Synthesis and anti‐inflammatory activity of 8H‐1‐thia‐8‐aza‐dibenzo[e,h]azulenes

Abstract

Synthesis of a novel class of fused heterotetracyclic compounds, 8H‐1‐thia‐8‐aza‐dibenzo[e,h]azulenes (VII), is described. Starting N‐benzoyl‐protected 5H‐dibenzo[b,f]azepine (XI, PG = Bz) was oxidized to 5‐benzoyl‐10,11‐epoxy‐10,11‐dihydro‐5H‐dibenzo[b,f]azepine (2), which subsequently rearranged in Lewis acid‐induced epoxide ring opening to give 5‐benzoyl‐5,11‐dihydro‐10H‐dibenzo[b,f]azepin‐10‐one (3). Vilsmeier reaction of 3 provided β‐chlorovinyl aldehyde 4 that readily cyclized with ethyl 2‐mercaptoacetate to form dibenzazepino[4,5]‐fused thiophene structure 5. Further transformation of substituent at C‐2 position of 5 and N‐deprotection led to final aminoalkoxy derivatives 9. All compounds with tetracyclic skeleton were tested in vitro for their anti‐inflammatory activity. J. Heterocyclic Chem., (2011).

In vitro and in vivo biological activities of azulene derivatives with potential applications in medicine

“…Ozimec Landek et al synthesized two series of azulene compounds fused with two benzene rings [ 44 , 45 ] and analyzed the influence of new compounds on tumor necrosis factor α (TNF-α) production. TNF-α can be considered an important inflammatory factor.…”

Effect of intermittency factor on singlet oxygen and PGE2 formation in azulene-mediated photodynamic therapy: A preliminary study

“…The relatively weak anti-inflammatory effect of azulene has lead to attempts to develop azulene derivatives with higher anti-inflammatory activity. For example, two thia-azulene derivatives that were developed by incorporating benzene rings into azulene’s structure with substitution of a sulphur atom for a carbon atom demonstrated dramatically high potency for TNF-alpha inhibition [ 54 , 55 ].…”

Palladium-Catalyzed Q-Tube-Assisted Protocol for Synthesizing Diaza-dibenzo[a,e]azulene and Diaza-benzo[a]fluorene Derivatives via O2 Acid-Promoted Cross-Dehydrogenative Coupling

“…Fused nitrogen-containing heterocycles are remarkable structural units, since they are the key motifs in several natural products and are effectively embedded in a variety of potent pharmacologically active compounds. − Consequently, such ring systems are often regarded as essential pillars in the development and design of novel drugs. Among these fused nitrogen-heteroaromatics are aza-benzoazulene and aza-benzofluorene derivatives and their analogy, which have a variety of medicinal and pharmacological activities such as anti-inflammatory, − anticancer, − antitumor, − antidiabetic, antimicrobial, and antimycobacterial . Also they can serve as dopamine D4 receptor ligands to treat erectile dysfunction , and as a dopamine D3 agonist for the treatment of several neurological disorders such as anxiety, major depression, and schizophrenia. , In addition, members of this class of compounds have been used as building blocks in materials developed with distinctive optical and electrical characteristics. − Therefore, it may be inferred that the azulene- and fluorene-based compounds are patentable and are regarded as essential motifs in drug development, even though they have not been extensively employed until now.…”