3-Propenylcephem derivative, preparation thereof, chemical intermediates therein, pharmaceutical composition and use

Claim 2

A 3-propenylcephem derivative of the following formula: wherein R 1 represents a fluoro-substituted lower alkyl group or a cyano-substituted lower alkyl group, and A represents a cyclic or an acylic ammonio group, or a pharmaceutically acceptable salt thereof.

Claim 3

The 3-propenylcephem derivative or a pharmaceutically acceptable salt thereof as claimed in claim

Claim 4

wherein A represents an acylic ammonio group of the following formula: in which R 2 . R 3 and R 4 are the same or different and mean individually a group selected from the group consisting of lower alkyl, hydroxyl-substituted lower alkyl. carbamoyl-substituted lower alkyl. cyanosub- stituted lower alkyl. amino. (lower alkyl)carbonylamino-substituted lower alkyl. aminosulfonylam l nocarbonyl- substituted lower alkyl. (lower alkyl)sulfonylaminocarbonyl-substituted lower alkyl. (lower alkyl)-aminocarbonyl-substituted lower alkyl, hydroxyl-and carbamoyl-substituted lower alkyl, hydroxyl-and hydroxy(lower alkyl)aminocarbonyl-substituted lower alkyl, (lower alkyloxy)aminocarbonyl-substituted lower alkyl, hydroxyaminocarbonyl-substituted lower alkyl, carbonyl(lower alkyl) aminocarbonyl-substituted lower alkyl, hydroxy(lower alkyl)aminocarbonyl-substituted lower alkyl, (lower alkyl)amino-substituted lower alkyl, carboxylate(lower alkyl)di(lower alkyl)ammonio-substituted lower alkyl, (lower alkyl)amino-substituted lower alkyl, (lower alkyl)amino-and hydroxyl-substituted lower alkyl, ureido, hydroxyl, carboxyl-substituted lower alkyl, hydroxyl-and carbamoyl-substituted lower alkyl, lower alkyloxy-substituted lower alkyl, di(lower alkyl)-aminocarbonyl-substituted lower alkyl, dicarbamoyl-substituted lower alkyl, bis[hydroxy(lower alkyl)-]aminocarbonyl-substituted lower alkyl, dihydroxyl-substituted lower alkyl, trihydroxyl-substituted lower alkyl, bis[hydroxy(lower alkyl)amino-substituted lower alkyl. amino-substituted lower alkyl, oxo-substituted lower alkyl. di-lower alkylamino-substituted lower alkyl. 5-membered heterocycle-substituted lower alkyl wherein said heterocycle stands for pyrazolyl, imidazolyl, oxadiazolyl or tetrazolyl, or A represents a cyclic ammonio group of one of the following formulae: in which R = means a group selected from lower alkyl, carbamoyl-substituted lower alkyl, amino-substituted lower alkyl, hydroxyl-substituted lower alkyl, carboxyl-substituted lower alkyl, cyano-substituted lower alkyl, dihydroxyl-substituted lower alkyl and ureido-substituted lower alkyl groups, said cyclic ammonio group optionally containing on the ring thereof one or more substituents selected from hydroxyl-substituted lower alkyl, hydroxyl, formyl, sulfonic, carboxyl-substituted lower alkyl, carbamoyl, sulfamoyl, carboxyl, hydroxyimino-substituted lower alkyl, imino-substituted lower alkyl, bis[hydroxy(lower alkyl)]aminocarbamoyl, hydroxy(lower alkyl)aminocarbamoyl, amino, morpholinocarbonyl, carboxy(lower alkyloxy)-substituted lower alkyl, carboxy(lower alkylthio)-substituted lower alkyl, and lower alkyl groups.

