JPH0426692A - Novel cephem compound - Google Patents

Abstract

NEW MATERIAL:A compound of formula I [R<1> is (protected) amino; R<2> is (substituted) lower alkyl; R<3> is-COO<-> or (protected) carboxyl; R<4> is lower alkyl; R<5> is N-contg. heterocycle; X is CH or N; Y<-> is anion; n is O or 1; when R<3> is-COO, n is O; when R<3> is (protected) carboxyl, n is 1]. EXAMPLE:7beta-[2-(2-aminothiazole-4-yl)-2-methoxyiminoacetamide]-3-[3(1- pyrrolidinyl)-2-methyl-1-pyrazolio]methyl-3-cephem-4-carboxylate. USE:An antifungal agent. PREPARATION:A reaction is made in an inert solvent between (A) a compound of formula II, its reactive derivative at the amino group or its salt and (B) a second compound of formula III, its reactive derivative at the carboxyl group or its salt.

Description

[Detailed description of the invention]

"Industrial Application Field" The present invention relates to a novel cephem compound having antibacterial activity and a pharmaceutically acceptable salt thereof, which is useful in the pharmaceutical field. Thus, it is an object of this invention to provide novel cephem compounds and pharmaceutically acceptable salts thereof that are effective against many pathogenic bacteria. “Means for solving the problem” The target cephem compound is new and has the following formula: [
1]. [In the formula, R1 is an amine group or a protected amine group, R2 is a lower alkyl group that may have an appropriate substituent, R3 is a 10,000 group, a carboxy group or a protected carboxy group, R4 is a lower alkyl group, R5 is an N-containing heterocyclic group, X is CH or N, and YO is an anion and n is 0 or 1, respectively. However, R3 is coo
When it is a Q group, n is O; when R' is a carboxy group or a protected carboxy group, n is 1. ] Regarding the target compound [+], it is necessary to pay attention to the following points. That is, the target compound [+] includes a syn isomer, an anti isomer, and a mixture thereof. A syn isomer means one geometric isomer having a partial structure of the formula: (wherein R'R2 and , R+SRz and X have the same meanings as before), and all such geometric isomers and mixtures thereof are included within the scope of this invention. In this specification, the partial structures of these geometric isomers and mixtures thereof will be shown by the following formulas for convenience. -R2 (wherein R'R' and X have the same meanings as before). Another point to note is that the pyrazolio moiety of compound N] can exist in tautomeric form, and such tautomeric equilibrium can be represented by the formula below. (In the formula, R4 and R5 each have the same meaning as before). Although all of the above tautomerisms are included within the scope of the present invention, in this specification, the target compound [1] will be expressed by one expression of the pyrazolio group of formula (A) for convenience. The cephem compound [1] of the present invention can be produced by the production method shown by the following reaction formula.

[Left below]

[11] Or a reactive derivative thereof at the amine 7 group, or a salt thereof 10-R2 [111] Or a reactive derivative thereof at the carboxy group, or a salt thereof [+] or a salt thereof r In the formula, R'R'R',R' R5, X1Y
o and n each have the same meaning as before]. In the foregoing and following description of this specification, preferred examples and explanations of various definitions falling within the scope of this invention are set forth in detail below. Lower terms are used, unless otherwise specified, to include groups having from 1 to 6 atoms. Suitable "lower alkyl groups" include methyl, ethyl,
Mention may be made of straight or branched alkyl groups such as propyl, isopropyl, butyl, isobutyl, tertiary butyl, pentyl, hexyl, and the like. Suitable "amino-protecting groups" for the "protected amino group" include acyl groups described below, such as substituted or unsubstituted alkylidene groups such as benzylidene and hydroxybenzylidene, such as benzyl, phenethyl, benzhydryl, trityl, etc. an al(lower)alkyl group, such as a mono- or di- or triphenyl(lower)alkyl group,
etc. Suitable "acyl groups" include, for example, lower alkanoyl groups such as formyl, acetyl, propionyl, hexanoyl, and pivaloyl, and mono(or di- or tri)halo(lower) groups such as chloroacetyl and trifluoroacetyl.
