Discovery of a series of potent arylthiadiazole H3 antagonists

A series of 2-piperidinopiperidine-5-arylthiadiazoles was synthesized and subjected to a structure–activity relationship (SAR) investigation. The potency of this series was improved to the single digit nanomolar range. The key analogs were shown to be free of P450 issues, and they also maintained good ex vivo activity and brain penetration.