The synthesis of a series of 6-(substituted-phenyl)-1,2,4-triazolo[4,3-b]pyridazines (VIII) is reported. Some of these derivatives show activity in tests predictive of anxiolytic activity [(a) protection against pentylenetetrazole-induced convulsions; (b) thirsty rat conflict procedure]. They also represent a new class of compound which inhibits [3H]diazepam binding. Structure--activity correlations, as well as the ability of structures VIII to inhibit [3H]diazepam binding (in vitro), are discussed.

Methods for the synthesis of (pyridinyl)‐1,2,4‐triazolo[4,3‐a]pyridines were developed. The principal route to the required intermediate 2‐chloropyridines was based on rearrangements of mono N‐oxides of 2,2′‐bipyridine, 2,3′‐bipyridine, 3,3′‐bipyridine, 2,4′‐bipyridine and 4,4′‐bipyridine with phosphorus oxychloride. Reaction of 3,3′‐bipyridine 1‐oxide or 2,2′‐bipyridine 1‐oxide with phosphorus oxychloride gave mixtures of chloro isomers. Reaction with acetic anhydride, 3,3′‐bipyridine 1‐oxide and 2,2′‐bipyridine 1‐oxide gave exclusively [3,3′‐bipyridine]‐2(1H)‐one and [2,2′‐bipyridine]‐6(1H)‐one, respectively. 1,2,4‐Triazolo[4,3‐a]pyridines with pyridinyl groups at the 5,6,7 and 8 positions were synthesized.

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The use of α‐(substituted‐phenyl)‐4‐morpholineacetonitriles in 1,4‐additions to ethyl acrylate, ethyl crotonate, methyl α‐methylacrylate, acrylonitrile, methylacrylonitrile, crotononitrile and cinnamonitrile was studied. A convenient route to 6‐aryl‐4,5‐dihydro‐3(2H) pyridazinones from aryl aldehydes and heterocyclic aldehydes was developed.

A series of polyfluoro-3-quinolonecarboxylic acids have been synthesized and their in vitro antibacterial activity evaluated. The desired 7-(substituted amino) derivatives were prepared from the 5,6,7,8-tetrafluoroquinolone acids. Conversely, amine displacement occurred primarily at the 5-position when the ester was used. Structure-activity studies indicated that the antibacterial activity was greatest when the N-1 substituent was cyclopropyl and the 7-substituent was 4-methyl-1-piperazinyl. All 5-(substituted amino) derivatives showed poor in vitro activity.