Enzyme interacting agents

Patent metadata

Field	Value
Publication number	US-9828351-B2
Application number	US-201515321693-A
Country	US
Kind code	B2
Filing date	Jun 26, 2015
Priority date	Jun 26, 2014
Publication date	Nov 28, 2017
Grant date	Nov 28, 2017

Abstract

The present disclosure relates generally, but not exclusively, to compounds and their use as enzyme interacting agents, in particular, agents which interact with one or more enzymes in the sphingolipid biosynthesis pathway. The disclosure further relates to the use of such compounds as research tools, use in therapy, to compositions and agents comprising said compounds, and to methods of treatment using said compounds.

First claim

The invention claimed is:

1. A compound of Formula (I);

wherein
Q is a 5-membered heteroaromatic ring having 2 or 3 ring heteroatoms, at least one of which must be N and the remaining selected from N, O and S, selected from the group consisting of;

L is a bivalent linker group selected from —NH—, and —*NH—CH 2 —, wherein the linker atom labelled * is bonded to Q;
R a is selected from hydrogen, halo, haloalkyl, haloalkoxy, alkyl, alkoxy, alkoxyalkyl, alkoxyalkoxy, carbocyclyl, carbocyclylalkyl, carbocyclyloxy, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, aryl, arylalkyl, heteroaryl, heteroarylalkyl, aryloxy or heteroaryloxy, and wherein each of carbocyclyl, carbocyclylalkyl, carbocyclyloxy, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, aryl, arylalkyl, heteroaryl, heteroarylalkyl, aryloxy or heteroaryloxy may be optionally substituted;
A is C—R b ,
wherein R b is C(═NR c )NHR d ;
wherein R c and R d are independently selected from hydrogen, hydroxy, alkyl, aryl, heteroaryl, carbocyclyl, heterocyclyl or acyl, each of which may be optionally substituted; or a pharmaceutically acceptable salt or solvate thereof.

2. The compound according to claim 1 wherein Q contains 2 ring heteroatoms.

3. The compound according to claim 1 wherein Q contains 3 ring heteroatoms.

4. The compound according to claim 3 wherein Q has at least 2 nitrogen ring atoms.

5. The compound according to claim 4 wherein Q is an oxadiazolyl group.

6. The compound according to claim 5 wherein Q is 1,3,4-oxadiazolyl.

7. The compound according to claim 1 wherein L is —NH—.

8. The compound according to claim 1 wherein R a is selected from hydrogen, halo (chloro, fluoro, bromo, iodo), C 1-6 alkyl, haloC 1-6 alkyl, C 1-6 alkoxy, haloC 1-6 alkoxy, C 1-6 alkoxy C 1-6 alkyl, C 1-6 alkoxy C 1-6 alkoxy, C 3-6 cycloalkyl, C 3-6 cycloalkylC 1-6 alkyl, C 3-6 cycloalkoxy, phenyl, phenylC 1-6 alkyl, 5-6 membered heterocyclyl, and 5-6 membered heteroaryl.

9. A composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable additive.

10. A method of inhibiting undesirable cell proliferation in a subject in need thereof comprising administering to said subject, a compound according to claim 1 , or a pharmaceutically acceptable salt or solvate thereof.

11. A method of treating a fibrotic disease in a subject in need thereof comprising administering to said subject, a compound according to claim 1 , or a pharmaceutically acceptable salt or solvate thereof.

12. A method of treating a disease or condition in which excessive or undesirable sphingolipid enzyme activity is implicated in a subject in need thereof comprising administering to said subject, a compound according to claim 1 , or a pharmaceutically acceptable salt or solvate thereof.

13. A method of inhibiting undesirable cell proliferation in a subject in need thereof comprising administering to said subject an amount of a compound according to claim 1 , or a pharmaceutically acceptable salt or solvate thereof effective to inhibit undesirable cell proliferation.

14. A method of treating a fibrotic disease in a subject in need thereof comprising administering to said subject an amount of a compound according to claim 1 , or a pharmaceutically acceptable salt or solvate thereof effective to treat said fibrotic disease.

15. The compound according to claim 1 wherein L is —*NH—CH 2 —.

16. The compound of claim 1 wherein R b is selected from C(═NH)NH 2 and C(═NH—OH)NH 2 .

17. The compound according to claim 1 selected from the group consisting of:

Assignees

• Univ Monash
• Univ South Australia
• Central Adelaide Local Health Network Incorporated

Inventors

• Flynn Bernard Luke
• Aurelio Luigi
• Scullino Carmen Vittoria
• Wang Bing Hui
• Pitson Stuart Maxwell
• Pitman Melissa Rose

Classifications

• A61P35/04

  specific for metastasis · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07D277/56

  Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen · CPC title

• C07D271/06

  1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles · CPC title