Renin Inhibitors

It is hoped that this chapter illustrates the decision-making processes that are associated with a drug discovery effort. The success of the renin inhibitor project was the direct result of the tight integration of the medicinal chemistry, biochemistry, pharmacology, and pharmacokinetic groups. As obstacles arose, a variety of approaches, often simultaneous, were taken to overcome them. Ultimately, although there were logical reasons for the choice of each of the compounds that the project synthesized, most of them were found not to lie on the critical path and were illustrative of the numerous dead ends that are to be expected in any scientific endeavor. Only the productivity of the medicinal chemists coupled with efficiency of our primary biological tests allowed sufficient avenues to be explored that we were able to achieve the project goals. Finally, our willingness to study enalkiren in the clinic early in our program provided valuable feedback and guidance for the discovery of the next generation of renin inhibitor.