Akkermansia muciniphila Modulates Central Nervous System Autoimmune Response and Cognitive Impairment by Inhibiting Hippocampal NLRP3-Mediated Neuroinflammation.

Background: Numerous studies have demonstrated the significant role of Akkermansia muciniphila (A. muciniphila) in enhancing host immune responses and metabolic functions. However, its increased presence in multiple sclerosis (MS) patients has led to a focus on the relationships between A.

Bridgehead modification of trihalocycloheptabenzopyridine leads to a potent farnesyl protein transferase inhibitor with improved oral metabolic stability.

Modification of the ethano bridge of the core structure of the antitumor agent, SARASAR (SCH66336) with concomitant introduction of a sulfonamide moiety off the distal piperidine afforded inhibitor 9-(S-), a compound with greatly improved PK profile. Other compounds with enhanced FPTase inhibitory activity were obtained as exemplified by amide 10-(S-) and urea 11-(S-): these compounds demonstrated activity in picomolar range.