# US 8,541,365 B2 · Dendrimeric compounds comprising amino acids, hyperbranched core compound, process for preparation of dendrimeric compounds comprising amino acids and hyperbranched core compound, and use thereof

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- Number: US 8,541,365 B2
- Document ID: US8541365B2
- Status: Granted
- Kind: B2
- Application number: 13/062,186
- Filed: 2009-09-18
- Published: 2011-06-23
- Granted: 2013-09-24
- Earliest claimed: 2008-09-22
- Assignees: Instytut Chemii Organicznej, Polska Akademia Nauk
- Applicants: Zofia Lipkowska; Piotr Polcyn; Andrzej Wojciech Lipkowski
- Inventors: Zofia Lipkowska; Piotr Polcyn; Andrzej Wojciech Lipkowski
- Web page: https://patentgrep.com/patent/US8541365B2

## CPC

- C07C 271/22: to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
- A61P 31/04: Antibacterial agents
- A61P 31/10: Antimycotics
- A61P 35/00: Antineoplastic agents
- C07C 237/06: having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07D 209/16: Tryptamines
- C07D 213/75: Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
- C07D 233/64: with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
- Y02P 20/55: Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- Y02P: CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS

## Abstract

The invention provides dendrimeric compounds of the formula 1 comprising amino acids, wherein n is an integer of 1-4, T is an alkylidene —(CH2)2CONH(CH2)2- group, R2 is an —NH2 group or a moiety of a primary organic amine, and P is an amino acid and/or peptide moiety, wherein at least one hydrogen atom of at least one amino group is optionally replaced by a protective group, and a hyperbranched core compound of the formula 3, wherein T and R2 are as defined above. The invention provides also a process for the preparation of a dendrimeric compound and a hyperbranched core, wherein the process employs addition reactions of alkyl acrylate and a basic amino acid, and use of a hyperbranched core for the preparation of a dendrimeric compound comprising amino acids. The invention provides also use of dendrimeric compounds for the preparation of the medicament for inhibiting growth of bacterial cells, fungi and tumor cells.

## Claims

### Claim 1

Dendrimeric compounds comprising amino acids, of the formula 1
comprising a branched core with four -T-NH— branches, wherein n is an integer from 1 to 4 inclusive, wherein T is an alkylidene group —(CH2)2CONH(CH2)2—, and one R2 branch, wherein R2 is an —NH2 group, or a moiety derived from a primary organic amine molecule, by removing a hydrogen atom from an amino group,
and comprising at least four P terminal fragments, wherein P is an amino acid and/or peptide moiety derived from an amino acid/peptide molecule by removing a hydroxy group from a carboxy group, said amino acid/peptide moiety having at least one hydrogen atom at least one amino group optionally replaced by a protective group.

### Claim 2 (depends on 1)

Compounds according to claim 1, of the formula 2
wherein
n is an integer of from 1 to 4 inclusive
P is a moiety derived from an amino acid molecule with two amino groups, by removing a hydroxy group from a carboxy group, at least one hydrogen atom of at least one amino group being optionally replaced by an R1 substituent selected from the group comprising: fatty alkylcarbonyl, fatty alkenylcarbonyl, alkoxycarbonyl, arylalkoxycarbonyl optionally substituted on the aryl by halo, arylsulfonyl substituted on the aryl by an alkylamino group, a moiety derived from an amino acid molecule with two amino groups, by removing a hydroxy group from a carboxy group, at least one hydrogen atom of at least one amino group being optionally replaced by a substituent selected from the group comprising fatty alkylcarbonyl, fatty alkenylcarbonyl, alkoxycarbonyl, arylalkoxycarbonyl optionally substituted on the aryl by halo, arylsulfonyl substituted on the aryl by an alkylamino group, or a moiety derived from a lysine, ornithine, 2,4-diaminobutyric acid or 2,3-diaminopropionic acid amino acid molecule, by removing a hydroxy group from a carboxy group;
R2 is a substituent independently selected from the group comprising an amino substituent, a substituent derived from an amide or C1-6alkyl ester of a natural amino acid by removing a hydrogen atom from an amino group, a substituent derived from C1-6alkyl ester of a linear or branched chain non-natural C3-6aliphatic amino acid by removing a hydrogen atom from an amino group, as well as a substituent derived by removing a hydrogen atom from an amino group of a tryptamine, benzylamine optionally substituted by alkyl, phenylamine optionally substituted by nitro, aminopyridine, histamine, C5-C22aliphatic amine, aminocoumarin, or cholesterylamine molecule.

### Claim 3 (depends on 2)

Compounds according to claim 2, characterized in that the compounds are in the form of a cationic salt with a pharmaceutically acceptable anion.

### Claim 4 (depends on 3)

Compounds according to claim 3, characterized in that the compounds are in the form of hydrochloride salts.

