MEPTAZINOL CARBAMATE PRODRUG SALTS
The present invention relates to salts of meptazinol carbamate prodrugs, and to their synthesis and use.
1 . A salt of a meptazinol prodrug of formula (I):
wherein:
R 1 is selected from the group consisting of hydroxy, carboxy, carboxamido, imino, alkanoyl, cyano, cyanomethyl, nitro, amino, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, aryl, aryl-C 1-6 alkyl and C 1-6 alkyl aryl;
R 2 is selected from the group consisting of: H, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxy, C 1-4 haloalkoxy;
W and U are each independently selected from the group consisting of: —CH═ and —N═;
R′ and R″ are each independently selected from the group consisting of: H, hydroxy, carboxy, carboxamido, imino, alkanoyl, cyano, cyanomethyl, nitro, amino, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 3-6 cycloalkyl, aryl, aryl-C 1-6 alkyl and C 1-6 alkyl aryl;
n and p are each independently 0, 1 or 2;
X − is an anion selected from the group comprising: phosphate, maleate, malonate, sulphate, and methane sulphonate.
2 . The salt according to claim 1 wherein R 2 is selected from the group consisting of: H and C 1-4 alkyl.
3 . The salt according to claim 1 of formula (II):
4 . The salt according to claim 1 wherein n is 0.
5 . The salt according to claim 1 wherein n is 1.
6 . The salt according to claim 5 wherein R 1 is selected from the group consisting of: hydroxy, halogen, C 1-6 alkyl, C 1-6 haloalkyl and C 1-6 alkoxy.
7 . The salt according to claim 6 wherein R 1 is selected from the group consisting of hydroxy, methyl and methoxy.
8 . The salt according to claim 1 wherein W is —CH═.
9 . The salt according to claim 1 wherein U is —CH═.
10 . The salt according to claim 1 wherein p is 0.
11 . The salt according to claim 1 wherein p is 1 and R′ and R″ are each H.
12 . The salt according to claim 1 wherein the meptazinol prodrug has the formula:
13 . Use of a salt according to claim 1 for the manufacture of a medicament.
14 . Use of claim 13 , wherein the medicament is for the treatment of pain.
15 . A pharmaceutical composition comprising a salt according to claim 1 and at least one pharmaceutically acceptable carrier.
16 . A method for of treating a patient having a pain disorder, comprising orally administering to the patient in need thereof a therapeutically effective amount of the salt according to claim 1 .
17 . (canceled)
18 . The method according to claim 16 , wherein the pain disorder is neuropathic or nociceptive pain.
19 . Use of claim 14 , wherein the pain is neuropathic or nociceptive pain.