1,5‐Benzodiazepines. Part 13. Substituted 4H‐[1,2,4]Triazolo[4,3‐a][1,5]benzodiazepin‐5‐amines and 4H‐Imidazo[1,2‐a][1,5]benzodiazepin‐5‐amines as Analgesic, Antiinflammatory and/or Antipyretic Agents with Low Acute Toxicity.

Abstract

Multi-membered N-heterocycles R 0690 1,5-Benzodiazepines. Part 13. Substituted 4H-[1,2,4]Triazolo[4,3-a][1,5]benzodiazepin-5-amines and 4H-Imidazo[1,2-a][1,5]benzodiazepin-5-amines as Analgesic, Antiinflammatory and/or Antipyretic Agents with Low Acute Toxicity. -A series of benzodiazepines is prepared and tested for pharmacological activity. Compounds (XIII) and (XV) show remarkable analgesic, anti-inflammatory and antipyretic activities at doses devoid of acute adverse effects. -(GROSSI, G.; DI BRACCIO, M.; ROMA*, G.; BALLABENI, V.; TOGNOLINI, M.; CALCINA, F.; BAROCELLI, E.; Eur.

A combined experimental and theoretical study of the synthesis of quinazolino[3,2-a][1,5]benzodiazepin-13-ones

“…-2-oxo-2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-1-yl) 10.72 (1H, s, 5 -NH). 13 Benzoyl-3-methyl-2-oxo-2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-1-yl) 10.71 (1H, s, 5 -NH). 13 and the reaction mixture was stirred at room temperature for 2-3 h. After completion of reduction, as observed by TLC monitoring, the reaction mixture was filtered.…”

“…The 1 H NMR spectra of starting compounds 1a-c, as well as of previously described 1d-i, 18 exhibited the signals of aliphatic protons (CH 3 , CH 2 or CH groups) of the heptatomic ring, the characteristic NH singlet at about 9.0 ppm and the resonances of aromatic protons in the range of 6.7 7.2 ppm integrated for nine protons. 13 C NMR spectra of 1a-c, in addition to the unambiguously assigned aromatic and aliphatic carbon resonances, revealed two appropriate downfield lying lines at 170.2 171.0 ppm (5-CO) and 173.6 175.7 ppm (C-2). The missing NH singlet and the appearance of four additional aromatic protons in 1 H NMR spectra pointed to the formation of compounds 2a-i.…”

“…In addition, two new resonances, singlets at 2.1 ppm (COCH 3 ) and 10.7 ppm (5 -NH), were observed in 1 H NMR spectra of compounds 4a-c. The resonances in 13 C NMR spectra of compounds 4a-c at 136.5 ppm, 137.8 ppm and 145.4 ppm were attributed to 1 -, 2 -, 5 -aryl ring carbons, respectively, and the resonance at 169.6 ppm was attributed to 5 -NHCO carbon atom. These assignments were made by detailed analysis of HMBC spectra.…”

“…13 C NMR spectra of 2a-c, compared to spectra of 1a-c, showed the typical resonances with almost the same chemical shift values (169.7 170.9 ppm) for 5-CO, upfield shifted 1.9 3.0 ppm for C-2 and the new signals at ~134.7 ppm, ~144.5 ppm and ~167.7 ppm assigned to C-1 , C-2 and 1-CO, respectively. The presence of diastereotopic methylene protons (5-CH 2 ) which resonances formed characteristic AB quartet at ~ 4.3 ppm and ~ 4.5 ppm in 1 H NMR spectra and the absence of the resonance of 5-CO group carbon in 13 C NMR spectra were intrinsic to compounds 2d-f compared to 2a-c. 1 H and 13 C NMR spectra of compounds 2g-i showed the presence of 5-CH 3 group which resonated at 2.8 ppm and 39.4 ppm, respectively. Broadened resonances of aliphatic and some of aromatic moieties were observed in the case of compounds 2d, 2g, 2h in 1 H and 13 C NMR spectra possibly due to the slow dynamic processes of heterocycle ring compared to the NMR time scale.…”

“…The essential feature of the formation of the compounds of structure 3 was the missing signal of C-2 (carbonyl group) at ~172.8 ppm and the appearance of resonance at ~ 154.0 ppm (3a,b) and ~156.1 ppm (3d,e,g,h) attributed to C=N group carbon compared to the corresponding 13 C NMR spectra of compounds 2. The resonances of 1-CO group were shifted upfield by approximately 7 ppm and were observed in the range of 160.6-160.9 ppm, the resonances of C-1' carbon were shifted upfield ~ 13.4 ppm and those of C-2' downfield ~ 2.2 ppm.…”