### Claim 5 (depends on 2)

Compounds according to claim 2, characterized in that:
n is an integer of from 1 to 4 inclusive,
P is a moiety derived from an amino acid molecule, in the D or L form, by removing a hydroxy group from a carboxy group of lysine, ornithine, arginine, 1,4-diaminobutyric acid (DAB), 1,3-diaminopropionic acid (DAP), at least one hydrogen atom of at least one amino group being optionally replaced by an R1 substituent,
R1 is a substituent independently selected from the group comprising a hydrogen atom (H), benzyloxycarbonyl (Z), 2-chlorobenzyloxycarbonyl (2-Cl-Z), 2-bromobenzyloxycarbonyl (2-Br-Z), 2-iodobenzyloxycarbonyl (2-I-Z), t-butyloxycarbonyl (Boc), fatty alkylcarbonyl, fatty alkenylcarbonyl, dansyl (DNS), naphthylsulfonyl, 9-fluorenylmethoxycarbonyl (Fmoc), and moieties derived by removing a hydroxy group from a carboxy group of the following molecules: Lysine (Lys), D-Lysine (D-Lys), Z-Lys, Z-D-Lys, Lys-(ε-Z), D-Lys-(ε-Z), (2-Cl-Z)-Lys, (2-Cl-Z)-D-Lys, Lys-(ε-2-Cl-Z), D-Lys-(ε-2-Cl-Z), DNS-(Lys), Lys-(ε-DNS), or Z-Arg, Z-D-Arg, (2-Cl-Z)-Arg, (2-Cl-Z)-D-Arg, Lys-(Z)Lys[Lys-(Z)], D-Lys-(Z)Lys[D-Lys-(Z)], Lys-(Z)Orn[Lys-(Z)], D-Lys-(Z)Orn[D-Lys-(Z)], Z-Lys-Lys-[Z-Lys], Z-Lys-D-Lys-[Z-Lys], Z-D-Lys-Lys-[Z-D-Lys], Z-D-Lys-D-Lys-[Z-D-Lys],
derivatives with analogous sequences, wherein the starting lysine moiety is replaced by an ornithine moiety (Orn),
derivatives with analogous sequences, wherein the starting lysine moiety is replaced by a 2,4-diaminobutyric acid (DAB) moiety,
derivatives with analogous sequences, wherein the starting lysine moiety is replaced by a 2,4-diaminopropionic acid (DAP) moiety,
Z-Arg-Lys[Z-Arg], Z-D-Arg-Lys[Z-D-Arg], Z-Arg-Orn[Z-Arg], Z-D-Arg-Orn[Z-D-Arg], Z-Arg-D-Lys-[Z-Arg], Z-D-Arg-D-Lys[Z-D-Arg], Z-Arg-D-Orn-[Z-Arg], Z-D-Arg-D-Orn[Z-D-Arg], (2-Cl-Z)-Arg-Lys[(2-Cl-Z)-Arg], (2-Cl-Z)-D-Arg-Lys[(2-Cl-Z)-D-Arg], (2-Cl-Z)-Arg-Orn[(2-Cl-Z)-Arg], (2-Cl-Z)-D-Arg-Orn[(2-Cl-Z)-D-Arg], (2-Cl-Z)-Arg-D-Lys-[(2-Cl-Z)-Arg], (2-Cl-Z)-D-Arg-D-Lys[(2-Cl-Z)-D-Arg], (2-Cl-Z)-Arg-D-Orn-[(2-Cl-Z)-Arg], (2-Cl-Z)-D-Arg-D-Orn[(2-Cl-Z)-D-Arg],
R2 is a substituent independently selected from the group comprising an amino substituent, a substituent derived from an amide or C1-6alkyl ester of Phe, D-Phe, Tyr, D-Tyr, Ala, D-Ala, Gly, Ile, D-Ile, L and D-Trp by removing a hydrogen atom from an amino group, a substituent derived from C1-6alkyl ester of a linear C3-6aliphatic amino acid by removing a hydrogen atom from an amino group, as well as a substituent derived by removing a hydrogen atom from an amino group of a tryptamine, methylbenzylamine, benzylamine, nitrophenylamine, phenylamine, aminopyridine, histamine, C5-C22aliphatic amine, 7-aminocoumarin, cholesterylamine, or glucosamine molecule.

