New cephem compounds, processes for preparation thereof and pharmaceutical composition containing them

Claim 2

A cephem compound of the formula: wherein R is amino substituted thiazolyl which may have halogen(s) , amino substituted thiazolyl which may have halogen(s), lower alkylamino substituted thiazolyl, substituted thiadiazolyl, amino-substituted thiadiazolyl, amino substituted pyridyl, protected amino substituted pyridyl, furyl, thiazolyl, thiadiazolyl, phenyl, or naphthyl, R 2 is carboxy(lower)alkyl or protected carboxy(lower)alkyl, R 3 is lower alkylthio, and R 4 ie carboxy or protected carboxy, an pharmaceutically acceptable salts thereof.

Claim 3

2, The compound of claim 1, wherein R 1 is amino substituted thiazolyl which may have halogen(s), acylamino substituted thiazolyl which may have halogen(s), lower alkylamino substituted thiazolyl, amino substituted thiadiazolyl, acylamino substituted thiadiazolyl, -amino substituted pyridyl, acylamino substituted pyridyl, furyl, thiazolyl, thiadiazolyl, phenyl, or naphthyl, R is carboxy(lower)alkyl or esterified carboxy(lower)alkyl, and R 4 is carboxy or esterified carboxy.

Claim 4

Syn isomer of the compound of claim 2.

Claim 5

The compound of claim 3, wherein R 1 is 2-aminothiazol-4-yl, R 2 is carboxy(lower)alkyl, lower alkoxycarbonyl(lower)alkyl, or ar(lower)alkoxycarbonyl(lower)alkyl, and R 4 is carboxy.

Claim 6

The compound of claim 4, which is 7-[2-(2-aminothiazol-4-yl)-2-(carboxymethoxyimino)-acetamido]-3-methylthio-3-cephem-4-carboxylic acid (syn isomer) or its hydrochloride.

Claim 7

The compound of claim 4, which is 7-[2-(2-aminothiazol-4-yl)-2-(1-carboxyethoxyimino)-acetamido]-3-methylthio-3-cephem-4-ca-rboxylic acid (syn isomer).

Claim 8

The compound of claim 4, which is 7-[2-(2-aminothiazol-4-yl)-2-methoxycarbonylmethoxy- imino)acetamido)-3-methylthio-3-cephem-4-carboxylic acid (syn isomer).

Claim 9

The compound of claim 4, which is 7-[2-(2-aminothiazol-4-yl)-2-benzhydryloxycarbonyl- methoxyiminoacetamido]-3-methylthio-3-cephem-4-carboxylic acid or its sodium salt (syn isomer).

Claim 10

The compound of claim 4, which is 7-[2-(2-aminothiazol-4-yl)-2-carboxymethoxy- iminoacetamidoj-3-ethylthio-3-cephem-4-carboxylic acid (syn isomer).

Claim 11

The compound of claim 4, which is 7-[2-(2-aminothiazol-4-yl)-2-(1-carboxyethoxyimino)-acetamido]-3-ethylthio-3-cephem-4-carboxylic acid (syn isomer).

Claim 12

The compound of claim 4, which is 7-[2-(2-aminothiazol-4-yl)-2-carboxymethoxyimino- acetamido]-3-propylthio-3-cephem-4-carboxylic acid (syn isomer)

Claim 13

The compound of claim 3, wherein R 1 is 2-amino-5-halothiazol-4-yl, R 2 is carboxy(lower)alkyl, lower alkoxycarbonyl(lower)alkyl, or ar(lower)alkoxycarbonyl(lower)alkyl, and R 4 is carboxy.

Claim 14

The compound of claim 12, which is 7-[2-(2-amino-5-chlorothiazol-4-yl)-2-(carboxy- methoxyiminoacetamido]-3-methylthio-3-cephem-4-carboxylic acid (syn isomer).

Claim 15

The compound of claim 12, which is 7-[2-(2-amino-5-chlorothiazol-4-yl)-2-carboxymethoxyiminoacetamido]-3-ethylthio-3-cephem-4-carboxylic acid (syn isomer).

Claim 16

The compound of claim 3, wherein R 1 is 5-amino-1,2,4-thiadiazol-3-yl, R is carboxy(lower)alkyl, or lower alkoxycarbonyl(lower)alkyl, and R 4 is carboxy .

