The compound CP-99994 was synthesized by replacing the quinuclidine ring with a piperidine ring and benzhydryl moiety by a benzyl group (figure 2). CP-99994 had a high affinity for the human NK1 receptor and it started a great number of structure–activity studies, each intending to identify the structural requirements for high-affinity interaction with the NK1 receptor, and to make the molecule even simpler and improve its chemico-physical and pharmacological properties. CP-99994 eased dental pain in humans and entered phase II clinical trials; these were discontinued because of poor bioavailability. Pfizer researched several other related NK1 receptor antagonists. CJ-11974, also called ezlopitant, was a close analog of CP-96345 that had an isopropyl group on the methoxybenzyl ring. It was developed up to phase II clinical trials for chemotherapy-induced emesis before development was discontinued. CP-122721 was a CP-99994 analog that had a trifluoromethoxy group in the o-methoxybenzyl ring. It entered phase II trials for the treatment of depression, emesis and inflammatory diseases, but no further development has been reported.