drug-selectivity - Question and answers

I'm a graduate student in pharmacology, and for my thesis, I'm developing a novel painkiller. My lead compound shows good binding affinity to the mu-opioid receptor, but in vitro tests indicate it also interacts significantly with delta and kappa receptors, which could lead to unwanted effects like respiratory depression or dysphoria. I've tried adjusting the basic nitrogen and aromatic rings based on literature, but the selectivity hasn't improved much. Are there specific pharmacophore elements or substitution patterns that are known to boost mu-opioid selectivity?