Claim 17

The compound of claim 15, which is 7-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-carboxymethoxyiminoacetamido]-3-methylthio-3-cephem-4-carboxylic acid (syn isomer).

Claim 18

The compound of claim 15, which is 7-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-carboxymethoxyiminoacetamido]-3-ethylthio-3-cephem-4-carboxylic acid (syn isomer).

Claim 19

The compound of claim 15, which is 7-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(1-carboxyethoxyimino)acetamido]-3-ethylthio-3-cephem-4-carboxylic acid (syn isomer).

Claim 20

The compound of claim 3, wherein R 1 is 6-aminopyridin-2-yl, R 2 is carboxy(lower)alkyl or lower alkoxycarbonyl(lower)alkyl, and R 4 is carboxy.

Claim 21

The compound of claim 19, which is 7-[2-(6-aminopyridin-2-yl)-2-carboxymethoxyimino- acetamido]-3-ethylthio-3-cephem-4-carboxylic acid (syn isomer).

Claim 22

The compound of claim 19, which is 7-[2-(6-aminopyridin-2-yl)-2-carboxymethoxyimino- acetamido]-3-methylthio-3-cephem-4-carboxylic acid (syn isomer).

Claim 23

The compound of claim 3, wherein R 1 is 2-lower alkylaminothiazol-4-yl, furyl, thiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, phenyl, or naphthyl, R 2 is carboxy(lower)alkyl or lower alkoxycarbonyl(lower)alkyl, and R 4 is carboxy.

Claim 24

The compound of claim 3, wherein R 1 is 2-lower alkanoylaminothiazol-4-yl, 2-lower alkanoylamino-5-halothiazol-4-yl, 5-lower alKanoylamino-1,2,4-thiadiazol-3-yl, or 6-lower alkanoylaminopyridin-2-yl, R 2 is carboxy(lower)alkyl, lower alkoxycarbonyl(lower)alkyl, or ar(lower)alkoxycarbonyl(lower)alkyl, and R is carboxy or ar(lower)alkoxycarbonyl.

Claim 25

The compound of claim 3, wherein R 2 is carboxy(lower)alkyl, lower alkoxycarbonyl(lower)alkyl, ar(lower)alkoxycarbonyl(lower)alkyl, lower alkanoyloxy(lower)alkoxycarbonyl(lower)alkyl, lower alkoxycarbonyloxy(lower)alkoxycarbonyl-(lower)alkyl, or (5-lower alkyl-2-oxo-1,3-dioxol-4-yl)(lower)-alkoxycarbonyl(lower)alkyl,and R 4 is ar(lower)alkoxycarbonyl, lower alkanoyloxy(lower)alkoxycarbonyl, lower alkoxycarbonyloxy(lower)alkoxycarbonyl, or (5-lower alkyl-2-oxo-1,3-dioxol-4-yl)(lower)-alkoxycarbonyl.

Claim 26

The compound of claim 24, wherein R 1 is 2-aminothiazol-4-yl, 2-amino-S-halothiazol-4-yl or 5-amino-1,2,4-thiadiazol-3-yl, R is carboxy(lower)alkyl, lower alkanoyloxy(lower)alkoxycarbonyl(lower)alkyl, lower alkoxycarbonyloxy(lower)alkoxycarbonyl(lower)-alkyl, or (5-lower alkyl-2-oxo-1,3-dioxol-4-yl)(lower)-alkoxycarbonyl(lower)alkyl, and R 4 is lower alkanoyloxy(lower)alkoxycarbonyl, lower alkoxycarbonyloxy(lower)alkoxycarbonyl or (5-lower alkyl-2-oxo-1,3-dioxol-4-yl)(lower)-alkoxycarbonyl.

Claim 27

The compound of claim 25, which is pivaloyloxymethyl 7-[2-(2-aminothiazol-4-yl)-2-carboxymethoxyiminoacetamido]-3-methylthio-3-cephem-4-carboxylate (syn isomer) or its hydrochloride.

Claim 28

The compound of claim 25, which is 1-propionyloxyethyl 7-[2-(2-aminothiazol-4-yl)-2-carboxymethoxyiminoacetamido]-3-methylthio-3-cephem-4-carboxylate (syn isomer) or its hydrochloride.

