.NH).

Synthesis example

Sodium 3— [D-2— (4-n-Amin-2,3-dioxo-1,1-biperazinocarboxamide) -1-2-Ferylacetamide] -1—2-year-old oxoazetidine 1-1 Sulfonate

IR vg¾cnf ¹ ; 3290, 1760, 1710. 1675, 1510.

1280-1240, 1195, 1050.

NMR (DMS0-d6.ppm) * '0,87 (t, CH ₃ ), 3.13 (dd, J "= 3, 6 Hz .C ₄ -3H), 3.4-4.1 (m, -CH _2- ), 3, 58 (t, J = 6Hz,

C4 one aH), 4.85 (. Ddd, J = 3,6 t 8Hz, C 3 -H) 5,44 (d f J = 7Hz, - (jJH -)., 7.2-7.5 (m, phenyl H) 9.25 (d, J = 8Hz, NH), 9.80 (d, J = 7Hz.NH).

Synthesis example

Sodium 3— [D “2— (4—n—Amyle 2,3— 1-biperazinokaboxamido) 1- 2-che-Λ-acetamide] 1-year-old xoazetidine 1- 1

IR

cm "¹; 3280, 1760. 1710, 1675, 1505,

1280-1230, 1195, 1050.

N li R (D S0 ~ d ₆ .ppm); 0.87 (. J = 7 Hz, CH3). 3.19 (dd, J = 3,6 Hz, 0 -3Η). 3.63 (t, J = 6Ez, C ^ -aH ), 3.4-4.1 (m, one CE2-), 4.88 (ddd, J = 3, 6.8H2. C3-H), 5.74 (d, J = 7Hz,-(-), 6.9-7.6 (m.thienyl H) ), 9.30 (d, J = 8Hz, liH). 9.74 (d, J = 7E2, NH).

Synthesis example <$:

Sodium 3- (2- (5-chloro-2-chloroacetylinoamino-4-oxazoli) -1-2-methoxyaminoacetamide) -1-oxoazetidine 1-1 sulfonate

IR jj cm * ¹ i 1760, 1665, 1540, 1270, 1240, 1050.

_{NMR (D S0-d 6,} ppm); 3.32 (dd, J = 3.6Hz, 0 4 - ^ Η),

3.68 (t, J = 6Hz, C4-aE), 3.94 (s, 0CH _S ), 4.40 (s, ClCHg-), 4.95 (ddd.J = 3, 6.8Ez, C3-E), 9.36 (d, J = 8Hz, NH).

The above compound was allowed to react with sodium monomethyl diammonium in an aqueous solution, and then purified with an XAD-I column to obtain sodium 3-! : 2- (2-amino-5-chloro-41-thiazolinole) -1-2-methoxyiminoacetamide] -1-oxoazetidine-11-sulfonate is obtained.

IR cm 1755, 1650, 1625, 1530, 1270, One δΐ —

1240.1050.

_{Κ Μ R (DMS0-d 6} .ppm); 3.26 (.? Dd J = 3, 6Hz, C 4 - H),

3.65 (t. J = 6Hz, C 4 -aH), 3 · 89 (s, 0CH 3), 4.91 (ddd. J = 3.6, 8E2, C3-H). 9.23 (d, J = 8Ez, NH).

Synthesis example

Sodium 3— [D—2— (4.6 (R) —Jeth 2,3, -dioxo—11-bis-dinocarboxamide) -1—2-Fe-acetamide—2-year-old xoazetidine I 1-sulfonate

IR

cm " ¹ i 3280. 1760, 1710. 1675, 1500.

1270, 1240, 1190.1050.

NR (D S0-d6 ppm. );... 0.89 (. T, J = 7Hz CH 3) 1.09 (t, J = 7Ez t CH3), 1, 58Cq intet J = 7Hz, -ΟΗβ-) 3.10 (dd , J = 3, 6H2. C4-? H). 3.57 (. J = 6Hz, C-«H),

4.85 (ddd, J = 3.6.8H2.C3-H), 5.40 (d, J = 7Ez, ~ (j; E-) • 7.2-7.5 (m, phenylH), 9.21 (d, J = 8Hz, NH ),

9.83 (d, J = 7Hz, NH).

