Frontiers in Medicinal Chemistry

Volume: 1

Indexed in: Scopus, EMBASE, Chemical Abstracts, EBSCO, Ulrich's Periodicals Directory.

Frontiers in Medicinal Chemistry is a book series devoted to the review of areas of important topical interest to medicinal chemists and others in allied disciplines. Frontiers in Medicinal Chemistry ...
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Non-peptide Opioid Receptor Ligands - Recent Advances. Part I - Agonists

Pp. 477-500 (24)

Agnieszka Kaczor and Dariusz Matosiuk


Developments in the domain of non-peptide opioid receptor agonists, beginning from the first evidence of opiate binding to definite receptors, are briefly summarized. The recent achievements are in a more detailed way depicted and discussed. Novel agonists for each of three opioid receptor basic types (d (DOR), k (KOR) and m (MOR)) are presented with the special emphasis on one-type-selective ligands. Such selective or even specific agonists have been synthesized with a moderate success. Considerably more serious difficulties concern searching for selective ligands for opioid receptor subtypes (m1 (MOR1), m2 (MOR2), d1 (DOR1), d2 (DOR2), k1 (KOR1), k2 (KOR2), k3 (KOR3)) which may be connected with the fact that dissimiliarities observed in vivo result from postbinding processes (signaling).

For the large number of opioid receptor ligands, their structural diversity and relative easiness of generating them from combinatorial libraries (not comparable even with that of orphanine receptors) it is justified to consider the plasticity of opioid receptors (MOR especially). This remark, in conjunction with the existence of opioid receptor types and subtypes, may enable to create new drugs with significantly reduced sideeffects.

The above facts and brand new reports about highly-active opioid agonists possessing no moieties thought to be essential for agonist activity make the need of reevaluation of classical opioid receptor pharmacophore model extremely important.

In general, research results suggest that selective agonists of opioid receptors can be found both in morphine type of ligands and new structures like pyrido-acridine derivatives (COMP1) or diphenylmethylpiperazine derivatives (SNC 80). Better understanding of the structural prerequisites of the opioid receptors binding domains will certainly lead to even more potent and more selective ligands in near future.


opioid receptors, non-peptide agonists, binding domain, pharmacophore models, morphine-like agonists, non-morphine-like agonists


Department of Synthesis and Technology of Drugs, Faculty of Pharmacy, Medical University at Lublin, 6 Staszica Str., PL-20081 Lublin, Poland