2011-67-8

Usage

Uses

Used in Pharmaceutical Industry:
Nimetazepam is used as a sedative and hypnotic agent for the treatment of insomnia. It helps in inducing sleep and reducing anxiety, making it a valuable component in the management of sleep disorders.
Used in Anticonvulsant Applications:
Nimetazepam is also utilized as an anticonvulsant, helping to control and prevent seizures in patients with epilepsy or other seizure disorders. Its effectiveness in controlling seizures contributes to its importance in the pharmaceutical industry.

Originator

Erimin,Sumitomo,Japan,1977

Manufacturing Process

To a suspension of 73.9 g of 1-methyl-5-nitro-3-phenylindole-2-carbonitrile in 1.5 liters of dry tetrahydrofuran is added dropwise a solution of 126 g of boron trifluoride etherate in 220 ml of dry tetrahydrofuran with stirring for 2 hours. After addition, stirring is continued for an additional 3 hours. To the reaction mixture is added dropwise 370 ml of water and then 370 ml of concentrated hydrochloric acid with stirring under ice-cooling.The resulting precipitate is collected by filtration, washed with water followed by ethanol, and dried to give 56.3 g of crude 2-aminomethyl-1-methyl-5- nitro-3-phenylindole hydrochloride, melting point 263°C to 267°C.To a suspension of 6.5 g of 2-aminomethyl-1-methyl-5-nitro-3-phenylindole in 65 ml of glacial acetic acid is added dropwise a solution of 6.5 g of chromic anhydride in 6.5 ml of water at 20°C with stirring. The mixture is stirred at room temperature overnight and thereto is added 195 ml of water. To the mixture is added dropwise 100 ml of 28% ammonia water with stirring under cooling. The resultant precipitate is collected by filtration, washed with water and dried to give 5.9 g of a crude product having melting point 135°C to 140°C. Fractional recrystallization from ethanol gives 3.8 g of 1-methyl-7- nitro-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepine-2-one as yellow plates, melting point 153°C to 156°C. Further recrystallization from the same solvent gives pale yellow plates having melting point 156°C to 156.5°C.

Therapeutic Function

Tranquilizer

InChI:InChI=1/C16H13N3O3/c1-18-14-8-7-12(19(21)22)9-13(14)16(17-10-15(18)20)11-5-3-2-4-6-11/h2-9H,10H2,1H3

Upstream product

• 30008-54-9 1-methyl-2-aminomethyl-3-phenyl-5-nitroindole 
• 100-14-1 4-nitrobenzyl chloride 
• 4958-56-9 [2-(methylamino)-5-nitrobenzo]phenone 
• 77-78-1 dimethyl sulfate 
• 146-22-5 nitrazepam 

Downstream Products

• 102725-60-0 {[1-(2-Methylamino-5-nitro-phenyl)-1-phenyl-meth-(Z)-ylidene]-amino}-acetic acid 
• 56-40-6 glycine 
• 4958-56-9 [2-(methylamino)-5-nitrobenzo]phenone 
• 4959-16-4 7-amino-1-methyl-5-phenyl-1H-benzo[e][1,4]diazepin-2(3H)-one 
• 36508-54-0 1-methyl-7-nitro-5-phenyl-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepine 
• 128493-72-1 {(nimetazepam)Au(PPh₃)⁽¹⁺⁾BF₄^(1-) 
• 82384-74-5 (1,3-dihydro-1-methyl-7-nitro-5-phenyl-2H-1,4-benzodiazepin-2-one)AuCl₃ 
• 2898-19-3 1-methyl-7-nitro-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepine 
• 55894-86-5 7-hydroxyamino-1-methyl-5-phenyl-1,3-dihydro-benzo[e][1,4]diazepin-2-one 

Relevant academic research and scientific papers

5-PHENYL-LH-BENZ0 [E] [1, 4] DIAZEPINE COMPOUNDS SUBSTITUTED WITH AN HYDROXAMIC ACID GROUP AS HISTONE DEACETYLASE INHIBITORS

Novel hydroxamate histone deacetylase inhibitors of formula (I) wherein X is C=O or CH2 used as antineoplastic agent.

Design, synthesis and preliminary biological evaluation of new hydroxamate histone deacetylase inhibitors as potential antileukemic agents

This study concerns the synthesis of new histone deacetylase inhibitors (HDACi) characterized by a 1,4-benzodiazepine ring used as the cap, joined through an amide function or a triple bond as connection units, to a linear alkyl chain bearing the hydroxamate function as Zn2+-chelating group. Biological tests performed in human acute promyelocytic leukemia NB4 cells showed that new hybrids can induce histone H3/H4 acetylation, growth arrest, and also apoptosis. Notably, chiral compounds exhibit stereoselective activity.

A NEW APPROACH TO THE SYNTHESIS OF 2-AMINOMETHYL-3-PHENYL-5-NITROINDOLE

Bromination of 2-methyl-3-phenyl-5-nitroindoles has given previously unknown 2-bromoethyl-3-phenyl-5-nitroindoles, which were converted by the Delepine reaction into 2-aminomethyl-3-phenyl-5-nitroindoles.One of these (1-methyl-2-aminomethyl-3-phenyl-5-nitroindole) was also obtained by reductive amination of 1-methyl-2-formyl-3-phenyl-5-nitroindole by the Leuckart-Wallach reaction.

Process for the preparation of 1,4-benzodiazepine derivatives

A 1,4-benzodiazepine derivative, or a pharmaceutically acceptable acid salt thereof, of the formula, SPC1 Wherein R1 is hydrogen, halogen, nitro or trifluoromethyl; R2 and R3 are independently hydrogen, halogen, lower alkyl or trifluoromethyl; R4 is lower alkyl, alkenyl, trihaloalkyl, alkoxyalkyl, alkenyloxyalkyl, alkoxyalkoxyalkyl, alkanoyloxyalkyl, cycloalkylalkyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl or a group of the formula EQU1 in which R6 and R7 are independently lower alkyl, and n is an integer of 1 to 4; and R5 is hydrogen or lower alkyl, is obtained by reacting a benzophenone derivative of the formula, SPC2 Wherein R1, R2, R3 and R4 are as defined above, with a 2-isocyanatoacetyl chloride derivative of the formula EQU2 wherein R5 is as defined above.