2095-95-6

Usage

InChI:InChI=1/C17H20N2/c18-12-5-13-19-16-8-3-1-6-14(16)10-11-15-7-2-4-9-17(15)19/h1-4,6-9H,5,10-13,18H2

Upstream product

• 494-19-9 9,10-dihydrodibenzazepine 
• 5460-29-7 2-(3-bromopropyl)isoindole-1,3-dione 
• 50-49-7 impramine 
• 16036-79-6 5-(3-chloropropyl)-10,11-dihydro-5H-dibenzo[b,f]azepine 
• 65100-49-4 5-[3-(N-trideuteromethylamino)propyl]iminodibenzyl 
• 50-47-5 desipramine 
• 866601-54-9 3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-3-oxopropanenitrile 
• 19054-67-2 3-chloro-1-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-1-propanone 
• 106561-78-8 2-[3-(10,11-dihydro-dibenzo[b,f]azepin-5-yl)-propyl]-isoindole-1,3-dione 
• 71366-84-2 3-(10,11-dihydro-dibenzo[b,f]azepin-5-yl)-propionitrile 

Downstream Products

• 50-49-7 impramine 
• 50-47-5 desipramine 

Relevant academic research and scientific papers

Bacterial Biosynthetic P450 Enzyme PikCD50N: A Potential Biocatalyst for the Preparation of Human Drug Metabolites

Human drug metabolites (HDMs) are important chemicals widely used in drug-related studies. However, acquiring these enzyme-derived and regio-/stereo-selectively modified compounds through chemical approaches is complicated. PikC is a biosynthetic P450 enz

HECT E3 LIGASE INHIBITORS AND USES THEREOF

The present invention relates to tricyclic derivatives of formula (I), which are useful as inhibitors of HECT-domain-containing E3 ligases, in particular NEDD4. The present invention also refers to pharmaceutical compositions comprising compounds of formu

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.

DNA-Encoded Dynamic Chemical Library and Its Applications in Ligand Discovery

Dynamic combinatorial library (DCL) has emerged as an efficient tool for ligand discovery and become an important discovery modality in biomedical research. However, the applications of DCLs have been significantly hampered by low library diversity and limited analytical methods capable of processing large libraries. Here, we report a strategy that has addressed this limitation and can select cooperatively binding small-molecule pairs from large-scale dynamic libraries. Our approach is based on DNA-mediated dynamic hybridization, DNA-encoding, and a photo-cross-linking-based decoding scheme. To demonstrate the generality and performance of this approach, a 10 000-member DNA-encoded dynamic library has been prepared and selected against six protein targets. Specific binders have been identified for each target, and we have validated the biological activities of selected ligands for the targets that are implicated in important cellular functions including protein deacetylation and sumoylation. Notably, a series of novel and selective sirtuin-3 inhibitors have been developed. Our study has circumvented a major obstacle in DCL and may provide a broadly applicable method for ligand discovery against biological targets.

Sequential metabolism of secondary alkyl amines to metabolic-intermediate complexes: Opposing roles for the secondary hydroxylamine and primary amine metabolites of desipramine, (S)-fluoxetine, and N-desmethyldiltiazem

