1-Azacycloalkyl-1,4-benzodiazepin-2-ones with antianxiety-antidepressant actions

Abstract

A series of 1-azacycloalkyl-1,4-benzodiazepin-2-ones were synthesized from 1-azacycloalkyl-2-benzoylanilines and corresponding imines and then evaluated for their central nervous system activities. Pharmacological data showed that some of these compounds have potent antidepressant properties, as assessed by their antagonism of tetrabenzine (TBZ) induced ptosis and their inhibition of [3H]norepinephrine uptake into rat brain synaptosomes, as well as their moderate antianxiety properties of preventing of pentylenetetrazol (PTZ) convulsion, suppressing conflict behavior, and displacing potential for [3H]diazepam binding. Introduction of a halogen substituent at position 7 of the 1,4-benzodiazepine ring lengthened the anti-PTZ effects, although the peak effect was slightly reduced and clearly enhanced the anti-PTZ and anticonflict properties. Introduction of Cl to the ortho position of the phenyl ring at position 5 greatly reduced the antidepressant properties. The secondary amine function of the azacyclic ring at position 1 was essential for the production of the antidepressant properties. Of these new series, 7-fluoro-5-(2-fluorophenyl)-1,3-dihydro-1-(4-piperidinyl)-2H-1,4-benzodi azepin-2 -one has the potential to become a useful antidepressant drug with a moderate antianxiety property.

Access to Optically Active 3-Azido- and 3-Aminopiperidine Derivatives by Enantioselective Ring Expansion of Prolinols

“…A great number of patents related to 3-aminopiperidine derivatives have been taken out due to the potential biological activities of these products. For example, 3-aminopiperidine derivatives can present antitumoral, antibacterial, anti-inflammatory, analgesic, antiviral, antidepressive, and anti-ischemic properties. They can also be receptor ligands of the CNS and can find applications as psychotropic agents as well as in the treatment of hormone deficiency and neurological disorders related to β-amyloid production .…”

Crystal structure, Hirshfeld surface analysis and interaction energy and DFT studies of (S)-10-propargylpyrrolo[2,1-c][1,4]benzodiazepine-5,11-dione

“…1,4-Benzodiazepines and their derivatives have attracted the attention of chemists since the early 1960s, mainly because of the broad spectrum of biological properties exhibited by this class of compounds, in particular their psychopharmacological properties (Thurston & Langley, 1986;Kamal et al, 2007;Antonow et al, 2007;Archer & Sternbach, 1968;Mohiuddin et al, 1986, Bose et al, 1992Gregson et al, 2004). The vast commercial success of these medicinal agents has resulted in their chemistry being a major focus of research in the field of medicinal chemistry and many such ring systems having been described (Benzeid et al, 2009a,b;Randles & Storr, 1984;Sugasawa et al, 1985;Cipolla et al, 2009). Pyrrolo [2,1-c] [1,4]benzodiazepines are a group of potent chemicals produced by Streptomyces species.…”

Palladium-Mediated Arylation of 3-Aminopiperidines and 3-Aminopyrrolidines

“…Aminopyrrolidine 1 and aminopiperidine 2 appended at heterocycles are building blocks or intermediates widely used in the drug discovery process. 3-( N -Arylamino)pyrrolidines are present in several potential or established biologically active compounds such as analgesics, antivirals, antidepressants, antibacterials, antiinflammatory drugs, anti-ischemia, antitumorals, or ligands of central nervous system . 3-( N -Arylamino)piperidines have found applications as psychotropic agents 9 or in the treatment of hormone deficiency and neurological disorders related to β-amyloid production…”