### Claim 6 (depends on 5)

Compounds according to claim 5, which compounds are selected from the group consisting of:
the compound of the formula 2, wherein n is 4, P—R1 is Nα-2-chlorobenzyloxy-carbonyl-L-Arg and R2 is a 3-aminopyridine moiety C5H4N—NH—, with the L-configuration on the chiral carbon atom linked to the —C(O)R2 group,
the compound of the formula 2, wherein n is 3, P—R1 is Nε-2-chlorobenzyloxy-carbonyl-L-Lys and R2 is a tryptamine moiety C8H6N—CH2—CH2—NH—, with the L-configuration on the chiral carbon atom linked to the —C(O)R2 group, in a hydrochloride salt form,
the compound of the formula 2, wherein n is 3, P—R1 is Nα-2-chlorobenzyloxy-carbonyl-L-Lys and R2 is a tryptamine moiety C8H6N—CH2—CH2—NH—, with the L-configuration on the chiral carbon atom linked to the —C(O)R2 group, in a hydrochloride salt form,
the compound of the formula 2, wherein n is 2, P—R1 is Nα-2-chlorobenzyloxy-carbonyl-L-Lys and R2 is a tryptamine moiety C8H6N—CH2—CH2—NH—, with the L-configuration on the chiral carbon atom linked to the —C(O)R2 group, in a hydrochloride salt form,
the compound of the formula 2, wherein n is 2, P—R1 is Nε-2-chlorobenzyloxy-carbonyl-L-Lys and R2 is a tryptamine moiety C8H6N—CH2—CH2—NH—, with the L-configuration on the chiral carbon atom linked to the —C(O)R2 group, in a hydrochloride salt form,
the compound of the formula 2, wherein n is 3, P—R1 is Nα-2-chlorobenzyloxy-carbonyl-L-Lys and R2 is a tryptamine moiety C8H6N—CH2—CH2—NH—, with the L-configuration on the chiral carbon atom linked to the —C(O)R2 group, in a hydrochloride salt form,
the compound of the formula 2, wherein n is 1, P—R1 is Nα-2-chlorobenzyloxy-carbonyl-L-Lys and R2 is a tryptamine moiety C8H6N—CH2—CH2—NH—, with the L-configuration on the chiral carbon atom linked to the —C(O)R2 group, in a hydrochloride salt form,
the compound of the formula 2, wherein n is 4, P—R1 is Nα-2-chlorobenzyloxy-carbonyl-L-Lys and R2 is a tryptamine moiety C8H6N—CH2—CH2—NH—, with the L-configuration on the chiral carbon atom linked to the —C(O)R2 group, in a hydrochloride salt form,
the compound of the formula 2, wherein n is 4, P—R1 is Nα-benzyloxycarbonyl-L-Lys and R2 is a tryptamine moiety C8H6N—CH2—CH2—NH—, with the L-configuration on the chiral carbon atom linked to the —C(O)R2 group, in a hydrochloride salt form,
the compound of the formula 2, wherein n is 4, P—R1 is Nε-benzyloxycarbonyl-L-Lys and R2 is a tryptamine moiety C8H6N—CH2—CH2—NH—, with the L-configuration on the chiral carbon atom linked to the —C(O)R2 group, in a hydrochloride salt form,
the compound of the formula 2, wherein n is 4, P—R1 is Nα-2-bromobenzyloxy- carbonyl-L-Lys and R2 is a tryptamine moiety C8H6N—CH2—CH2—NH—, with the L-configuration on the chiral carbon atom linked to the —C(O)R2 group, in a hydrochloride salt form,
the compound of the formula 2, wherein n is 4, P—R1 is Nα-benzyloxycarbonyl-L-DAP and R2 is a tryptamine moiety C8H6N—CH2—CH2—NH—, with the L-configuration on the chiral carbon atom linked to the —C(O)R2 group, in a hydrochloride salt form,
the compound of the formula 2, wherein n is 4, P—R1 is Nα-2-chlorobenzyloxy-carbonyl-L-Orn and R2 is a tryptamine moiety C8H6N—CH2—CH2—NH—, with the L-configuration on the chiral carbon atom linked to the —C(O)R2 group, in a hydrochloride salt form,
the compound of the formula 2, wherein n is 3, P—R1 is Nα-2-chlorobenzyloxy-carbonyl-L-Lys and R2 is a histamine moiety C3H3N2—CH2—CH2—NH—, with the L-configuration on the chiral carbon atom linked to the —C(O)R2 group, in a hydrochloride salt form,
the compound of the formula 2, wherein n is 3, P—R1 is Nε-2-chlorobenzyloxycarbonyl -L-Lys and R2 is a histamine moiety C3H3N2—CH2—CH2—NH—, with the L-configuration on the chiral carbon atom linked to the —C(O)R2 group, in a hydrochloride salt form, and
the compound of the formula 2, wherein n is 3, P—R1 is Nα-2-chlorobenzyloxy-carbonyl-L-Lys and R2 is a dodecylamine moiety C12H25NH—, with the L-configuration on the chiral carbon atom linked to the —C(O)R2 group, in a hydrochloride salt form.

### Claim 7

A hyperbranched core compound, of the formula 3
comprising four -T-NH2 branches, wherein n is an integer from 1 to 4 inclusive, wherein T is an alkylidene —(CH2)2CONH(CH2)2—group, and one R2 branch, wherein R2 is an —NH2 group or a moiety derived from a primary organic amine molecule, by removing a hydrogen atom from an amino group.

