The discovery and development of angiotensin II antagonists.

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During the development of losartan, various issues arose that could have stopped losartan and hampered the successful development of the angiotensin II antagonists in general. Some of these issues were real problems that had to be solved if losartan was to advance, such as the need for a commercially viable synthesis. Other issues, such as whether EXP3174 would form in humans, were anticipated as potential problems that should be addressed. Because of the combined efforts of discovery and development groups at DuPont, and later at Merck and DuPont Merck, the development of losartan was rapid. While some people were working to answer questions such as the antihypertensive efficacy of losartan in humans as quickly as possible, other people were searching for potential backups to losartan. Without an efficient integration of Discovery and Development efforts, the commercially successful development of any drug would be threatened, and it helped to give losartan a critical 2-year lead on the most advanced competitive Ang II antagonists.