Alka/yl groups, such as lower alkoxycarbonyl groups such as methoxycarbonyl, ethoxycarbonyl, tertiary butoxycarbonyl, tertiary pentyloxycarbonyl, hexyloxycarbonyl; carbamoyl groups, such as gamma-royl groups such as benzoyl, toluoyl, naphthoyl; For example, an alkanoyl group such as phenylacetyl or phenylpropionyl, an aryloxycarbonyl group such as phenoxycarbonyl or naphthyloxycarbonyl, an aryloxy(lower)alkanoyl group such as phenoxyacetyl or phenoxypropionyl, such as phenylglyoxyloyl. , arylglyoxyloyl groups such as naphthylglyoxyloyl, e.g. benzyloxycarbonyl, phenethyloxycarbonyl,
Examples include an alkoxycarbonyl group (lower) which may have a suitable substituent such as P-nitrobenzyloxycarbonyl. Suitable "protected carboxy groups" include esterified carboxy groups, and specific examples of the ester moieties of the esterified carboxy groups include, for example, those which may have appropriate substituents. Lower alkyl esters such as methyl ester, ethyl ester, propyl ester, isopropyl ester, butyl ester, isobutyl ester, tertiary butyl ester, pentyl ester, tertiary pentyl ester, hexyl ester, 1-cyclopropylnisal, examples thereof Examples include acetoxymethyl ester, propionyloxyethyl ester, butyryloxymethyl ester, imbutyryloxymethyl ester, valeryloxymethyl ester, pivaloyloxymethyl ester, ■-acetoxyethyl ester, 1-propionyloxyethyl ester, 2
- lower alkanoyloxy (lower) alkyl esters such as propionyloxyethyl ester, hexanoyloxymethyl ester, lower alkanesulfonyl (lower) alkyl esters such as e.g. 2-mesylethyl ester, or e.g. 2-iodoethyl ester, 2.2+
Mono (or di or tri) halo (lower) alkyl esters such as 2-trichloroethyl ester; lower alkenyl esters such as vinyl esters and allyl esters; lower alkynyl esters such as ethynyl esters and propynyl esters; e.g. benzyl esters; 4-methoxybenzyl ester, 4-nitrobenzyl ester, phenethyl ester trityl ester, benzhydryl ester, bis(3-methoxyphenyl)methyl ester, 3゜4-dimethoxyphenyl ester, 4
Al(lower) alkyl esters optionally having suitable substituents such as -hydroxy-3,5-ditertiary butylbenzyl esters; e.g. phenyl esters, 4-chlorophenyl esters, tolyl esters, 4-tertiary butyl benzyl esters; Examples include aryl esters which may have appropriate substituents, such as butylphenyl ester, xylyl ester, mesityl ester, and cumenyl ester. Suitable substituents for the "lower alkyl group which may have a suitable substituent" include, for example, halogen, carboxy group and the like. A suitable "N-containing heterocyclic group" means a saturated or unsaturated, monocyclic or polycyclic heterocyclic group having a nitrogen atom. Preferred N-containing heterocyclic groups are as follows. Unsaturated 3- to 8-membered heteromonocyclic groups containing 1 to 4 nitrogen atoms, such as pyrrolyl, pyrrolinyl, imidazolyl, pyrazolyl, pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, triazolyl (e.g. 4H-1,2,4- ) Riazolyl; IH-1゜2.3-1-riazolyl; 2H-1
, 2,3-)riazolyl, etc.), tetrazolyl (e.g. IH tetrazolyl, 2H-tetrazolyl, etc.)
