Receptor antagonist libraries opioid

Fig. 1.14. Kappa ( ) opioid receptor antagonist optimization library (reprinted ( adapted or in part ) with permission from Journal of the American Chemical Society. Copyright 1999 American Chemical Society).

Dooley, C.T., Chung, N.N., Schiller, P.W. and Houghten, R.A., Acetalins Opioid receptor antagonists determined through the use of synthetic peptide combinatorial libraries, Proc. Natl. Acad. Sci. USA, 90 (1993) 10811-10815. 

Researchers from the Banyu Tsukuba Research Institute reported the first nonpeptide antagonist for ORLl receptors (1037). Starting from a lead (269) from their chemical library, which again exhibited reasonable affinity but poor selectivity for ORLl receptors, these researchers identified J-113397 (270), which exhibits high affinity (K = 1.8 nM) and high selectivity for ORLl receptors over opioid receptors (1037-1039). This compound is an antagonist of OFQ/N in uitro and in vivo after subcutaneous administration (1038,1039). A series of 4-aminoquinolines (271) has also been examined for antagonist activity, based on the weak affinity of the lead compound... 

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