Claim 29

The compound of claim 25, which is 1-ethoxycarbonyloxyethyl 7-[2-(2-aminothiazol-4-yl)-2-carboxymethoxyiminoacetamidoJ-3-methylthio-3-cephem-4-carboxylate (syn isomer) or its hydrochloride.

Claim 30

The compound of claim 25, which is (5-methyl-2-oxo-l,3-dioxol-4-yl)methyl 7-[2-(2-aminothiazol-4-yl)-2-carboxymethoxyiminoacetamido]-3-methylthio-3-cephem-4-carboxylate (syn isomer) or its hydrochloride.

Claim 31

The compound of claim 25, which is 1-ethoxycarbonyloxyethyl 7-[2-(2-amino-S-chlorothiazol-4-yl)-2-carboxymethoxyiminoacetamido]-3-methylthio-3-cephem-4-carboxylate (syn isomer) or its hydrochloride.

Claim 32

The compound of claim 25, which is 1-propionyloxyethyl 7-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(1-propionyloxyethoxycarbonylmethoxyimino)-acetamido]-3-methylthio-3-cephem-4-carboxylate (syn isomer) or its hydrochloride

Claim 33

A process for preparing a cephem compound of the formula: wherein R is amino substituted thiazolyl which may have halogen(s), protected amino substituted thiazolyl which may have halogen(s), lower alkylamino substituted thiazolyl, amino substituted thiadiazolyl, protected amino substituted thiadiazolyl, amino substituted pyridyl, protected amino substituted pyridyl, furyl, thiazolyl, thiadiazolyl, phenyl, or naphthyl, R 2 is carboxy(lower)alkyl or protected carboxy(lower)alkyl, R 3 is lower alkylthio, and R 4 is carboxy or protected carboxy, or a pharmaceutically acceptable salt thereof, which comprises. i) reacting a compound of the formula: wherein R 3 and R 4 are each as defined above. or its reactive derivative at the amino group or a salt thereof with a compound of the formula: therein R 1 and R 2 are each as defined above, or its reactive derivative at the carboxy group or a salt thereof to give a compound of the formula: wherein R 1 , R 2 , R 3 and R 4 are each as defined above, or a salt thereof, or ii) subjecting a compound of the formula: wherein R 1 , R 3 and R 4 are each as defined above, and R 2 a is protected carboxy(lower)alkyl, or a salt thereof, to elimination reaction of the c arbaxy protective group on R 2 a , to give a compound of the formula: wherein R 1 2 , R 3 and R 4 are each as defined above, and R 2 b is carboxy(lower)alkyl, or a salt thereof, or iii) subjecting a compound of the formula: wherein R 2 , R 3 and R 4 are each as defined above, and R 1 a is protected amino substituted thiazolyl which may have halogen(s), protected amino substituted thiadiazolyl or protected amino substituted pyridyl, or a salt thereof, to elimination reaction of the amino protective group on R 1 a , to give a compound of the formula: wherein R 2 , R 3 and R 4 are each as defined above, and R 1 b is amino substituted thiazolyl which may have halogen(s), amino substituted thiadiazolyl or amino substituted pyridyl, or a salt thereof, or iv) subjecting a compound of the formula: wherein R 1 , R 2 .and R 3 are each as defined above, and R 4 a is protected carboxy, or a salt thereof to elimination reaction of the carboxy protective group on R 4 a to give a compound of the formula: wherein R 1 , R 2 and R 3 are each as defined above, or a.salt thereof, or v) reducing a compound of the formula: wherein R 1 , R 2 , R 3 and R 4 are each as defined above, or a salt thereof, to give a compound of the formula: wherein R 1 , R 2 , R 3 and R 4 are each as defined above, or a salt thereof, or vi) reacting a compound of the formula: wherein R 2 , R 3 and R 4 are each as defined above, and X 1 is halogen, or a salt thereof, with a compound of the formula: wherein R 5 is amino, protected amino or lower alkylamino, to give a compound of the formula: wherein R 2 , R 3 , R 4 and R 5 are each as defined above, or a salt thereof, or vii) subjecting a compound of the formula: wherein R 1 , R and R 3 are each as defined above, or a salt thereof, to esterification, to give a compound of the formula: wherein R 1 , R and R 3 are each as defined above, and R 6 is ester moiety of esterified carboxy represented by a group of the formula: -COOR 6 , or a salt thereof.