, dihydrotriazinyl (e.g. 4,5-dihydro-1
,2,4-triazinyl:2,5-dihydro1.2.4
-) riazinyl; others), etc.; saturated 3- to 8-membered heteromonocyclic groups containing 1 to 4 nitrogen atoms, such as pyrrolidinyl, imidazolidinyl, piperidino, piperazinyl, etc.; however, the "N-containing heterocyclic group ” is, for example, the following 1
It may have up to 3 suitable substituents. Hydroxy; lower alkyl (e.g. methyl, ethyl,
Propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, hexyl, etc.); Amino: Halogen (e.g. chlorine, bromine, iodine or fluorine); Lower alkoxy (e.g. methoxy, ethoxy, propoxylate, etc.); Lower Alkylthio (e.g. methylthio, ethylthio, propylthio, isopropylthio, etc.); carboxy; protected carboxy; lower alkenyl/hydroxy(lower) alkyl (e.g. hydroxymethyl,
hydroxymethyl, etc.); etc. Suitable anions include formate, acetate, trifluoroacetate, maleate, tartrate, methanesulfonate, benzenesulfonate, toluenesulfonate, chloride, bromide, iosite, sulfate, phosphate, and the like. Suitable salts of the target compound [I] include pharmaceutically acceptable salts, especially commonly used non-toxic salts, such as alkali metal salts such as sodium salts, potassium salts, and calcium salts, magnesium salts, etc. Metal salts such as alkaline earth metal salts, ammonium salts such as triethylamine salts, pyridine salts, picoline salts, dicyclohexylamine salts, organic salts such as NIN'-dibenzylethylenediamine salts, such as hydrochlorides, hydrobromic acid Inorganic acid salts such as salts, sulfates, phosphates, such as formates, acetates, trifluoroacetates, maleates, tartrates, methanesulfonates, benzenesulfonic acid m, P-)luenesulfonates and salts with amino acids such as arginine salt, aspartate, and glutamate. The method for producing the target compound [1] will be explained in detail below. 3 The target compound [N or its salt is obtained by reacting the compound [■] or its reactive derivative at the amino group or its salt with the compound [111] or its reactive derivative at the carboxy group or its salt. It can be manufactured by Suitable reactive derivatives at the amine 7 group of compound [n] include Schiff's base type imino or its enamine type tautomer produced by the reaction of compound [11] with a carbonyl compound such as an aldehyde, ketone, etc. ; Compound [11] and bis(trimethylsilyl)acetamide, such as hl-()limethylsilyl)acetamide, mono(
Examples include silyl derivatives produced by reaction with a silyl compound such as trimethylsilyl)urea; derivatives produced by reaction of compound [11] with phosphorus trichloride or phosgene, and the like. For suitable salts of compound [11] and its reactive derivatives, refer to those exemplified for compound [I]. Suitable reactive derivatives at the carboxy group of the compound [■] include acid halides, acid anhydrides, activated amides,
Examples include activated esters. Suitable examples of reactive derivatives include acid chlorides; acid azides; substituted phosphoric acids such as dialkyl phosphoric acid, phenyl phosphoric acid, diphenyl phosphoric acid, dibenzyl phosphoric acid, halogenated phosphoric acid, dialkyl phosphorous acid, sulfurous acid, thiosulfuric acid, sulfuric acid. , sulfonic acids such as methanesulfonic acid, such as acetic acid, propionic acid, butyric acid, imbutyric acid, pivalic acid, pentanoic acid,
Mixed acid anhydrides with acids such as aliphatic carboxylic acids such as inpentanoic acid, 2-ethylbutyric acid, trichloroacetic acid or aromatic carboxylic acids such as benzoic acid; symmetrical acid anhydrides: imidazole, 4-substituted imidazole, Activated amides with dimethylpyrazole, triazole, IH-benzotriazole, or tetrazole; or e.g. cyanomethyl ester, methoxymethyl ester, dimethyliminomethyl ester, vinyl ester, propargyl ester, p-nitrophenyl ester, 2,4-dinitro Phenyl ester, trichlorophenyl ester, pentachlorophenyl ester, mesylphenyl ester,
Phenylazophenyl ester, phenylthioester, p-nitrophenylthioester, p-talesylthioester, carboxymethylthioester, pyranyl ester, pyridyl ester, piperidyl ester, 8-
Activated esters such as quinolyl thioester or N,
N-dimethylhydroxylamine, 1-hydroxy 2-
(2H)-pyridone, N-hydroxysuccinimide,
N-hydroquine phthalimide, 1-hydroxy-IH-
Examples include esters with N-hydroxy compounds such as benzotriazole. These reactive derivatives can be arbitrarily selected from them depending on the type of compound [I[1] to be used. For suitable salts of compound [111] and its reactive derivatives, refer to those exemplified for compound [1]. The reaction is usually carried out in conventional solvents such as water, alcohols such as methanol, ethanol, acetone, dioxane, acetonitrile, chloroform, methylene chloride, ethylene chloride, tetrahydrofuran, ethyl acetate, NlN-dimethylformamide, pyridine, etc. The reaction can be carried out in any other organic solvent as long as it does not adversely affect the reaction. These conventional solvents may be used in mixtures with water. When compound [1111] is used in the free form or its salt form in this reaction, N,N'-') cyclohexylcarbodiimide; N-cyclohexyl-N'
