The primary biological target of substance P is neurokinin 1 (NK1) a G-protein coupled receptor that has intrigued scientists for 20 years with the promise of therapies for CNS and related disorders. The advent of high throughput screening, coupled with informed medicinal chemistry design and synthesis, enabled the identification of selective and metabolically stable non-peptide ligands to aid in a full characterization of this receptor. Since the original discovery and optimization of early leads at Pfizer, the structure activity relationships have facilitated the synthesis of many novel NK1 templates with potent antagonist activity, including some that have been investigated in the clinic. This talk will review the chemistry efforts in the NK1 area at Pfizer, initiated by John Lowe and colleagues in the early 90's, and the impact of this effort on the study of multiple disease areas.

Review of SAR studies at Pfizer on non-peptide antagonists of substance P

241st National Meeting (2011)

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