Thiocolchicine derivatives, method of making and methods of use thereof
Disclosed herein are thiocolchicine derivatives suitable for use as muscle relaxants, methods of making the derivatives, and compositions comprising the derivatives.
1. A compound according to structure (I)
wherein R is
b.) an amino acid derivative linked through the carboxylate group selected from the group consisting of alanine and tyrosine;
c.) —CH 2 —O(C═O)R 2 where R 2 is methyl, ethyl, n-propyl, isopropyl and * is in the S configuration;
d.) —C(═O)R 3 , where R 3 is pyridyl and * is in the S configuration; or
f.) —C(═O)(CH 2 ) x SO 3 R 4 where R 4 is hydrogen or C 1 -C 3 alkyl, x is 1 or 2 and * is in the S configuration;
or a pharmaceutically acceptable salt, crystalline form, non-crystalline form, or stereoisomer thereof.
2. The compound of claim 1 , wherein R is
b.) an amino acid derivative linked through the carboxylate group selected from the group consisting of alanine and tyrosine,
or a pharmaceutically acceptable salt, crystalline form, or non-crystalline form thereof.
3. The compound of claim 1 , comprising the S isomer, wherein R is
c.) —CH 2 —O(C═O)R 2 where R 2 is methyl, ethyl, n-propyl, or isopropyl,
or a pharmaceutically acceptable salt, crystalline form, or non-crystalline form thereof.
4. The compound of claim 1 , comprising the S isomer, wherein R is
d.) —C(═O)R 3 , where R 3 is pyridyl,
or a pharmaceutically acceptable salt, crystalline form, or non-crystalline form thereof.
5. The compound of claim 1 , comprising the S isomer, wherein R is
f.) —C(═O)(CH 2 ) x SO 3 R 4 where R 4 is hydrogen or C 1 -C 3 alkyl and x is 1 or 2,
or a pharmaceutically acceptable salt, crystalline form, or non-crystalline form thereof.
6. The compound of claim 1 , wherein the compound is