-Morpholinoethylcarbodiimide. N-cyclohexyl-N"-(4-diethylaminocyclohexyl)carbodiimide, N,N'diethylcarbodiimide, N,N'-diisopropylcarbodiimide;N-ethyl-N'=(3dimethylaminopropyl)carbodiimide; N.N゛ -Carbonylbis-(2-methylimidazole)
;pentamethyleneketene-N-cyclohexylimine;
Diphenylketene-N-cyclohexylimine; ethoxyacetylene; 1-alkoxy1-chloroethylene; trialkyl phosphite; isopropyl polyphosphate; phosphorus oxychloride (phosphoryl chloride); phosphorus trichloride; thionyl chloride; oxalyl chloride; e.g. ethyl chloroformate , lower alkyl haloformates such as isopropyl chloroformate; triphenylphosphine; 2-ethyl-7-hydroxybenzisoxazolium salt; 2-ethyl-5-(m-sulfophenyl)
Isoxazolium hydroxide/inner salt; 1-
(p-chlorobenzenesulfonyloxy)-6-chloro-IH-benzotriazole; the so-called Vilsmeier reagent prepared by the reaction of N,N-dimethylformamide with thionyl chloride, phosgene, trichloromethyl chloroformate, phosphorus oxychloride, etc. Preferably, the reaction is carried out in the presence of a conventional condensing agent such as. The reaction can also be carried out in the presence of inorganic or organic bases such as alkali metal bicarbonates, tri(lower)alkylamines, pyridine, N-(lower)alkylmorpholines, N,N-di(lower)alkylbenzylamines, etc. A reaction may also be carried out. Although the reaction temperature is not particularly limited, the reaction is usually carried out under cooling or heating. "Effects of the Invention" The object compound (1) of the present invention and its salts are novel compounds that exhibit strong antibacterial activity and inhibit the growth of a wide range of pathogenic bacteria, including gram-positive and gram-negative bacteria, and can be used as antibacterial agents. Useful. For therapeutic purposes, the compounds according to the invention are mixed with pharmaceutically acceptable carriers such as organic or inorganic solid or liquid excipients suitable for oral, parenteral or topical administration. It can be used in the form of conventional pharmaceutical preparations containing it as an active ingredient. Pharmaceutical formulations may be in solid form, such as capsules, tablets, dragees, ointments, or halves, or in liquid form, such as solutions, suspensions, or emulsions. If desired, auxiliaries, stabilizers, wetting agents or emulsifiers, buffers, and other agents such as lactose, fumaric acid, citric acid, tartaric acid, stearic acid, maleic acid, succinic acid, malic acid, magnesium stearate, White clay, sucrose, cornstarch, talc, gelatin, agar, pectin, peanut oil, olive oil,
Commonly used additives such as cocoa butter, ethylene glycol, etc. may also be included. Although the dosage of the compound varies depending on the age and condition of the patient, the compound according to the present invention has an average single dose of about 10 m
g, 50■, 100mg, 250mg, 50
It is effective in treating infections at doses of 0 mg and 1000 μg. - In terms of numbers, Img/individual per day, approximately 6000+
An amount between ng/individual or more may be administered. "Examples" The present invention will be described below according to production examples and examples. 1.4- of Ll 5-amino-]-methylpyrazole (3g)
l,4-dibromobutane ('1.06ml) and triethylamine (9,4
7rnl) at room temperature. After stirring the mixture at 100° C. for 24 hours, the precipitate formed is filtered off. The solvent of the filtrate was distilled off under reduced pressure, and the residue was subjected to column chromatography using silica gel and eluted with ethyl acetate.
-pyrrolidinyl)-1-methylpyrazole (1,2]g
) is obtained as an oil. IR (Nujicol): 3400. 2970
．． 1550. 1490. 1460cm' NMR (CDCl2.δ): 1.86-2.03(4
H, m), 3.05-3.12 (4H. m), 3.76 (3H, s), 5.60 (II,
d, J=3 Hz), 7.26<111, d, J=
311z) Production Example 2 7β-tertiary butoxylponylamino-3-chloromethyl-3-cephem-4-carboxylic acid benzhydryl ester (8,74 g) and sodium iodide (2,54 g)
g) with N,N-dimethylformamide (8,7 ml'
) 5-(1-pyrrolidinyl)-1-methylpyrazole (7.7 g) is added to the warm mixture at room temperature. After stirring at the same temperature for 5 hours, the reaction mixture is poured into a mixture of water and ethyl acetate. The organic layer is separated, washed with water and brine, and dried over magnesium sulfate. The solvent was distilled off under reduced pressure, and 7
β-tertiary butoxycarbonylamino-3-[3-(1
-pyrrolidinyl)-2-methyl-1-virazoliocomethyl-3-cephem-4-carboxylic acid benzhydryl ester iodide (10.93 g) was obtained. IR (null): 3370.
