78756-33-9

Usage

Uses

Used in Pharmaceutical Industry:
Ro 15-3505 is used as an impurity in the production of Flumazenil, a medication that selectively blocks the central effects of classic benzodiazepines. This allows for the development and manufacturing of safer and more effective medications for the treatment of benzodiazepine overdose or intoxication.

InChI:InChI=1/C15H14ClN3O3/c1-3-22-15(21)13-12-7-18(2)14(20)10-6-9(16)4-5-11(10)19(12)8-17-13/h4-6,8H,3,7H2,1-2H3

Upstream product

• 52141-89-6 ethyl 2-(methylideneamino)acetate 
• 2999-46-4 Ethyl isocyanoacetate 
• 5973-29-5 3,4-dihydro-7-chloro-4-methyl-2H-1,4-benzodiazepine-2,5(1H)-dione 
• 865-47-4 potassium tert-butylate 
• 814-49-3 diethyl chlorophosphate 
• 1027918-09-7 C₁₄H₁₈ClN₂O₅P 

Relevant academic research and scientific papers

Synthesis and Evaluation of Imidazobenzodiazepine Esters with High Affinities and Selectivities at "Diazepam-Insensitive" Benzodiazepine Receptors

A series of imidazobenzodiazepine esters have been synthesized with varying esters side chains and 8-position substituents.The affinities of these compounds were evaluated at both "diazepam-insensitive" (DI) and diazepam-sensitive (DS) subtypes of the benzodiazepine receptor (BZR).A profound steric effect of the 3-position ester side chain moiety was observed on ligand affinity at DI.In contrast ester size had a less robust effect on ligand affinity at DS.The tert-butyl ester compound 8 displayed the highest affinity (Ki = 1.7 nM) for DI within a series of a 8-chloro esters.Furthermore, halogens at the 8-position resulted in an enhancement of both ligand affinity and selectivity at DI among the series of tert-butyl esters examined.The 8-nitro derivative 23 and 8-isothiocyanato congener 25 had high affinities for both DI and DS but exhibited little subtype selectivity (10.8 and 2.7 nM at DI versus 14 and 3.7 nM at DS, respectively).The 8- azido tert-butyl ester 29 exhibited a significantly higher affinity (Ki = 0.43 nM) and selectivity (DI/DS ratio of 0.2) than the corresponding ethyl ester, the prototypic DI ligand 1 (Ro 15-4513).Among the compounds synthesized, 29 is the highest affinity ligand for DI described to date while its 8-bromo analog 18 is the most selective ligand (DI/DS ratio of 0.17) for this novel BZR subtype.

An improved process for the synthesis of 4H-imidazo[1,5-a][1,4] benzodiazepines

The construction of CNS active imidazo[1,5-a][1,4]benzodiazepines has been improved in a one-pot annulation process. Georg Thieme Verlag Stuttgart.

GABAERGIC AGENTS TO TREAT MEMORY DEFICITS

The present invention provides molecules and methods for the prevention and/or treatment of memory deficit related conditions and/or enhancement of cognizance. In a preferred embodiment, the invention includes compounds, salts and prodrugs thereof for the prevention and/or treatment of these conditions.

Method of antagonizing excitatory amino acids by administration of imidazobenzodiazepine compounds

A method of antagonizing the biological effects of an excitatory amino acid of a subject in need of such antagonization comprising the step of administering to said subject an effective amount of a compound having the formula STR1 wherein R 3 is hydrogen, C 1-8 -alkyl which may be branched, or cycloalkylmethyl;R 7 and R 8 are independently hydrogen, halogen, CF 3, CN, NO 2, NH 2, C 1-4 -alkyl or C 1-4 -alkoxy; andR 4 is hydrogen and R 5 is hydrogen or C 1-7 -alkyl; or R 4 and R 5 together signify (CH 2) n wherein n is an integer of 2-3.

Novel Benzodiazepine Receptor Partial Agonists: Oxadiazolylimidazobenzodiazepines

The synthesis and biochemical evaluation of a series of oxadiazole derivatives of imidazobenzodiazepines related to the benzodiazepine antagonist Ro 15-1788 (2a) are reported.Although the oxadiazole ring is seen as an isosteric replacement for the ester linkage, significant differences in structure-activity trends were observed.Specifically, oxadiazoles 9-12 invariably had increased receptor efficacy (as witnessed by measurements of the GABA shift) relative to the corresponding ester.Additionally, and in direct contrast to the classical agonists such as diazepam, affinity for the benzodiazepine receptor was enhanced by a 7- rather than 8-halo substituent.The results are discussed in terms of a six-point receptor-binding model originally based on the X-ray structure of 2a.For comparison, the crystal structures of two representative oxadiazole derivatives, 10h and 12o, having a 6-oxo and 6-phenyl group, respectively, were determined and the data incorporated into a modified binding model to account for the greater efficacy of these compounds.It is concluded that the antagonist behavior of 2a relies upon the hydrogen-bond-acceptor properties of the ester carbonyl oxygen whereas for the oxadiazole series this site is localized at the imidazole nitrogen.

Imidazodiazepine derivatives

Imidazodiazepine derivatives of the formula STR1 wherein A together with the two carbon atoms denoted as α and β is selected from the group consisting of STR2 the dotted line represents the double bond present in groups (a) and (b), D is >C O or >C S, R 1 is selected from the group consisting of cyano, lower alkanoyl and a group of the formula --COOR 4, R 4 is selected from the group consisting of methyl, ethyl, isopropyl and 2-hydroxyethyl, R 5 is selected from the group consisting of hydrogen, trifluoromethyl and halogen and R 6 is selected from the group consisting of hydrogen, trifluoromethyl, halogen and lower alkyl and either R 2 is hydrogen and R 3 is hydrogen or lower alkyl or R 2 and R 3 together are trimethylene or propenylene and the carbon atom denoted as γ has the S- or R,S-configuration, and pharmaceutically acceptable salts thereof are presented and have utility for antagonizing the central-depressant, muscle relaxant, ataxic, blood pressure-lowering and respiratory-depressant properties of 1,4-benzodiazepines which have tranquillizing activity. They can be used, for example, as antidotes in the case of intoxications in which excessive intake of 1,4-benzodiazepines which have tranquillizing participates, or for shortening an anaesthesia induced by such 1,4-benzodiazepines. They can also be used for suppressing the activities on the central nervous system of 1,4-benzodiazepines used in other fields of indication, for example of schistosomicidally-active 1,4-benzodiazepines such as (+)-5-(o-chlorophenyl)-1,3-dihydro-3-methyl-7-nitro-2H-1,4-benzodiazepin-2-one.Also presented are processes to produce the imidazodiazepine derivatives and intermediates therefor.