Mitochondrial activity inhibitors targeting tumoral metabolism
The invention relates to compounds of formula (I) as follows: (I) wherein X 1 and X 2 , identical or different, are NR 5 or a sulfur atom, Y is a group (C 1 -C 10 )alkanediyl, Ar 1 and Ar 2 , identical or different, are an aryl group optionally substituted by one or several groups selected from a halogen atom, a (C 1 -C 6 ) alkyl, —OR 1 , —NR 1 R 2 and —COOR 3 ′ with R 1 and R 2 , independently of each other, are a hydrogen atom, a (C- 1 -C 6 ) alkyl group or a —COR 3 group, R 3 and R 4 ′ independently of each other, are a hydrogen atom or a (C 1 -C 6 ) alkyl group, and R 5 is a hydrogen atom or a (C 1 -C 6 )alkyl group, or a pharmaceutically acceptable salt and/or solvate thereof, in particular for use in cancer treatment.
1. A method for treating a cancer comprising administering to a patient in need thereof an effective amount of a compound of formula (I) as follows:
wherein
X 1 and X 2 , identical or different, are NR 5 or a sulfur atom, and at least one of X 1 and X 2 is a sulfur atom,
Y is a group (C 1 -C 10 ) alkanediyl,
Ar 1 and Ar 2 , identical or different, are each a naphthyl group optionally substituted by one or several groups selected from a halogen atom, a (C 1 -C 6 ) alkyl, —OR 1 , —NR 1 R 2 and —COOR 3 ,
with R 1 and R 2 , independently of each other, are a hydrogen atom, a (C 1 -C 6 ) alkyl group or
a —COR 4 group,
R 3 and R 4 , independently of each other, are a hydrogen atom or a (C 1 -C 6 ) alkyl group, and
R 5 is a hydrogen atom or a (C 1 -C 6 ) alkyl group,
or a pharmaceutically acceptable salt and/or solvate thereof.
2. The method according to claim 1 , wherein Y is a group —(CH 2 ) n — and n is an integer between 1 and 10.
3. The method according to claim 1 , wherein X 1 and X 2 are a sulfur atom.
4. The method according to claim 1 , wherein Ar 1 and Ar 2 are identical.
5. The method according to claim 1 , wherein Ar 1 and/or Ar 2 is an unsubstituted naphthyl group.
6. The method according to claim 1 , wherein the compound of formula (I) is selected from the group consisting of:
and the pharmaceutically acceptable salts and solvates thereof.
7. The method according to claim 1 , wherein the cancer is selected from the group consisting of haematological cancers, lung cancers, cervix cancers, prostate cancer, melanoma and neuroendocrine tumors.
8. The method according to claim 1 , wherein the cancer is a LKB-1 gene-deficient cancer.
9. A method for treating a cancer comprising administering to a patient in need thereof an effective amount of a pharmaceutical composition comprising a compound of formula (I) as defined in claim 1 and at least one pharmaceutically acceptable excipient.
10. The method according to claim 9 , wherein the cancer is selected from the group consisting of haematological cancers, lung cancers, cervix cancers, prostate cancer, melanoma and neuroendocrine tumors.
11. The method according to claim 9 , wherein the cancer is a LKB-1 gene-deficient cancer.
12. A method for inhibiting mitochondrial complex I, comprising administering to a patient in need thereof an effective amount of a compound of formula (I) as follows:
wherein
X 1 and X 2 , identical or different, are NR 5 or a sulfur atom, and at least one of X 1 and X 2 is a sulfur atom,
Y is a group (C 1 -C 10 ) alkanediyl,
Ar 1 and Ar 2 , identical or different, are each a naphthyl group optionally substituted by one or several groups selected from a halogen atom, a (C 1 -C 6 ) alkyl, —OR 1 , —NR 1 R 2 and —COOR 3 ,
with R 1 and R 2 , independently of each other, are a hydrogen atom, a (C 1 -C 6 ) alkyl group or a —COR 4 group,
R 3 and R 4 , independently of each other, are a hydrogen atom or a (C 1 -C 6 ) alkyl group, and
R 5 is a hydrogen atom or a (C 1 -C 6 ) alkyl group,
or a pharmaceutically acceptable salt and/or solvate thereof or a composition comprising said compound of formula (I) and at least one pharmaceutically acceptable excipient.
13. A compound selected from the group consisting of:
and the pharmaceutically acceptable salts and solvates thereof.