Ten 9-amino-1,2,3,4-tetrahydroacridinediols were prepared as potential mono-hydroxy metabolites of velnacrine. They were tested for acute toxicity as well as for their ability to inhibit acetylcholinesterase in vitro and to reverse scopolamine-induced memory impairment in mice.We recently reported the synthesis of a series of 9-amino-1,2,3,4-tetrahydro-1-acridinols. These compounds were acetylcholinesterase inhibitors and were active in a dementia paradigm in mice, reversing the impairment of 24-h memory induced by scopolamine. Based on these data (and data from an nbM lesion model), one of these compounds (velnacrine maleate, 1a) was chosen for clinical trials in Alzheimer's disease. The pharmacokinetic profile of 1a in normal young and elderly volunteers is predictable,2 and clinical trials in Alzheimer's patients have been highly encouraging.3 Since oxidation by the cytochrome P-450 mixed function oxidase system is a fundamental means by which drugs are metabolized in mammals4 and since 1a itself has been shown to be one of several hydroxylated metabolites of 9-amino-1,2,3,4-tetrahydroacridine (THA, tacrine, 1b) in the rat,5 hydroxylation was considered to be a likely pathway for the metabolism of 1a. Thus, as the clinical trials with 1a progressed, it was desirable to have the hydroxylated derivatives of 1a in hand to be used as standards for chromatographic and spectral comparison with metabolites of 1a isolated from biological fluids. This paper describes the synthesis of ten such actidinediols, four hydroxylated on the aromatic ring (2a-d) and six hydroxylated on the alicyclic ring (3-5, each consisting of two diastereomers), along with the results of the initial biological testing.