Claim 5

wherein A represents an acylic ammonio group of the following formula: in which R 2 . R 3 and R 4 are the same or different and mean individually a group selected from the group consisting of lower alkyl, hydroxyl-substituted lower alkyl. carbamoyl-substituted lower alkyl. cyanosub- stituted lower alkyl. amino. (lower alkyl)carbonylamino-substituted lower alkyl. aminosulfonylam l nocarbonyl- substituted lower alkyl. (lower alkyl)sulfonylaminocarbonyl-substituted lower alkyl. (lower alkyl)-aminocarbonyl-substituted lower alkyl, hydroxyl-and carbamoyl-substituted lower alkyl, hydroxyl-and hydroxy(lower alkyl)aminocarbonyl-substituted lower alkyl, (lower alkyloxy)aminocarbonyl-substituted lower alkyl, hydroxyaminocarbonyl-substituted lower alkyl, carbonyl(lower alkyl) aminocarbonyl-substituted lower alkyl, hydroxy(lower alkyl)aminocarbonyl-substituted lower alkyl, (lower alkyl)amino-substituted lower alkyl, carboxylate(lower alkyl)di(lower alkyl)ammonio-substituted lower alkyl, (lower alkyl)amino-substituted lower alkyl, (lower alkyl)amino-and hydroxyl-substituted lower alkyl, ureido, hydroxyl, carboxyl-substituted lower alkyl, hydroxyl-and carbamoyl-substituted lower alkyl, lower alkyloxy-substituted lower alkyl, di(lower alkyl)-aminocarbonyl-substituted lower alkyl, dicarbamoyl-substituted lower alkyl, bis[hydroxy(lower alkyl)-]aminocarbonyl-substituted lower alkyl, dihydroxyl-substituted lower alkyl, trihydroxyl-substituted lower alkyl, bis[hydroxy(lower alkyl)amino-substituted lower alkyl. amino-substituted lower alkyl, oxo-substituted lower alkyl. di-lower alkylamino-substituted lower alkyl. 5-membered heterocycle-substituted lower alkyl wherein said heterocycle stands for pyrazolyl, imidazolyl, oxadiazolyl or tetrazolyl, or A represents a cyclic ammonio group of one of the following formulae: in which R = means a group selected from lower alkyl, carbamoyl-substituted lower alkyl, amino-substituted lower alkyl, hydroxyl-substituted lower alkyl, carboxyl-substituted lower alkyl, cyano-substituted lower alkyl, dihydroxyl-substituted lower alkyl and ureido-substituted lower alkyl groups, said cyclic ammonio group optionally containing on the ring thereof one or more substituents selected from hydroxyl-substituted lower alkyl, hydroxyl, formyl, sulfonic, carboxyl-substituted lower alkyl, carbamoyl, sulfamoyl, carboxyl, hydroxyimino-substituted lower alkyl, imino-substituted lower alkyl, bis[hydroxy(lower alkyl)]aminocarbamoyl, hydroxy(lower alkyl)aminocarbamoyl, amino, morpholinocarbonyl, carboxy(lower alkyloxy)-substituted lower alkyl, carboxy(lower alkylthio)-substituted lower alkyl, and lower alkyl groups.

Claim 6

The 3-propenylcephem derivative as claimed in claim 1 or 2 wherein R 1 represents fluoromethyl group, or a pharmaceutically acceptable salt thereof.

Claim 7

The 3-propenylcephem derivative as claimed in claim 1 or 2 wherein R 1 represents cyanomethyl group, or a pharmaceutically acceptable salt thereof.

Claim 8

The compound as claimed in Claim 3, which is 7β-[2-(5-amino-1,2,4-thiadiazof-3-yl)-(Z)-2-fluoromethoxyiminoacetamido]-3-[(E)-3-(carbamoylmethylethylmethylammonio)-1-propen-1-yl]-3-cephem-4-carboxylate.

Claim 9

The compound as claimed in Claim 3, which is 7β-[2 (5-amino-1,2,4-thiadiazol-3-yl)-(Z)-2-fluoromethoxyiminoacetamido]-3-[(E)-3-(1-(2-hydroxyethyt)-4-carbamoy!-1-piperidinio]-1-propen-1-yl]-3-cephem-4-carboxylate.

Claim 10

The compound as claimed in Claim 3, which is 7β-[2-(5-amino-1,2,4-thiadiazol-3-yl)-(Z)-2-fluoromethoxyiminoacetamido]-3-[(E)-3-[(1 S-carbamoylethyl)dimethylammonio]-1-propen-1-yl]-3-cephem-4-carboxylate.

Claim 11

The compound as claimed in Claim 3, which is 7β-[2-(5-amino-1,2,4-thiadiazol-3-yl)-(Z)-2-fluoromethoxyiminoacetamido]-3-[(E)-3-[(1 R-carbamoylethyl)dimethylammonio]-1-propen-1-yl]-3-cephem-4-carboxylate.

