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The structure-activity relationship (SAR) studies conducted by Chugai and subsequently by Eli Lilly explored modifications across the molecule's three principal domains: the tetrahydropyran ring system, the indazole heterocycle, and the substituted phenyl ring
lancet, Gastroenterol Hepatol
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Whether similar changes in these enzymes are also evident in other organs is not certain as they were not determined in this study but the presence of these differences in the kidney during the pre-hypertensive period suggests a potential role for them in the pathogenesis of hypertension
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