Pyrrole-containing drugs

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 contrast to the pyrrole and thiophene series, the furan nucleus occurs in many plant-derived terpenes such as 2.11. The most important furan-containing drug is 2.12, which reduces gastric acid secretion and is important in the treatment of ulcers. 

Indole, which is a fusion between pyrrole and benzene, also has the same acidic properties as the pyrrole ring. An example of an indole-containing drug is psilodn (Fig. 4.48). 

These alkaloids contain pyrrole or modified pyrrole, e.g. pyrrolidine, ring system. The simplest example of this class is nicotine. A pyrrolidine ring is the central structure of the amino acids proline and hydroxyproline. These alkaloids are also found in many drug preparations, e.g. procyclidine hydrochloride, which is an antichohnergic drug mainly used for the treatment of drug-induced Parkinsonism, akathisia and acute dystonia. 

A number of new drugs have been approved for human therapeutic use since the early 1980s that contain pyrrole, indole, carbazole, and related ring systems. 

Baraldi and co-workersl have designed and synthesized distamycin-PBD and netropsin-PBD conjugates as novel sequence selective C8-linked PBD hybrids. These h)Hbrids containing 1 to 4 pyrrole units have been investigated for the sequence selectivity and stability of DNA drug complexes. 

Silicon-containing nitrogen heterocycles are often biologically active and are extensively explored as starting materials for the synthesis of drugs [669]. In this line, the reaction of N-vinylpyrroles hydrosilylation provokes a certain interest. It is known [670] that N-[Y-(trialkoxysilyl)propyl]pyrroles are employed to improve the adhesion of polypyrrole films to n-type silicon photoanodes. Such pyrroles are obtained by multistage synthesis (Scheme 2.201). 

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