Claim 12

The compound as claimed in Claim 3, which is 7β-[2-(5-amino-1,2,4-thiadiazol-3-yl)-(Z)-2-fluoromethoxyiminoacetamido]-3-[(E)-3-[(1R-carbamoyl-2-hydroxyethyl)dimethylammonio]-1-propen-1-yl]-3-cephem-4-carboxylate.

Claim 13

The compound as claimed in claim 3, which is 7β-[2-(5-amino-1,2,4-thiadiazol-3-yl)-(Z)-2-fluoromethoxyiminoacetamido]-3-[(E)-3-(5-aza-1-methyl-2,8-dioxabicyclo[3.3,1 ]nona-1-io)-1-propen-1-yl]-3-cephem-4-carboxylate.

Claim 14

The compound as claimed in claim 3. which is 7β-[2-(5-amino-1,2.4-thiadiazol-3-yl)-(Z)-2-fluoromethoxyiminoacetamido)-3-[(E)-3-(carbamoylmethyldiethylammonio)-1-propen-1-yl]-3-cephem-4-carboxylate.

Claim 15

The compound as claimed in claim 3. which is 7β-[2-(5-amino-1,2,4-thiadiazol-3-yl)-(Z)-2-fluoromethoxyiminoacetamido]-3-[(E)-[(2-oxopropyl)dfmethylammonio]-1-propen-1-yl]-3-cephem-4-carboxylate.

Claim 16

The compound as claimed in claim 4, which is 7β-[2-(5-amino-1,2.4-thiadiazol-3-yl)-(Z)-2-cyanomethoxyiminoacetamido]-3-[(E)-3[(2-oxopropyl)dimethylammonio]-1-propen-1-yl]-3-cephem-4-carboxylate.

Claim 17

The compound as claimed in claim 4, which is 7S-[2-(5-amino-1,2,4-thiadiazol-3-yl)-(Z)-2-cyanomethoxyiminoacetamido]-3-[(E)-3-[(1S-carbamoylethyl)dimethylammonio]-1-propen-1-yl]-3-cephem-4-carboxylate.

Claim 18

The compound as claimed in claim 4, which is 7β-[2-(5-amino-1,2,4-thiadiazol-3-yl)-(Z)-2-cyano methoxyiminoacetamido]-3-[(E)-3-[(1R-carbamoylethyl)dimethylammonio]-1-propen-1-yI]-3-cephem-4-carboxylate.

Claim 19

A process for the preparation of a 3-propenylcephem derivative of the formula: wherein R. represents a fluoro-substituted lower alkyl group or a cyano-substituted lower alkyl group, and A represents a cyclic or an acyclic ammonio group, or a pharmaceutically acceptable salt thereof, which comprises reacting a compound of the following formula: wherein R. has the same meaning as defined above and X represents a halogen atom, a compound wherein said amino and / or carboxyl groups are protected with protecting groups. or a salt thereof with a compound of the following formula: A' wherein A' represents an amine corresponding to A, a compound wherein the functional groups are protected with protecting groups, or a salt thereof, followed by optionally removing the protecting groups.

Claim 20

A process for the preparation of a 3-propenylcephem derivative of the formula: wherein R. represents a fluoro-substituted lower alkyl group or a cyano-substituted lower alkyl group, and A represents a cyclic or an acyclic ammonio group, or a pharmaceutically acceptable salt thereof, which comprises reacting a compound of the following formula: wherein R. has the same meaning as defined above and X represents a halogen atom, a compound wherein said amino and / or carboxyl groups are protected with protecting groups. or a salt thereof with a compound of the following formula: A' wherein A' represents an amine corresponding to A, a compound wherein the functional groups are protected with protecting groups, or a salt thereof, followed by optionally removing the protecting groups.

Claim 21

A pharmaceutical composition which comprises an effective amount of a 3-propenylcephem derivative of the formula: wherein R· represents a fluoro-substituted lower alkyl group or a cyano-substituted lower alkyl group, and A represents a cyclic or an acyclic ammonio group, or a pharmaceutically acceptable salt thereof, and optionally a pharmacologically acceptable. carrier.