1785. 1720. 1600 cm-'N
MR (DMSO-de, δ): 1.41 (9■,
s), 1.79-2.03(4H,m)+3,30
(211,brs), 3.45(411,brs),
3.50 (3H, s), 5゜15 (IH, d,
J=5Hz), 5.18 (2L brs), 5.
57 (IH, dd. J=8Hz, 5Hz), 6.08 (Itl, d
, J=3Hz), 6.90(Ill, s). 7.07-7.49 (1011, m), 7.95 (
III, d, J=8Jlz), 8.07(JIt,
d, J=311z)
methylene chloride (33 m
Trifluoroacetic acid (22 mf) is added dropwise to a mixture of f) and anisole (11 mυ) under water cooling. After stirring at room temperature for 2 hours, the mixture is diisopropyl ether (200 mF).
) and ethyl acetate (200 ml), the resulting precipitate was collected by filtration, and 7β-amino-3-[3-(]
-pyrrolidinyl)-2-methyl-1-virazolio]methyl-3-cephem-4-carboxylade di(trifluoroacetic acid) salt (6.71 g) is obtained. IR (null): 1780. 16
65. 1595. cm-'NMR (DMSO-
dll, δ): 1.82-2.05 (4H, m),
3.42 (2H, brs) 3, 43-3.61 (411
, m), 3.79 (311, s), 5.23 (21
1,brs), 5.23 and 5.45(2H,
^Bq, J=15Hz), 6.15 (Ill. d, J=311z), 8.20 (III, d,
J=3Hz) 11 towns↓ 7β-amino-3-[3-(1-pyrrolidinyl)-2-
Methyl-1-virazolio]methyl-3-cephem-4-
Di(trifluoroacetic acid) salt of carboxylade (], 5
g) water (15ml) and tetrahydrofuran (30ml)
f) with sodium bicarbonate solution at room temperature.
1-[2-(2-aminothiazol-4-yl)-2-methoxyiminoacetyl]-1H-benzotriazole-3-oxide (synisomer) adjusted to H6,5 and containing N,N-dimethylformamide. body) (1,49g)
Add. At the same temperature, p
After keeping in H7 for 5 hours, the mixture is washed with ethyl acetate. This solution was adjusted to pH 3 with IN hydrochloric acid, washed with ethyl acetate, and subjected to column chromatography using "Diaion HP-20" (trademark: manufactured by Mitsubishi Kasei Corporation).
Elute with 10% isopropyl alcohol. Both fractions containing the target compound were collected, the solvent was distilled off under reduced pressure, and lyophilized to give 7β-r2- (2-aminothiazol-4-yl)-2-methoxyiminoacetamide] -3-[3-
(1-pyrrolidinyl)-2-methyl-1-viraprio]
Methyl-3-cephem-4-carboxilade (syn isomer) (683 mg) is obtained. IR (Nujifur) + 3300. 1770. 1
660 am-'NMR (D, O, δ): 1.83
~2.07 (411, m), 3.07 and 3.
33 (2II, ABq, J=18Hz), 3.3
7-3.58 (4H, m), 3.73 (3H, s)3
, 96 (3H, s), 4.87 and 5.23 (
2H,ABq, J=15Hz)5,18(18,d,
J=5H7,), 5.78(IH,d, J=5H
z), 5.88 (IH, d, J=3Hz), 6.
