Purine derivatives as drugs for the treatment of neonatal hypoxia-ischemia brain injury and related diseases

1 . A method for treating non-traumatic acquired brain injury, wherein the brain injury is caused by oxygen deficiency, in an individual in need thereof, comprising administering an effective amount of a compound of formula (I)

in which

M represents a NR 1 R 2 group or an OR 1 group,

A represents a NR 4 R 5 group,

R 1 is an aryl group, or a —CH 2 -aryl group, said aryl being optionally substituted with one or more substituents independently chosen from a halogen atom, a CF 3 group, an OR 6 group, an aryl group, a heteroaryl group and a (C 1 -C 6 )alkyl group,

R 2 is a (C 1 -C 6 )alkyl group,

R 6 and R 7 represent independently of each other a hydrogen atom or a (C 1 -C 6 )alkyl group,

R 3 is a (C 1 -C 6 )alkyl group, a (C 3 -C 6 )cycloalkyl group, or a —CH 2 -aryl group,

R 4 is a hydrogen atom or a (C 1 -C 6 )alkyl group,

R 5 is a (C 1 -C 8 )alkyl group or a (C 3 -C 6 )cycloalkyl group, said alkyl and cycloalkyl group being substituted with one or more substituents independently chosen from a hydroxyl group, and a —OCOR a group,

R a represents a (C 1 -C 6 )alkyl group, said alkyl group being substituted by an amino group,

or alternatively R 4 and R 5 may form with the nitrogen atom bearing them a heterocycloalkyl group, said heterocycloalkyl group being selected from the group consisting of morpholinyl, piperidinyl, pyrrolidinyl, piperazinyl and homopiperazinyl groups, and being optionally substituted by one or more substituents independently chosen from a (C 1 -C 4 )alkyl group, a NR 6 R 7 group and a halogen atom,

or an addition salt with a pharmaceutically acceptable acid.

2 . The method according to claim 1 , wherein

M represents a NR 1 R 2 group, and said NR 1 R 2 radical is chosen from the following radicals:

or an addition salt with a pharmaceutically acceptable acid.

3 . The method according to claim 1 , wherein

A represents a NR 4 R 5 group,

R 4 is a hydrogen atom,

R 5 is a (C 1 -C 8 ) alkyl group, said alkyl group being substituted with one or more substituents independently chosen from, a hydroxyl group and a —OCOR a group,

R a represents a (C 1 -C 6 )alkyl group, said alkyl group being substituted by an amino group,

or alternatively R 4 and R 5 may form with the nitrogen atom bearing them a heterocycloalkyl group, said heterocycloalkyl group being selected from the group consisting of morpholinyl, piperidinyl, pyrrolidinyl, piperazinyl and homopiperazinyl groups, and being optionally substituted by one or more substituents independently chosen from a (C 1 -C 4 )alkyl group, a NR 6 R 7 group and a halogen atom, and

R 6 and R 7 represent independently of each other a hydrogen atom or a (C 1 -C 6 )alkyl group,

or an addition salt with a pharmaceutically acceptable acid.

4 . The method according to claim 1 , wherein

A represents a group a NR 4 R 5 group selected from the following radicals

or an addition salt with a pharmaceutically acceptable acid.

5 . The method according to claim 1 , wherein the compound is selected from compound 13, 14, 15, 18, 20, 23, 26, 31, 38 and Aftin-5 as defined herein after

No

Structure

13

14

15

18

20

23

26

31

38

Aftin-5

6 . The method according to claim 1 , wherein the brain injury is caused by hypoxic brain injury/anoxic brain injury, hypoxia-ischemia, hypoxic-ischemic encephalopathy, diffuse cerebral hypoxia, focal cerebral ischemia, cerebral infarction, and global cerebral ischemia.

7 . The method according to claim 1 , wherein the non-traumatic acquired brain injury is a hypoxic injury.

8 . The method according to claim 7 , wherein the non-traumatic acquired brain injury is a neonatal encephalopathy, including neonatal hypoxia-ischemia and neonatal hypoxic-ischemic encephalopathy.

9 . The method according to claim 1 , wherein said compound of formula (I) decreases and/or repairs the brain injury lesions.