Modulators of S1P and Methods of Making And Using

A compound of Formula I:

• or a stereoisomer or mixture of isomers thereof and optionally as a pharmaceutically acceptable salt thereof, where
• R1 is hydrogen or —P(O)(OR6)2;
• R2 and R2a are independently hydrogen, cyano, halo, alkyl, haloalkyl, alkoxy, or haloalkoxy;
• Ring A is phenyl, 5-membered heteroaryl, 6-membered heteroaryl, or imidazo[2,1-b]thiazolyl;
• each R3 is independently cyano, halo, alkyl, haloalkyl, hydroxy, alkoxy, haloalkoxy, alkoxyalkyloxy, cycloalkyloxy, heterocycloalkyloxy, nitro, phenyl, amino, alkylamino, dialkylamino, aminocarbonyl, alkylcarbonylamino, or alkoxycarbonylamino;
• n is 0, 1, or 2;
• R4 is hydrogen, alkyl, cyano, halo, or haloalkyl;
• R5 is hydrogen or alkyl;
• R5a is hydrogen, alkyl, alkylcarbonyl, or alkoxycarbonyl;
• each R6 is independently hydrogen or alkyl;
• R7, R7a, R7b, and R7c are independently hydrogen or alkyl;
• and
• R8 is hydrogen, alkyl, or hydroxyalkyl.