93 (Ill, s), 7.85 (IH, d, J=
3H Example 2 7β-[2-(2-aminothiazol-4-yl)-2
-methoxyiminoacetamide] -3-[3-(1-
pyrrolidinyl)-2-methyl-■-virazolio]methyl-3-cephem-4-carboxilade (syn isomer)
(0.6 g) in water (06 mJ) was added 2M sulfuric acid (0.6 g)
Add 6 mO and ethanol (2.4 mF) at room temperature. The mixture was stirred at the same temperature for 3 hours, the resulting precipitate was collected, and 7β-[2-(2-aminothiazol-4-yl)-
2-Methoxyimino-acetamide] -3-[3-(
1-pyrrolidinyl)-2-methyl-1-virazolio]methyl-3-cephem-4-carboxilade sulfate (
Syn isomer) (0.37 g) is obtained as crystals. IR (Nujigor): 3540. 32
00. +790. 1670. 1635am
'NMR (DMSO-d, δ): 1.7g-2,01
(4H, m), 3.27 (2H, brs) 3.37-
3.54 (4H, m), 3.74 (3H, s), 3
．． 81 (3B, s). 5,08 and 5.35 (2N, ^Bq, J=+
51h), 5.13 (IH, d, J=5Hz),
5,'/7(IN, dd, J=lH?z, 5+I
z), 6.11 (III, d, J31fz),
6.68 ([I, s), 7.13 (2+1. br
s), 8.09 (JJI. d, J=3Hz), 9.51 ([1, d, J=8
Hz>Example 3 Di(trifluoroacetic acid) salt of 7β-amino-3-[3-(1-pyrrolidinyl)2-methyl-1-virazoliocomethyl-3-cephem-4-carboxilade (L5 g)
and N-(trimethylsilyl)acetamide (3,3
2-(5-
Amino-1゜2,4-thiadiazol-3-yl)-2
-Methoxyiminoacetyl chloride hydrochloride (syn isomer) (0.78 g) is added under water cooling. After stirring for 1 hour at the same temperature under water cooling, the reaction mixture was poured into ethyl acetate. The precipitate formed is collected by filtration, dissolved in water and adjusted to pH 4 with sodium bicarbonate solution. This solution was subjected to column chromatography using a Diaion HP-20J and eluted with a 10% isopropyl alcohol aqueous solution. Both fractions containing the target compound were collected, the solvent was distilled off under reduced pressure, and lyophilized. , 7β-[2-(5-amino-1,2,4
-thiadiazol-3-yl)-2-methoxyiminoacetamide] -3-[3-(1-pyrrolidinyl)-2
-Methyl-1-virazolio]methyl-3-cephem-4
- Obtain carboxylad (syn isomer) (510 mg). IR (N7 goals): 3270.
1760. 1665 cm-'11MR (DMS
O-do, δ): 1°78-2.01 (411, m),
2.97 and 3゜25 (211, ABq, J
=I811z), 3.32-3.53(411,m
), 3.86 (3II, s), 3.90 (31
1, s), 4.97 (IH, d, J=5Hz), 5
．． 07 and 5.38 (2tl, ABq, J1
5Hz), 5.59 (III, dd, J□81
1z. 511z), 6.060H,d, J=311z)
, 8.10 (211, br, s). 8.21 (18, d, J=3Hz), 9.41. (
lH, d, J・811z) Example 4 Di(trifluoroacetic acid) salt of 7β-amino-3-[3-(1-pyrrolidinyl)2-methyl-1-virazolio]methyl-3-cephem-4-carboxilade (1.5g
) and N-(trimethylsilyl)acetamide (3,
33g) of methylene chloride (20if), 2-(5
-amino-1゜2.4-thiadiazol-3-yl)
-2-(1-carboxy-1-methylethoxyimino)
Acetic acid methanesulfonic anhydride (syn-g form) (1,07
Add g) under water cooling. After stirring at the same temperature for 1 hour, the reaction mixture was poured into ethyl acetate, and the resulting precipitate was collected by filtration. The precipitate was suspended in water and added to pH 2 with sodium bicarbonate solution.
, 5, and subjected to column chromatography using Diaion HP-204 and eluted with a 10% aqueous inpropyl alcohol solution. Both fractions containing the target compound were collected, the solvent was distilled off under reduced pressure, and lyophilized to give 7β-[
2-(5-amino-1,2,4-thiadiazole-3-
yl')-2-(1-carboxy-1-methylethoxyimino)acetamide]-3-,[3-(1-pyrrolidinyl)-2-methyl-1-virazolio]methyl-3-cephem-4-carboxilade isomer) (423m
g) is obtained. IR (null): 1770.
1670. 1630 cm-'NMR (D, O
+NaHCO,, δ): 1.55 (6H, s),
1.85-2.04 (4) 1゜m), 3.09 an
d 3.34 (2H, ^Bq, J=18Hz), 3
．． 39-3°68 (411, m),' 3.77 (3H
,s), 4.88 and 5.23(2H, ABq
, J=15Hz), 5.20(III, d, J
=5Hz), 5.8'1 (IH, d.

Claims (1)

[Claims] Formula: ▲ Numerical formula, chemical formula, table, etc.▼ [In the formula, R^1 is an amino group or a protected amino group, and R^2 may have an appropriate substituent. Lower alkyl group, R^3 is -COO■ group, carboxy group or protected carboxy group, R^4 is lower alkyl group, R^5 is N-containing heterocyclic group, X is CH or N Y■ is an anion n means 0 or 1, respectively. However, R^3 is -C
When it is an OO^- group, n is 0, and when R^3 is a carboxy group or a protected carboxy group, n is
is 1. ] A novel cephem compound and its salt.