3489-59-6

Upstream product

• 146-22-5 nitrazepam 
• 74-88-4 methyl iodide 
• 143-33-9 sodium cyanide 
• 28611-28-1 1-Methyl-5-phenyl-7-bromo-1,3-dihydro-2H-1,4-benzodiazepin-2-one 

Relevant academic research and scientific papers

Studies in the search for α5 subtype selective agonists for GABA(A)/BzR sites

In the search for α5 selective ligands, several series of diazepam analogs with individual and/or simultaneous modifications at positions-2, -5 and -7 were prepared and their in vitro affinities determined on recombinant receptors. These ligands were deliberately designed to test the effects of interaction at H1, H2, L2 and L3 of the pharmacophore/receptor model on ligand binding affinities and selectivities at different GABA(A)/BzR subtypes. In agreement with previous reports, none of these 1,4- benzodiazepines bound to the α4β3γ2 and α6β3γ2 receptor isoforms, two diazepam-insensitive(DI) GABA(A) receptor subtypes which appear to be devoid of lipophilic pocket L3. The presence of a 2'-fluorophenyl or 2'-nitrophenyl group at the C(5) position enhanced ligand affinity for the receptors but favored α1β3γ2 subtypes over α5β3γ2 subtypes. Replacement of the 2'- fluorophenyl or 2'-nitrophenyl group with a phenyl, 2'-thienyl or 2'-furyl moiety at the same position resulted in lower affinities of the ligands at all GABA(A) subtypes. Most importantly, when the carbonyl groups at position- 2 were replaced by methylene moieties (21 and 23), the affinities for all subtypes diminished. These results strongly suggest that the hydrogen bonding interaction of the ligand at H1 (as well as H2) with the receptor protein is important for high affinity at all DS sites. This implies that H1 is very similar in all receptor isoforms and may not be a descriptor which will readily lend itself to pharmacological receptor subtype selectivity.

Benzodiazepine derivatives

There is presented benzodiazepine derivatives of the formula STR1 wherein A is the group STR2 R1 is lower alkyl, R2 and R3 each are hydrogen or lower alkyl, R4 is the group STR3 R5 is hydrogen or halogen, R8 is hydrogen or lower alkyl, R9 is lower alkyl or lower alkoxyalkyl, R10 is lower alkyl, R11 is hydrogen, lower alkyl or lower hydroxyalkyl, R12 is hydrogen or lower alkyl and R14 is lower alkyl or aryl, and either R6 is hydrogen or lower alkyl and R7 is lower alkyl or lower hydroxyalkyl or R6 and R7 together with the nitrogen atom are a 3- to 7-membered heterocycle which, when it is at least 5-membered, can contain as a ring member an oxygen or sulphur atom or a group of the formula >N-R13, in which R13 is hydrogen or lower alkyl, and either R6 ' is hydrogen or lower alkyl and R7 ' is lower alkyl or R6 ' and R7 ' together with the nitrogen atom are a 3- to 7-membered heterocycle which, when it is at least 5-membered, can contain as a ring member an oxygen or sulphur atom or a group of the formula > N-R13 ', in which R13 ' is lower alkyl, with the proviso that R4 is the group R6 ' R7 ' N--CO--NH--CH(R8)-- when A is the group (c), and pharmaceutically acceptable acid addition salts thereof. The compounds exhibit aldosterone-antagonistic properties and are suitable for the control or prevention of heart failure, hepatic ascites, primary aldosteronism and idiopathic hypertension.