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Synthesis and Antiproliferative Activity in Vitro of Novel 1,5‐Benzodiazepines. Part II
Author(s) -
Nawrocka Wanda,
Sztuba Barbara,
Opolski Adam,
Wietrzyk Joanna,
Kowalska Maria W.,
Glowiak Tadeusz
Publication year - 2000
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/1521-4184(200101)334:1<3::aid-ardp3>3.0.co;2-2
Subject(s) - chemistry , benzodiazepine , in vitro , stereochemistry , chloride , biochemistry , organic chemistry , receptor
The reaction of 2,2,4‐trimethyl‐1 H ‐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‐1 H ‐2,3,4,5‐tetrahydro‐1,5‐benzodiazepine ( 3 ) and 1‐cinnamoyl‐2,2,4‐trimethyl‐1 H ‐2,3,4,5‐tetrahydro‐1,5‐benzodiazepine ( 4 ), were synthesized by the reduction of 1 and 2 using NaBH 4 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, 1 H NMR, and MS). 7‐Carboxy‐2,2,4‐trimethyl‐1 H ‐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).