### Claim 8 (depends on 7)

The compound according to claim 7, of the formula 4
wherein
n is an integer of from 1 to 4 inclusive
R2 is a substituent independently selected from the group comprising an —NH2 group, a substituent derived from an amide or C1-6alkyl ester of a natural amino acid by removing a hydrogen atom from an amino group, a substituent derived from C1-6alkyl ester of a linear or branched chain non-natural C3-6aliphatic amino acid by removing a hydrogen atom from an amino group, as well as a substituent derived by removing a hydrogen atom from an amino group of a tryptamine, benzylamine optionally substituted by alkyl, phenylamine optionally substituted by nitro, aminopyridine, histamine, C5-C22aliphatic amine, aminocoumarin, cholesterylamine, or glucosamine molecule.

### Claim 9 (depends on 8)

Compound according to claim 8, wherein
R2 is a substituent independently selected from the group comprising an —NH2 group, a substituent derived from an amide or C1-6alkyl ester of Phe, D-Phe, Tyr, D-Tyr, Ala, D-Ala, Gly, lle, D-lle, L and D-Trp by removing a hydrogen atom from an amino group, a substituent derived from C1-6alkyl ester of a linear C3-6aliphatic amino acid by removing a hydrogen atom from an amino group, as well as a substituent derived by removing a hydrogen atom from an amino group of a tryptamine, methylbenzylamine, benzylamine, nitrophenylamine, phenylamine, aminopyridine, histamine, C5-C22aliphatic amine, 7-aminocoumarin, cholesterylamine, or glucosamine molecule.

### Claim 10

A process for the preparation of the dendrimeric compound comprising amino acids, characterized in that the process comprises reacting an amino acid compound, in the D, L form or a mixture of the D and L forms, of the formula 5
wherein n is an integer of from 1 to 4 inclusive,
with C1-6 alkyl acrylate, optionally in the presence of a base, to yield a compound of the formula 6
followed by reacting the obtained compound of the formula 6, after optional acidification, with a primary organic amine or ammonia and the first coupling reagent to obtain an amide derivative of the formula 7
which derivative of the formula 7 is subjected to aminolysis with ethylenediamine, to yield a branched core compound of the formula 3
followed by coupling the compound of the formula 3, wherein T is —(CH2)2CONH(CH2)2-, and R2 is an —NH2 group or a moiety derived from a primary organic amine molecule by removing a hydrogen atom from an amino group, with an amino acid and/or peptide, wherein at least one hydrogen atom at least one amino group is optionally replaced by a protective group, in the presence of a second coupling reagent, to obtain a compound of the formula 1
wherein R2 and T have meanings as disclosed above, and P is an amino acid and/or peptide moiety derived from an amino acid/peptide molecule by removing a hydroxy group from a carboxy group, in which amino acid/peptide moiety at least one hydrogen atom of at least one amino group is optionally replaced by a protective group,
optionally deprotecting the protected amino group and optionally converting into a pharmaceutically acceptable salt.

### Claim 11 (depends on 10)

The process according to claim 10, characterized in that the compound of the formula 2 is obtained,
wherein
P is a moiety derived from an amino acid molecule, in the D or L form, by removing a hydroxy group from a carboxy group of lysine, ornithine, arginine, 1,4-diaminobutyric acid (DAB), 1,3-diaminopropionic acid (DAP), at least one hydrogen atom of at least one amino group being optionally replaced by an R1 substituent,
R1 is a substituent independently selected from the group comprising a hydrogen atom (H), benzyloxycarbonyl (Z), 2-chlorobenzyloxycarbonyl (2-Cl-Z), 2-bromo-benzyloxycarbonyl (2-Br-Z), 2-iodobenzyloxycarbonyl (2-I-Z), t-butyloxycarbonyl (Boc), fatty alkylcarbonyl, fatty alkenylcarbonyl, dansyl (DNS), naphthylsulfonyl, 9-fluorenylmethoxycarbonyl (Fmoc), and moieties derived by removing a hydroxy group from a carboxy group of the following molecules: Lysine (Lys), D-Lysine (D-Lys), Z-Lys, Z-D-Lys, Lys-(ε-Z), D-Lys-(ε-Z), (2-Cl-Z)-Lys, (2-Cl-Z)-D-Lys, Lys-(ε-2-Cl-Z), D-Lys-(ε-2-Cl-Z), DNS-(Lys), Lys-(ε-DNS), or Z-Arg, Z-D-Arg, (2-Cl-Z)-Arg, (2-Cl-Z)-D-Arg, Lys-(Z)Lys[Lys-(Z)], D-Lys-(Z)Lys[D-Lys-(Z)], Lys-(Z)Orn[Lys-(Z)], D-Lys-(Z)Orn[D-Lys-(Z)], Z-Lys-Lys-[Z-Lys], Z-Lys-D-Lys-[Z-Lys], Z-D-Lys-Lys-[Z-D-Lys], Z-D-Lys-D-Lys-[Z-D-Lys],
derivatives with analogous sequences wherein the starting lysine moiety is replaced by an ornithine moiety (Orn),
derivatives with analogous sequences wherein the starting lysine moiety is replaced by a 2,4-diaminobutyric acid (DAB) moiety,
derivatives with analogous sequences wherein the starting lysine moiety is replaced by a 2,4-diaminopropionic acid (DAP) moiety,
Z-Arg-Lys[Z-Arg], Z-D-Arg-Lys[Z-D-Arg], Z-Arg-Orn[Z-Arg], Z-D-Arg-Orn[Z-D-Arg], Z-Arg-D-Lys-[Z-Arg], Z-D-Arg-D-Lys[Z-D-Arg], Z-Arg-D-Orn-[Z-Arg], Z-D-Arg-D-Orn[Z-D-Arg], (2-Cl-Z)-Arg-Lys[(2-Cl-Z)-Arg], (2-Cl-Z)-D-Arg-Lys[(2-Cl-Z)-D-Arg], (2-Cl-Z)-Arg-Orn[(2-Cl-Z)-Arg], (2-Cl-Z)-D-Arg-Orn[(2-Cl-Z)-D-Arg], (2-Cl-Z)-Arg-D-Lys-[(2-Cl-Z)-Arg], (2-Cl-Z)-D-Arg-D-Lys[(2-Cl-Z)-D-Arg], (2-Cl-Z)-Arg-D-Orn-[(2-Cl-Z)-Arg], (2C1-Z)-D-Arg-D-Orn[(2-Cl-Z)-D-Arg],
R2 is a substituent independently selected from the group comprising an amino substituent, a substituent derived from an amide or C1-6alkyl ester of Phe, D-Phe, Tyr, D-Tyr, Ala, D-Ala, Gly, lle, D-lle, L and D-Trp by removing a hydrogen atom from an amino group, a substituent derived from C1-6alkyl ester of a linear C3-6aliphatic amino acid by removing a hydrogen atom from an amino group, as well as a substituent derived by removing a hydrogen atom from an amino group of a tryptamine, methylbenzylamine, benzylamine, nitrophenylamine, phenylamine, aminopyridine, histamine, C5-C22aliphatic amine, 7-aminocoumarin, cholesterylamine, or glucosamine molecule.

