# US 2022/0033430 A1 · Orally active prodrug of gemcitabine

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- Number: US 2022/0033430 A1
- Document ID: US20220033430A1
- Status: Published application
- Kind: A1
- Application number: 17/296,403
- Filed: 2019-11-22
- Published: 2022-02-03
- Earliest claimed: 2018-11-25
- Assignees: TNT Medical Corporation
- Applicants: TNT Medical Corporation
- Inventors: Xiang Li; Bing Ying Li; Starr Sing Chung Cheng; Andrew Wang
- Web page: https://patentgrep.com/patent/US20220033430A1

## CPC

- C07H 19/06: Pyrimidine radicals
- A61P 35/00: Antineoplastic agents
- 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

The disclosure includes compounds of Formula (I): wherein R1, R2, and R3, are defined herein. Also disclosed is a method for treating a neoplastic disease with these compounds.

## Claims

### Claim 1

A compound of Formula (I), or an N-oxide thereof, or a pharmaceutically acceptable salt, solvate, polymorph, tautomer, stereoisomer, an isotopic form, or a prodrug of said compound of Formula (I) or N-oxide thereof:
wherein
R1 is
in which m is an integer from 1 to 20; and
each of R2, and R3, independently, is

### Claim 2 (depends on 1)

A compound according to claim 1 or an N-oxide thereof, or a pharmaceutically acceptable salt, solvate, polymorph or tautomer thereof, wherein the compound is
(2R,3R,5R)-4,4-difluoro-2-((isobutyryloxy)methyl)-5-(2-oxo-4-(2-propylpentanamido)pyrimidin-1(2H)-yl)tetrahydrofuran-3-yl isobutyrate,
(2R,3R,5R)-4,4-difluoro-2-((isobutyryloxy)methyl)-5-(2-oxo-4-(2-propylpentanamido)pyrimidin-1(2H)-yl)tetrahydrofuran-3-yl L-valinate,
((2R,3R,5R)-3-((L-valyl)oxy)-4,4-difluoro-5-(2-oxo-4-(2-propylpentanamido)pyrimidin-1(2H)-yl)tetrahydrofuran-2-yl)methyl valinate,
((2R,3R,5R)-4,4-difluoro-3-(isobutyryloxy)-5-(2-oxo-4-(2-propylpentanamido)pyrimidin-1(2H)-yl)tetrahydrofuran-2-yl)methyl L-valinate,
(2R,3R,5R)-4,4-difluoro-2-((isobutyryloxy)methyl)-5-(2-oxo-4-(((pentyloxy)carbonyl)amino)pyrimidin-1(2H)-yl)tetrahydrofuran-3-yl L-valinate,
((2R,3R,5R)-4,4-difluoro-3-(isobutyryloxy)-5-(2-oxo-4-(((pentyloxy)carbonyl)amino)pyrimidin-1(2H)-yl)tetrahydrofuran-2-yl)methyl L-valinate,
(2R,3R,5R)-4,4-difluoro-2-((isobutyryloxy)methyl)-5-(2-oxo-4-(((pentyloxy)carbonyl)amino)pyrimidin-1(2H)-yl)tetrahydrofuran-3-yl isobutyrate,
((2R,3R,5R)-3-((L-valyl)oxy)-4,4-difluoro-5-(2-oxo-4-(((pentyloxy)carbonyl)amino)pyrimidin-1(2H)-yl)tetrahydrofuran-2-yl)methyl L-valinate,
(2R,3R,5R)-4,4-difluoro-5-(4-(((hexyloxy)carbonyl)amino)-2-oxopyrimidin-1(2H)-yl)-2-((isobutyryloxy)methyl)tetrahydrofuran-3-yl L-valinate,
(2R,3R,5R)-5-(4-((butoxycarbonyl)amino)-2-oxopyrimidin-1(2H)-yl)-4,4-difluoro-2-((isobutyryloxy)methyl)tetrahydrofuran-3-yl L-valinate,
(2R,3R,5R)-4,4-difluoro-5-(2-oxo-4-(2-propylpentanamido)pyrimidin-1(2H)-yl)-2-((pivaloyloxy)methyl)tetrahydrofuran-3-yl L-valinate,
(2R,3R,5R)-4,4-difluoro-5-(4-(((hexyloxy)carbonyl)amino)-2-oxopyrimidin-1(2H)-yl)-2-((pivaloyloxy)methyl)tetrahydrofuran-3-yl L-valinate.

### Claim 3 (depends on 1)

A pharmaceutical composition comprising a compound of Formula (I) or an N-oxide thereof as defined in claim 1, or a pharmaceutically acceptable salt, solvate, polymorph, tautomer, stereoisomer, an isotopic form, or a prodrug of said compound of Formula (I) or an N-oxide thereof, and a pharmaceutically acceptable diluent or carrier.

### Claim 4 (depends on 1)

A method of treating a neoplastic disease comprising administering to a subject in need thereof an effective amount of a compound of Formula (I) or an N-oxide thereof as defined in claim 1, or a pharmaceutically acceptable salt, solvate, polymorph, tautomer, stereoisomer, an isotopic form, or a prodrug of said compound of Formula (I) or an N-oxide thereof.