Calcium channel blockers comprising two benzhydril moieties
View Patent ↗Certain piperazine substituted compounds are described which are useful in altering calcium channel activity.
1. A method to treat a condition selected from the group consisting of pain, stroke, epilepsy, anxiety and depression in a subject, which method comprises administering to a subject in need of such treatment an amount of a compound of formula (1) effective to treat said condition wherein said compound of formula (1) is:
or a pharmaceutically acceptable salt thereof
wherein each R 1 -R 5 is independently optionally substituted alkyl (1-10C), alkenyl (2-10C), alkynyl (2-10C), aryl (6-10C), alkylaryl (7-16C) or alkenylaryl (7-16C) each optionally further containing 1-4 heteroatoms (N, O or S) and wherein said optional substituents may include ═O; or
each of R 1 -R 5 is independently halo, NO 2 , SO, SO 2 , SO 2 NH 2 , —OH, SH or NH 2 , and wherein R 3 may be keto if n 3 =1; and
wherein two substituents on adjacent positions of the same ring may form a 3-7 membered saturated or unsaturated ring fused to said substituted ring, said fused ring itself optionally substituted and optionally containing one or more heteroatoms (N, S, O); or
wherein a combination of R 1 and R 2 and/or R 4 and R 5 may form a bond or a bridge between phenyl groups A and B and/or C and D; and
wherein each n 1 -n 2 and n 4 -n 5 is independently 0-4, and n 3 is 1-4; and/or
the compound of formula (1) is in the form of an isolated stereoisomer; or
the compound of formula (1) is P49 or P50 in FIG. ( 1 ) or a salt thereof.
2. The method of claim 1 wherein each of R 1 , R 2 , R 4 and R 5 is independently halo, or is optionally heteroatom containing and/or optionally substituted alkyl, alkenyl, aryl, alkylaryl, alkenylaryl, or phenoxy.
3. The method of claim 1 wherein R 1 and R 2 and/or R 4 and R 5 form a bridge of 1-3 members.
4. The method of claim 1 wherein n 3 is 1 and R 3 is COOH or an alkyl ester thereof.
5. The method of claim 1 wherein all of n 1 -n 2 and n 4 -n 5 are 0.
6. The method of claim 1 wherein one of n 1 -n 2 and n 4 -n 5 is 1 and the other n are 0.
7. The method of claim 1 wherein one of n 1 -n 2 and n 4 -n 5 is 2 and the other n are 0.
8. The method of claim 1 wherein one of n 1 -n 2 and n 4 -n 5 is 3 and the other n are 0.
9. The method of claim 1 which is compound P37-P50 in FIG. 1 or a salt thereof.
10. The method of claim 1 wherein the condition is pain.
11. The method of claim 1 wherein the condition is stroke.
12. The method of claim 1 wherein the condition is epilepsy.
13. The method of claim 1 wherein the condition is anxiety or depression.
14. The method of claim 5 wherein the condition is pain.
15. The method of claim 5 wherein the condition is stroke.
16. The method of claim 5 wherein the condition is epilepsy.
17. The method of claim 5 wherein the condition is anxiety or depression.