Synthesis example, a

Sodium 3— [D—2— (4.6 (3) —Jet-1,2,3-dioxo-11-biperazinocarboxamide) —1-Fe-acetamide] -1-2-oxoazetidine I-1 Snolephonate

I R J ^ £ cuT] i 3280. 1760, 1710, 1675, 1500,

1270, 1240, 1190. 1050.

_{NMR (DMS0-d 6, ppm} ) J 0.81 (t, J = 7Hz, CH3), 1 .10 (t J = 7Hz, CH 3.), 1.3-1.7 (m.-CH 2 -), 3 · ] 3 (dd, J "= 3, 6 Hz, C ₄ -i5H), 3.58Ct, J = 7Hz, C ₄ -aH). 4.85 (ddd. J =

0? IPI 3,6,8Hz, C3-H), 5.5 (d, J = 7Hz.- <jJH-), 7.2-7.5

(m, phenyl H), 9.25 (d, J = 8Hz, NE), 9.83 (d.J = 7 Hz.NH).,

Synthesis example //

Sodium 3- (2-phen-2-p-trithioiminoacetamide) -1-oxoazetidine-11-sulfonate

I R J / J cm "'I 1760, 1655, 1505, 1265, 1240,

1050.

NMR (DMS0 ~ d6 »ppm) i 2.34 (s .CE3), 3.33-6 (m, C4-? H), 3.70,3.75 (t, J = 6Ez, C4 ^ aH), 4 — 5 · 2 (m, C ₃ —

H), 7.2-7.8 (m.phenyl H), 9.02, 9.59 (d, J = 8Hz, NE).

Synthesis example / «2

Sodium 3— [D—2— (4-cyclohexyl-1,2,3-dioxane 1-piperazinocaboxamide) -1-2-phenylacetamide] -1 2-oxoazetidine 1-1-sulfonate

I R v ¾ cnT «; 2925. 1760, 1705, 1665, 1505,

1250.1180.1045.

N li R (DMS0-d6, ppm); 3 · 1] (<i (i,; r = 3.6Hz, C ₄ -3H),

3.4-4.0 (m, -CE _2- ), 3.57 (, J = 6Hz, C ₄ ~ aH), 4.83

(ddd, J = 3, 6, 8Hz.C3-E), 5.42 (d, J = 7Hz,-(jJE-),

7-2-7.5 (m, phenyl H), 9.22 (d, J = 8Hz, H), 9.77 (d, J = 7Ez.NH).

Synthesis example /

Sodium 3— (2,6-dimethoxy ^ penzamide) -1-oxooxo C-PI Azetidine 1 11 sulfonate

I R v ^ £ cm ~ '' i 3300. 1755. 1648. 1595. 1513.

1470.1250.1100.1050.

N R (DS0-d6, ppm); 3.27 (dd. J = 3, 6Hz. C4-H).

3.62 (t. J = 6Hz C4-H). 3.71 (s .0CH ₃ ) »4.93 (ddd.

J = 3.6.8Hz .C3-H) _t 6.60 (d, J = 9Hz .aromatic H), 7.24 (t. J = 9Hz, aromatic H), 8.71 (d, J = 8Hz, NH).

Sodium 3— [D—2— (4-n-ami-6 (R) -methyl-2.3-dioxo-1 1-biperazinocaboxamide) 1—2-Chaseacetamide] 1—2-year-old quinone 1 Source Hornet

IR vg¾ cnf ¹ i 3275. 1760, 1710, 1678, 1503,

1272.1240.1198.1050

NMR (DMSO-de .ppm); .. 0.88 (. T, J = 7Hz CH3) 1 .25 (. D, J = 6Hz CH3), 3.19 (. Dd, J = 2, 6Hz C 4 -H) 3.63 (t. J =

6HZ.C4-H), 4.67 (m .- (j; H-). 4.89 Cddd, J = 2, 6.7Hz, C3-H) .5.70 (d, 6.94-7.16 (m.

thienyl E), 7.42-7.54 (m, thienyl H), 9.78 (d, J = 7Hz, NH).

Synthesis example / J:

Sodium 3— [D—2— (4-n-ami-6 (S) —methyl 2.3-dioxo-one-biperazinocarboxamide) 1—2-Chenium / rarecetamide] 1 2—One year old kissazetidine

IR v ¾ cm " ¹ i 3275.〗 760, 1710. 1678, 1503.

