1-Sulfo-2-oxoazetidine derivatives and their production

Claim 1

A compound of the formula ##STR808## wherein R 1 represents (1) amino, (2) an acylated amino group wherein the acyl moiety is (i) a group of the formula: R.sup.5 --CO-- wherein R 5 is an alkyl other than C 1-5 alkyl--CH 2 or a heterocyclic* group; (ii) a group of the formula: ##STR809## wherein R 6 is hydrogen, glycyl, alanyl, valyl, leucyl, isoleucyl, seryl, threonyl, cysteinyl, cystyl, methionyl, α- or β-aspartyl, α- or γ-glutamyl, lysyl, arginyl, phenylalanyl, phenylglycyl, tyrosyl, histidyl, tryptophanyl, an amino-protective group or a group R 8 --(CH 2 )n 1 --CO-- where R 8 is a heterocyclic* group and n 1 is an integer of 0 to 2, and R 7 is an alkyl, phenyl*, heterocyclic*-carbonylamino or a heterocyclic* group; (iii) a group of the formula: R.sup.9 --R.sup.10 --CO-- wherein R 9 is a group ##STR810## where R 11 is alkyl*, heterocyclic* group or phenyl* and R 12 is hydrogen, an alkyl, alkenyl or a group --R 13 --R 14 where R 13 is an alkylene or alkenylene and R 14 is phenyl*, carboxyl or an alkyl ester thereof or mono- or di-alkylamino, and R 10 is a direct bond or a group ##STR811## where R 15 is an alkyl, phenyl* or thiazolyl*; (iv) a group of the formula: ##STR812## wherein R 16 is hydroxyl, hydroxysulfonyloxy, carboxy, ureido*, sulfamoyl*, sulfo, phenoxycarbonyl* or formyloxy and R 17 is hydrogen, an alkyl, an alkoxy, halogen, nitro or hydroxy; or (v) a group of the formula: ti R 18 --R 19 --CH 2 --CO-- wherein R 18 is cyano, phenyl*, phenoxy*, an alkyl*, alkenyl* or a heterocyclic* group and R 19 is a direct bond or --S--; and, in symbols R 5 through R 19 , (a) the heterocyclic group is 2- or 3-pyrrolyl, 2- or 3-furyl, 2- or 3-thienyl, 2- or 3-pyrrolidinyl, 2-, 3- or 4-pyridyl, N-oxido-2-, 3- or 4-pyridyl, 2-, 3- or 4-piperidinyl, 2-, 3- or 4-pyranyl, 2-, 3- or 4-thiopyranyl, pyrazinyl, 2-, 4- or 5-thiazolyl, 2-, 4- or 5-oxazolyl, 3-, 4- or 5-isothiazolyl, 3-, 4- or 5-isoxazolyl, 2-, 4- or 5-imidazolyl, 3-, 4- or 5-pyrazolyl, 3- or 4-pyridazinyl, N-oxido-3- or 4-pyridazinyl, 2-, 4- or 5-pyrimidinyl, N-oxido-2-, 4- or 5-pyrimidinyl, piperazinyl, 4- or 5-(1,2,3-thiadiazolyl), 3- or 5-(1,2,4-thiadiazolyl), 1,3,4-thiadiazolyl, 1,2,5-thiadiazolyl, 4- or 5-(1,2,3-oxadiazolyl), 3- or 5-(1,2,4-oxadiazolyl), 1,3,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,2,3- or 1,2,4-triazolyl, 1H- or 2H-tetrazolyl, pyrido[2,3-d]-pyrimidyl; benzopyranyl; 1,8-, 1,5-, 1,6-, 1,7-, 2,7- or 2,6-naphthyridyl; quinolyl or thieno[2,3-b]-pyridyl, (b) the amino-protective group in R 6 is phthaloyl, p-nitrobenzoyl, p-tert-butyl-benzoyl, p-tert-butylbenzenesulfonyl, benzenesulfonyl, toluenesulfonyl, formyl, acetyl, propionyl, monochloroacetyl, dichloroacetyl, trichloroacetyl, methanesulfonyl, ethanesulfonyl, trifluoroacetyl, maleyl, succinyl, methoxycarbonyl, ethoxycarbonyl, t-butoxycarbonyl, isopropoxycarbonyl, 2-cyanoethoxycarbonyl, β,β,β-trichloroethoxycarbonyl, β-trimethylsilylethoxycarbonyl, β-methylsulfonylethoxycarbonyl, benzyloxycarbonyl, p-nitrobenzyloxycarbonyl, p-methoxybenzyloxycarbonyl, diphenylmethyloxycarbonyl, methoxymethyloxycarbonyl, acetylmethyloxycarbonyl, isobornyloxycarbonyl, phenyloxycarbonyl, trityl, 2-nitrophenylthio, benzylidene, 4-nitro benzylidene, trialkylsilyl, benzyl or p-nitrobenzyl, (c) the heterocyclic, phenyl, thiazolyl, phenoxycarbonyl and phenoxy with a superscript asterisk "*" may be substituted with one to three substituents from the group consisting of alkyl, alkoxy, alkenyl, aryl, aralkyl, mercapto, alkylthio, arylthio, aralkylthio, alkylsulfonyl, arylsulfonyl, aralkylsulfonyl, mono- to