6-N-or N'-Alkylation of 6-N-acyl adenosine derivatives with alkyl halides in CH,CI,-l mol dm-3 NaOH in the presence of Bu,NBr has been studied. A variety of N-acyl groups have been examined. Consequently, the use of the acetyl and 2-(trimethylsilyl)ethoxycarbonyl groups resulted in the corresponding 6-N-alkylated products in high yields. It was also found that, when the benzoyl group was chosen as the N-acyl group, N l-alkylated products were obtained along with 6-N-alkylated products. The structure of the 6-N-and N -alkylated adenosine derivatives has been determined by 'H and 13C NMR spectroscopy.Paper 5/00999E

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The steroidal glucocorticoid antagonist mifepristone has been reported to improve the symptoms of depression. We report the discovery of 6-(3,5-dimethylisoxazol-4-yl)-2,2,4,4-tetramethyl-2,3,4,7,8,9-hexahydro-1H-cyclopenta[h]quinolin-3-one 3d (QCA-1093) as a novel nonsteroidal glucocorticoid receptor antagonist. The compound displayed potent in vitro activity, high selectivity over other steroid hormone receptors, and significant antidepressant-like activity in vivo.

Summary Lumazine-6-(8) and 7-carboxylic acid (23) and their N-methyl derivatives (12, 13, 21, 26, 28, 29) have been synthesized and characterized by the determination of their pK values and the UV spectra of the neutral, mono and dianion species. It was noticed that the acidities of the two N-H protons of the pyrimidine moiety are almost the same indicating that the dianions of 8 and 23, respectively, are I: 1 mixtures of the corresponding N-l and N-3 deprotonated forms. The lumazine-7-carboxylic acids (23, 26, 28, 29, 31, 33) are in comparison to their 6-carboxyJic acid counterparts (8, 12, 13, 21, 39) stronger acids by about I pK unit due to the resonance effect of the 4-oxo function on C-7 but not C-6. Alkaline KMn04 oxidation of 6.7-dimethyl-Iumazine (30) forms expectedly 6-methyl-Iumazine-7-carboxylic acid (31) in high yield according to the activation of the 7-methyl group by the electron-attracting 4-carbonyl residue.

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