Claim 22

A pharmaceutical composition which comprises an effective amount of a 3-propenylcephem derivative of the formula: wherein R· represents a fluoro-substituted lower alkyl group or a cyano-substituted lower alkyl group, and A represents a cyclic or an acyclic ammonio group, or a pharmaceutically acceptable salt thereof, and optionally a pharmacologically acceptable. carrier.

Claim 23

A compound of the formula: wherein R. represents a fluoro-substituted lower alkyl group or a cyano-substituted lower alkyl group, and X represents a halogen atom, a compound wherein said amino group and/or carboxyl groups are protected with a protective group, or salts of their compounds.

Claim 24

A compound of the formula: wherein R. represents a fluoro-substituted lower alkyl group or a cyano-substituted lower alkyl group, and X represents a halogen atom, a compound wherein said amino group and/or carboxyl groups are protected with a protective group, or salts of their compounds.

Claim 25

A process for the preparation of a compound of the formula: wherein R. represents a fluoro-substituted lower alkyl group or a cyano-substituted lower alkyl group. and X represents a halogen atom, a compound wherein said amino group and/or carboxyl groups are protected with a protective group. or salts of their compounds, which comprises reacting a compound of the formulae: wherein R· has the same meanings as defined above a reactive acid derivative thereof, a compound wherein said amino group is protected with a protective group, or a salt thereof with a compound of the formula: wherein X has the same meanings as defined above, a compound wherein said carboxyl group is protected with a protective group, or a salt thereof, followed by optionally removing the protective group and/or converting the halogen atom into the other halogen atom.

Claim 26

A process for the preparation of a compound of the formula: wherein R. represents a fluoro-substituted lower alkyl group or a cyano-substituted lower alkyl group. and X represents a halogen atom, a compound wherein said amino group and/or carboxyl groups are protected with a protective group. or salts of their compounds, which comprises reacting a compound of the formulae: wherein R· has the same meanings as defined above a reactive acid derivative thereof, a compound wherein said amino group is protected with a protective group, or a salt thereof with a compound of the formula: wherein X has the same meanings as defined above, a compound wherein said carboxyl group is protected with a protective group, or a salt thereof, followed by optionally removing the protective group and/or converting the halogen atom into the other halogen atom.

Claim 27

A compound of the formula: wherein R 6 represents a carboxyl, a halogenocarbonyl, carbamoyl or cyano group, a compound wherein said amino and/or carboxyl group is protected with a protective group, or a salt thereof.

Claim 28

A compound of the formula: wherein R 6 represents a carboxyl, a halogenocarbonyl, carbamoyl or cyano group, a compound wherein said amino and/or carboxyl group is protected with a protective group, or a salt thereof.

Claim 29

A process for the preparation of a compound of the formula: a compound wherein said amino and or carboxyl group is protected with a protective group, or a salt thereof. which comprises (1) reacting a compound of the formula: wherein said amino group and carboxyl group are protected with a protective group, or a salt thereof. with a halogeno-fluoro methane. followed by optionally removing the protective groups; or (2) hydrolyzing a compound of the formula: a compound wherein said amino group is protected with a protective group, or a salt thereof in the presence of a base, followed by optionally removing the protective group.

Claim 30

A process for the preparation of a compound of the formula: a compound wherein said amino and or carboxyl group is protected with a protective group, or a salt thereof. which comprises (1) reacting a compound of the formula: wherein said amino group and carboxyl group are protected with a protective group, or a salt thereof. with a halogeno-fluoro methane. followed by optionally removing the protective groups; or (2) hydrolyzing a compound of the formula: a compound wherein said amino group is protected with a protective group, or a salt thereof in the presence of a base, followed by optionally removing the protective group.

Claim 31

Use of a compound according to any of claims 1 to 15 in the preparation of an anti-bacterial medicament.

Claim 32

Claims for the following contracting stste: GR

Claim 33

A 3-propenylcephem derivative of the following formula: wherein R 1 represents a fluoro-substituted lower alkyl group or a cyano-substituted lower alkyl group, and A represents a cyclic or an acylic ammonio group, or a pharmaceutically acceptable salt thereof.

Claim 34

A 3-propenylcephem derivative of the following formula: wherein R 1 represents a fluoro-substituted lower alkyl group or a cyano-substituted lower alkyl group, and A represents a cyclic or an acylic ammonio group, or a pharmaceutically acceptable salt thereof.

