Structure-activity relationships between different SARs

Most relevant for the affinity for A9-THC and analogs to CB-receptors are the phenolic hydroxyl group at C-1, the kind of substitution at C-9, and the properties of the side chain at C-3. Relating to the structure-activity relationships (SAR) between cannabinoids and the CB-receptors, many different modified strucfures of fhis subsfance group were developed and fesfed. The most important variations include variations of the side chain at the olivetolic moiety of the molecules and different substitutions at positions C-11 and C-9. One of the most popular analogous compounds of A9-THC is HU-210 or (-)-trans-ll-OH-A8-THC-DMH, a cannabinoid with a F,l-dimethylheptyl side... 

With qualitative structure-activity relationships (SARs), the correlation of toxic effect with structure is made by visual comparison of the structures of the chemicals in a series of congeneric substances and the corresponding effects their structural differences have on toxic potency, for example, as represented by their LD50 values. From qualitative examination of structure-activity data the chemist may be able to see a relationship between structure and toxicity, and identify the least toxic members of the class as possible commercial alternatives to the more toxic members. 

A successful lead optimization process is, in general, a result of careful and systematic analysis of structure-activity relationships (SAR) within an active series of compounds. The validity of the SAR obtained from screening a combinatorial library is a reflection of an accurate knowledge of the identity, purity and quantity of each library member. Also important is the ease and speed with which information can be relayed from the biological screen to the medicinal chemist. In fact, herein lies the main difference between the two techniques discussed so far. 

On the other hand, there is a great deal of experimental data accumulated on different biological activities of chemicals with known molecular constitution and structure. The empirical approach to the problem, which side-steps knowing the biomechanism of activity, is to compare all the active compounds with inactive compounds having related structures and to reveal the similarities and differences between them. Based on this information the main features of the molecules responsible for the activity can be determined. Many such approaches have been investigated during the past two decades, and work in this area is usually published under the title structure-activity relationships (SAR), or quantitative SAR (QSAR). Full development of the QSAR approaches was reached when use of computers became widespread. 

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