### Claim 12 (depends on 11)

The process according to claim 11, characterized in that the first coupling reagent is a combination of N,N′-dicyclohexylcarbodiimide (DCC) and N-hydroxysuccinimide, and the second coupling reagent is a combination of N,N′-dicyclohexylcarbodiimide (DCC) and N-hydroxysuccinimide.

### Claim 13 (depends on 11)

The process according to claim 11, characterized in that the reaction of the amino acid compound of the formula 5 with C1-6alkyl acrylate is carried out in the presence of an alcoholic solvent.

### Claim 14 (depends on 13)

The process according to claim 13, characterized in that the reaction is carried out at 60-90° C., for 24-48 hours.

### Claim 15

A process for the preparation of a hyperbranched core compound, characterized in that the process comprises reacting an amino acid compound, in the D, L form or a mixture of the D and L forms, of the formula 5
wherein n is an integer of from 1 to 4 inclusive,
with C1-6alkyl acrylate, optionally in the presence of a base, to yield a compound of the formula 6
followed by reacting the obtained compound of the formula 6, after optional acidification, with a primary organic amine or ammonia and a coupling reagent, to obtain an amide derivative of the formula 7
which derivative of the formula 7 is subjected to aminolysis with ethylenediamine, to yield a branched core compound of the formula 3
wherein T is —(CH2)2CONH(CH2)2-, and R2 is an —NH2 group or a moiety derived from a primary organic amine molecule by removing a hydrogen atom from an amino group.

### Claim 16 (depends on 15)

The process according to claim 15, characterized in that a compound of the formula 4 is obtained
wherein
n is an integer of from 1 to 4 inclusive
R2 is a substituent independently selected from the group comprising an —NH2 group, a substituent derived from an amide or C1-6alkyl ester of Phe, D-Phe, Tyr, D-Tyr, Ala, D-Ala, Gly, lle, D-ll e, L and D-Trp by removing a hydrogen atom from an amino group, a substituent derived from C1-6alkyl ester of a linear C3-6aliphatic amino acid by removing a hydrogen atom from an amino group, as well as a substituent derived by removing a hydrogen atom from an amino group of a tryptamine, methylbenzylamine, benzylamine, nitrophenylamine, phenylamine, aminopyridine, histamine, C5-C22aliphatic amine, 7-aminocoumarin, cholesterylamine, or glucosamine molecule.

### Claim 17 (depends on 16)

The process according to claim 16, characterized in that the coupling reagent is a combination of N,N′-dicyclohexylcarbodiimide (DCC) and N-hydroxysuccinimide.

### Claim 18 (depends on 16)

The process according to claim 16, characterized in that the reaction of the amino acid compound of the formula 5 with C1-6alkyl acrylate is carried out in the presence of an alcoholic solvent.

### Claim 19 (depends on 18)

The process according to claim 18, characterized in that the reaction is carried out at 60-90° C., for 24-48 hours.

