title: An Update on the Synthesis of Pyrrolo[1,4]benzodiazepines.
abstract: Pyrrolo[1,4]benzodiazepines are tricyclic compounds that are considered "privileged structures" since they possess a wide range of biological activities. The first encounter with these molecules was the isolation of anthramycin from cultures of Streptomyces, followed by determination of the X-ray crystal structure of the molecule and a study of its interaction with DNA. This opened up an intensive synthetic and biological study of the pyrrolo[2,1-c][1,4]benzodiazepines that has culminated in the development of the dimer SJG-136, at present in Phase II clinical trials. The synthetic efforts have brought to light some new synthetic methodology, while the contemporary work is focused on building trimeric pyrrolo[2,1-c][1,4]benzodiazepines linked together by various heterocyclic and aliphatic chains. It is the broad spectrum of biological activities of pyrrolo[1,2-a][1,4]benzodiazepines that has maintained the interest of researchers to date whereas several derivatives of the even less studied pyrrolo[1,2-d][1,4]benzodiazepines were found to be potent non-nucleoside HIV-1 reverse transcriptase inhibitors. The present review is an update on the synthesis of pyrrolo[2,1-c][1,4]benzodiazepines since the last major review of 2011, while the overview of the synthesis of the other two tricyclic isomers is comprehensive.
authors.affiliation: Department of Chemistry, Section of Organic Chemistry and Biochemistry, University of Ioannina, 451 10 Ioannina, Greece. gvarvoun@cc.uoi.gr.
authors.forename: George
authors.initials: G
authors.lastname: Varvounis
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D001569:Benzodiazepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002986:Clinical Trials as Topic; D003500:Cyclization; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy; D006801:Humans; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D000970:Antineoplastic Agents; D011758:Pyrroles; C438462:pyrrolo(2,1-c)(1,4)benzodiazepine; D001569:Benzodiazepines; D004247:DNA
keywords: DNA-interactive agents; anti-HIV activity; anticancer activity; heterocycles; pyrrolobenzodiazepines; small molecules
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