Hypophosphorous acid derivatives having antihyperalgic activity and biological applications thereof
The invention relates to hypophosphorous acid derivatives of formula (I) wherein —X is H or OH, —R represents one or several radicals R 1 -R 5 , identical or different, two of R 1 -R 5 optionally occupying the same position on the phenyl group, one to four of R 1 -R 5 being H and the others being selected in the group comprising -0-(CH 2 ) n —COOH; —S—(CH 2 ) n —COOH; —NH—(CH 2 ) n —COOH; -0-(CH,R′)—COOH; —O—(CH 2 ) n —OH; OR′, —R′ being a C 1 -C 3 alkyl radical; —OH; —COOH; halogen, particularly —F, —CI, —Br, —I, —CF 3 ; —OCF 3 ; —N0 2 ; —CH═CH—COOH; —(CH 2 ) n —COOH; O—(CH 2 ) n —P0 3 H 2 ; O—(CF 2 ) n —P0 3 H 2 ; O—(CH 2 ) n —S0 3 H; O—(CH 2 ) n —CONHOH; O—(CH 2 ) n -tetrazol; O—(CH 2 ) n -hydroxyisoxazol—n=1 to 5, preferably 1-3; said hypophosrous acid derivatives being diastereoisomers or enantiomers.
1. Hypophosphorous acid derivatives of formula
said hypophosphorous acid derivatives being diastereoisomers or enantiomers.
2. A pharmaceutical composition comprising at least one of the hypophosphorous acid derivatives according to claim 1 , in combination with a pharmaceutically acceptable carrier.
3. The pharmaceutical composition of claim 2 , wherein the at least one hypophosphorous acid derivative simultaneously activates metabotropic glutamate receptor (mGluR) subtypes 4 and 7 for the treatment of neuropathic and inflammatory pain.
4. The pharmaceutical composition of claim 2 , wherein the at least one hypophosphorous acid derivative has an EC 50 with respect to mGluR7 receptors greater than 1 μM.
5. The pharmaceutical composition of claim 2 , wherein the at least one hypophosphorous acid derivative has an EC 50 mGlu8>10 μM, and an EC 50 mGlu4<0.5 μM.
6. The pharmaceutical composition of claim 2 , in a form suitable for oral administration.
7. The pharmaceutical composition of claim 6 , comprising 1 to 100 mg of the hypophosphorous acid derivative per dose unit.
8. The pharmaceutical composition of claim 2 , in a form suitable for administration by injection.
9. The pharmaceutical composition of claim 8 , comprising 1 to 30 mg of the hypophosphorous acid derivative per dose unit.
10. The pharmaceutical composition of claim 6 , in the form of a tablet, pill or capsule.
11. The pharmaceutical composition of claim 8 , in form of an injectable solution for intravenous, subcutaneous or intramuscular injection.