Dipeptide derivatives, processes for preparing them, pharmaceutical composition and use

Claim 2

A dipeptide derivative of the general formula: (wherein m is an integer of 1 to 8; n is 0 or an integer of 1 to 6; R 1 is hydrogen atom; R 2 is hydrogen atom, a branched alkyl group having 3 to 5 carbon atoms, phenyl group, hydroxyphenyl group or methylthio group, or R 1 and R 2 together represent a single bond between carbon atom and nitrogen atom; and R 3 represents a lower alkyl ester group, hydroxymethyl group or formyl group; provided that when n is 0, R 2 represents one of said groups except hydrogen atom).

Claim 3

A dipeptide derivative according to Claim 1, which is expressed by the general formula: (wherein m is an integer of 1 to 8; n is 0 or an integer of 1 to 6; R 4 is hydrogen atom, a branched alkyl group having 3 to 5 carbon atoms, phenyl group, hydroxyphenyl group or methylthio group, and R 3 is a lower alkyl ester group, hydroxymethyl group or formyl group; provided that when n is 0, R 4 represents one of said groups except hydrogen atom}.

Claim 4

A dipeptide derivative according to Claim 1, which is expressed by the general formula: (wherein m is an integer of 1 to 8; and R 3 is a lower alkyl ester group, hydroxymethyl group or formyl group).

Claim 5

A dipeptide derivative according to Claim 2, wherein, in said -(CH 2 ) n -R 4 group, when n is an integer of 1 to 6 , R 4 is hydrogen atom, a branched alkyl group having 3 to 5 carbon atoms, phenyl group, hydroxyphenyl group or methylthio group; and when n is 0, R 4 is a branched alkyl group having 3 to 5 carbon atoms.

Claim 6

A dipeptide derivative according to any of Claims 1 to 3, wherein R 3 is methoxycarbonyl group, ethoxycarbonyl group, propoxycarbonyl group, isopropoxycarbonyl group, butoxycarbonyl group, sec-butoxycarbonyl group, t-butoxycarbonyl group, hydroxymethyl group or formyl group.

Claim 7

A process for producing a dipeptide derivative of the general formula: , (wherein m is an integer of 1 to 8; n is 0 or an integer of 1 to 6; R1 is hydrogen atom; R 2 is hydrogen atom, a branched alkyl group having 3 to 5 carbon atoms, phenyl group, hydroxyphenyl group or methylthio group, or R 1 and R 2 together represent a single bond between carbon atom and nitrogen atom; and R 3 represents a lower alkyl ester group, hydroxymethyl group or formyl group; provided that when n is 0, R 2 represents one of said groups except hydrogen atom), said process comprising the steps of i) reacting a carboxylic acid, acid halide or acid anhydride having the general formula: (wherein m has the same meaning as defined above and A is hydroxyl group, a halogen atom or a group: (wherein m has the same meaning as defined above)) with a peptide ester derivative of the general formula: (wherein n, R 1 and R 2 are as defined above; and B is a lower alkyl group), in the presence of a base to obtain an acyl peptide ester of the general formula: (wherein m, n, R 1 , R 2 and B , respectively, have the same meanings as defined above); and ii) if necessary, reducing the compound so produced to give a compound of the formula (1) in which R represents -CH 2 OH, and iii) if necessary, oxidizing the compound so produced to give a compound of the formula (1) in which R 3 represents -CHO.

