5358-44-1

Upstream product

• 604-75-1 oxazepam 
• 17977-76-3 2-chloro-N-{4-chloro-2-[(hydroxyimino)(phenyl)methyl]phenyl}acetamide 
• 18097-52-4 2-amino-5-chlorobenzophenone oxime 
• 719-59-5 5-chloro-2-aminobenzophenone 

Downstream Products

• 84044-34-8 7-Chloro-5-phenyl-3-(3',5'-dimethyl-1'-pyrazolyl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one 
• 61984-08-5 7-chloro-3-hydroxyamino-5-phenyl-1,3-dihydro-benzo[e][1,4]diazepin-2-one 
• 18878-33-6 7-chloro-3-(4,5-dihydro-thiazol-2-ylsulfanyl)-5-phenyl-1,3-dihydro-benzo[e][1,4]diazepin-2-one 
• 84044-28-0 7-Chloro-5-phenyl-3-(2',6'-dimethoxybenzoylhydrazino)-2,3-dihydro-1H-1,4-benzodiazepin-2-one 
• 84044-29-1 7-Chloro-5-phenyl-3-(3',4',5'-trimethoxybenzoylhydrazino)-2,3-dihydro-1H-1,4-benzodiazepin-2-one 
• 84044-33-7 7-Chloro-3-{N'-[1-(2-hydroxy-phenyl)-meth-(E)-ylidene]-hydrazino}-5-phenyl-1,3-dihydro-benzo[e][1,4]diazepin-2-one 
• 84044-30-4 7-Chloro-5-phenyl-3-pivaloyhydrazino-2,3-dihydro-1H-1,4-benzodiazepin-2-one 
• 84044-25-7 7-Chloro-5-phenyl-3-acetylhydrazino-2,3-dihydro-1H-1,4-benzodiazepin-2-one 
• 84044-31-5 6-Chloro-4-phenylquinazoline-2-aldehyde benzoylhydrazone 
• 84044-32-6 7-Chloro-3-(N'-isopropylidene-hydrazino)-5-phenyl-1,3-dihydro-benzo[e][1,4]diazepin-2-one 

Relevant academic research and scientific papers

In vivo evaluation of substituted 3-amino-1,4-benzodiazepines as anti-depressant, anxiolytic and anti-nociceptive agents

Oxazepam (CAS 604-75-1) 4 a served as building block in the synthesis of substituted 3-amino-l,4-benzodiazepines, which were subsequently tested in various CNS animal models. The hydroxy group of oxazepam was either activated as a chloride (Method A) or as a phos- phor-oxy derivative (Method B) giving the desired 3-amino-l,4-benzodiapines 6 a- 6r in high yields with primary and secondary amines in a typical nucleophilic substitution reaction. Eighteen 3-substi- tuted 1,4-benzodiazepines were prepared and served as new chemical entities and for lead structure discovery. The mixed cholecystokinin (CCK) antagonist 6 e showed anxiolytic and antidepressant effects from 10μg/kg in mice in the elevated x-maze test and the forced swimming test. The CCK 1 antagonist 6 g has shown antidepressant effects from the same dose, but lacked anxiolytic properties. Both compounds potentiated at a dose of 0.5 mg/kg morphine antinocicep- tion with a maximum possible effect (MPE) about 35 %. By assessing initially the MPE of antinocipection for the 18 newly synthesised benzodiazepines in the tail-flick test, 4 other benzodiazepines were found active. In further in vivo evaluation the cyclohexyl derivative 6 i displayed anxiolytic, antidepressant and antinociceptive properties as single agent at a dose of 5 mg/kg without toxicity. The benzodiazepines 6i and 6p, which initially showed a higher MPE in terms of morphine potentiation (43/44%) showed analgesic effects as single agents, without having anxiolytic or antidepressant properties. The amino-piperidinyl derivative 6 p displayed a similar dose-response relationship to morphine, but was 3 times more potent. ECV Editio Cantor Verlag, Aulendorf (Germany).

Synthesis of substituted 3-anilino-5-phenyl-1,3-dihydro-2H-1,4- benzodiazepine-2-ones and their evaluation as cholecystokinin-ligands

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 CCK 1 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.

NOVEL 3-SUBSTITUTED-1,4-BENZODIAZEPINES

The present invention relates to compounds of formula (I). The invention also relates to methods for preparing the compounds and their uses as CCK receptor ligands and CCK antagonists.

Diazepam enzyme conjugates

Novel compositions are provided for the determination of one or a group of organic materials (hereinafter referred to as "ligands"), where the compositions have a ligand or ligand counterfeit bonded to an enzyme, the conjugate referred to as "enzyme-bound