Oligopeptide anticancer and antiviral agents

Claim 2

A compound of the formula I: A-(NHCO).sub.m -Het-(NHCO-Het).sub.n -NH-R-NH-(Het-CONH).sub.n -Het-(CONH).sub.m -A wherein: A is a moiety bearing a positive charge and of a size which does not inhibit binding of said compounds to deoxyribonucleic acid sequences; R is a moiety derived from a residue of carbonic acid or a residue of a dicarboxylic acid selected from the group consisting of: (i) a residue of a dicarboxylic acid of the formula -CO-C p H 2p -CO-where p equals 1 to 16; (ii) a residue of an unsaturated aliphatic dicarboxylic acid of the formula -CO-C p H 2p-2 -CO- where p equals 2 to 16; (iii) a residue of an aromatic dicarboxylic acid; (iv) a residue of a cycloalkane dicarboxylic acid of the formula -CO-C p H 2p-2 -CO- where p equals 3 to 7, and (v) a residue of a cycloalkene dicarboxylic acid of the formula -CO-C p H 2p-4 -CO- where p equals 5 to 7; Het is a five-membered heterocyclic moiety selected from the group consisting of a pyrrole, an imidazole, a triazole, a pyrazole, a thiazole, a thiophene, a furan and an oxazole; n is 1, 2, or 3; and m is 0 or 1 and salts thereof.

Claim 3

A compound of claim 1 wherein A is a moiety selected from the group consisting of an amidine, a guanidine, secondary ammonium salts, tertiary ammonium salts, quaternary ammonium salts, sulfonium salts and phosphonium salts.

Claim 4

A compound of claim 1 wherein Het is an N-alkyl pyrrole with said alkyl group consisting of 1 to 6 carbon atoms.

Claim 5

A compound of claim 1 wherein Het is an N-alkyl imidazole with said alkyl group consisting of 1 to 6 carbon atoms.

Claim 6

A compound of claim 1, wherein Het is an N-alkyl pyrazole with said alkyl group consisting of 1 to 6 carbon atoms.

Claim 7

A compound of claim 1 wherein Het is an N-alkyl triazole with said alkyl group consisting of 1 to 6 carbon atoms.

Claim 8

A compound of claim 1, wherein Het in said formula I is at least two different moieties selected from said group.

Claim 9

A compound of claim 7, wherein at least one Het moiety is an N-alkyl pyrrole which has said alkyl group of 1 to 6 carbon atoms.

Claim 10

A compound of claim 7, wherein at least one Het moiety is an N-alkyl imidazole which has said alkyl group of 1 to 6 carbon atoms.

Claim 11

A compound of claim 7, wherein at least one Het moiety is an N-alkyl triazole which has said alkyl group of 1 to 6 carbon atoms.

Claim 12

A compound of claim 7, wherein at least one Het moiety is an N-alkyl pyrazole which has said alkyl group of 1 to 6 carbon atoms.

Claim 13

A compound of claim 1 wherein R is ##STR15##

Claim 14

A compound of claim 1, wherein R is a residue of a dicarboxylic acid of the formula -CO-C p H 2p -CO-where p equals 1 to 16.

Claim 15

A compound of claim 1, wherein R is a residue of an unsaturated aliphatic dicarboxylic acid of the formula --CO--C p H 2p-2 --CO-- where p equals 2 to

Claim 16

A compound of claim 1, wherein R is a residue of an aromatic dicarboxylic acid.

Claim 17

A compound of claim 1, wherein R is a residue of a cycloalkane dicarboxylic acid of the formula --CO--C p H 2p-2 --CO-- where p equals 3 to 7.

Claim 18

A compound of claim 1, wherein R is a residue of a cycloalkene dicarboxylic acid of the formula --CO--C p H 2p-4 --CO-- where p equals 5 to 7.

Claim 19

A compound of claim 2, wherein A is an amidine of the formula: ##STR16## where p equals 0 to 5 and X is --H; --OH; --NH 2 ; --CH 3 ; --C 2 H 5 ; --C 3 H 7 .

Claim 20

A compound of claim 2, wherein A is an amidine in which nitrogen atoms are in a five-membered cyclic structure.

Claim 21

A compound of claim 2, wherein A is guanidine of the formula: ##STR17## where p equals 0 to 5 and X equals --H; --OH; --NH 2 ; --CH 3 ; --C 2 H 5 ; --C 3 H 7 .

Claim 22

A compound of claim 2 wherein A is a quaternary, tertiary or secondary ammonium salt of the formula: -C.sub.p H.sub.2p -.sup.+ NH.sub.q [Z]X(3-q) wherein p equals 0 to 5 and q equals 0 to 3 and X is an alkyl or alkenyl group consisting of 1 to 3 carbon atoms.

Claim 23

A compound of claim 2 wherein A is a sulfonium salt of the formula: --C.sub.p --H.sub.2p --SXY wherein p equals 0 to 5 and X and Y are alkyl or alkenyl groups of 1 to 3 carbon atoms.

Claim 24

A compound of claim 18, wherein Het is pyrrole and m is 1.

Claim 25

A compound of claim 23, wherein A is ##STR18##

Claim 26

A compound of claim 24, wherein R is -CO(CH 2 ) l CO- and l equals 0 to 16.

Claim 27

A compound of claim 25, wherein l is 2, and n is 1.