Claim 34

A process for preparing a cephem compound of the formula: wherein R is amino substituted thiazolyl which may have halogen(s), protected amino substituted thiazolyl which may have halogen(s), lower alkylamino substituted thiazolyl, amino substituted thiadiazolyl, protected amino substituted thiadiazolyl, amino substituted pyridyl, protected amino substituted pyridyl, furyl, thiazolyl, thiadiazolyl, phenyl, or naphthyl, R 2 is carboxy(lower)alkyl or protected carboxy(lower)alkyl, R 3 is lower alkylthio, and R 4 is carboxy or protected carboxy, or a pharmaceutically acceptable salt thereof, which comprises. i) reacting a compound of the formula: wherein R 3 and R 4 are each as defined above. or its reactive derivative at the amino group or a salt thereof with a compound of the formula: therein R 1 and R 2 are each as defined above, or its reactive derivative at the carboxy group or a salt thereof to give a compound of the formula: wherein R 1 , R 2 , R 3 and R 4 are each as defined above, or a salt thereof, or ii) subjecting a compound of the formula: wherein R 1 , R 3 and R 4 are each as defined above, and R 2 a is protected carboxy(lower)alkyl, or a salt thereof, to elimination reaction of the c arbaxy protective group on R 2 a , to give a compound of the formula: wherein R 1 2 , R 3 and R 4 are each as defined above, and R 2 b is carboxy(lower)alkyl, or a salt thereof, or iii) subjecting a compound of the formula: wherein R 2 , R 3 and R 4 are each as defined above, and R 1 a is protected amino substituted thiazolyl which may have halogen(s), protected amino substituted thiadiazolyl or protected amino substituted pyridyl, or a salt thereof, to elimination reaction of the amino protective group on R 1 a , to give a compound of the formula: wherein R 2 , R 3 and R 4 are each as defined above, and R 1 b is amino substituted thiazolyl which may have halogen(s), amino substituted thiadiazolyl or amino substituted pyridyl, or a salt thereof, or iv) subjecting a compound of the formula: wherein R 1 , R 2 .and R 3 are each as defined above, and R 4 a is protected carboxy, or a salt thereof to elimination reaction of the carboxy protective group on R 4 a to give a compound of the formula: wherein R 1 , R 2 and R 3 are each as defined above, or a.salt thereof, or v) reducing a compound of the formula: wherein R 1 , R 2 , R 3 and R 4 are each as defined above, or a salt thereof, to give a compound of the formula: wherein R 1 , R 2 , R 3 and R 4 are each as defined above, or a salt thereof, or vi) reacting a compound of the formula: wherein R 2 , R 3 and R 4 are each as defined above, and X 1 is halogen, or a salt thereof, with a compound of the formula: wherein R 5 is amino, protected amino or lower alkylamino, to give a compound of the formula: wherein R 2 , R 3 , R 4 and R 5 are each as defined above, or a salt thereof, or vii) subjecting a compound of the formula: wherein R 1 , R and R 3 are each as defined above, or a salt thereof, to esterification, to give a compound of the formula: wherein R 1 , R and R 3 are each as defined above, and R 6 is ester moiety of esterified carboxy represented by a group of the formula: -COOR 6 , or a salt thereof.

Claim 35

A cephem compound of the formula: wherein X is -S- or R is amino substituted thiazolyl which may have halogen(s), protected amino substituted thiazolyl which may have halogen(s), lower alkylamino substituted thiazolyl, amino substituted thiadiazolyl, protected amino substituted thiadiazolyl, amino substituted pyridyl, protected amino substituted pyridyl, furyl, thiazolyl, thiadiazolyl, phenyl, or naphthyl, R 2 is carboxy(lower)alkyl or protected carboxy(lower)alkyl, R 4 is carboxy or protected carboxy, and R 9 is a group of the formula: -O-SO 2 -R 7 (wherein R is lower alkyl or aryl which may have suitable substituent(s)), or lower alkylthio, provided that X is when R 9 is lower alkylthio, and a salt thereof.

