# US 11,299,510 B2 · Substituted pyridopyrrolopyrimidine ribonucleosides for therapeutic uses

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- Number: US 11,299,510 B2
- Document ID: US11299510B2
- Status: Granted
- Kind: B2
- Application number: 16/978,093
- Filed: 2019-03-04
- Published: 2021-01-07
- Granted: 2022-04-12
- Earliest claimed: 2018-03-12
- Assignees: Ustav Organicke Chemie A Biochemie Av Cr, V.V.I.; Univerzita Palackeho V Olomouci
- Applicants: Ustav Organicke Chemie A Biochemie Av Cr, V.V.I.; Univerzita Palackeho V Olomouci
- Inventors: Lucia Veselovska; Michal Hocek; Marian Hajduch; Petr Dzubak
- Web page: https://patentgrep.com/patent/US11299510B2

## CPC

- C07H 19/23: Heterocyclic radicals containing two or more heterocyclic rings condensed among themselves or condensed with a common carbocyclic ring system, not provided for in groups C07H19/14 - C07H19/22
- A61P 35/00: Antineoplastic agents
- A61P 35/04: specific for metastasis
- C07H: SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS (derivatives of aldonic or saccharic acids C07C, C07D; aldonic acids, saccharic acids C07C59/105, C07C59/285; cyanohydrins C07C255/16; glycals C07D; compounds of unknown constitution C07G; polysaccharides, derivatives thereof C08B; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; sugar industry C13)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Substituted pyridopyrrolopyrimidine ribonucleosides of general formula I, wherein R is as described in the independent claim, preferably R is selected from the group comprising thiophen-3-yl, furan-2-yl, furan-3-yl, benzofuran-2-yl, methylsulfanyl, methoxy, amino, dimethylamino, methyl; and pharmaceutically acceptable salt thereof, their optical isomers and mixtures of such optical isomers. Compounds according to the invention show strong cytostatic and cytotoxic effects on cell lines of tumor origin in a wide variety of diseases including tumors of different histogenetic origin.

## Claims

### Claim 1

Substituted pyridopyrrolopyrimidine ribonucleosides of general formula I:
wherein
X is a nitrogen atom and Y is a carbon atom; or
X is a carbon atom and Y is a nitrogen atom;
and wherein
R is selected from the group consisting of
C1-C5 alkyl, optionally substituted by at least one substitutent selected from hydroxy, sulfanyl, amino, C1-C5 alkoxy, C1-C5 sulfanyl, C1-C5 alkylamino, and di(C1-C5 alkyl)amino;
C2-C6 alkenyl, optionally substituted by at least one substitutent selected from hydroxy, sulfanyl, amino, C1-C5 alkoxy, C1-C5 sulfanyl, C1-C5 alkylamino, and di(C1-C5 alkyl)amino;
C6-C12 aryl, optionally substituted by at least one substitutent selected from C1-C5 alkyl, hydroxy, sulfanyl, amino, C1-C5 alkoxy, C1-C5 sulfanyl, C1-C5 alkylamino, and di(C1-C5 alkyl)amino;
C4-12 heteroaryl, comprising at least one heteroatom selected from O and S; optionally substituted by at least one substituent selected from C1-C5 alkyl, hydroxy, sulfanyl, amino, C1-C5 alkoxy, C1-C5 sulfanyl, C1-C5 alkylamino, and di(C1-C5 alkyl)amino;
amino,
C1-C5 alkylamino,
di(C1-C5 alkyl)amino,
C1-C5 alkoxy, and
C1-C5 alkylsulfanyl,
and pharmaceutically acceptable salt thereof, their optical isomers and mixtures of such optical isomers, or racemic mixtures.

### Claim 2 (depends on 1)

Substituted pyridopyrrolopyrimidine ribonucleosides of general formula I according to claim 1, where R is selected from the group consisting of amino, C1-C5 alkyl, phenyl, naphthyl, furan-2-yl, furan-3-yl, thiophen-2-yl, thiophen-3-yl, benzofuryl, C1-C5 alkylsulfanyl, C1-C5 alkylamino, di(C1-C5 alkyl)amino, and C1-C5 alkoxy group.

### Claim 3 (depends on 1)

Substituted pyridopyrrolopyrimidine ribonucleosides of general formula I according to claim 1, where R is selected from the group consisting of amino, thiophen-3-yl, furan-2-yl, furan-3-yl, benzofuran-2-yl, methylsulfanyl, methoxy, dimethylamino, methyl and chloro.

### Claim 4 (depends on 1)

Substituted pyridopyrrolopyrimidine ribonucleosides of general formula I according to claim 1, being selected from the following compounds:
4-methyl-9-(β-D-ribofuranosyl)-9H-pyrido[2′,3′:4,5]pyrrolo[2,3-d]pyrimidine
4-amino-9-(β-D-ribofuranosyl)-9H-pyrido[2′,3′:4,5]pyrrolo[2,3-d]pyrimidine
4-(benzofuran-2-yl)-9-(β-D-ribofuranosyl)-9H-pyrido[4′,3′:4,5]pyrrolo[2,3-d]pyrimidine
4-methyl-9-(β-D-ribofuranosyl)-9H-pyrido[4′,3′:4,5]pyrrolo[2,3-d]pyrimidine
4-amino-9-(β-D-ribofuranosyl)-9H-pyrido[4′,3′:4,5]pyrrolo[2,3-d]pyrimidine
4-methoxy-9-(β-D-ribofuranosyl)-9H-pyrido[4′,3′:4,5]pyrrolo[2,3-d]pyrimidine, and
4-(methylsulfanyl)-9-(β-D-ribofuranosyl)-9H-pyrido[4′,3′:4,5]pyrrolo[2,3-d]pyrimidine.

### Claim 5 (depends on 1)

Method of inhibition of pathological cell proliferation of tumor or non-tumor origin, the method comprising the step of administering substituted pyridopyrrolopyrimidine ribonucleosides of general formula I according to claim 1 to a subject in need thereof.

### Claim 6 (depends on 1)

Method of treatment of tumor or cancer diseases, the method comprising the step of administering substituted pyridopyrrolopyrimidine ribonucleosides of general formula I according to claim 1 to a subject in need thereof.

### Claim 7 (depends on 1)

Method of treatment of non-tumor disease associated with cell hyperproliferation, the method comprising the step of administering substituted pyridopyrrolopyrimidine ribonucleosides of general formula I according to claim 1 to a subject in need thereof.

### Claim 8 (depends on 1)

A pharmaceutical composition characterised in that it comprises a therapeutically effective amount of at least one compound of general formula I according to claim 1, and optionally also at least one pharmaceutically acceptable excipient.

### Claim 9 (depends on 8)

Method of inhibition of pathological cell proliferation of tumor or non-tumor origin and/or of treatment of tumor or non tumor or cancer disease associated with cell hyperproliferation, the method comprising the step of administering the pharmaceutical composition according to claim 8 to a subject in need of such treatment.

### Claim 10 (depends on 1)

Method of treatment of tumor or non-tumor or cancer disease associated with cell hyperproliferation, said method comprising the step of administering substituted pyridopyrrolopyrimidine ribonucleosides of general formula I according to claim 1 to a subject in need of such treatment.

### Claim 11 (depends on 1)

Method of treatment of epithelial, mesenchymal or neuroectoderm origin tumors, said method comprising the step of administering substituted pyridopyrrolopyrimidine ribonucleosides of general formula I according to claim 1 to a subject in need of such treatment.