1272, 1240, 1198, 1050.C, FI NR (D SO-de. Ppm ) i 0.87 (t, J = 7Ez, CH3). 1.21 (d, J = 6Hz.CH s), 3.19 (dd, J = 2, 6Hz, C4-H), 3.61 ( t, J = 6HZ.C4-H), 4.66 (m .- {^ H-), .87 (dd.J = 2, 6.7Hz, C3-H) .5.73 (d, J = 8Hz, `` g ^H ~). 6.92-7.16 Cm,

thienyl E) .7.42-7.53 (m.tienyl E), 9.76 (d.

J = 7Hz.KE).

Synthesis example /

Sodium 3— [D—2— (4 1 n—ami 1 6—meth / I ^ 1,2,3 1 dioxono 1 1 biradino force boxa amide) 1 3—black pi 2-oxozetidine 1-sulfonate

IR

cnf ¹ ; 1760, 1712, 1680, 1520. 1240,

1055, 1010.

NMR (DMSO-d.6.ppm) i 0.88 (, J = 6Hz.CH3), 1.24 (d, J = 6Hz, CH3), 3.60 (t.J = 6Hz, C-H), 4.0 (broad s, -CH _2- ), 4.48 (m, C ₃ -H) .8.90 (d, J = 8Hz, NH) .9, 28 (d, J = 7Hz.KH).

Synthesis Example / 7. Sodium 3— [D—2 — [[3— (2,6-dioctylphenyl) -1-5-methisoxazo-1-4-1] carboxamide] -12-Chenylacetamide] One two-year-old oxoazetidine one one one sulfonate

IR νξ¾ cm "¹; 1760, 1665. 1603, 1508, 1271.

1240, 1200, 1050.

NMR (DMSO-de.ppm) ί 2.7] (s, CH3), 3.16 (dd, J = 3, 6

Hz, C ₄ -E), 3.60 (, J = 6Hz .C4-E), 4.81 Cm, C3-H),

5.70 (d, J = 8Hz, -CH-), 6.93 (m, thienyl H), 7.3

»

C iPI (m.thienyl H). 7.59 (s.aromatic H), 7.93 (d, J = 7HZ.NH), 9.14 (d.J = 8Hz.NH).

Synthesis example / ^ '

Sodium 3— [1> -2-1 (4 ェ 1〃5 (R) —- メ 2.

3-dioxo- 1-biperazinocaboxamide) 2- 2-che =: acetamido] 1- 2-xoxoazetidine 1-1-sulfonate

IR

cm " ¹ 3275, 1759. 1703, 1667. 1505.

275, 1240. 1190.

_{NMR (DMS0-d 6 .Ppm)} ;.. 1 · 13 (t,, CH3), 3.18 (. Dd J = 3.6Hz, C -H) 4.87 (m, C4-H), 5, 72 (d J = 7Hz •-(jJH-), 9.28 (d.J = 8Hz.NH), 9.70 (d.J = 7Hz, NH). Synthesis example /

Sodium 3 -— [D-2— (4-Chinole 5 (S) —Methynole 2,3-Dioxo-1—1-Biperazino-forced Revoxamide) 1—2-Chase Amide] 1—2-year-old xoazetidine Pace honate

IR

cm "¹; 3275. 1759, 1703, 1667, 1505,

1275.1240.1190.

NMR (DMSO-de.ppm);. 1.18 (t, J = 7Hz, CH 3) 1.24 (t, * J = 6Hz, CH3), 3.19 (dd, J = 3.6Hz, C4-H), 3.62 (t ... J = 6Hz C4- H) 4.88 (m, C 3 -H), 5.69 (d J = 7Hz -.. (fH-)... 9.29 (. d J = 8Hz, NH) 9.69 (d J = 7Hz .NH).

Synthesis example << 2 (2

Zinatridium 3— [D-2 — [(2-oxo-one 3-s-honotoimi-dazolidin-1-y) Power-boxamido] -1-2-Che-L-acetamide Ί1-2-oxo-zetidine-1-1-sulfonate G IR ^ m ^ ¹ * "^1; 3470, 3300,] 755, 1710, 1668,

1260, 1052.

_{NMR (DMSO-d 6 .ppm)} i 3.25 (dd, J = 3, 6Hz, C4-H).