### Claim 20 (depends on 1)

A method for the treatment of a human or animal body with a dendrimeric compound comprising amino acids, the method comprising the administration of a medicament for bacterial cell growth inhibition, the medicament comprising the dendrimeric compound comprising amino acids of the formula 1 according to claim 1.

### Claim 21 (depends on 20)

The method according to claim 20, characterized in that the dendrimeric compound of the formula 2 is used
wherein
n is an integer of from 1 to 4 inclusive
P is a moiety derived from an amino acid molecule with two amino groups, by removing a hydroxy group from a carboxy group, at least one hydrogen atom of at least one amino group being optionally replaced by an R1 substituent selected from the group comprising: fatty alkylcarbonyl, fatty alkenylcarbonyl, alkoxycarbonyl, arylalkoxycarbonyl optionally substituted on the aryl by halo, arylsulfonyl substituted on the aryl by an alkylamino group, a moiety derived from an amino acid molecule with two amino groups, by removing a hydroxy group from a carboxy group, at least one hydrogen atom of at least one amino group being optionally replaced by a substituent selected from the group comprising fatty alkylcarbonyl, fatty alkenylcarbonyl, alkoxycarbonyl, arylalkoxycarbonyl optionally substituted on the aryl by halo, arylsulfonyl substituted on the aryl by an alkylamino group, or a moiety derived from a lysine, ornithine, 2,4-diaminobutyric acid or 2,3-diaminopropionic acid amino acid molecule, by removing a hydroxy group from a carboxy group;
R2 is a substituent independently selected from the group comprising an amino substituent, a substituent derived from an amide or C1-6alkyl ester of a natural amino acid by removing a hydrogen atom from an amino group, a substituent derived from C1-6alkyl ester of a linear or branched chain non-natural C3-6aliphatic amino acid by removing a hydrogen atom from an amino group, as well as a substituent derived by removing a hydrogen atom from an amino group of a tryptamine, benzylamine optionally substituted by alkyl, phenylamine optionally substituted by nitro, aminopyridine, histamine, C5-C22aliphatic amine, aminocoumarin, or cholesterylamine molecule.

### Claim 22 (depends on 21)

The method according to claim 21, characterized in that the compound of the formula 2 is used in the form of a cationic salt with a pharmaceutically acceptable anion, especially in the form of the hydrochloride salt.

### Claim 23 (depends on 21)

The method according to claim 21, characterized in that the compound of the formula 2 is used, wherein:
n is an integer of from 1 to 4 inclusive,
P is a moiety derived from an amino acid molecule, in the D or L form, by removing a hydroxy group from a carboxy group of lysine, ornithine, arginine, 1,4-diaminobutyric acid (DAB), 1,3-diaminopropionic acid (DAP), at least one hydrogen atom of at least one amino group being optionally replaced by an R1 substituent,
R1 is a substituent independently selected from the group comprising a hydrogen atom (H), benzyloxycarbonyl (Z), 2-chlorobenzyloxycarbonyl (2-Cl-Z), 2-bromobenzyloxycarbonyl (2-Br-Z), 2-iodobenzyloxycarbonyl (2-1-Z), t-butyloxycarbonyl (Boc), fatty alkylcarbonyl, fatty alkenylcarbonyl, dansyl (DNS), naphthylsulfonyl, 9-fluorenylmethoxycarbonyl (Fmoc), and moieties derived by removing a hydroxy group from a carboxy group of the following molecules: Lysine (Lys), D-Lysine (D-Lys), Z-Lys, Z-D-Lys, Lys-(ε-Z), D-Lys-(ε-Z), (2-Cl-Z)-Lys, (2-Cl-Z)-D-Lys, Lys-(ε-2-Cl-Z), D-Lys-(ε-2-Cl-Z), DNS-(Lys), Lys-(ε-DNS), or Z-Arg, Z-D-Arg, (2-Cl-Z)-Arg, (2-Cl-Z)-D-Arg, Lys-(Z)Lys[Lys-(Z)], D-Lys-(Z)Lys[D-Lys-(Z)], Lys-(Z)Orn[Lys-(Z)], D-Lys-(Z)Orn[D-Lys-(Z)], Z-Lys-Lys-[Z-Lys], Z-Lys-D-Lys-[Z-Lys], Z-D-Lys-Lys-[Z-D-Lys], Z-D-Lys-D-Lys-[Z-D-Lys],
derivatives with analogous sequences wherein the starting lysine moiety is replaced by an ornithine moiety (Orn),
derivatives with analogous sequences wherein the starting lysine moiety is replaced by a 2,4-diaminobutyric acid (DAB) moiety,
derivatives with analogous sequences wherein the starting lysine moiety is replaced by a 2,4-diaminopropionic acid (DAP) moiety,
Z-Arg-Lys[Z-Arg], Z-D-Arg-Lys[Z-D-Arg], Z-Arg-Orn[Z-Arg], Z-D-Arg-Orn[Z-D-Arg], Z-Arg-D-Lys-[Z-Arg], Z-D-Arg-D-Lys[Z-D-Arg], Z-Arg-D-Orn-[Z-Arg], Z-D-Arg-D-Orn[Z-D-Arg], (2-Cl-Z)-Arg-Lys[(2-Cl-Z)-Arg], (2-Cl-Z)-D-Arg-Lys[(2-Cl-Z)-D-Arg], (2-Cl-Z)-Arg-Orn[(2-Cl-Z)-Arg], (2-Cl-Z)-D-Arg-Orn[(2-Cl-Z)-D-Arg], (2-Cl-Z)-Arg-D-Lys-[(2-Cl-Z)-Arg], (2-Cl-Z)-D-Arg-D-Lys[(2-Cl-Z)-D-Arg], (2-Cl-Z)-Arg-D-Orn-[(2-Cl-Z)-Arg], (2C1-Z)-D-Arg-D-Orn[(2-Cl-Z)-D-Arg],
R2 is a substituent independently selected from the group comprising an amino substituent, a substituent derived from an amide or C1-6alkyl ester of Phe, D-Phe, Tyr, D-Tyr, Ala, D-Ala, Gly, lle, D-lle, L and D-Trp by removing a hydrogen atom from an amino group, a substituent derived from C1-6alkyl ester of a linear C3-6aliphatic amino acid by removing a hydrogen atom from an amino group, as well as a substituent derived by removing a hydrogen atom from an amino group of a tryptamine, methylbenzylamine, benzylamine, nitrophenylamine, phenylamine, aminopyridine, histamine, C5-C22aliphatic amine, 7-aminocoumarin, cholesterylamine, or glucosamine molecule.

