By J. M. ESSERY and K. SCHOFIELD.%Methyl-, 3-ethyl-, and 3-isopropyl-pyridine, and 3,5-dimethyl-and 2,3,5,6-tetramethyl-pyridine have been converted into the 4-nitropyridine l-oxides, and thence into the 4-chloropyridine 1-oxides from which were derived the 4-amino-, 4-methylamino-, and (except in the cases of the tetramethyl compound) the 4-dimethylamino-pyridine 1 -oxides. These series of l-oxides provided, on deoxygenation, series of 4-nitro-, 4-aniino-, 4-methylamino-, and 4-dimethylamino-pyridines.Nitration of 3-t-butylpyridine 1-oxide proceeds a t position 2 or 6.

The synthesis of some 1,6-dihydro-6-oxo-2-phenylpyrimidine-5-carboxylic acids and esters with potent oral and intravenous antiallergic activity against passive cutaneous anaphylaxis in the rat is described. Requirements for high activity include a free NH group in the pyrimidinone nucleus and a small to medium size ortho alkoxy or alkenyloxy group on the phenyl ring. It is suggested that in the case of the highly active compounds hydrogen bonding occurs between a nitrogen of the pyrimidine ring and the ethereal oxygen. The nature of this bonding and its possible contribution to an optimum configuration for the molecules is discussed.

Some 2-(2-alkoxyphenyl)-and 2-[2-(alkenyloxy)phenyl]-5-(l/f-tetrazol-5-yl)pyrimidin-4(3fí)-ones were prepared and found to be about 5-10 times more potent than the corresponding pyrimidine-5-carboxylic acids when tested orally against passive cutaneous anaphylaxis in the rat. Structure-activity relationships within the two series are similar. 2-(2-n-Propoxyphenyl)-5-(lH-tetrazol-5-yl)pyrimidin-4(3H)-one is in clinical trial for the prophylactic treatment of asthma.

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A series of derivatives of 5-methoxysterigmatocystin (3a,12c-dihydro-8-hydroxy-6,11-dimethoxy-7H-furol[3',2':4,5]furo[2,3-c]xanthen-7-one) has been prepared and evaluated for antitumor activity. The potency of the parent compound has been associated with the intact bisfurano ring system and with the double bond in the terminal furan ring. It has been shown that new substituents can be introduced in the xanthone portion of the molecule and that the antitumor activity is in some cases preserved.