Claim 35

The 3-propenylcephem derivative or a pharmaceutically acceptable salt thereof as claimed in claim 1, wherein A represents an acylic ammonio group of the following formula: in which R 2 , R 3 and R 4 are the same or different and mean individually a group selected from the group consisting of lower alkyl, hydroxyl-substituted lower alkyl, carbamoyl-substituted lower alkyl, cyano-substituted lower alkyl, amino, (lower alkyl)carbonylamino-substituted lower alkyl, aminosulfonylaminocarbonyl- substituted lower alkyl, (lower alkyl)sulfonylaminocarbony!-substituted lower alkyl, (lower alkyl)-aminocarbonyl-substituted lower alkyl, hydroxyl-and carbamoyl-substituted lower alkyl, hydroxyl-and hydroxy(lower alkyl)aminocarbonyl-substituted lower alkyl, (lower alkyloxy)aminocarbonyl-substituted lower alkyl, hydroxyaminocarbonyl-substituted lower alkyl, carbonyl(lower alkyl) aminocarbonyl-substituted lower alkyl, hydroxy(lower alkyl)aminocarbonyl-substituted lower alkyl, (lower alkyl)amino-substituted lower alkyl. carboxylate(lower alkyl)di(lower alkyl)ammonio-substituted lower alkyl, (lower alkyl)amino-substituted lower alkyl, (lower alkyl)amino-and hydroxyl-substituted lower alkyl, ureido, hydroxyl, carboxyl-substituted lower alkyl, hydroxyl-and carbamoyl-substituted lower alkyl, lower alkyloxy-substituted lower alkyl. di(lower alkyl)-aminocarbonyl-substituted lower alkyl, dicarbamoyl-substituted lower alkyl. bis[hydroxy(lower alkyl)-]aminocarbonyl-substituted lower alkyl. dihydroxyl-substituted lower alkyl. trihydroxyl-substituted lower alkyl. bis[hydroxy(lower alkyl)amino-substituted lower alkyl, amino-substituted lower alkyl, oxo-substituted lower alkyl, di-lower alkylamino-substituted lower alkyl. 5-membered heterocycle-substituted lower alkyl wherein said heterocycle stands for pyrazolyl, imidazolyl, oxadiazolyl or tetrazolyl, or A represents a cyclic ammonio group of one of the following formulae: in which R 5 means a group selected from lower alkyl, carbamoyl-substituted lower alkyl, amino-substituted lower alkyl, hydroxyl-substituted lower alkyl, carboxyl-substituted lower alkyl, cyano-substituted lower alkyl, dihydroxyl-substituted lower alkyl and ureido-substituted lower alkyl groups, said cyclic ammonio group optionally containing on the ring thereof one or more substituents selected from hydroxyl-substituted lower alkyl, hydroxyl, formyl, sulfonic, carboxyl-substituted lower alkyl, carbamoyl, sulfamoyl, carboxyl, hydroxyimino-substituted lower alkyl, imino-substituted lower alkyl. bis[hydroxy(lower alkyl)]aminocarbamoyl, hydroxy(lower alkyl)aminocarbamoyl, amino, morpholinocarbonyl, carboxy(lower alkyloxy)-substituted lower alkyl, carboxy(lower alkylthio)-substituted lower alkyl, and lower alkyl groups.

Claim 36

The 3-propenylcephem derivative as claimed in claim 1 or 2 wherein R. represents fluoromethyl group, or a pharmaceutically acceptable salt thereof.

Claim 37

The 3-propenylcephem derivative as claimed in claim 1 or 2 wherein R. represents cyanomethyl group, or a pharmaceutically acceptable salt thereof.

Claim 38

The compound as claimed in Claim 3. which is 7β-[2-(5-amino-1.2.4-thiadiazol-3-yl)-(Z)-2- fλuoromethoxyiminoacetamido]-3-[(E)-3-(carbamoylmethylethylmethylammonioj-1-propen-1-yl]-3-cephem-4-carboxylate.

Claim 39

The compound as claimed in Claim 3, which is 7β-[2-(5-amino-1,2,4-thiadiazol-3-yl)-(Z)-2-fluoromethoxyiminoacetamido]-3-[(E)-3-(1-(2-hydroxyethyl)-4-carbamoyl-1-piperidinio]-1-propen-1-yl]-3-cephem-4-carboxylate.

