Derivatives of substituted morpholines and uses thereof
A compound of Formula I includes a stereoisomer thereof and/or a salt thereof; wherein R 1 is a substituted alkane group, a heterocylic group, or a pyridine group; X is hydrogen, a halogen, an amino acid residue, a substituted amino acid residue, an alkyl group, or an ester. Such compounds may be used in pharmaceutical compositions and for the treatment of central nervous system (CNS) disorders:
1. A compound of Formula II, stereoisomer thereof, and/or a salt thereof:
wherein:
L is alkyl, a substituted pyridinecarboxylic acid, or a substituted azanediyl acetate;
R 2 is alkyl, aryl, heteroaryl, or heterocyclyl; and
R 3 -R 14 are each independently H, F, Cl, Br, I, CN, NO 2 , alkyl, aryl, heteroaryl, or heterocyclyl.
2. The compound of claim 1 , wherein L is CH 2 .
3. The compound of claim 1 that is:
4. The compound of claim 1 , wherein L is a substituted pyridinecarboxylic acid group.
5. The compound of claim 4 , wherein the substituted pyridinecarboxylic acid group is a dimethyl pyridine-dicarboxylate.
6. The compound of claim 1 that is:
7. The compound of claim 1 , wherein the substituted azanediyl acetate group is a methylazanediyl acetate.
8. The compound of claim 1 that is:
9. A composition comprising a compound of claim 1 , and a pharmaceutically acceptable excipient.
10. A method for the treatment of a central nervous system disorder, the method comprising administering to a subject the composition of claim 9 .
11. A method of making a compound of Formula II
wherein:
L is alkyl, a substituted pyridinecarboxylic acid, or a substituted azanediyl acetate;
R 2 is alkyl, aryl, heteroaryl, or heterocyclyl; and
R 3 -R 14 are each independently H, F, Cl, Br, I, CN, NO 2 , alkyl, aryl, heteroaryl, or heterocyclyl, comprising contacting (a) 2-((2-ethoxyphenoxy)methyl)morpholine or a salt thereof, or
(b) a compound of formula:
(c) a compound of formula:
(d) a compound of formula:
with a reactive compound suitable for forming the compound of Formula II.
12. The method of claim 11 , wherein (b) a compound of formula:
is formed by reacting 2-((2-ethoxyphenoxy)methyl)morpholine or a salt thereof with sodium bicarbonate.
13. The method of claim 11 , wherein (c) a compound of formula:
is formed by reacting 2-((2-ethoxyphenoxy)methyl)morpholine or a salt thereof with 1-chloromethyl chloroformate.
14. The method of claim 11 , wherein (d) a compound of formula:
is formed by reacting 2-((2-ethoxyphenoxy)methyl)morpholine or a salt thereof with 1-chloroethyl chloroformate.
15. The method of claim 11 , wherein the reactive compound is selected from the group consisting of methylene dibromide, 3,5-pyridinedicarboxylic acid, and methyliminodiacetic acid.