1,3-Dihydro-2H-1,4-benzodiazepine-2-ones and Their 4-Oxides

Bell, Stanley C.; Sulkowski, Theodore S.; Gochman, Carl; Childress, Scott J.

doi:10.1021/jo01049a052

Cited by 77 publications

(17 citation statements)

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“…Oxazepam was claimed to be synthesized via the known Polonowski rearrangement of the N-oxide on an industrial scale [28]. The chloroacetamide amide 1 was converted into a quinazoline structure [29] in presence of a Lewis acid, such as ZnCl 2 .…”

Section: Chemistrymentioning

confidence: 99%

Synthesis of Substituted 3‐Anilino‐5‐phenyl‐1,3‐dihydro‐ 2H‐1,4‐benzodiazepine‐2‐ones and their Evaluation as Cholecystokinin‐Ligands

Offel

Lattmann

Singh

et al. 2006

Archiv der Pharmazie

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3-Amino-1,4-benzodiazepines as well as chemically related diverse amines were prepared from oxazepam and subsequently screened on the cholecystokinin receptor in a radiolabel binding assay. Oxazepam 2 was activated via its 3-chloro-1,4-benzodiazepine intermediate 3 and was reacted with a large series of aliphatic and aromatic amines. The substituted 3-anilino-1,4-benzodiazepine structure was identified as lead structure in a diverse series of 3-amino-1,4-benzodiazepines 4-38 and the full SAR (structure-activity relationship) optimisation provided 3-anilinobenzodiazepines 16-38 with CCK1 receptor selectivity to CCK2. The compounds 18, 24, 28 and 33 have shown affinities at the CCK1 receptor of 11, 10, 11 and 9 nM, respectively. These equipotent CCK1 ligands were fully evaluated in behaviour pharmacological essays. An antidepressant effect was identified in the tail suspension- and the Porsolt swimming-test. The ED50 values for 24 and 28 were determined in these assays as 0.46 and 0.49 mg/kg. The mixed antagonist 37 showed in addition to the antidepressant effects anxiolytic properties.

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Section: Chemistrymentioning

confidence: 99%

Synthesis of Substituted 3‐Anilino‐5‐phenyl‐1,3‐dihydro‐ 2H‐1,4‐benzodiazepine‐2‐ones and their Evaluation as Cholecystokinin‐Ligands

Offel

Lattmann

Singh

et al. 2006

Archiv der Pharmazie

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“…In addition to esters of glycine, esters of methionine and tyrosine have been used (27). Even a spiro compound has been made from the acid chloride prepared from 1-aminocyclopentane carboxylic acid (3).…”

Section: Chi Cbhs CImentioning

confidence: 99%

“…Since there is at present only one route to the 2-aminobenzodiazepine 4-oxides that is independent of the benzodiazepin-2-ones-namely, the rearrangement by amines of the 2-chloromethylquinazoline 3-oxides (see Scheme VII) -the hydrolysis method is of limited value. This is particularly so since 2-chloromethylquinazoline 3-oxides rearrange analogously with sodium hydroxide directly to benzodiazepin-2-one 4-oxides (2,3). A host of such reactions has been carried out and this is probably the preferred synthesis when the 4-oxides are wanted.…”

Section: Chi Cbhs CImentioning

confidence: 99%

See 1 more Smart Citation

1,4-Benzodiazepines

Childress¹,

Gluckman²

1964

Journal of Pharmaceutical Sciences

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“…We have selected the first approach in view of a. well known, technical-scale N-oxidation of N-demethyl analogue of 1,4-benzodiazepine 1 in the production of therapeutically important 3-hydroxy derivative 14 (Praxiten®, generic name Oxazepam), b. the observation that in the 1 H-NMR spectra of 1 and 2 AB system of C(3)H 2 protons is centered at 4.31 ppm and 4.64 ppm, respectively, and in their 13 C-NMR spectra C(3) carbon appears at 56.59 ppm and at 67.68, respectively. This reveals strong electron-deshielding effect of the N-O group and consequently higher C(3)-H acidity in 2.…”

Section: Introductionmentioning

confidence: 99%