Claim 40

The compound as claimed in Claim 3, which is 7β-[2-(5-amino-1,2.4-thiadiazol-3-yl)-(Z)-2-fluoromethoxymmoacetamido]-3-[(E)-3-[(1S-carbamoylethyl)dimethylammonio)-1-propen-1-yl)-3-cephem-4-carboxylate.

Claim 41

The compound as claimed in Claim 3, which is 7β-[2-(5-amino-1,2,4-thiadiazol-3-yl)-(Z)-2-. fluoromethoxyiminoacetamido]-3-[(E)-3-[(1R-carbamoylethyl)dimethylammonio]-1-propen-1-ylj-3-cephem-4-carboxylate.

Claim 42

The compound as claimed in Claim 3. which is 7β-[2-(5-amino-1,2.4-thiadiazol-3-yl)-(Z)-2-fluoromethoxyiminoacetamido]-3-[(E)-3-[l1R-carbamoyl-2-hydroxyethyl)dimethylammonio]-1-propen-1-yl]-3-cephem-4-carboxylate.

Claim 43

. 10. The compound as claimed in claim 3, which is 7β-[2-(5-amino-1.2.4-thiadiazol-3-yl)-(Z)-2-fluoromethoxymmoacetamido]-3-[(Ej-3-(5-aza-1-methyl-2,8-dioxabicyclo[3.3.1]nona-1-io)-1-propen-1-yl]-3-cephem-4-carboxylate.

Claim 44

The compound as claimed in claim 3, which is 7β-[2-(5-amino-1.2,4-thiadiazol-3-yl)-(Z)-2-fluoromethoxyiminoacetamido]-3-[(E)-3-(carbamoylmethyldiethylammonio)-1-propen-1-yl]-3-cephem-4-carboxylate.

Claim 45

The compound as claimed in claim 3, which is 7β-[2-(5-amino-1,2.4-thiadiazoi-3-yl)-(Z)-2-fluoromethoxyminoacetamido]-3-[(E)-[(2-oxopropyl)dimethylammonio]-1-propen-1-yl]-3-cephem-4-carboxylate.

Claim 46

The compound as claimed in claim 4, which is 7β-[2-(5-amino-1,2,4-thiadiazol-3-yl)-(Z)-2-cyanomethoxyiminoacetamido]-3-[(E)-3[(2-oxopropyl)dimethylammonio]-1-propen-1-yl]-3-cephem-4-carboxylate.

Claim 47

The compound as claimed in claim 4, which is 7β-[2-(5-amfno-1,2,4-thiadiazol-3-yl)-(Z)-2-cyanomethoxyiminoacetamido]-3-[(E)-3-[(1S-carbamoylethyl)dimethylammonio]-1-propen-1-yl)-3-cephem-4-carboxylate.

Claim 48

The compound as claimed in claim 4, which is 7β-[2-(5-amino-1,2,4-thiadiazol-3-yl)-(Z)-2-cyano methoxyiminoacetamido]-3-[(E)-3-[(1R-carbamoylethyl)dimethylammonio]-1-propen-1-yl]-3-cephem-4-carboxylate.

Claim 49

A process for the preparation of a 3-propenylcephem derivative of the formula: wherein R 1 represents a fluoro-substituted lower alkyl group or a cyano-substituted lower alkyl group, and A represents a cyclic or an acyclic ammonio group, or a pharmaceutically acceptable salt thereof, which comprises reacting a compound of the following formula: wherein R. has the same meaning as defined above and X represents a halogen atom, a compound wherein said amino and/or carboxyl groups are protected with protecting groups, or a salt thereof with a compound of the following formula: A ' wherein A' represents an amine corresponding to A, a compound wherein the functional groups are protected with protecting groups, or a salt thereof, followec by optionally removing the protecting groups.

Claim 50

A process for the preparation of a 3-propenylcephem derivative of the formula: wherein R 1 represents a fluoro-substituted lower alkyl group or a cyano-substituted lower alkyl group, and A represents a cyclic or an acyclic ammonio group, or a pharmaceutically acceptable salt thereof, which comprises reacting a compound of the following formula: wherein R. has the same meaning as defined above and X represents a halogen atom, a compound wherein said amino and/or carboxyl groups are protected with protecting groups, or a salt thereof with a compound of the following formula: A ' wherein A' represents an amine corresponding to A, a compound wherein the functional groups are protected with protecting groups, or a salt thereof, followec by optionally removing the protecting groups.

