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To function as a specific inhibitor of CYP707A, previous studies indicated that an enlarged analogue of UNI requires a longer alkyl chain to increase the selectivity for CYP707A over CYP701A 22. However, because the longer alkyl chain results in greater hydrophobicity, it was replaced by the ethylene glycol chain 25, 26. It remains unclear whether the 1,2,3-triazolyl ring, which enters the p -position of the phenyl group in UNI by a click reaction 27, of Abz-E2B is required for the selective inhibition of CYP707A.
Additionally, the click chemistry requires three steps (amination, azidation and click reaction), which was the leading cause of the low synthetic yield of Abz-E2B.