SPHINGOSINE 1 PHOSPHATE RECEPTOR MODULATORS
Compounds are provided having the structure of Formula (I) or (II) or a pharmaceutically acceptable salt, homolog, hydrate or solvate thereof, wherein R a , R d and R e are as defined herein. Such compounds serve as modulators of the sphingosine-1-phosphate receptor, and have utility for treatment of a malcondition for which activation of this receptor is medically indicated.
1 . A compound having the structure of Formula (I):
or a pharmaceutically acceptable salt, homolog, hydrate or solvate thereof,
wherein
R a is H or C 1-4 alkyl; and
R d is —OR d1 or —N(R d2 )(R d3 );
and wherein
R d1 , R d2 and R d3 are independently H or C 1-4 alkyl, or
R d2 and R d3 are taken together with the nitrogen to which they are attached form a heterocyclyl or substituted heterocyclyl.
2 . The compound of claim 1 wherein R d is —OR d1 .
3 . The compound of claim 1 wherein R d is —N(R d2 )(R d3 ).
4 . The compound of claim 3 wherein R d2 and R d3 are independently H or C 1-4 alkyl.
5 . The compound of claim 3 wherein R d2 and R d3 are taken together with the nitrogen to which they are attached form a heterocyclyl or substituted heterocyclyl.
6 . The compound of claim 1 wherein R a is H.
7 . The compound of claim 1 wherein R a is methyl.
8 . The compound of claim 1 wherein the compound has one of the following structures, or a pharmaceutically acceptable salt, homolog, hydrate or solvate thereof:
Cpd
No.
Structure
5-1
5-2
5-3
5-4
9 . A compound having the structure of Formula (II):
or a pharmaceutically acceptable salt, homolog, hydrate or solvate thereof,
wherein
R e is —OR e1 or —N(R e2 )(R e3 );
and wherein
R e1 , R e2 and R e3 are independently H or C 1-4 alkyl, or
R e2 and R e3 are taken together with the nitrogen to which they are attached form a heterocyclyl or substituted heterocyclyl.
10 . The compound of claim 9 wherein R e is —OR e1 .
11 . The compound of claim 9 wherein R e is —N(R e2 )(R e3 ).
12 . The compound of claim 11 wherein R e2 and R e3 are independently H or C 1-4 alkyl.
13 . The compound of claim 11 wherein R e2 and R e3 are taken together with the nitrogen to which they are attached form a heterocyclyl or substituted heterocyclyl.
14 . The compound of claim 9 wherein the compound has one of the following structures, or a pharmaceutically acceptable salt, homolog, hydrate or solvate thereof:
Cpd
No.
Structure
6-1
6-3