Synthesis and Structure−Activity Relationships of Novel Histamine H₁ Antagonists: Indolylpiperidinyl Benzoic Acid Derivatives

A series of indolylpiperidinyl derivatives were prepared and evaluated for their activity as histamine H1 antagonists. Structure−activity relationship studies were directed toward improving in vivo activity and pharmacokinetic profile of our first lead (1). Substitution of fluorine in position 6 on the indolyl ring led to higher in vivo activity in the inhibition of histamine-induced cutaneous vascular permeability assay but lower selectivity...