# US 2024/0199677 A1 · Glycosyltransferase inhibitors

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- Number: US 2024/0199677 A1
- Document ID: US20240199677A1
- Status: Published application
- Kind: A1
- Application number: 18/104,297
- Filed: 2023-02-01
- Published: 2024-06-20
- Earliest claimed: 2018-01-12
- Assignees: California Institute of Technology; University of Tennessee Fresearch Foundation
- Applicants: California Institute of Technology; University of Tennessee Fresearch Foundation
- Inventors: William M. Clemons; Michio Kurosu
- Web page: https://patentgrep.com/patent/US20240199677A1

## CPC

- C07H 19/06: Pyrimidine radicals
- A61K 31/7068: having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 31/04: Antibacterial agents
- A61P 35/00: Antineoplastic agents
- C07H 1/00: Processes for the preparation of sugar derivatives
- A61K 31/337: having four-membered rings, e.g. taxol
- A61K 31/7072: having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- 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)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

The present invention relates to methods of treating bacterial infections and cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of at least one compound provided herein.

## Claims

### Claim 1

A compound of Formula I:
or a pharmaceutically acceptable salt thereof;
wherein
R1 is piperazine-O-Ph-O-CF3, piperazine-O-Ph-CF3 or C7 alkyl;
R2 is H or CH3;
X is absent
Y is absent or —(CH2)n—; and
n is 1, 2, or 3.

### Claim 2 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula I is:
R1 is
Y is —CH2—.

### Claim 3 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula I is:

### Claim 4 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula I is:

### Claim 5 (depends on 4)

The compound of claim 4, or a pharmaceutically acceptable salt thereof, wherein the compound has the following stereochemistry:

### Claim 6 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula I is:
R1 is piperazine-O-Ph-O-CF3; and
Y is CH2.

### Claim 7 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula I is:
R1 is C7 alkyl; and
Y is absent.

### Claim 8 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula I is:

### Claim 9 (depends on 8)

The compound of claim 8, or a pharmaceutically acceptable salt thereof, wherein the compound has the following stereochemistry:

### Claim 10 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula I is:

### Claim 11 (depends on 10)

The compound of claim 10, or a pharmaceutically acceptable salt thereof, wherein the compound has the following stereochemistry:

### Claim 12 (depends on 1)

A pharmaceutical composition comprising a compound according to claim 1, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.

### Claim 13 (depends on 1, 12)

A method of treating cancer in an individual in need thereof, comprising administering to the individual a therapeutically effective amount of a compound according to claim 1 or a composition according to claim 12.

### Claim 14 (depends on 13)

The method of claim 13, wherein the method further comprises administering a second compound that is taxol or gemcitabine.

### Claim 15

A process for preparing a compound of Formula III:
comprising reacting a compound of Formula II:
with a copper reagent in the presence of a solvent and a base, and further reacting the compound of Formula II with a protecting group reagent;
wherein
R2 is H or CH3;
PG is a protecting group selected from the group consisting of acetyl (Ac), benzyl (Bn), tert-butyloxycarbonyl (Boc), benzoyl (Bz), carboxybenzyl (Cbz), carbamoyl, 3,4-dimethoxy-benzyl (DMPM), 9-fluorenylmethyloxycarbonyl (Fmoc), p-methoxybenzyl carbonyl (Moz), 4-nitrobenzylsulfonyl (Nos), p-methoxybenzyl (PMB), p-methoxyphenyl (PMP), 4-toluenesulfonyl (Tos), and 2,2,2-trichloroethoxycarbonyl trichloroethyl chloroformyl (Troc); and
the copper reagent is selected from the group consisting of CuSO4, Cu(OAc)2, and CuCl2.

### Claim 16

The process for preparing a composition comprising a compound of Formula V:
comprising reacting a compound of Formula III:
with a compound of Formula IV:
under basic conditions in a solvent;
wherein
R2 is H or CH3;
PG is a protecting group selected from the group consisting of acetyl (Ac), benzyl (Bn), tert-butyloxycarbonyl (Boc), benzoyl (Bz), carboxybenzyl (Cbz), carbamoyl, 3,4-dimethoxy-benzyl (DMPM), 9-fluorenylmethyloxycarbonyl (Fmoc), p-methoxybenzyl carbonyl (Moz), 4-nitrobenzylsulfonyl (Nos), p-methoxybenzyl (PMB), p-methoxyphenyl (PMP), 4-toluenesulfonyl (Tos), and 2,2,2-trichloroethoxycarbonyl trichloroethyl chloroformyl (Troc); and
R3 is selected from the group consisting of OC1-C4 alkyl, tosylate, mesylate, iodo, bromo, chloro, imidazolyl, and triflate.

### Claim 17

The process for preparing a composition comprising a compound of Formula I:
comprising treating a compound of Formula V:
with an acid in a solvent;
wherein:
R1 is piperidinepiperidinyl-O-Ph, wherein Ph is optionally substituted with C1-C4 alkyl or OC1-C4 alkyl, wherein OC1-C4 alkyl is optionally further substituted with 1, 2, or 3 halo;
R2 is H or CH3;
X is absent;
Y is —(CH2)n—;
PG is a protecting group selected from the group consisting of acetyl (Ac), benzyl (Bn), tert-butyloxycarbonyl (Boc), benzoyl (Bz), carboxybenzyl (Cbz), carbamoyl, 3,4-dimethoxy-benzyl (DMPM), 9-fluorenylmethyloxycarbonyl (Fmoc), p-methoxybenzyl carbonyl (Moz), 4-nitrobenzylsulfonyl (Nos), p-methoxybenzyl (PMB), p-methoxyphenyl (PMP), 4-toluenesulfonyl (Tos), and 2,2,2-trichloroethoxycarbonyl trichloroethyl chloroformyl (Troc); and
n is 1.