14439-61-3

Hazards Identification

Pictogram(s):

Signal:

Warning

GHS Hazard Statements:

H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]

Precautionary Statement Codes:

P264, P270, P301+P317, P330, and P501

Hazard Classes and Categories:

Acute Tox. 4 (100%)

Usage

Uses

Used in Pharmaceutical Research:
4'-CHLORODIAZEPAM is used as a translocator protein ligand for mitochondrial functional studies. It aids in understanding the role and behavior of these proteins within the cellular context, particularly in relation to mitochondrial function and its implications in various diseases and conditions.
Used in Neuroprotective Research:
4'-CHLORODIAZEPAM is used as a neuroprotective agent for glucose-deprived T98G astrocyte cell lines. It helps researchers investigate the compound's potential protective effects on these cells under conditions of glucose deprivation, which can be relevant to understanding and treating certain neurological disorders and conditions related to energy metabolism in the brain.

Biochem/physiol Actions

4′-Chlorodiazepam (Ro5-4864) is a potent selective ligand for the mitochondrial translocator protein 18kDa (TSPO), formerly known as the peripheral benzodiazepine receptor (PBR). Ro5-4864 does not bind to GABA(A) receptors and lacks typical benzodiazepine effects, but has been found to be neuroprotective in several studies.

InChI:InChI=1/C16H12Cl2N2O/c1-20-14-7-6-12(18)8-13(14)16(19-9-15(20)21)10-2-4-11(17)5-3-10/h2-8H,9H2,1H3

Synthetic route

N-<4-chloro-2-(4-chlorobenzoyl)phenyl>-N-methylchloroacetamide (99833-82-6) → 4-chlorodiazepam (14439-61-3)

Conditions	Yield
With hexamethylenetetramine In methanol; water for 22h; Heating;	94%

N-<4-chloro-2-(4-chlorobenzoyl)phenyl>-N-methylphthalimidoacetate (99833-83-7) → 4-chlorodiazepam (14439-61-3)

Conditions	Yield
With hydrazine In methanol; water at 60℃; for 3h;	80%

7-chloro-5-(4-chlorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one (5571-60-8) + methyl iodide (74-88-4) → 4-chlorodiazepam (14439-61-3)

Conditions	Yield
With sodium methylate In toluene at 20℃; for 168h;	37%

3-(4-chlorobenzene)-5-chloro-2,1-benzoisoxazole (724-07-2) → 4-chlorodiazepam (14439-61-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: 2) Fe, aq. HCl / 1) 5h, 80 deg C; 2) ethanol, water, 3 h, reflux 2: 95 percent / CHCl3 / 8 h / Heating 3: 80 percent / N2H4 / methanol; H2O / 3 h / 60 °C View Scheme
Multi-step reaction with 3 steps 1: 2) Fe, aq. HCl / 1) 5h, 80 deg C; 2) ethanol, water, 3 h, reflux 2: 86 percent / benzene / 1) 10 deg C, 50 min. (addition); 2) 90 min. 3: 94 percent / hexamethylenetetramine / methanol; H2O / 22 h / Heating View Scheme

5,4'-dichloro-2-methylaminobenzophenone (78961-59-8) → 4-chlorodiazepam (14439-61-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 95 percent / CHCl3 / 8 h / Heating 2: 80 percent / N2H4 / methanol; H2O / 3 h / 60 °C View Scheme
Multi-step reaction with 2 steps 1: 86 percent / benzene / 1) 10 deg C, 50 min. (addition); 2) 90 min. 2: 94 percent / hexamethylenetetramine / methanol; H2O / 22 h / Heating View Scheme

4-chlorobenzonitrile (100-00-5) → 4-chlorodiazepam (14439-61-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: 43 percent / KOH / methanol; benzene / 3 h / Ambient temperature 2: 2) Fe, aq. HCl / 1) 5h, 80 deg C; 2) ethanol, water, 3 h, reflux 3: 95 percent / CHCl3 / 8 h / Heating 4: 80 percent / N2H4 / methanol; H2O / 3 h / 60 °C View Scheme
Multi-step reaction with 4 steps 1: 43 percent / KOH / methanol; benzene / 3 h / Ambient temperature 2: 2) Fe, aq. HCl / 1) 5h, 80 deg C; 2) ethanol, water, 3 h, reflux 3: 86 percent / benzene / 1) 10 deg C, 50 min. (addition); 2) 90 min. 4: 94 percent / hexamethylenetetramine / methanol; H2O / 22 h / Heating View Scheme

p-chlorobenzyl cyanide (140-53-4) → 4-chlorodiazepam (14439-61-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: 43 percent / KOH / methanol; benzene / 3 h / Ambient temperature 2: 2) Fe, aq. HCl / 1) 5h, 80 deg C; 2) ethanol, water, 3 h, reflux 3: 95 percent / CHCl3 / 8 h / Heating 4: 80 percent / N2H4 / methanol; H2O / 3 h / 60 °C View Scheme
Multi-step reaction with 4 steps 1: 43 percent / KOH / methanol; benzene / 3 h / Ambient temperature 2: 2) Fe, aq. HCl / 1) 5h, 80 deg C; 2) ethanol, water, 3 h, reflux 3: 86 percent / benzene / 1) 10 deg C, 50 min. (addition); 2) 90 min. 4: 94 percent / hexamethylenetetramine / methanol; H2O / 22 h / Heating View Scheme

Upstream product

• 5571-60-8 7-chloro-5-(4-chlorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one 
• 74-88-4 methyl iodide 
• 100-00-5 4-chlorobenzonitrile 
• 140-53-4 p-chlorobenzyl cyanide 
• 78961-59-8 5,4'-dichloro-2-methylaminobenzophenone 
• 724-07-2 3-(4-chlorobenzene)-5-chloro-2,1-benzoisoxazole 
• 99833-83-7 N-<4-chloro-2-(4-chlorobenzoyl)phenyl>-N-methylphthalimidoacetate 
• 99833-82-6 N-<4-chloro-2-(4-chlorobenzoyl)phenyl>-N-methylchloroacetamide 

Relevant academic research and scientific papers

Synthesis and Spectral Properties of 7-Chloro-5-[(o- and p-R1)phenyl]-1-R2-3H-[1,4]benzodiazepin-2-ones

A series of twelve new 7-chloro-5-[(o- and p-R1)phenyl]-1-R2-3H-[1,4] benzo-diazepin-2-ones, which have possible pharmocological properties were synthesized. The synthesis of all the final compounds was carried out by four steps. The structure of all final products was corroborated by ir, 1H nmr, 13C nmr and ms, and have been obtained in 35-94 percent yield.

Method for inhibiting the proliferation of tumor cells

A method of inhibiting the proliferation of tumor cells is disclosed which comprises the treatment of such tumor cells with a benzodiazepine having a selective affinity to bind peripheral binding sites on the tumor cell in order to induce non-proliferation of said tumor cells.