# US 10,501,428 B2 · Thymoquinone derivatives for treatment of cancer

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- Number: US 10,501,428 B2
- Document ID: US10501428B2
- Status: Granted
- Kind: B2
- Application number: 15/502,944
- Filed: 2014-08-09
- Published: 2017-11-23
- Granted: 2019-12-10
- Earliest claimed: 2014-08-09
- Assignees: United Arab Emirates University
- Applicants: United Arab Emirates University
- Inventors: Alaa Eldin Salem; Ismail El Haty; Ibrahim Abdou; Abdu Adem; Samir Attoub
- Web page: https://patentgrep.com/patent/US10501428B2

## CPC

- C07D 295/13: to an acyclic saturated chain
- A61K 31/122: having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
- A61K 31/5375: 1,4-Oxazines, e.g. morpholine
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 35/00: Antineoplastic agents
- C07C 221/00: Preparation of compounds containing amino groups and doubly-bound oxygen atoms bound to the same carbon skeleton
- C07C 225/28: of non-condensed quinone rings
- 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
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS

## Abstract

The present invention describes thymoquinone compounds formula (I): (i) These compounds have been identified as being useful in the treatment of cancer.

## Claims

### Claim 1

A compound of formula (I)
or a pharmaceutically acceptable salt or solvate thereof, wherein
R1 and R2 are selected from CH3 and isopropyl, wherein R1 and R2 are different;
X is NR3R4, wherein:
R3 is selected from H or —(CH2)2—OH; and
R4 is selected from H or —(C1-C4alkyl)R5, wherein:
R5 is selected from:
a) —OH,
b) phenyl substituted by 1-3 substituents independently selected from —CF3, —F, —OCH3, —NH2 and —SO2NH2,
c) a 5 or 6 membered heterocyclic ring having 1 or 2 hetero atoms selected from O and N, and wherein the heterocyclic ring is optionally substituted by 1-2 substituents independently selected from —OH and CH3,
d) a ring system having the formula of:
and
e) NR6R7, wherein:
R6 is selected from H or CH3; and
R7 is selected from CH3, phenyl, and a ring system having the formula of:
wherein the ring system is optionally substituted by 1-2 substituent of CH3; and
Y is H,
wherein R3 and R4 are not both H.

### Claim 2 (depends on 1)

A pharmaceutical composition comprising the compound of formula (I) according to claim 1 and a pharmaceutically acceptable diluent or carrier, wherein the pharmaceutical composition is in the form of a tablet, capsule, pill, powder, solution, suspension, or emulsion.

### Claim 3 (depends on 1)

The compound of claim 1, wherein R3 is H.

### Claim 4 (depends on 1)

The compound of claim 1, wherein R4 is (C1-C4alkyl)R5 and R5 is selected from:
a) —OH,
b) phenyl substituted by 1-3 substituents independently selected from —CF3, —F, —OCH3, —NH2 and —SO2NH2,
c) a 5 or 6 membered heterocyclic ring selected from morpholinyl, pyranyl, piperidinyl, pyrrolidinyl, piperazinyl, pyridinyl, and pyrimidinyl, wherein the heterocyclic ring is optionally substituted by 1-2 substituents independently selected from —OH and CH3,
d) a ring system having the formula of:
and
e) NR6R7, wherein:
R6 is selected from H or CH3; and
R7 is selected from CH3, phenyl, and a ring system having the formula of:
wherein the ring system is optionally substituted by 1-2 substituent of CH3.

### Claim 5 (depends on 1)

The compound of claim 1 wherein R4 is H or —(C1-C2alkyl)R5, wherein R5 is selected from OH, morpholinyl and phenyl substituted with 1 or 2 substituents selected from —CF3, —F and —OCH3.

### Claim 6 (depends on 1)

The compound of claim 1, wherein R1 is CH3 and R2 is isopropyl.

### Claim 7 (depends on 1)

The compound of claim 1, wherein the compound is selected from the group consisting of:
5-Isopropyl-2-methyl-3-((2-morpholinoethyl)amino)-1,4-benzoquinone;
5-Isopropyl-2-methyl-3-(4-trifluoromethylbenzylamino)-1,4-benzoquinone;
5-Isopropyl-2-methyl-3-(4-fluorobenzylamino)-1,4-benzoquinone;
5-Isopropyl-2-methyl-3-(3,5-ditrifluoromethylbenzylamino)-1,4-benzoquinone;
5-isopropyl-2-methyl-3-(2-hydroxyethylamino)-1,4-benzoquinone; and
5-isopropyl-2-methyl-3-(3,4-dimethoxylbenzylamino)-1,4-benzoquinone.