5,6-cis-Carbapenem derivatives, their production and use

Claim 2

A compound of the general formula: wherein R is alkyl, cycloalkyl, cycloalkenyl, alkynyl, aryl, aralkyl, or a 5 to 8 membered heterocyclic group containing 1 to 4 hetero-atoms, each of the above members may be further substituted; and R2 is hydrogen or hydroxy-protecting group, or a pharmaceutically acceptable salt thereof, or an ester thereof.

Claim 3

A compound as claimed in Claim 1, wherein alkyl or alkynyl represented by R 1 may be substituted by one to three substituents selected from cycloalkyl, cycloalkenyl, aryl, a 5 to 8 membered heterocylcic group containing 1 to 4 hetero-atoms, alkoxycarbonyl, acyl, oxo, halogen, cyano, hydroxy, alkoxy, aryloxy, acyloxy, carbamoyloxy, hydroxysulfonyloxy, alkylsulfonyloxy, arylsulfonyloxy, nitro, amino, carboxy, aminocarbonyl, alkylthiocarbonyl, mercapto, alkylthio, aminoalkylthio, acylaminoalkylthio, aralkylthio, arylthio, a group of Het-S in which Het means a 5 to 8 membered heterocyclic group containing 1 to 4 hetero-atoms and quaternary ammonium, and cycloalkyl, cycloalkenyl, aryl or aralkyl or a 5 to 8 membered heterocyclic group containing 1 to 4 hetero-atoms represented by R 1 may be substituted by 1 to 3 substituents selected from alkyl, alkoxy, alkenyl, aryl, aralkyl, mercapto, alkylthio, arylthio, aralkylthio, alkylsulfonyl, arylsulfonyl, aralkylsulfonyl, trihalogenoalkyl, hydroxy, oxo, thioxo, halogen, nitro, amino, cyano, carbamoyl, carboxy, acyl, acyloxy, acylamino, hydroxyalkyl, carboxyalkyl, halogenoalkyl and mono- or di-alkylaminoalkyl.

Claim 4

A compound as claimed in Claim 1, wherein R 1 is alkyl of 1 to 6 carbon atoms which may be substituted by 1 to 3 substituents selected from amino, carboxyl, alkylamino and a 5 to 6 membered cyclic amino, or alternatively R 1 is pyridazinyl.

Claim 5

A compound as claimed in Claim 1, which is 5,6-cis-3-(2-aminoethylthio)-6-(1-hydroxy-1-methylethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid or a pharmaceutically acceptable salt thereof.

Claim 6

A compound as claimed in Claim 1,which is 5,6-cis-3-(3-pyridazinylthio)-6-(1-hydroxy-1-methylethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid or a pharmaceutically acceptable salt thereof.

Claim 7

A compound as claimed in Claim 1, which is 5,6-cis-3-[2-(N,N-dimethylaminoethyl)thio]-6-(1-hydroxy-1-methylethyl)-7-oxo-l-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid or a pharmaceutically acceptable salt thereof.

Claim 8

A compound as claimed in Claim 1, which is 5,6-cis-3-(3-aminopropylthio)-6-(1-hydroxy-1-methylethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid or a pharmaceutically acceptable salt thereof.

Claim 9

A compound as claimed in Claim 1, which is 5,6-cis-3-(2-formimidoylaminoethylthio)-6-(l-hydroxy-l-methylethyl)-7-oxo-l-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid or a pharmaceutically acceptable salt thereof.

Claim 10

A compound as claimed in Claim 1, which is 5,6-cis-3-(3-formimidoylaminopropylthio)-6-(1-hydroxy-1-methylethyl)-7-oxo-l-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid or a pharmaceutically acceptable salt.

Claim 11

A compound as claimed in Claim 1, which is 5,6- cis-3-(2-pyrrolidinoethylthio)-6-(2-hydroxy-l-methylethyl)-7-oxo-l-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid or a pharmaceutically acceptable salt thereof.

Claim 12

A compound as claimed in Claim 1, which is 5,6-cis-3-(2-piperidinoethylthio)-6-(l-hydroxy-l-methylethyl)-7-oxo-l-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid or a pharmaceutically acceptable salt thereof.

Claim 13

A compound as claimed in Claim 1, which is 5,6- cis-3-(2-amino-2-carboxyethylthio)-6-(l-hydroxy-l-methylethyl)-7-oxo-l-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid or a pharmaceutically acceptable salt thereof.

Claim 14

A process for producing a compound of the general formula: wherein R 1 is alkyl, cycloalkyl, cycloalkenyl, alkynyl, aryl, aralkyl, or a 5 to 8 membered heterocyclic group containing 1 to 4 hetero-atoms, each of the above members may be further substituted; and R 2 is hydrogen or hydroxy-protecting group, or a pharmaceutically acceptable salt thereof, or an ester thereof, which comprises reacting a compound of the general formula: wherein X is a group to be eliminated; and R 2 is of the same meaning as defined above, or a salt thereof or an ester thereof with a compound of the general formula: R 1 S H wherein R 1 is of the same meaning as defined above, or a salt thereof.

Claim 15

A process for producing a compound of the general formula: wherein R 1 is alkyl, cycloalkyl, cycloalkenyl, alkynyl, aryl, aralkyl, or a 5 to 8 membered heterocyclic group containing 1 to 4 hetero-atoms, each of the above members may be further substituted; and R 2 is hydrogen or hydroxy-protecting group, or a pharmaceutically acceptable salt thereof, or an ester thereof, which comprises reacting a compound of the general formula: wherein X is a group to be eliminated; and R 2 is of the same meaning as defined above, or a salt thereof or an ester thereof with a compound of the general formula: R 1 S H wherein R 1 is of the same meaning as defined above, or a salt thereof.

Claim 16

A pharmaceutical composition which contains a medicinally effective amount of a compound of the general formula: wherein R 1 is alkyl, cycloalkyl, cycloalkenyl, alkynyl, aryl, aralkyl, or a 5 to 8 membered heterocyclic group containing 1 to 4 hetero-atoms, each of the above members may be further substituted; and R 2 is hydrogen or hydroxy-protecting group, or a pharmaceutically acceptable salt thereof, or an ester thereof.

Claim 17

A pharmaceutical composition which contains a medicinally effective amount of a compound of the general formula: wherein R 1 is alkyl, cycloalkyl, cycloalkenyl, alkynyl, aryl, aralkyl, or a 5 to 8 membered heterocyclic group containing 1 to 4 hetero-atoms, each of the above members may be further substituted; and R 2 is hydrogen or hydroxy-protecting group, or a pharmaceutically acceptable salt thereof, or an ester thereof.