Neurokinins, discovery

The tachykinins [substance P (SP), neurokinin A (NKA), and neurokinin B, (NKB)] mediate a wide variety of physiological activities, being associated with bronchoconstriction, pain, and hypotension, as well as numerous other biological effects. The NK-1 receptor binds SP most efficiently and is the target of numerous drug discovery programs. An SP antagonist would have... 

One of the modem ways of CNS disorders diagnostics depends on the development of new radiolabeled NKl receptor antagonists. Some examples of fluorine-18 labeling compounds are known [171,172], effective radioligands for imaging brain neurokinin type-1 (NKl) receptors in clinical research and drug discovery with positron emission tomography, like [ F]SPA-RQ 198. 

Pfizer s contributions to the discovery of novel NK-2 receptor antagonists include Libraries 3.10 and 3.11 [42,66]. Library 3.10, composed of several parts and totaling 1180 members, is based on the 3,4-dichlorophenylalkyldiamine pharmacophore found in Sanofi Wnthrop s neurokinin-2 antagonist 25 (Fig-... 

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