Claim 51

A compound of the formula: wherein R 1 represents a fluoro-substituted lower alkyl group or a cyano-substituted lower alkyl group, and X represents a halogen atom, a compound wherein said amino group and/or carboxyl groups are protected with a protective group, or salts of their compounds.

Claim 52

A compound of the formula: wherein R 1 represents a fluoro-substituted lower alkyl group or a cyano-substituted lower alkyl group, and X represents a halogen atom, a compound wherein said amino group and/or carboxyl groups are protected with a protective group, or salts of their compounds.

Claim 53

A process for the preparation of a compound of the formula: wherein R represents a fluoro-substituted lower alkyl group or a cyano-substituted lower alkyl group. and X represents a halogen atom, a compound wherein said amino group and-or carboxyl groups are protected with a protective group, or salts of their compounds, which comprises reacting a compound of the formula: wherein R, has the same meanings as defined above, a reactive acid derivative thereof, a compound wherein said amino group is protected with a protective group, or a salt thereof with a compound of the formula: wherein X has the same meanings as defined above, a compound wherein said carboxyl group is protected with a protective group, or a salt thereof, followed by optionally removing the protective group and/or converting the halogen atom into the other halogen atom.

Claim 54

A process for the preparation of a compound of the formula: wherein R represents a fluoro-substituted lower alkyl group or a cyano-substituted lower alkyl group. and X represents a halogen atom, a compound wherein said amino group and-or carboxyl groups are protected with a protective group, or salts of their compounds, which comprises reacting a compound of the formula: wherein R, has the same meanings as defined above, a reactive acid derivative thereof, a compound wherein said amino group is protected with a protective group, or a salt thereof with a compound of the formula: wherein X has the same meanings as defined above, a compound wherein said carboxyl group is protected with a protective group, or a salt thereof, followed by optionally removing the protective group and/or converting the halogen atom into the other halogen atom.

Claim 55

A compound of the formula: wherein R E represents carboxyl, a halogenocarboyl, carbamoyl or cyano group. a compound wherein said amino and/or carboxyl group is protected with a protective group, or a salt thereof.

Claim 56

A compound of the formula: wherein R E represents carboxyl, a halogenocarboyl, carbamoyl or cyano group. a compound wherein said amino and/or carboxyl group is protected with a protective group, or a salt thereof.

Claim 57

A process for the preparation of a compound of the formula: a compound wherein said amino and or carboxyl group is protected with a protective group. or a salt thereof, which comprises (1) reacting a compound of the formula: wherein said amino group and carboxyl group are protected with a protective group, or a salt thereof. with a halogeno-fluoro methane, followed by optionally removing the protective groups: or (2) hydrolyzing a compound of the formula: a compound wherein said amino group is protected with a protective group. or a salt thereof in the presence of a base, followed by optionally removing the protective group.

Claim 58

A process for the preparation of a compound of the formula: a compound wherein said amino and or carboxyl group is protected with a protective group. or a salt thereof, which comprises (1) reacting a compound of the formula: wherein said amino group and carboxyl group are protected with a protective group, or a salt thereof. with a halogeno-fluoro methane, followed by optionally removing the protective groups: or (2) hydrolyzing a compound of the formula: a compound wherein said amino group is protected with a protective group. or a salt thereof in the presence of a base, followed by optionally removing the protective group.

Claim 59

Use of a 3-propenylcephem derivative of the following formula: wherein R. represents a fluoro-substituted lower alkyl group or a cyano-substituted lower alkyl group, and A represents a cyclic or an acylic ammonio group, or a pharmaceutically acceptable salt thereof in the preparation of an anti-bactenai medicament.

Claim 60

Use of a 3-propenylcephem derivative of the following formula: wherein R. represents a fluoro-substituted lower alkyl group or a cyano-substituted lower alkyl group, and A represents a cyclic or an acylic ammonio group, or a pharmaceutically acceptable salt thereof in the preparation of an anti-bactenai medicament.