### Claim 24 (depends on 23)

The method according to claim 23, characterized in that the compound is selected from the group consisting of:
the compound of the formula 2, wherein n is 4, P—R1 is Nα-2-chlorobenzyloxy-carbonyl-L-Arg and R2 is a 3-aminopyridine moiety C5H4N—NH—, with the L-configuration on the chiral carbon atom linked to the —C(O)R2 group,
the compound of the formula 2, wherein n is 3, P—R1 is Nε-2-chlorobenzyloxy-carbonyl-L-Lys and R2 is a tryptamine moiety C8H6N—CH2—CH2—NH—, with the L-configuration on the chiral carbon atom linked to the —C(O)R2 group, in a hydrochloride salt form,
the compound of the formula 2, wherein n is 3, P—R1 is Nα-2-chlorobenzyloxy-carbonyl-L-Lys and R2 is a tryptamine moiety C8H6N—CH2—CH2—NH—, with the L-configuration on the chiral carbon atom linked to the —C(O)R2 group, in a hydrochloride salt form,
the compound of the formula 2, wherein n is 2, P—R1 is Nα-2-chlorobenzyloxy-carbonyl-L-Lys and R2 is a tryptamine moiety C8H6N—CH2—CH2—NH—, with the L-configuration on the chiral carbon atom linked to the —C(O)R2 group, in a hydrochloride salt form,
the compound of the formula 2, wherein n is 2, P—R1 is Nε-2-chlorobenzyloxy-carbonyl-L-Lys and R2 is a tryptamine moiety C8H6N—CH2—CH2—NH—, with the L-configuration on the chiral carbon atom linked to the —C(O)R2 group, in a hydrochloride salt form,
the compound of the formula 2, wherein n is 3, P—R1 is Nα-2-chlorobenzyloxy-carbonyl-L-Lys and R2 is a tryptamine moiety C8H6N—CH2—CH2—NH—, with the L-configuration on the chiral carbon atom linked to the —C(O)R2 group, in a hydrochloride salt form,
the compound of the formula 2, wherein n is 1, P—R1 is Nα-2-chlorobenzyloxy-carbonyl-L-Lys and R2 is a tryptamine moiety C8H6N—CH2—CH2—NH—, with the L-configuration on the chiral carbon atom linked to the —C(O)R2 group, in a hydrochloride salt form,
the compound of the formula 2, wherein n is 4, P—R1 is Nα-2-chlorobenzyloxycarbonyl-L-Lys and R2 is a tryptamine moiety C8H6N—CH2—CH2—NH—, with the L-configuration on the chiral carbon atom linked to the —C(O)R2 group, in a hydrochloride salt form,
the compound of the formula 2, wherein n is 4, P—R1 is Nα-benzyloxycarbonyl-L-Lys and R2 is a tryptamine moiety C8H6N—CH2—CH2—NH—, with the L-configuration on the chiral carbon atom linked to the —C(O)R2 group, in a hydrochloride salt form,
the compound of the formula 2, wherein n is 4, P—R1 is Nε-benzyloxycarbonyl-L-Lys and R2 is a tryptamine moiety C8H6N—CH2—CH2—NH—, with the L-configuration on the chiral carbon atom linked to the —C(O)R2 group, in a hydrochloride salt form,
the compound of the formula 2, wherein n is 4, P—R1 is Nα-2-bromobenzyloxy-carbonyl-L-Lys and R2 is a tryptamine moiety C8H6N—CH2—CH2—NH—, with the L-configuration on the chiral carbon atom linked to the —C(O)R2 group, in a hydrochloride salt form,
the compound of the formula 2, wherein n is 4, P—R1 is Nα-benzyloxycarbonyl-L-DAP and R2 is a tryptamine moiety C8H6N—CH2—CH2—NH—, with the L-configuration on the chiral carbon atom linked to the —C(O)R2 group, in a hydrochloride salt form, the compound of the formula 2, wherein n is 4, P—R1 is Nα-2-chlorobenzyloxy-carbonyl-L-Orn and R2 is a tryptamine moiety C8H6N—CH2—CH2—NH—, with the L-configuration on the chiral carbon atom linked to the —C(O)R2 group, in a hydrochloride salt form, the compound of the formula 2, wherein n is 3, P—R1 is Nα-2-chlorobenzyloxy-carbonyl-L-Lys and R2 is a histamine moiety C3H3N2—CH2—CH2—NH—, with the L-configuration on the chiral carbon atom linked to the —C(O)R2 group, in a hydrochloride salt form, the compound of the formula 2, wherein n is 3, P—R1 is Nε-2-chlorobenzyloxy-carbonyl-L-Lys and R2 is a histamine moiety C3H3N2—CH2—CH2—NH—, with the L-configuration on the chiral carbon atom linked to the —C(O)R2 group, in a hydrochloride salt form, and the compound of the formula 2, wherein n is 3, P—R1 is Nα-2-chlorobenzyloxy-carbonyl-L-Lys and R2 is a dodecylamine moiety C12H25NH—, with the L-configuration on the chiral carbon atom linked to the —C(O)R2 group, in a hydrochloride salt form.

