Fatty acid amide hydrolase (FAAH) cleavable prodrugs of brain-targeted actives and combinations with peripherally restricted FAAH inhibitors

Provided herein are fatty acid amide (FAAH) cleavable prodrugs of compounds that modulate a target in the brain, the target comprising the sphingosine-1-phosphate receptor (S1P1), the lysophosphatidic acid receptor 1 (LPA1), the G protein coupled receptor 120 (GPR120), the prostacyclin (PGI2), and the transthyretin (TTR). Also provided are pharmaceutical compositions comprising these prodrugs, including in combination with a peripherally restricted FAAH inhibitor, and at least one pharmaceutically acceptable excipient; and the use of these compounds and compositions in the treatment of CNS diseases or disorders. 本文提供了调节脑中的靶标的化合物的脂肪酸酰胺(FAAH)可裂解前药，该靶标包括鞘氨醇-1-磷酸受体(S1P1)、溶血磷脂酸受体1(LPA1)、G蛋白偶联受体120(GPR120)、前列环素(PGI2)和转甲状腺素蛋白(TTR)。还提供了药物组合物，该药物组合物包含这些前药，包括与外周限制性FAAH抑制剂的组合，以及至少一种药学上可接受的赋形剂；以及这些化合物和组合物在CNS疾病或病症的治疗中的用途。