Conformationally Rigid Analogues of Aldose Reductase Inhibitor, Tolrestat. Novel Syntheses of Naphthalene-Fused γ-, δ-, and ε-Lactams

Article abstract of DOI:10.1021/jo00296a028

Cyclic analogues (4-6) of tolrestat (1) and oxotolrestat (2) were prepared by employing novel synthesis routes for the formation of the required γ-, δ-, and ε-lactams.In this regard 2,3,4,5-tetrahydro-9-methoxy-1H-naphth<1,2-c>azepin-1-one, 7, and 3,4-dihydro-8-methoxybenzisoquinolin-1(2H)-one, 8, were prepared from a common precursor, namely 2,3-dihydro-7-methoxy-4(1H)-phenanthrenone, 13, and further elaborated to compounds 4a-b and 5a-d, respectively.Compounds 6a-b were prepared from a tolrestat precursor, 5-methyl-2-methoxy-1-(trifluoromethyl)naphthalene, 35.Six- and seven-membered lactam acetic acid methyl esters, 29, resisted vigorous thioamidation condition; therefore, the corresponding thiolactam analogues 4 and 5 could not be prepared.However, thioamidation was achieved in the five-membered ring series, leading to thiolactam 6b.Lactams in the series 4 or 5 were considerably weaker than 1 or 2 as inhibitors of bovine lens aldose reductase although thiolactam 6b had high inhibitory activity.

Full text of DOI:10.1021/jo00296a028

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Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.

Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.

Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.