Structure-activity relationships of dopamine receptor agonists

4 Structure-activity relationships of dopamine receptor agonists 

Through the years a number of different structure-activity relationships (SARs) and receptor models have been developed (for reviews see refs. 91, 92). Therefore this introduction will only give a short overview of the general aspects of dopamine receptor agonist SARs. 

The growing interest in unravelling the mechanism of action of dopamine and related compounds at the molecular level started with the considerations of the conformation(s) of the dopamine molecule when bound to the receptor site. Dopamine itself is a conformationally flexible molecule that can adopt specific conformation(s) needed to achieve appropriate three dimensional interaction with various groups located at or near the recognition (receptor) site(s). 

When the conformation of the ethylamine side-chain with respect to the aromatic nucleus is considered as the starting-point, the dopamine molecule may exist either in a trans (extended) conformation, or in a cis (gauche) conformation. Single crystal x-ray analysis of dopamine hydrochloride indicates that the ethylamine chain is in a nearly completely extended conformation which resides on a plane almost perpendicular to the plane of the catechol ring.93 

Chart 1.3 Gauche conformation of dopamine (1) and the two retainers of the extended conformation of dopamine (1 a-conformer and 1 (3-conformer), and the corresponding 2-aminotetralins S-(-)-5-OH-DPAT (9) and R-(+)-7-OH-DPAT (10). 

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The author of the previous article has highlighted some of the salient features that have emerged over recent years with regard to structure activity relationships of dopamine receptor agonists and their application to the design of new agents. 

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