Claim 8

A process for producing a dipeptide derivative of the general formula: , (wherein m is an integer of 1 to 8; n is 0 or an integer of 1 to 6; R1 is hydrogen atom; R 2 is hydrogen atom, a branched alkyl group having 3 to 5 carbon atoms, phenyl group, hydroxyphenyl group or methylthio group, or R 1 and R 2 together represent a single bond between carbon atom and nitrogen atom; and R 3 represents a lower alkyl ester group, hydroxymethyl group or formyl group; provided that when n is 0, R 2 represents one of said groups except hydrogen atom), said process comprising the steps of i) reacting a carboxylic acid, acid halide or acid anhydride having the general formula: (wherein m has the same meaning as defined above and A is hydroxyl group, a halogen atom or a group: (wherein m has the same meaning as defined above)) with a peptide ester derivative of the general formula: (wherein n, R 1 and R 2 are as defined above; and B is a lower alkyl group), in the presence of a base to obtain an acyl peptide ester of the general formula: (wherein m, n, R 1 , R 2 and B , respectively, have the same meanings as defined above); and ii) if necessary, reducing the compound so produced to give a compound of the formula (1) in which R represents -CH 2 OH, and iii) if necessary, oxidizing the compound so produced to give a compound of the formula (1) in which R 3 represents -CHO.

Claim 9

A process according to Claim 6, wherein said dipeptide derivative has the general formula: (wherein m is an integer of 1 to 8; n is 0 or an integer of 1 to 6; R 4 is hydrogen atom, a branched alkyl group having 3 to 5 carbon atoms, phenyl group, hydroxyphenyl group or methylthio group; and R 3 is a lower alkyl ester group, hydroxymethyl group or formyl group; provided that when n is 0, R 4 represents one of said groups except hydrogen atom).

Claim 10

A process according to Claim 6, wherein said dipeptide derivative has the general formula: (wherein m is an integer of 1 to 8; and R 3 is a Lower alkyl ester group, hydroxymethyl group or formyl group).

Claim 11

A process according to any of Claims 6 to 8, wherein said base is trialkylamine, aqueous alkali metal hydroxide, or alkali metal carbonate.

Claim 12

A pharmaceutical composition containing a dipeptide derivative of the following formula as an active ingredient: (wherein m is an integer of 1 to 8; n is 0 or an integer of 1 to 6; R 1 is hydrogen atom; R 2 is hydrogen atom, a branched alkyl group having 3 to 5 carbon atoms, phenyl group, hydroxyphenyl group or methylthio group, or R 1 and R 2 together represent a single bond between carbon atom and 3 nitrogen atom; and R represents a lower alkyl ester group, hydroxymethyl group or formyl group; provided that when n is 0, R 2 represents one of said groups except hydrogen atom), together with an acceptable carrier.

Claim 13

A pharmaceutical composition containing a dipeptide derivative of the following formula as an active ingredient: (wherein m is an integer of 1 to 8; n is 0 or an integer of 1 to 6; R 1 is hydrogen atom; R 2 is hydrogen atom, a branched alkyl group having 3 to 5 carbon atoms, phenyl group, hydroxyphenyl group or methylthio group, or R 1 and R 2 together represent a single bond between carbon atom and 3 nitrogen atom; and R represents a lower alkyl ester group, hydroxymethyl group or formyl group; provided that when n is 0, R 2 represents one of said groups except hydrogen atom), together with an acceptable carrier.

Claim 14

Use of a dipeptide derivative of the general formula: (wherein m is an integer of 1 to 8; n is 0 or an integer of 1 to 6; R 1 is hydrogen atom; R 2 is hydrogen atom, a branched alkyl group having 3 to 5 carbon atoms, phenyl group, hydroxyphenyl group or methylthio groups or R 1 and R 2 together represent a single bond between carbon atom and nitrogen atom; and R 3 represents a lower alkyl ester group, hydromethyl group or formyl group; provided that when n is 0, R 2 represents one of said groups except hydrogen atom), for the preparation of a medicament for the prevention and treatment of amnesia.

Claim 15

Use of a dipeptide derivative of the general formula: (wherein m is an integer of 1 to 8; n is 0 or an integer of 1 to 6; R 1 is hydrogen atom; R 2 is hydrogen atom, a branched alkyl group having 3 to 5 carbon atoms, phenyl group, hydroxyphenyl group or methylthio groups or R 1 and R 2 together represent a single bond between carbon atom and nitrogen atom; and R 3 represents a lower alkyl ester group, hydromethyl group or formyl group; provided that when n is 0, R 2 represents one of said groups except hydrogen atom), for the preparation of a medicament for the prevention and treatment of amnesia.