Quinazoline 3-Oxide Structure of Compounds Previously Described in the Literature as 3.1.4-Benzoxadiazepines¹

The benzodiazepine story

“…This approach did not appear to be very promising, since the 0022-2623/79/1822-0001$01.00/0 © 07110. Received September 5,1978 then known tranquilizers were intensively studied by several groups of investigators, e.g., meprobamate (Miltown) at Wallace Laboratories, reserpine by the Ciba research group, and chlorpromazine by the SKF research team.…”

“…Neither removal of the Ñ-oxide oxygen nor hydrogenation at the 3,4 position yielded anything of interest. 5,6 At that time (this was the second half of 1955) we had to stop our work in the quinazoline field since other problems seemed to be of greater importance. We became involved with other synthetic projects and the isolation, purification, and degradation of various antibiotics.…”

Elaboration of Benzoxadiazepine and Benzotriazocine Scaffolds

“…Benzoxadiazepines have been the subject of several studies and assumptions before elucidation of their structure. [11][12][13][14][15][16] The first publication about the synthesis of these fused seven-membered heterocycles was reported in 1962 by Sulkowski and Childress. [17] They described the treatment of 2-amino-5- In 1967, Kaneko and Yamada described the photolysis of 4phenylquinazoline-3-oxides to benzo[f][1,3,5]-oxadiazepines.…”

Natural Product Scaffolds as Leads to Drugs

“…A seven-membered di-aza ring was reported before the turn of the 20th Century as a potential dyestuff under the name 'benzheptodiazine' (or 4,5-benzo-[hept-1,2,6-oxdiazine] in the German literature). Sternbach remembered this work from his earlier years as a synthetic chemist in Poland before the Second World War and, although he subsequently corrected the structure to a quinazoline 3-oxide (not a seven-membered ring system), the previous structure formed the basis for his work leading to Librium ® and Valium ® [3][4][5], building upon the simple syntheses of the benzodiazepines from O-phenylene diamine and benzaldehyde reported in 1934 [6]. Subsequently, close to 40 years after the first correct report of this structural class, natural product-derived molecules containing this structural feature, the tomaymycins, were identified in 1971 [7].…”