### Claim 25 (depends on 7)

A method for the preparation of macromolecular dendrimeric compounds comprising amino acids, the method comprising the step of coupling the hyperbranched core compound of the formula 3 according to claim 7 with an amino acid and/or peptide.

### Claim 26 (depends on 25)

The method according to claim 25, characterized in that the hyperbranched core compound is a compound of the formula 4
wherein
n is an integer of from 1 to 4 inclusive
R2 is a substituent independently selected from the group comprising an —NH2 group, a moiety derived from an amide or C1-6alkyl ester of a natural amino acid by removing a hydrogen atom from an amino group, a substituent derived from C1-6alkyl ester of a linear or branched chain non-natural C3-6aliphatic amino acid, as well as a substituent derived by removing a hydrogen atom from an amino group of a tryptamine, benzylamine optionally substituted by alkyl, phenylamine optionally substituted by nitro, aminopyridine, histamine, C5-C22aliphatic amine, aminocoumarin, cholesterylamine, or glucosamine molecule.

### Claim 27 (depends on 26)

The method according to claim 26, characterized in that the compound of the formula 4 is used, wherein
R2 is a substituent independently selected from the group comprising an —NH2 group, a substituent derived from an amide or C1-6alkyl ester of Phe, D-Phe, Tyr, D-Tyr, Ala, D-Ala, Gly, lle, D-lle, L and D-Trp by removing a hydrogen atom from an amino group, a substituent derived from C1-6alkyl ester of a linear C3-6aliphatic amino acid by removing a hydrogen atom from an amino group, as well as a substituent derived by removing a hydrogen atom from an amino group of a tryptamine, methylbenzylamine, benzylamine, nitrophenylamine, phenylamine, aminopyridine, histamine, C5-C22aliphatic amine, aminocoumarin, cholesterylamine, or glucosamine molecule.

### Claim 28 (depends on 6)

A method for the treatment of a human or animal body with a dendrimeric compound comprising amino acids, the method comprising the administration of a medicament for melanoma cell growth inhibition, the medicament comprising the dendrimeric compound comprising amino acids of the formula 1 according to claim 6, and wherein the dendrimeric compound is selected from the group consisting of:
the compound of the formula 2, wherein n is 3, P—R1 is Nα-2-chlorobenzyloxycarbonyl-L-Lys and R2 is a tryptamine moiety C8H6N—CH2—CH2—NH—, with the L-configuration on the chiral carbon atom linked to the —C(O)R2 group, in a hydrochloride salt form;
the compound of the formula 2, wherein n is 4, P—R1 is Nα-2-chlorobenzyloxycarbonyl-L-Lys and R2 is a tryptamine moiety C8H6N—CH2—CH2—NH—, with the L-configuration on the chiral carbon atom linked to the —C(O)R2 group, in a hydrochloride salt form; and
the compound of the formula 2, wherein n is 3, P—R1 Nα-2-chlorobenzyloxycarbonyl-L-Lys and R2 is a dodecylamine moiety C12H25NH—, with the L-configuration on the chiral carbon atom linked to the —C(O)R2 group, in a hydrochloride salt form.