Claim 36

A cephem compound of the formula: wherein X is -S- or R is amino substituted thiazolyl which may have halogen(s), protected amino substituted thiazolyl which may have halogen(s), lower alkylamino substituted thiazolyl, amino substituted thiadiazolyl, protected amino substituted thiadiazolyl, amino substituted pyridyl, protected amino substituted pyridyl, furyl, thiazolyl, thiadiazolyl, phenyl, or naphthyl, R 2 is carboxy(lower)alkyl or protected carboxy(lower)alkyl, R 4 is carboxy or protected carboxy, and R 9 is a group of the formula: -O-SO 2 -R 7 (wherein R is lower alkyl or aryl which may have suitable substituent(s)), or lower alkylthio, provided that X is when R 9 is lower alkylthio, and a salt thereof.

Claim 37

A process for preparing a cephem compound of the formula: wherein X is -S- or R is amino substituted thiazolyl which may have halogen(s), protected amino substituted thiazolyl which may have halogen(s), lower alkylamino substituted thiazolyl, amino substituted thiadiazolyl, protected amino substituted thiadiazolyl, amino substituted pyridyl, protected amino substituted pyridyl, furyl, thiazolyl, thiadiazolyl, phenyl, or naphthyl, R 2 is carboxy(lower)alkyl or protected carboxy(lower)alkyl, R 4 is carboxy or protected carboxy, and R 9 is a group of the formula: -0-SO 2 -R 7 (wherein R 7 is lower alkyl or aryl which may have suitable substituent(s)), or lower alkylthio, provided that X is when R 9 is lower alkylthio, or a salt thereof, which comprises i) reacting a compound of the formula: wherein R 4 and R 7 are each as defined above, or its reactive derivative at the amino group or a salt thereof, with a compound of the formula: wherein R 1 and R 2 are each as defined above, or its reactive derivative at the carboxy group or a salt thereof, to give a compound of the formula: wherein R 1 R 2 , R 4 and R 7 are each as defined above, or a salt thereof, or ii) oxidizing a compound of the formula: wherein R 1 , R 2 , R 4 and R 7 are each as defined above, or a salt thereof, to give a compound of the formula: wherein R 1 , R 2 , R 4 and R 7 are each as defined above, or a salt thereof, or iii) reacting a compound of the formula: wherein R 1 , R 2 , R 4 and R 7 are each as defined above, or a salt thereof, with a compound of the formula: R a 3 - SH wherein R a 3 is lower alkyl, or its reactive derivative at the mercapto group, to give a compound of the formula: wherein R 1 , R 2 and R 4 are each as.defined above, and R 3 is lower alkylthio, or a salt thereof.

Claim 38

A process for preparing a cephem compound of the formula: wherein X is -S- or R is amino substituted thiazolyl which may have halogen(s), protected amino substituted thiazolyl which may have halogen(s), lower alkylamino substituted thiazolyl, amino substituted thiadiazolyl, protected amino substituted thiadiazolyl, amino substituted pyridyl, protected amino substituted pyridyl, furyl, thiazolyl, thiadiazolyl, phenyl, or naphthyl, R 2 is carboxy(lower)alkyl or protected carboxy(lower)alkyl, R 4 is carboxy or protected carboxy, and R 9 is a group of the formula: -0-SO 2 -R 7 (wherein R 7 is lower alkyl or aryl which may have suitable substituent(s)), or lower alkylthio, provided that X is when R 9 is lower alkylthio, or a salt thereof, which comprises i) reacting a compound of the formula: wherein R 4 and R 7 are each as defined above, or its reactive derivative at the amino group or a salt thereof, with a compound of the formula: wherein R 1 and R 2 are each as defined above, or its reactive derivative at the carboxy group or a salt thereof, to give a compound of the formula: wherein R 1 R 2 , R 4 and R 7 are each as defined above, or a salt thereof, or ii) oxidizing a compound of the formula: wherein R 1 , R 2 , R 4 and R 7 are each as defined above, or a salt thereof, to give a compound of the formula: wherein R 1 , R 2 , R 4 and R 7 are each as defined above, or a salt thereof, or iii) reacting a compound of the formula: wherein R 1 , R 2 , R 4 and R 7 are each as defined above, or a salt thereof, with a compound of the formula: R a 3 - SH wherein R a 3 is lower alkyl, or its reactive derivative at the mercapto group, to give a compound of the formula: wherein R 1 , R 2 and R 4 are each as.defined above, and R 3 is lower alkylthio, or a salt thereof.

