Possible Liabilities of Pyrrole-Containing Drugs

As one could imagine, the highly reactive intermediates from pyrrole could wreak havoc in the physiological system. Nucleophiles such as the thiol group could induce toxicities. As a result, the development of mopidralazine was subsequently discontinued. 

Similar oxidative metabolism was observed for premazepam, an antianxiety drug, in the rat and the dog prinomide, an anti-inflammatory agent, in six i ecies of laboratory animals and pyrrolnitrin, an anti-fungal agent, in rats.  

Nonetheless, if one assumes that all pyrrole-containing drugs are toxic, we would have missed atorvastatin (Lipitor). Atorvastatin is remarkably safe barring the mechanism-based safety concerns such as rhabdomyolysis that are associated with all HMG-CoA inhibitors. Although atorvastatin contains the pyrrole ring, it has at least three factors that strongly attenuate its nucleophilicity. First, it is fully substituted at all 

In drug discovery, as in many other things in life, there are always exceptions to the rules. Frequently, the safety and efficacy of a drug can only be determined by clinical trials as the touchstone. 

1 Explain why the dipole moments for pyrrole and pyrrolidine have the opposite directions  

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