Claim 61

Claims for the following contracting state: ES

Claim 62

A process for the preparation of a 3-propenylcephem derivative of the formula: wherein R. represents a fluoro-substituted lower alkyl group or a cyano-substituted lower alkyl group, and A represents a cyclic or an acyclic ammonio group, or a pharmaceutically acceptable salt thereof, which comprises reacting a compound of the following formula: wherein R 1 has the same meaning as defined above and X represents a halogen atom, a compound wherein said amino and/or carboxyl groups are protected with protecting groups. or a salt thereof with a compound of the following formula: A ' wherein A' represents an amine corresponding to A, a compound wherein the functional groups are protected with protecting groups, or a salt thereof, followed by optionally removing the protecting groups.

Claim 63

A process for the preparation of a 3-propenylcephem derivative of the formula: wherein R. represents a fluoro-substituted lower alkyl group or a cyano-substituted lower alkyl group, and A represents a cyclic or an acyclic ammonio group, or a pharmaceutically acceptable salt thereof, which comprises reacting a compound of the following formula: wherein R 1 has the same meaning as defined above and X represents a halogen atom, a compound wherein said amino and/or carboxyl groups are protected with protecting groups. or a salt thereof with a compound of the following formula: A ' wherein A' represents an amine corresponding to A, a compound wherein the functional groups are protected with protecting groups, or a salt thereof, followed by optionally removing the protecting groups.

Claim 64

A process for the preparation of a compound of the formula: wherein R 1 represents a fluoro-substituted lower alkyl group or a cyano-substituted lower alkyl group. and X represents a halogen atom, a compound wherein said amino group and or carboxyl groups are protected with a protective group, or salts of their compounds. which comprises reacting a compound of the formula: wherein R. has the same meanings as defined above, a reactive acid derivative thereof, a compound wherein said amino group is protected with a protective group, or a salt thereof with a compound of the formula: wherein X has the same meanings as defined above, a compound wherein said carboxyl group is protected with a protective group, or a salt thereof, followed by optionally removing the protective group and/or converting the halogen atom into the other halogen atom.

Claim 65

A process for the preparation of a compound of the formula: wherein R 1 represents a fluoro-substituted lower alkyl group or a cyano-substituted lower alkyl group. and X represents a halogen atom, a compound wherein said amino group and or carboxyl groups are protected with a protective group, or salts of their compounds. which comprises reacting a compound of the formula: wherein R. has the same meanings as defined above, a reactive acid derivative thereof, a compound wherein said amino group is protected with a protective group, or a salt thereof with a compound of the formula: wherein X has the same meanings as defined above, a compound wherein said carboxyl group is protected with a protective group, or a salt thereof, followed by optionally removing the protective group and/or converting the halogen atom into the other halogen atom.

Claim 66

A process for the preparation of a compound of the formula: a compound wherein said amino and/or carboxyl group is protected with a protective group, or a salt thereof, which comprises (1) reacting a compound of the formula: wherein said amino group and carboxyl group are protected with a protective group, or a salt thereof, with a halogeno-fluoro methane. followed by optionally removing the protective groups; or (2) hydrolyzing a compound of the formula: a compound wherein said amino group is protected with a protective group, or a salt thereof in the presence of a base. followed by optionally removing the protective group.

Claim 67

A process for the preparation of a compound of the formula: a compound wherein said amino and/or carboxyl group is protected with a protective group, or a salt thereof, which comprises (1) reacting a compound of the formula: wherein said amino group and carboxyl group are protected with a protective group, or a salt thereof, with a halogeno-fluoro methane. followed by optionally removing the protective groups; or (2) hydrolyzing a compound of the formula: a compound wherein said amino group is protected with a protective group, or a salt thereof in the presence of a base. followed by optionally removing the protective group.

Claim 68

Use of a 3-propenylcephem derivative of the following formula: wherein R. represents a fluoro-substituted lower alkyl group or a cyano-substituted lower alkyl group, and A represents a cyclic or an acylic' ammonio group. or a pharmaceutically acceptable salt thereof in the preparation of an anti-bacterial medicament.

Claim 69

Use of a 3-propenylcephem derivative of the following formula: wherein R. represents a fluoro-substituted lower alkyl group or a cyano-substituted lower alkyl group, and A represents a cyclic or an acylic' ammonio group. or a pharmaceutically acceptable salt thereof in the preparation of an anti-bacterial medicament.