trihaloalkyl, hydroxyl, oxo, thioxo, halogen, nitro, amino cyano, carbamoyl, carboxyl, acyl, acyloxy, acylamino, hydroxyalkyl, carboxyalkyl, and mono- or dialkylaminoalkyl, wherein the acyl and the acyl moiety of the acyloxy and acylamino are C 1-6 alkylcarbonyl; benzoyl which may be substituted with hydroxyl or methoxy; C 7-9 aralkylcarbonyl which may be substituted with hydroxyl or methoxy; 2-thienylcarbonyl; 2-furylcarbonyl; 2-, 4- or 5-thiazolylacetyl; 2- or 3-thienylacetyl; 2- or 3-furylacetyl or 2-amino-4- or 5-thiazolylacetyl, (d) the alkyl with a superscript asterisk "*" may be substituted with one to three substituents selected from halogen, hyroxyl, cyano and trifluoromethyl, (e) the ureido with a superscript asterisk "*" may be substituted with sulfo in the form of salt with sodium or potassium, carbamoyl, sulfamoyl, amidino or alkyl, (f) the sulfamoyl with a superscript asterisk "*" may be substituted with an alkyl or amidino, and (g) the alkenyl with a superscript asterisk "*" may be substituted with one to three substituents selected from carboxyl and cyano, wherein the amino group, the carboxyl group and the hydroxyl group may be protected, or (3) amino protected with phthaloyl, p-nitrobenzoyl, p-tert-butylbenzoyl, p-tert-butylbenzenesulfonyl, benzenesulfonyl, toluenesulfonyl, formyl, monochloroacetyl, dichloroacetyl, trichloroacetyl, methanesulfonyl, ethanesulfonyl, trifluoroacetyl, maleyl, succinyl, methoxycarbonyl, ethoxycarbonyl, t-butoxycarbonyl, isopropoxycarbonyl, 2-cyanoethoxycarbonyl, β,β,β-trichloroethoxycarbonyl, β-trimethylsilylethoxycarbonyl, β-methylsulfonylethoxycarbonyl, benzyloxycarbonyl, p-nitrobenzyloxycarbonyl, p-methoxybenzyloxycarbonyl, di-phenylmethyloxycarbonyl, methoxymethyloxycarbonyl, acetylmethyloxycarbonyl, isobornyloxycarbonyl, phenyloxycarbonyl, trityl, 2-nitrophenylthio, benzylidene, 4-nitrobenzylidene, trialkylsilyl, benzyl or p-nitrobenzyl, X represents hydrogen or methoxy, and one of Q 3 and Q 4 is hydrogen or alkyl*, and the other of them is hydrogen; alkyl*; alkoxy; amino; aralkyl*; aryl*; heterocyclic* group; sulfo; alkylsulfonyl; aralkyl*-sulfonyl; aryl*-sulfonyl; alkoxycarbonyl; aralkyl*-oxycarbonyl; aryl*-oxycarbonyl; a group of the formula: ##STR813## phthaloyl; p-nitrobenzoyl; p-tert-butylbenzoyl; formyl; monochloroacetyl; dichloroacetyl; trichloroacetyl; trifluoroacetyl; maleyl; succinyl; 2-cyanoethoxycarbonyl; β,β,β-trichloroethoxycarbonyl; β-trimethylsilylethoxycarbonyl; β-methylsulfonylethoxycarbonyl; di-phenylmethyloxycarbonyl; methoxymethyloxycarbonyl; acetylmethyloxycarbonyl; isobornyloxycarbonyl; trityl; 2-nitrophenylthio; benzylidene; 4-nitrobenzylidene or trialkylsilyl, wherein the alkyl*, the heterocyclic*, R 5 , R 6 , R 7 , R 9 , R 10 , R 16 , R 17 , R 18 and R 19 are as defined above in the group R 1 , and the aralkyl* and aryl* are respectively aralkyl and aryl which may be substituted with the substituents as mentioned above in the heterocyclic* group in the group R 1 , and, in the groups represented by R 1 , Q 3 and Q 4 , the alkyl and alkoxy group have 1 to 6 carbon atoms, the alkenyl group has 2 to 6 carbon atoms, the alkylene group has 1 to 3 carbon atoms, the alkenylene group has 2 to 4 carbon atoms, the aryl group has 6 to 14 carbon atoms, and the aralkyl group has 7 to 11 carbon atoms, or a pharmaceutically acceptable salt or an alkoxymethyl ester, α-alkoxyethyl ester, alkylthiomethyl ester, pivaloyloxymethyl ester, α -acetoxybutyl ester, ethoxycarbonyloxymethyl ester or α-ethoxycarbonyloxyethyl ester formed at the carboxyl group or groups contained in R 1 and/or Q 3 and Q 4 thereof.