Claim 28

A process for producing a compound of the formula: A-(NHCO).sub.m -Het-(NHCO-Het).sub.n -NH-R-NH-(Het-CONH).sub.n -Het-(CONH).sub.m -A wherein: A is a moiety bearing a positive charge and of a size which does not inhibit binding of said compounds to deoxyribonucleic acid sequences; R is a moiety derived from a dicarboxylic acid and selected from group consisting of: (i) a residue of a dicarboxylic acid of the formula --CO--C p H 2p --CO-- where p equals 1 to 16; (ii) a residue of an unsaturated aliphatic dicarboxylic acid of the formula --CO--C p H 2p-2 --CO-- where p equals 2 to 16; (iii) a residue of an aromatic dicarboxylic acid; (iv) a residue of a cycloalkane dicarboxylic acid of the formula --CO--C p H 2p-2 --CO-- where p equals 3 to 7, and (v) a residue of a cycloalkene dicarboxylic acid of the formula --CO--C p H 2p-4 --CO-- where p equals 5 to 7; Het is a five-membered heterocyclic moiety selected from the group consisting of a pyrrole, an imidazole, a triazole, a pyrazole, a thiazole, a thiophene, a furan and an oxazole; n is 1, 2, or 3; and m is 0 or 1 and salts thereof; said process comprising reacting a compound of the formula: B-(NHCO).sub.m -Het-(NHCO-Het).sub.n -NH.sub.2 wherein m and n are as defined above, and B is the same as A or is a group containing nitrile, halogen or sulfide substituent; with a dicarboxylic acid of the formula: X-R-X wherein R is as defined above and X is halogen or imidazolide and converting B to A to form said moiety bearing a positive charge by selecting one of the following reaction conditions: (i) reduction of nitrile to a primary amide followed by protonation; (ii) displacement of said halogen with an amine; or (iii) alkylation of said sulfide with an alkyl halide.

Claim 29

A process for producing a compound of the formula: A-(NHCO).sub.m -Het-(NHCO-Het).sub.n -NH-R-NH-(Het-CONH).sub.n -Het-(CONH).sub.m -A wherein: A is a moiety bearing a positive charge and of a size which does not inhibit binding of said compounds to deoxyribonucleic acid sequences; R is a moiety derived from a dicarboxylic acid and selected from group consisting of: (i) a residue of a dicarboxylic acid of the formula --CO--C p H 2p --CO-- where p equals 1 to 16; (ii) a residue of an unsaturated aliphatic dicarboxylic acid of the formula --CO--C p H 2p-2 --CO-- where p equals 2 to 16; (iii) a residue of an aromatic dicarboxylic acid; (iv) a residue of a cycloalkane dicarboxylic acid of the formula --CO--C p H 2p-2 --CO-- where p equals 3 to 7, and (v) a residue of a cycloalkene dicarboxylic acid of the formula --CO--C p H 2p-4 --CO-- where p equals 5 to 7; Het is a five-membered heterocyclic moiety selected from the group consisting of a pyrrole, an imidazole, a triazole, a pyrazole, a thiazole, a thiophene, a furan and an oxazole; n is 1, 2, or 3; and m is 0 or 1 and salts thereof; said process comprising reacting a compound of the formula: B-(NHCO).sub.m -Het-(NHCO-Het).sub.n -NH.sub.2 wherein m and n are as defined above, and B is the same as A or is a group containing nitrile, halogen or sulfide substituent; with a dicarboxylic acid of the formula: X-R-X wherein R is as defined above and X is halogen or imidazolide and converting B to A to form said moiety bearing a positive charge by selecting one of the following reaction conditions: (i) reduction of nitrile to a primary amide followed by protonation; (ii) displacement of said halogen with an amine; or (iii) alkylation of said sulfide with an alkyl halide.

Claim 30

A process of claim 27, wherein X is a group Cl-C p H 2p , p being equal 0 to 5.

Claim 31

A process of claim 27, wherein B is CN-C p H 2p -, converting B to an amidine hydrochloride salt moiety of ##STR19## by further reacting substituent B with hydrochloric acid in the presence of an alcohol and subsequent treatment with ammonia, p being equal 0 to 5.

Claim 32

A process of claim 27, wherein B is Cl-C p H 2p -, converting B to an ammonium salt of X.sub.(3-q) + NH q -C p H 2p by further reacting B with NH q X.sub.(3-q), p being equal to 0 to 5, q being equal 0 to 3, and X being an alkyl or alkenyl group having 1 to 3 carbon atoms.

Claim 33

A process of claim 27, wherein B is XS-C p H 2p -, converting B to a sulfonium salt of XYS + -C p H 2p - by further reacting B with Y(hal), p being equal 0 to 5, and X and Y being selected from the group consisting of an alkyl and an alkenyl group having 1 to 3 carbon atoms.

Claim 34

A process of claim 27, wherein A is selected from the group consisting of an amidine, a guanidine, secondary ammonium salts, tertiary ammonium salts, quaternary ammonium salts, sulfonium salts and phosphonium salts.

Claim 35

A process of claim 29 for preparing a compound wherein Het is pyrrole and m is 1.

Claim 36

A process of claim 33 for preparing a compound wherein a hydrochloride salt of A is ##STR20## and B is CN-C p H 2p - wherein p is 2.

Claim 37

A process of claim 31 for preparing a compound wherein R is --CO(CH 2 ).sub.[1]l CO-- and l equals 0 to 16.

Claim 38

A process of claim 27, wherein B is a guanidine derivative of the formula: ##STR21## and p equals 0 to 5.

Claim 39

A process of claim 27, wherein B is an amidine derivative of the formula: ##STR22## and p equals 0 to 5.