Derivatives of 11-(1-piperazinyl)-5H-pyrrolo[2,1-c][1,4]benzodiazepine as central nervous system agents

Abstract

Four 11-(1-piperazinyl)-5H-pyrrolo[2,1-c][1,4]benzodiazepines were prepared and evaluated as central nervous system agents. All were active psychotropic agents as determined by animal screening tests. The most interesting compound, 11-(1-piperazinyl)-5H-pyrrolo[2,1-c][1,4]benzodiazepine, showed dual activity as an antidepressant against tetrabenazine depression and as a neuroleptic as measured by protection vs. amphetamine lethality in grouped mice.

Development of a Novel Nonpeptidic 18F-Labeled Radiotracer for in Vivo Imaging of Oxytocin Receptors with Positron Emission Tomography

“…To couple the biaryl units with the benzopyrrolodiazepine moiety, the methyl ester functionality was hydrolyzed and converted to its acid chloride. Subsequent reaction with 10,11-dihydro-5 H -pyrrolo­[2,1- c ]­[1,4]­benzodiazepine, 8 , synthesized according to reported procedures, − provided the desired biaryl functionalized benzopyrrolodiazepines ( 4a – 4c ). To introduce a carboxyl group solely at the 3-position of the tricycle, aromatic acylation with trichloroacetyl chloride in the presence of Hünig’s base was performed followed by a haloform type reaction with aqueous NaOH to give the corresponding carboxylic acids ( 5a – 5c ).…”

Application of Privileged Molecular Framework of 7‐Fluoro‐1,4‐benzodiazepin‐2‐one‐5‐methylcarboxylate to the Synthesis of Its 1‐ and 5‐Disubstituted Analogs of Medicinal Interest

“…A further study involved the conversion of 4 to 7 through the reaction of the former with CH 3 I . The resulting lactim thioether function of 7 underwent facile nucleophilic displacements with a wide variety of cyclic secondary amines to give compounds 10a , 10b , 10c , 10d , 10e , 10f , 10g , 10h . Compounds 10a , 10b , 10c , 10d , 10e , 10f , 10g , 10h were characterized on the basis of their spectral data.…”

Using Genome Sequence to Enable the Design of Medicines and Chemical Probes

“…(304–306) In 1978, a limited clinical trial of anthramycin was conducted for reduction of anxiety(307) followed by a study two years later in mice to study the effects on the central nervous system, in particular depression. (308) Shortly thereafter, Hurley & Thurston showed that anthraymcin’s position 11 forms adducts with the exocyclic amine of guanosine residues in the dsDNA minor groove and may have sequence selectivity. (309) A detailed structure–activity relationship (SAR) study by Thurston indeed revealed sequence selectivity of PBDs for the DNA minor groove,(310) culminating in the discovery that PBDs form a covalent bond with the exocyclic amine of guanosine in the minor groove, preferring R-G-R triples (where R is A or G) and indicating that the small molecule binding site spans three base pairs.…”