Tropane urea derivatives, preparation thereof and therapeutic application thereof as modulators of the activity of 11betaHSD1
The invention relates to tropane urea derivatives of general formula (I) and to the application thereof as modulators of the activity of 11β-hydroxysteroid dehydrogenose type 1 (11βHSD1).
1. A compound corresponding to formula (I)
in which
A is a bond or an —O—(CH 2 ) n — group with n being a number equal to 0 or 1,
D is a bond or an oxygen atom,
G is a carbon or nitrogen atom,
Ar1 is an aryl or heteroaryl group,
Ar2 is an aryl or heteroaryl or heterocycloalkyl group,
R1 is a hydrogen atom, or a (C1-C6)alkyl, —SO 2 —(C1-C6)alkyl, —SO 2 -halo(C1-C6)alkyl, (C1-C6)alkoxy or —Si(alkyl) 3 group,
R2 is a hydrogen atom or a hydroxyl group or, when G is a nitrogen atom, R2 is absent,
R3 is a hydroxyl or —C(O)-NH 2 group,
in the form of a base or of an addition salt with an acid.
2. A compound of formula (I) as claimed in claim 1 , wherein the substituents of the Ar1 group are in the para-position with respect to one another.
3. A compound of formula (I) as claimed in claim 1 , wherein the substituents of the Ar2 group are in the para-position with respect to one another.
4. A compound of formula (I) as claimed in claim 1 , wherein G is a carbon atom.
5. A compound of formula (I) as claimed in claim 1 , wherein G is a nitrogen atom.
6. A compound of formula (I) as claimed in claim 1 , wherein R3 is —C(O)—NH 2 .
7. A process for preparing a compound of formula (I) as claimed in claim 1 , wherein a compound of formula (IV):
in which A, D, G, Ar1, Ar2, R1 and R2 are as defined in claim 1 and Lg is a leaving group, is reacted with a compound of formula (V):
in which R3 is as defined in claim 1 ,
in the presence of a solvent and of a base.
8. A pharmaceutical composition, comprising the compound of formula (I) as claimed in claim 1 or a pharmaceutically acceptable salt, and at least one pharmaceutically acceptable excipient.
9. The A method of treating obesity, diabetes, insulin resistance, metabolic syndrome, Cushing's syndrome, hypertension, atherosclerosis, cognition and dementia, glaucoma, and osteoporosis by increasing the effectiveness of the immune system in a patient in need thereof comprising administering to said patient a therapeutically effecti ve amount of the pharmaceutical composition of claim 8 .