. 3.52 (. T J = 6Hz , C4-E), 3.61 (S.-CE2-) 4.83 (m, C 3 -E), 5.64 (d, J- = 8Hz, -. (PH-) 6.9 ~ 7.5 (m.

thienyl H). 8.92 Cd. J = 8Hz. NH). 9.25 (d. J = 9Hz, NE)

Synthesis example << 2Ζ

Sodium 3— [D—2 — [(2-oxomidazolidinyl) -carboxamide] -1-2-cha-acetamide-1-2-oxazetidine-1-sulfonate '

IR

cm "¹; 3420, 3270, 1750, 1730, 1650,

1270, 1240. 1045.

N M R (DMS0-d6.ppm) i 3.17 (dd, J "= 2, 5Hz, C4-H),

3.10-3.47 (m, -CH £-) .3.58 (, J = 5Hz, C4-E), 3.57 -3.70 (m, »CH2-) .4.83 (m.C3-H), 5.63 (d.J = 8Hz .- (jJH-), 6.87-7.47 (m, thienyl H) .7.54 (s, NH), 9.02 (d, J = 8Hz, NH) 9.25 (d, J = 8Hz.NH)

Synthesis example2.2

Sodium 3— [D— 2— [(5-Metric ^ force /! Bo = No 3 – Methyl 2 – Oxidone Midazolidin 1 – 1-Carboxamide) 1 2-Phenoinoreacetamide] 1 2-oxozetidine 101 sulfonate

IR ξ¾ cm "¹; 3480. 3260. 1750. 1728, 1662, 1260, 1048.

_{NMR (DMS0- d 6, pOffi)} i 2.76 (s, CH3). 3.1 OCdd, J = 3.5 Hz.C4-H), 3.70 (s, CH3) .4.65 (dd, J = .10Hz.

-(jJH-). 4.84 (mC ₃ -H). 5.38 Cd .J = 8Hz,-(j5H ~),

7.34 (s. Aromatic H). 9.12 (d, J = 8Hz, NH). 9.21 (d. J = 8Hz.NH).

Synthesis example << 2

Sodium 3— [D—2 — [(5-Pendioxy ^ carbo-Lu-3 1-methyl-2-oxomidazolidin-1 1-) carboxamide] -1-2-phenylacetamide-1-2-oxazetidine-1 1 Source Honeichi

IR vggj cm " ¹ i 3470. 3290, 1750. 1720. 1665,

1245, 1190.1048.

_{NMR (D S0-d 6,} ppm);.. 2.76 (s.CH3) 3.08 (dd, J = 3.5 Hz, C 4 -E) 3.25 (. Dd J = 4.10Hz, -CH2-), 3.56 (t , J = 5Hz, C -H) 3.70 C t, J = 1 OHz - CH 2 -) 4.71 (dd, J = 4, 10Hz, ~ (j;... H-), 4.80 (m, C 3 - H), 5.18 (s, -CH _2- ).

5.40 (d, J = 8Hz,-(j; H-), 7.36 (s .aromatic H) .7,38 Cs, romatic H), 9〗 2 (d, J "= 8HzNH), 9.21 ( d.J = 8E2.NH).

When an aqueous solution of the above compound is treated in a stream of hydrogen in the presence of palladium black, sodium 3- [D-2-[(5-carboxy-3-methyl-2-oxomidazolidine-11-yl) carboxamide ] 1-2-Fenacetamide]-2-oxozetidine-1 sulphonate is obtained.

IR

cm "¹; 3430. 3300, 1750. 1720, 1663,

1250.1050.

_{.. NMR (DMS0-d 6} .ppm) i 2.75 (s.CH 3) 3.10 (dd, J = 3.5 v ':::. _{Hz.C 4 -H), 3.25-3.80 (.} . M C4-E.-CH2-) 4.48 (m one (JH -.)., 5.38 (d J = 8Hz, 7.33Cs .aromatic

H), 9.12Cd. J = 8Hz.NE), 9.20 (d.J = 8Ez, NH).

Synthesis example << 2

Sodium 3- (2- (4-ethyl-2,3-dioxo-1-1-radinocarboxamide) -1- (2-chloro-1-cyclohexene-1-acetamide) One 2-year-old quinosetidine one-one-honorate IR ν ^, cm " ¹ ϊ 1760, 1708, 1680. 1510, 1260.

