# US 2019/0315772 A1 · Glucose uptake inhibitors

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- Number: US 2019/0315772 A1
- Document ID: US20190315772A1
- Status: Published application
- Kind: A1
- Application number: 16/397,043
- Filed: 2019-04-29
- Published: 2019-10-17
- Earliest claimed: 2015-06-26
- Assignees: Kadmon Corporation, LLC
- Applicants: Kadmon Corporation, LLC
- Inventors: Kellen L. Olszewski; Ji-In Kim; Masha V. Poyurovsky; Kevin G. Liu; Anthony Barsotti; Koi Morris
- Web page: https://patentgrep.com/patent/US20190315772A1

## CPC

- C07D 513/04: Ortho-condensed systems
- A61K 31/519: ortho- or peri-condensed with heterocyclic rings
- A61K 31/52: Purines, e.g. adenine
- A61K 31/5377: not condensed and containing further heterocyclic rings, e.g. timolol
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 35/04: specific for metastasis
- C07D 471/04: Ortho-condensed systems
- C07D 473/34: attached in position 6, e.g. adenine
- C07D 487/04: Ortho-condensed systems
- C07D 491/04: Ortho-condensed systems
- C07D 491/048: the oxygen-containing ring being five-membered
- C07D 495/04: Ortho-condensed systems
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- 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

## Abstract

Provided hererin are compounds that modulate glucose uptake activityand are useful for treating cancer, autoimmune diseases, inflammation, infectious diseases, and metabolic diseases. In certain embodiments, the compounds modulate glucose uptake activity by modulating cellular components, including, but not limited to those related to glycolysis and the known transporters/co-transporters of glucose such as GLUT1 and other GLUT family members/alternative hexose transporters. In certain embodiments, the compounds have the structure of formula I: wherein the variables have the values disclosed herein.

## Claims

### Claim at position 1

1-15. (canceled)

### Claim 16

A compound having the formula I:
or a pharmaceutically acceptable salt thereof,
wherein:
A is a group having the formula:
Ring B is a five- or six-membered ring containing 1 or 2 heteroatoms selected from the group consisting of N, O and S;
Ring C is a five- or six-membered aryl or heteroaryl ring containing from 0 to 2 heteroatoms selected from the group consisting of N, O and S;
each R1 is independently selected from the group consisting of halo, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkoxy, C3-C6 cycloalkyl, oxo, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
n is selected from 0, 1, or 2;
each R2 is independently selected from the group consisting of halo, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkoxy, C3-C6 cycloalkyl, oxo, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
m is selected from 0, 1, or 2;
R3 and R4 are H;
D is selected from the group consisting of —O—(CH2)y—C(═O)NR5R6, —O—C(═O)—(CH2)y—NR5R6, —O—(CH2)y—NR5R6, —NH—C(═O)—(CH2)y—NR5R6, —NH—C(═O)—(CH2)y—R7, and —NH—(CH2)y—NR5R6;
y is selected from 1, 2, or 3;
R5 and R6 are independently selected from the group consisting of H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), aryl, aralkyl, heteroaryl, and C3-C6 cycloalkyl,
or R5 and R6 may be taken together with the nitrogen to which they are attached to form a 5- to 6-membered heterocyclic ring having up to 3 heteroatoms selected from N, O, and S, and which is optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkoxy, C3-C6 cycloalkyl, oxo, hydroxy, amino, cyano and C1-C3 perfluoro alkyl; and
R7 is selected from the group consisting of aryl, heteroaryl, and a hetercyclic group.

### Claim 17 (depends on 16)

The compound of claim 16, wherein the sub-structure
is selected from the group consisting of:
wherein X is selected from O and S, and R11 is selected from H and C1 to C6 alkyl,
wherein R is selected from C1-C6 alkyl, and C3-C6 cycloalkyl.

### Claim 18 (depends on 16)

The compound of claim 16, having the formula IIIa:
or a pharmaceutically acceptable salt thereof, wherein:
Ring B is a five- or six-membered ring containing 1 or 2 heteroatoms selected from the group consisting of N, O and S;
each R1 is independently selected from the group consisting of halo, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkoxy, C3-C6 cycloalkyl, oxo, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
n is selected from 0, 1, or 2;
each R2 is independently selected from the group consisting of halo, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkoxy, C3-C6 cycloalkyl, oxo, hydroxy, amino, cyano and C1-C3 perfluoro alkyl;
m is selected from 0, 1, or 2;
R3 and R4 are H;
D is selected from the group consisting of —O—(CH2)y—C(═O)NR5R6, —O—C(═O)—(CH2)y—NR5R6, —O—(CH2)y—NR5R6, —NH—C(═O)—(CH2)y—NR5R6, —NH—C(═O)—(CH2)y—R7, and —NH—(CH2)y—NR5R6;
y is selected from 1, 2, or 3;
R5 and R6 are independently selected from the group consisting of H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, —(C1-C6 alkyl)-O—(C1-C6 alkyl), aryl, aralkyl, heteroaryl, and C3-C6 cycloalkyl,
or R5 and R6 may be taken together with the nitrogen to which they are attached to form a 5- to 6-membered heterocyclic ring having up to 3 heteroatoms selected from N, O, and S, and which is optionally substituted by from 1 to 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkoxy, C3-C6 cycloalkyl, oxo, hydroxy, amino, cyano and C1-C3 perfluoro alkyl; and
R7 is selected from the group consisting of aryl, heteroaryl, and a hetercyclic group.

### Claim 19 (depends on 16)

A pharmaceutical composition comprising the compound of claim 16 and a pharmaceutically acceptable excipient.

### Claim 20 (depends on 19)

A method of inhibiting tumor growth or metastasis comprising administering to a patient in need thereof a therapeutically effect amount of the pharmaceutical composition of claim 19.

### Claim 21 (depends on 19)

A method of inhibiting angiogenesis comprising administering to a patient in need thereof a therapeutically effect amount of the pharmaceutical composition of claim 19.

### Claim 22 (depends on 19)

A method of inhibiting inflammation comprising administering to a patient in need thereof a therapeutically effect amount of the pharmaceutical composition of claim 19.

### Claim 23 (depends on 19)

A method of treating an autoimmune disease comprising administering to a patient in need thereof a therapeutically effect amount of the pharmaceutical composition of claim 19.