Claim 39

A cephem compound of the formula: wherein R 2 is carboxy(lower)alkyl or protected carboxy(lower)alkyl, R 3 is lower alkylthio, R 4 is carboxy or protected carboxy, and X 1 is halogen, and a salt thereof.

Claim 40

A cephem compound of the formula: wherein R 2 is carboxy(lower)alkyl or protected carboxy(lower)alkyl, R 3 is lower alkylthio, R 4 is carboxy or protected carboxy, and X 1 is halogen, and a salt thereof.

Claim 41

. A process for preparing a cephem compound of the formula: wherein R 2 is carboxy(lower)alkyl or protected carboxy(lower)alkyl, R 3 is lower alkylthio, R 4 is carboxy or protected carboxy, and X 1 is halogen, or a salt thereof, which comprises i) reacting a compound of the formula: wherein R 2 and X 1 are each as defined above, or its reactive derivative at the carboxy group or a salt thereof, with a compound of the formula: wherein R 3 and R 4 are each as defined above, or its reactive derivative at the amino group or a salt thereof, to give a compound of the formula: wherein R 2 , R 3 , R 4 and X 1 are each as defined above, or a salt thereof, or ii) subjecting a compound of the formula: wherein R Z , R 3 and X 1 are each as defined above, and R 4 a is protected carboxy, or a salt thereof, to elimination reaction of the carboxy protective group, to give a compound of the formula: wherein R 2 , R 3 and X 1 are each as defined above, or a salt thereof.

Claim 42

. A process for preparing a cephem compound of the formula: wherein R 2 is carboxy(lower)alkyl or protected carboxy(lower)alkyl, R 3 is lower alkylthio, R 4 is carboxy or protected carboxy, and X 1 is halogen, or a salt thereof, which comprises i) reacting a compound of the formula: wherein R 2 and X 1 are each as defined above, or its reactive derivative at the carboxy group or a salt thereof, with a compound of the formula: wherein R 3 and R 4 are each as defined above, or its reactive derivative at the amino group or a salt thereof, to give a compound of the formula: wherein R 2 , R 3 , R 4 and X 1 are each as defined above, or a salt thereof, or ii) subjecting a compound of the formula: wherein R Z , R 3 and X 1 are each as defined above, and R 4 a is protected carboxy, or a salt thereof, to elimination reaction of the carboxy protective group, to give a compound of the formula: wherein R 2 , R 3 and X 1 are each as defined above, or a salt thereof.

Claim 43

A compound of the formula: wherein R 1 a is 1,2,5-thiadiazolyl or naphthyl, R 2 is carboxy(lower)alkyl or protected carboxy(lower)alkyl, and R 8 is carboxy or protected carboxy, and a salt thereof.

Claim 44

A compound of the formula: wherein R 1 a is 1,2,5-thiadiazolyl or naphthyl, R 2 is carboxy(lower)alkyl or protected carboxy(lower)alkyl, and R 8 is carboxy or protected carboxy, and a salt thereof.

Claim 45

A process for preparing a compound of the formula: wherein R 1 a is 1,2,5-thiadiazolyl or naphthyl, R 2 is carboxy(lower)alkyl or protected carboxy(lower)alkyl, and R 8 is carboxy or protected carboxy or a salt thereof, which comprises reacting a compound of the formula: wherein R 1 a and R 8 are each as defined above, or a salt thereof, with a compound of the formula: wherein R 2 is as defined above, or a salt thereof.

Claim 46

A process for preparing a compound of the formula: wherein R 1 a is 1,2,5-thiadiazolyl or naphthyl, R 2 is carboxy(lower)alkyl or protected carboxy(lower)alkyl, and R 8 is carboxy or protected carboxy or a salt thereof, which comprises reacting a compound of the formula: wherein R 1 a and R 8 are each as defined above, or a salt thereof, with a compound of the formula: wherein R 2 is as defined above, or a salt thereof.

Claim 47

A pharmaceutical composition comprising a compound of claim 1 in association with a pharmaceutically acceptable substantially non-toxic carrier or excipient,

Claim 48

A compound as defined in any of claims 1 to 31, or a pharmaceutically-acceptable salt thereof, for use as a pharmaceutical.

Claim 49

A compound as defined in any of claims 1 to 31, or a pharmaceutically-acceptable salt thereof, for use in the treatment of infectious diseases.