72106-00-4

Upstream product

• 120-20-7 2-(3,4-dimethoxyphenyl)-ethylamine 
• 2043-61-0 cyclohexanecarbaldehyde 
• 1215113-37-3 C₁₇H₂₅NO₂ 

Downstream Products

• 1215113-29-3 (R,S)-1-cyclohexyl-6,7-dimethoxy-3,4-dihydroisoquinoline-2(1H)-sulfonamide 
• 69743-45-9 1-cyclohexyl-3,4-dihydro-6,7-dimethoxyisoquinoline 

Relevant academic research and scientific papers

In Vivo Evaluation of Selective Carbonic Anhydrase Inhibitors as Potential Anticonvulsant Agents

Epilepsy is a common neurological disorder caused by an imbalance between inhibitory and excitatory neurotransmission. It is well known that neuronal excitability is related to γ-aminobutyric acid (GABA)ergic depolarization. HCO3?-dependent depolarization can be suppressed by membrane-permeable inhibitors of carbonic anhydrase. We previously identified some isoquinoline sulfonamides as potent and selective inhibitors of the human carbonic anhydrase II and VII (hCA II and hCA VII) isoforms. Given that hCA II and hCA VII are specific isoforms involved in GABA-mediated neuronal excitation, we hypothesized that they could represent the biological target for the development of new anticonvulsant agents. Therefore, for selected isoquinoline sulfonamides, we preliminarily tested their ability to prevent audiogenic seizures in DBA/2 mice. All compounds were evaluated after intraperitoneal administration, and some of them proved to protect the mice against convulsions. Among this series of compounds, several derivatives showed combined in vivo efficacy with inhibitory effects toward the targeted carbonic anhydrases (i.e., hCA II and hCA VII). Specifically, the most interesting molecule was 1-(4-aminophenyl)-6,7-dimethoxy-3,4-dihydroisoquinoline-2(1H)-sulfonamide (6), which proved to be a more active and selective hCA VII inhibitor than the reference compound topiramate. Further studies to explore the in vivo pharmacokinetic profile of the most active compounds may help to provide insight into the future design of selective hCA VII inhibitors.

Identification of 3,4-dihydroisoquinoline-2(1H)-sulfonamides as potent carbonic anhydrase inhibitors: Synthesis, biological evaluation, and enzyme-ligand X-ray studies

Following previous studies we herein report the exploration of the carbonic anhydrase (CA, EC 4.2.1.1) inhibitory effects and enzyme selectivity of a small class of l-(cyclo)alkylisoquinolines containing a sulfonamide function considered a key feature for inhibiting CA. The results of enzymatic assays against human (h) CA isoforms, hCA I and hCA II (cytosolic, ubiquitous enzymes), hCA IX (transmembrane, tumor-associated), and hCA XIV (transmembrane), suggested that the presence of C-I small substituents on isoquinoline scaffold controls both inhibitory potency and selectivity. Some derivatives showed potent hCA IX and hCA XIV inhibitory effects at nanomolar concentrations as well as low affinity for the ubiquitous hCA II. Moreover, we report the X-ray crystal structure of one of these derivatives in complex with dominant human isoform II, thus confirming the sulfonamide-zinc interactions. Finally, the results of docking experiments suggested the hypothetic interactions in the catalytic binding site for the most active and selective hCA IX and hCA XIV inhibitor.