Syntheses and interferon inducing acitivites are reported for 137 relatives of 1,3-dimethyl-4-(3-dimethylamino-propylamino)-1H-pyrazolo[3,4-b]quinoline (1). Three different generalized synthetic schemes for the preparation of pyrazolo[3,4-b]quinolines are presented and limitations contrasted. Other heterocyclic nuclei containing the 3-dimethylaminopropylamino side chain include pyridine, quinoline, acridine, pyrazolo[3,4-b]pyridine, pyrazolo[3,4-B][1,8]naphthyridine, pyrazolo[4',3':5,6]pyrido[2,3-d]pyrimidine, dipyrazolo[3,4-b:4',3'-e]pyridine, pyrrolo-[2,3-b]quinoline, isothiazolo[5,4-b]quinoline, and pyrido[2,3-h]pyrazolo[3,4-b]quinoline. Structural requirements for interferon induction in this series are discussed and two of the more active compounds (172 and 196) are compared directly with tilorone.

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The syntheses of tritium labeled (S)‐3‐(5‐chloro‐2‐[OC3H3]methoxyphenyl‐1,3‐dihydro‐3‐fluoro‐6‐(trifluoromethyl)‐1H‐indol‐2‐one, and carbon‐14 (S)‐3‐(5‐chloro‐2‐methoxyphenyl)‐1,3‐dihydro‐3‐fluoro‐6‐(trifluoromethyl)‐2H‐[2,3‐14C2] indol‐2‐one are reported. The 3H‐labeled compound was prepared in a two‐step synthesis from C3H3I. The final product was purified via chiral HPLC to yield the desired enantiomer in a 4% radiochemical yield and a specific activity of 60 Ci/mmol. The 14C‐labeled compound was prepared in a four‐step synthesis from diethyl [carboxylate‐14C1,2] oxalate. The final product was purified via chiral HPLC to yield the desired enantiomer in a 20% radiochemical yield and a specific activity of 28.4 μCi/mg. Copyright © 2002 John Wiley & Sons, Ltd.

A series of new substituted benzamides has been synthesized and evaluated for dopamine antagonist activity and for antagonism of cisplatin-induced emesis in the dog and in the ferret. It was found that modification of the 2-methoxy substituent of metoclopramide was detrimental to dopaminergic D2 antagonism but not necessarily to antagonism of cisplatin-induced emesis. A number of analogues having a beta-keto, beta-hydroxy, beta-methoxy, beta-imino, or beta-unsaturated alkyloxy substituent instead of methoxy have shown equal or superior protection from emesis to that of metoclopramide. At the same time these compounds were found to be free of dopaminergic D2 antagonism in both in vitro ([3H]spiperone binding) and in vivo tests (rat catalepsy, antagonism of apomorphine-induced stereotypy in the rat, and apomorphine-induced emesis in the dog).

A reliable synthesis of 14 C labeled 6-hydroxy-buspirone is described. The molecule belongs to a unique class of compounds with the potential for anxiolytic activity. A radiolabeled analog was prepared to support the development of 6-hydroxy-buspirone. Specifically, a labeled variant was designed to meet the requirements of a human adsorption-distribution-metabolism-elimination (ADME) study. Multiple 14 C labels were needed to fully track the potential metabolic transformation of the molecule. Labeled 6-hydroxy-buspirone was prepared by oxidation of separately labeled versions of [ 14 C]buspirone. The final product was isolated in reasonable yield with a radiochemical purity of 99.8%.