Three secondary amines desipramine (DES), (S)-fluoxetine [(S)-FLX], and N-desmethyldiltiazem (MA) undergo N-hydroxylation to the corresponding secondary hydroxylamines [N-hydroxydesipramine, (S)-N-hydroxyfluoxetine, and N-hydroxy-N-desmethyldiltiazem] by cytochromes P450 2C11, 2C19, and 3A4, respectively. The expected primary amine products, N-desmethyldesipramine, (S)-norfluoxetine, and N,N-didesmethyldiltiazem, are also observed. The formation of metabolic-intermediate (MI) complexes from these substrates and metabolites was examined. In each example, the initial rates of MI complex accumulation followed the order secondary hydroxylamine > secondary amine ? primary amine, suggesting that the primary amine metabolites do not contribute to formation of MI complexes from these secondary amines. Furthermore, the primary amine metabolites, which accumulate in incubations of the secondary amines, inhibit MI complex formation. Mass balance studies provided estimates of the product ratios of N-dealkylation to N-hydroxylation. The ratios were 2.9 (DES-CYP2C11), 3.6 [(S)-FLX-CYP2C19], and 0.8 (MA-CYP3A4), indicating that secondary hydroxylamines are significant metabolites of the P450-mediated metabolism of secondary alkyl amines. Parallel studies with N-methyl-d3-desipramine and CYP2C11 demonstrated significant isotopically sensitive switching from N-demethylation to N-hydroxylation. These findings demonstrate that the major pathway to MI complex formation from these secondary amines arises from N-hydroxylation rather than N-dealkylation and that the primary amines are significant competitive inhibitors of MI complex formation. Copyright

DIPEPTIDYL PEPTIDASE-IV INHIBITORS

The present invention relates generally to pyrrolidine and thiazolidine DPP-IV inhibitor compounds. The present invention also provides synthetic methods for preparation of such compounds, methods of inhibiting DPP-IV using such compounds and pharmaceutical formulations containing them for treatment of DPP-IV mediated diseases, in particular, Type-2 diabetes.

Influence of chain length and N-alkylation on the selective serotonin receptor ligand 9-(aminomethyl)-9,10-dihydroanthracene

Comparison of the serotonin 5-HT2A receptor affinities of chain lengthened and N-alkylated analogues of the novel ligand 9-aminomethyl-9.10-dihydroanthracene (AMDA) and a structurally similar prototypical tricyclic amine imipramine suggests that the two agents bind to the receptor in different fashions. The demonstration that AMDA is highly selective for serotonin receptors (5-HT2A, Ki = 20 nM: 5-HT2C, Ki = 43 nM) versus the dopamine D2 receptor (Ki > 10,000 nM). as well as the serotonin and norepinephrine transporters (Ki >10.000nM) further suggests that AMDA and the nonselective ligand imipramine interact with these target macromolecules in different ways.

EXPERIMENTAL ANTIULCER AGENTS: N-SUBSTITUTED 2-(4-METHYL-1-PIPERAZINYL)ACETAMIDES AS PIRENZEPINE MODELS AND SOME RELATED COMPOUNDS

Reactions of N-cyclohexyl-2-chloroacetamide, N-phenyl-2-chloroacetamide, N-(4-dimethylaminophenyl)-2-chloroacetamide, N-(2-nitrophenyl)-N-phenyl-2-chloroacetamide, its 3-nitrophenyl and 4-nitrophenyl analogues, N-(2-benzylphenyl)-2-chloroacetamide, 5-(chloroacetyl)dibenzazepine, and its 10,11-dihydro derivative with piperazine, 1-methylpiperazine, 2-(1-piperazinyl)ethanol, and 3-(1-piperazinyl)propanol resulted in compounds II, III, V -XV, XVIII, XXI, and XXIII, simple analogues of the antiulcer agent pirenzepine (I).Contributions to the syntheses and characterization of mianserin (XIX), bisnor analogue of imipramine (XXV), and pirenzepine (I) are presented.Two 2-aryl-2-(2-pyridyl)thioacetamides XXXVIII and XL were synthesized via nitriles XXXIX and XLI.Compounds XI (VUFB-17 104) and XXI (VUFB-17 113) were found to be rather effective as anti-ulcer agents and anticholinergics.

TRICYCLIC DERIVATIVES AND PHARMACEUTICAL USE

This invention describes tricyclic derivatives which are useful as histamine H 1-antagonists. A particular compound of this invention is 3-3-(pyrido 3,2-b! 1,4!-benzothiazin-10-yl)propylamino!-4-(pyrid-4-ylmethylamino)-1,2,5-thiadi azole-1-oxide.