Lipoic acid derivatives, their preparation, and pharmaceutical compositions containing them
AssigneeSociete de Conseils de Recherches et d'Applications Scientifiques (S.C.R.A.S.)
InventorsJeremiah Harnett, Michel Auguet, Pierre-Etienne Chabrier de Lassauniere
Life of this patent
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Abstract
The invention concerns novel lipoic acid derivatives, which have an inhibiting action with respect to NO-synthase enzymes producing nitrogen monoxide NO and/or are agents enabling the regeneration of antioxidants or entities trapping reactive oxygen species (ROS) and intervening in a more general manner in the redox status of thiol groups. The invention also concerns methods for preparing them, pharmaceutical compositions containing them and their use for therapeutic purposes, particularly their use as NO-synthase inhibitors and/or as agents acting more generally in the redox status of thiol groups.
Claims11
A compound of the formula
- wherein
- R1 and R2 are individually hydrogen or alkyl of 1 to 6 carbon atoms;
- A is —(CH2)mCONR3—(CH2)n—
- m and n are individually integers from 0 to 6,
- and R3 is hydrogen or alkyl of 1 to 6 carbon atoms;
- X is
- wherein the T group, which is attached to the Y group, is —(CH2)1—, i is 0;
- and R5 is selected from a group consisting of hydrogen, alkyl of 1 to 6 carbon atoms, and —(CH2)m—Q,
- Q is selected from the group consisting of halogen, hydroxy, cyano, amino, alkoxy, alkylamino, dialkylamino and a heterocycle with 5 to 6 ring members with the heterocyclic members selected from the group consisting of —O—, —N(R6)— and —S—,
- R6 is hydrogen or alkyl of 1 to 6 carbon atoms orthe bond to the phenyl ring of X;
- Y is
- B is selected from the group consisting of alkyl of 1 to 6 carbon atoms, carbocyclic or heterocyclic aryl with 5 or 6 ring members containing 1 to 4 heteroatoms selected from the group consisting of O, S, N, the aryl being optionally substituted by at least one member selected from the group consisting of alkyl, alkenyl and alkoxy of up to 6 carbon atoms,
- NR8R9 and SR10, R8 and R9 are individually hydrogen or alkyl of 1 to 6 carbon atoms, or
- one of R8 and R9 is nitro while the other is hydrogen or alkyl of 1 to 6 carbon atoms, or
- R8 and R9 together form with the nitrogen atom a non-aromatic heterocycle with five to six ring members, the elements of the ring being selected from the group consisting of —CH2—, —NH—, —O— and —S—,
- R10 is hydrogen or alkyl of 1 to 6 carbon atoms,
- and R7 is hydrogen or alkyl of 1 to 6 carbon atoms and a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.