2064-28-0

Upstream product

• 256-96-2 dibenzoazepine 
• 1262142-21-1 N-(2-(5H-dibenzo[b,f]azepin-5-yl)ethyl)-2,2,2-trifluoroacetamide 
• 244059-01-6 5-(cyanomethyl)dibenzazepine 

Relevant academic research and scientific papers

A Focused Library of Psychotropic Analogues with Neuroprotective and Neuroregenerative Potential

Overcoming the lack of effective treatments and the continuous clinical trial failures in neurodegenerative drug discovery might require a shift from the prevailing paradigm targeting pathogenesis to the one targeting simultaneously neuroprotection and neuroregeneration. In the studies reported herein, we sought to identify small molecules that might exert neuroprotective and neuroregenerative potential as tools against neurodegenerative diseases. In doing so, we started from the reported neuroprotective/neuroregenerative mechanisms of psychotropic drugs featuring a tricyclic alkylamine scaffold. Thus, we designed a focused-chemical library of 36 entries aimed at exploring the structural requirements for efficient neuroprotective/neuroregenerative cellular activity, without the manifestation of toxicity. To this aim, we developed a synthetic protocol, which overcame the limited applicability of previously reported procedures. Next, we evaluated the synthesized compounds through a phenotypic screening pipeline, based on primary neuronal systems. Phenothiazine 2Bc showed improved neuroregenerative and neuroprotective properties with respect to reference drug desipramine (2Aa). Importantly, we have also shown that 2Bc outperformed currently available drugs in cell models of Alzheimer's and Parkinson's diseases and attenuates microglial activation by reducing iNOS expression.

Direct, one-pot reductive alkylation of anilines with functionalized acetals mediated by triethylsilane and tfa. straightforward route for unsymmetrically substituted ethylenediamine

A new, robust, and reliable method has been developed for the selective reductive N-alkylation of primary and secondary aromatic amines with some functionalized acetals using TFA/Et3SiH as a reagent combination. A variety of unsymmetrically sub

Tricyclic alkylamides as melatonin receptor ligands with antagonist or inverse agonist activity

This work reports the design and synthesis of novel alkylamides, characterized by a dibenzo[a,d] cycloheptene nucleus, as melatonin (MLT) receptor ligands. The tricyclic scaffold was chosen on the basis of previous quantitative structure-activity studies on MT1 and MT2 antagonists, relating selective MT2 antagonism to the presence of an aromatic substituent out of the plane of the MLT indole ring. Some dibenzo seven-membered structures were thus selected because of the noncoplanar arrangement of their benzene rings, and an alkylamide chain was introduced to fit the requirements for MLT receptor binding, namely, dibenzocycloheptenes with an acylaminoalkyl side chain at position 10 and dibenzoazepines with this side chain originating from the nitrogen atom bridging the two phenyl rings. Binding affinity at human cloned MT1 and MT2 receptors was measured by 2[125I] iodomelatonin displacement assay and intrinsic activity by the GTPγS test. The majority of the compounds were characterized by higher affinity at the MT2 than at the MT 1 receptor and by very low intrinsic activity values, thus confirming the importance of the noncoplanar arrangement of the two aromatic rings for selective MT2 antagonism. Dibenzocycloheptenes generally displayed higher MT1 and MT2 affinity than dibenzoazepines. N-(8-Methoxy-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-10-ylmethyl)propionamide (4c) and -butyramide (4d) were the most selective MT2 receptor antagonists of the series, with MT2 receptor affinity comparable to that of melatonin and as such among the highest reported in the literature for MLT receptor antagonists. The acetamide derivative 4b produced a noticeable reduction of GTPγS binding at MT2 receptor, thus being among the few inverse agonists described.

Synthesis and characterization of fluorescent ligands for the norepinephrine transporter: Potential neuroblastoma imaging agents

Radiolabeled m-iodobenzylguanidine (MIBG) is a tumor-seeking radioactive drug used in the diagnosis and treatment of pheochromocytomas and neuroblastomas. It is transported into the tumor cells by the neuronal norepinephrine (NE) transporter (NET) which is expressed in almost all neuroblastoma cells. Here, we describe the synthesis and some pharmacological properties of a series of fluorescent compounds structurally related to the NET substrate, MIBG, or to the NET inhibitors, (-)-(2R,3S)-cocaine and nisoxetine. Three of 10 synthesized fluorescent compounds, 1-(1- naphthylmethyl)guanidinium sulfate (1), 1-[2-(dibenz[b,f]azepin-5- yl)ethyl]guanidinium sulfate (2), and (2R,3S)-2β-ethoxycarbonyl-3β-tropanyl 5-(dimethylamino)naphthalene-1-sulfonate (6), exhibited high affinity (IC50 about 50 nM) for the NET. The nisoxetine derivatives 8 (rac-N-[(3- methylamino-1-phenyl)propyl]-5-(dimethylamino)-1-naphthalene-sulfonamide) and 9 (rac-4-[(3-methylamino-1-phenyl)propyl]amino-7-nitro-2,1,3-benzoxadiazole) and especially the guanidine derivative 4 (1-[4-(4-phenyl-l,3- butadienyl)benzyl]guanidinium sulfate) which are characterized by intermediate affinity for the NET (IC50 370-850 nM) caused significant and nisoxetine-sensitive cell fluorescence. At least the guanidine derivative 4 might represent a potentially useful agent for imaging of neuroblastoma cells.