Identification of benzoxazole analogs as novel, S1P3 sparing S1P1 agonists

A novel series of benzoxazole-derived S1P1 agonists were designed based on scaffold hopping molecular design strategy combined with computational approaches. Extensive SAR studies led to the discovery of compound 17d as a selective S1P1 agonist (over S1P3) with high CNS penetration and favorable DMPK properties. 17d also demonstrated in vivo pharmacological efficacy to reduce blood lymphocyte in mice after oral administration.