Indole compounds bearing aryl or heteroaryl groups having sphingosine 1-phosphate (S1P) receptor biological activity

A compound having the structure:

• wherein:
• each Ar is independently substituted or unsubstituted phenyl;
• each L is independently alkylene, alkenylene, oxyalkylene, oxyalkenylene, aminoalkylene, or aminoalkenylene;
• R1 is lower alkyl or alkylacyl or hydroxyalkyl;
• each R2 is independently H, lower alkyl, halide, trifluoromethyl, lower alkenyl, lower alkynyl, cycloalkyl, —CN, —CH2CN, —CH2SR3, —CH2N(R3)2, —CH2OR3, —CH═NOR3, —OR3, —SR3, —N(R3)2, —C(O)R4, heterocycle, substituted heterocycle, aryl, substituted aryl, heteroaryl, substituted heteroaryl;
• or
• R2 is
• wherein R5 is —CO2H or PO3H2 and p is 0-2;
• or
• when n is 2, each R2 taken together with carbon atoms to which each R2 is attached forms an aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl or substituted cycloalkyl;
• each R3 is independently H, lower alkyl, cycloalkyl, allyl, phenyl, substituted phenyl, heteroaryl, or substituted heteroaryl;
• each R4 is independently H, lower alkyl, cycloalkyl, alkoxy, alkylamino, dialkylamino, phenyl, substituted phenyl, heteroaryl, substituted heteroaryl, or trifluoromethyl;
• E=O;
• x is 1;
• and
• n is 0-5;
• or pharmaceutically acceptable salts thereof.