1050.

NMR (D S0-d ₆ .Ppm) i 1.10 Ct, J = 7Hz .CH3) .1.60

(broad s 2.03 (broad s,-CE _2- ), 2,33

(broad s .-CH £-). 3.53 (m, -CH _2- ), 3.90 (m .-CH2-) • 4.83 (m.C4-H). 5.43 (d .J = 7Hz .- (jiH- ), 8.66 (d, J = 8Hz, NH), 9.46 (d, J = 7Hz, NH),

Synthesis example << 2

Dinatrium 3- (2- (5-S-Honatonaminothiazoline 1-41-) 1-2-[(1-Butoxycabo-isopropoxy) imino] acetoamide] 1-Oxoazetidine 1-1-Shonate

IR ^ mx ^cm "~ ^{1 J} 60, 1730,〗 665, 1630, 1525.

1250, 11 5.1050.

NMR (DMS0-d ₆ .ppm) i 1.39 (s.CH ₃ ), 1.40 (s, CE ₃ ), 3.35 (m, C-; S), 4.95 (m, C ₃ -H), 6,83 ( s, f), 9.10 (d, J = 8H2, NH)

Synthesis example << 2

Sodium 3— [2— (5—triaminothiazol 4- ) 1-2-[(1-t-butoxycarbo-isobroboxy) imino] acetamide] -1-oxoazetidine-11-sulfonate

IR v ^ l cm " ¹ I 1760. 1730, 1675. 1590. 1570.

1280.1250.1200.11 0.1040.

_{NMR (DMS0-d 6 ppm.} );. 1.39 (s.CH 3) 1.40 (s, CH 3).

H

4.35 (mC ₄ -E). 4.90 (mC ₃ -H) 6.75 (s.)) 7.33 (s.aromatic H), 9.03 (d, J = 8 Hz, NH) .Synthesis example 《27

Sodium 3- [2- (5-Chloroacetylaminothiazole-4-1) -1-2-isopropoxyminoacetamide] -1-oxoazetidine-1] -Sulfonate

IR

cm "¹; 1755, 1700, 1540; 1250, 1050.

NMR (DiiSO-de .ppm) 5 1.22 (d, J = 6Ez. CH 3), 3,66 (t, J = 6Ez.C4-aH), 4.33 (s.-CH2-). 4.33 (quintet, J = 6Hz, -.. CH < ), 4.96 (m.C3- «H), 7.36 (s, γ α), 9.23 (d J = 8Hz.NH) example /

Fill a sterile vial with an internal volume of〗 2 W with Compound No. 325 Omg, and seal it. Example2

Compound No. 9 500 fflg is filled into a 17 W vial and sealed. Example

Compound incense 1 2 1 25nig Lactose 50 mg Magnesium oxide 20 Eg

Is uniformly mixed to obtain a powder or a glaze as a powder. This powder is put into a forceps container to make a force bushel. '

Example

Mix Cefotiam 250 S and Compound No. 344 · 3 g with a bacterium, apply the residue to a sterile 12 ml internal vial, apply 25 Offig (force), and vacuum seal at 50 nmHg. . Add 3 ml of distilled water to dissolve, and dissolve it.

Example

In the same manner as Jeongjeong example, compounded with cefazolin 500 g ¾J number 9

Mix 15.2 g, fill into a 17 W vial with δ 00fflg (¾S), and seal.

Example ά

250 g of force / u ぺ -silicone and compound number 127.02 s by aseptic manipulation] and mixed, and filled with sterile and dried pials with a capacity of 17 * by applying 25 Omg (titer). , Seal.

Example

250 g of sterile, dust-free compound No. 2635 · 2 g was mixed under aseptic conditions, and the mixture was filled into a 9 * paia internal volume, charged with ί25 ng (titer), and sealed.

Example

Cephalexin 1 25 mg

Compound number 1 2 1 25

Lactose 50 //

Magnesium oxide 10

CO:? I Is uniformly mixed to make a powder, and put into a capsule container to obtain a turnip agent.

Claims

The scope of the claims

1. —general formula

[Wherein Ri is an amino group which may be protected or protected, and X represents hydrogen or methoxy. Containing a compound represented by 3- lactamase inhibitor composition ¾I ₀

2. The composition according to claim 1, further comprising a? -Lactam antibiotic.