Pyrrolo[3,2-c]pyridine-6-amino derivatives

Patent metadata

Field	Value
Publication number	US-10501462-B2
Application number	US-201616064297-A
Country	US
Kind code	B2
Filing date	Dec 20, 2016
Priority date	Dec 21, 2015
Publication date	Dec 10, 2019
Grant date	Dec 10, 2019

Abstract

The present invention relates to novel pyrrolo[3,2-c]pyridine-6-amino derivatives that inhibit the spindle checkpoint function of Monospindle 1 (Mps1—also known as TTK) kinases. In particular, the present invention relates to isopropyl 6-(2-methoxy-4-(1-methyl-1H-1,2,3-triazol-5-yl)phenylamino)-2-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[3,2-c]pyridine-1-carboxylate and isopropyl 6-(2-methoxy-4-(1-methyl-1H-tetrazol-5-yl)phenylamino)-2-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[3,2-c]pyridine-1-carboxylate and their use as therapeutic agents for the treatment and/or prevention of proliferative diseases, such as cancer. The present invention also relates to processes for the preparation of these compounds and to pharmaceutical compositions comprising them.

First claim

The invention claimed is:

1. A compound which is one of the following:
isopropyl 6-(2-methoxy-4-(1-methyl-1H-1,2,3-triazol-5-yl)phenylamino)-2-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[3,2-c]pyridine-1-carboxylate; or
isopropyl 6-(2-methoxy-4-(1-methyl-1H-tetrazol-5-yl)phenylamino)-2-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[3,2-c]pyridine-1-carboxylate;
or a pharmaceutically acceptable salt or solvate thereof.

2. A compound which is:
isopropyl 6-(2-methoxy-4-(1-methyl-1H-1,2,3-triazol-5-yl)phenylamino)-2-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[3,2-c]pyridine-1-carboxylate
or a pharmaceutically acceptable salt or solvate thereof.

3. A compound which is:
isopropyl 6-(2-methoxy-4-(1-methyl-1H-tetrazol-5-yl)phenylamino)-2-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[3,2-c]pyridine-1-carboxylate
or a pharmaceutically acceptable salt or solvate thereof.

4. A pharmaceutical composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable excipient.

5. A method of treating a proliferative disorder in a patient in need of such treatment, said method comprising administering to said patient a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt or solvate thereof, according to claim 1 , wherein the proliferative disorder is breast, ovarian, lung or colon cancer.

6. A method of synthesising a compound according to claim 1 , the method comprising:
a) reacting an intermediate of formula A:

wherein LG is a suitable leaving group;
with an intermediate of formula B:

wherein x is N or CH; and
optionally thereafter:
i) removing any protecting groups present; and/or
ii) forming a pharmaceutically acceptable salt or solvate thereof.

7. The method of claim 5 , wherein the compound is isopropyl 6-(2-methoxy-4-(1-methyl-1H-1,2,3-triazol-5-yl)phenylamino)-2-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[3,2-c]pyridine-1-carboxylate or a pharmaceutically acceptable salt or solvate thereof.

8. The method of claim 5 , wherein the compound is isopropyl 6-(2-methoxy-4-(1-methyl-1H-tetrazol-5-yl)phenylamino)-2-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[3,2-c]pyridine-1-carboxylate or a pharmaceutically acceptable salt or solvate thereof.

9. The method of claim 6 , wherein the compound is isopropyl 6-(2-methoxy-4-(1-methyl-1H-1,2,3-triazol-5-yl)phenylamino)-2-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[3,2-c]pyridine-1-carboxylate or a pharmaceutically acceptable salt or solvate thereof.

10. The method of claim 6 , wherein the compound is isopropyl 6-(2-methoxy-4-(1-methyl-1H-tetrazol-5-yl)phenylamino)-2-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[3,2-c]pyridine-1-carboxylate or a pharmaceutically acceptable salt or solvate thereof.

Assignees

• Cancer Research Tech Ltd

Inventors

• Naud Sebastien Gaston Andre
• Blagg Julian

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• C07D471/04 Primary

  Ortho-condensed systems · CPC title