Synthesis and Antiproliferative Activityin Vitro of Novel 1,5-Benzodiazepines. Part II

Abstract

The reaction of 2,2,4‐trimethyl‐1H‐2,3‐dihydro‐1,5‐benzodiazepine (1) with cinnamoyl chloride leading to the formation of 1‐cinnamoyl derivative 2 is described. Two novel benzodiazepines, 2,2,4‐trimethyl‐1H‐2,3,4,5‐tetrahydro‐1,5‐benzodiazepine (3) and 1‐cinnamoyl‐2,2,4‐trimethyl‐1H‐2,3,4,5‐tetrahydro‐1,5‐benzodiazepine (4), were synthesized by the reduction of 1 and 2 using NaBH4 in i‐PrOH and two other derivatives 5 and 6 were obtained by reaction of 4 with equimolar and dimolar quantity of cinnamoyl chloride, respectively. The structures of 1—6 were confirmed by analytical and spectral data (IR, 1H NMR, and MS). 7‐Carboxy‐2,2,4‐trimethyl‐1H‐2,3‐dihydro‐1,5‐benzodiazepine (7) was synthesized and its crystals were subjected to X‐ray analysis. Benzodiazepines 1—6 were evaluated for antiproliferative activity in vitro. Among the compounds tested, 4—6 exhibited cytotoxic activity against human cancer cell lines, namely SW707 (colon cancer), MCF‐7 (breast cancer), A549 (lung cancer), and HCV29T (bladder cancer).

Synthesis and antiproliferative activity of some diaryldiazepines and diarylpyrimidines

“…Recent reports indicate the multifarious activities [13] of various benzodiazepines and diazepines condensed with different heterocyclic systems. In light of the reports available for diaryl heterocyclic systems, we envisaged the synthesis of diaryldiazepines and diaryl pyrimidines from a common intermediate.…”

Synthesis of Novel 3-Amino-2-(1H)-Thioxo-4(3H)-Quinazolinone Derivatives. Part 3

“…The presence of oxalyl ( COCO ) or malonyl ( COCH 2 CO ) groups in heterocyclic compounds belonging to various chemical families is known to be related to psychotropic, antiaggregation, anti-inflammatory, anti-HIV, and antiproliferative activity of these compounds. [21][22][23][24][25][26] It is reasonable to assume that the presence of analogous units in derivatives of quinazolinone 1 yields bioactive compounds as well. Similar situation is assumed for the presence of pharmacophor substituents in the ester 5.…”

Synthesis of novel tricyclic 4‐chloro‐7,8,10,11‐tetrahydro‐5H‐benzo[e]pyrimido[4,5‐b][1,4]diazepin‐9(6H)‐ones

“…For example, clozapine is used to treat schizophrenia; pirenzepine acts selectively as a muscarinic receptor (M1) antagonist; and apafant acts as the platelet activating factor inhibitors [1]. Consequently, syntheses of benzodiazepine derivatives or diazepine-containing heterocycles are of interest to organic and medicinal chemists.…”

“…Consequently, syntheses of benzodiazepine derivatives or diazepine-containing heterocycles are of interest to organic and medicinal chemists. Thus, dibenzo[b,e] [1,4]diazepines and other tricyclic systems with a 1,4-diazepine moiety are well documented in the literature [2][3][4][5][6][7][8][9].…”

“…These methodologies entail Bischler-Napieralski cyclization reactions and iminium cyclization reactions as the key transformation steps. To expand the scope of the iminium-cyclization reaction, we envisioned that enaminones 1 could be reacted with various aldehydes to prepare 7,8,10,11tetrahydro-5H-benzo[e]pyrimido [4,5-b] [1,4]diazepin-9(6H)ones [16], as depicted in Scheme 1. Although syntheses of dibenzo [b,e] [1,4]diazepines are frequently reported, there is few report of aminopyrimidines as substrates for such cyclization reactions [16].…”