4649-12-1

Usage

Uses

Used in Pharmaceutical Industry:
2-(2,9-diazabicyclo[4.3.0]nona-2,4,7,10-tetraen-7-yl)ethanamine is used as a building block for the synthesis of various drugs and biologically active molecules. Its specific structure and reactivity make it a crucial component in the development of novel therapeutic agents.
Used in Organic Synthesis:
In the field of organic synthesis, 2-(2,9-diazabicyclo[4.3.0]nona-2,4,7,10-tetraen-7-yl)ethanamine is used as a reagent or intermediate for the creation of complex organic molecules. Its unique properties facilitate the formation of new chemical bonds and the synthesis of target compounds.
Used in Medicinal Chemistry:
2-(2,9-diazabicyclo[4.3.0]nona-2,4,7,10-tetraen-7-yl)ethanamine is employed as a key component in the design and synthesis of new pharmaceuticals. Its potential applications in medicinal chemistry include the development of drugs targeting specific biological pathways or receptors, contributing to the advancement of personalized medicine and treatment options for various diseases.
Used in Research and Development:
In the realm of research and development, 2-(2,9-diazabicyclo[4.3.0]nona-2,4,7,10-tetraen-7-yl)ethanamine is utilized as a tool to investigate the biological activity of substances. Its unique structure allows researchers to probe the interactions between molecules and their biological targets, leading to a better understanding of molecular mechanisms and the discovery of new therapeutic agents.

InChI:InChI=1/C9H11N3/c10-4-3-7-6-12-9-8(7)2-1-5-11-9/h1-2,5-6H,3-4,10H2,(H,11,12)

Upstream product

• 4414-87-3 1H-Pyrrolo[2,3-b]pyridin-3-yl-acetonitrile 
• 271-63-6 7-Azaindole 
• 56-45-1 L-serin 
• 49758-35-2 (S)-2-amino-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)propanoic acid 
• 83393-47-9 2-chloro-1-(1H-pyrrolo[2,3-b]pyridin-3-yl)ethan-1-one 
• 183208-29-9 3-(2-nitroethyl)-1H-pyrrolo[2,3-b]pyridine 
• 183208-28-8 3-(2-nitroethenyl)-1H-7-aza-indole 
• 4649-09-6 1H-pyrrolo[2,3-b]pyridin-3-carbaldehyde 
• 90929-74-1 3-(2-Chloro-ethyl)-1H-pyrrolo[2,3-b]pyridine 
• 214604-08-7 3-(2-Iodo-ethyl)-1H-pyrrolo[2,3-b]pyridine 
• 7664-41-7 ammonia 
• 5654-92-2 7-azagramine 
• 7303-50-6 7-azatryptophan 

Downstream Products

• 1354893-21-2 6,7,8,9-tetrahydro-5H-pyrrolo[2,3-b:5,4-c']dipyridine 
• 895168-37-3 8-(3-methoxyphenyl)-6,7,8,9-tetrahydro-5H-pyrido[4′,3′:4,5]pyrrolo[2,3-b]pyridine 
• 895168-35-1 3-methoxy-N-[2-(1H-pyrrolo[2,3-b]pyridin-3-yl)ethyl]benzamide 

Relevant academic research and scientific papers

ONO-8430506: A Novel Autotaxin Inhibitor That Enhances the Antitumor Effect of Paclitaxel in a Breast Cancer Model

Lysophosphatidic acid (LPA) is a bioactive lipid mediator that elicits a number of biological functions, including smooth muscle contraction, cell motility, proliferation, and morphological change. LPA is endogenously produced by autotaxin (ATX) from extracellular lysophosphatidylcholine (LPC) in plasma. Herein, we report our medicinal chemistry effort to identify a novel and highly potent ATX inhibitor, ONO-8430506 (20), with good oral availability. To enhance the enzymatic ATX inhibitory activity, we designed several compounds by structurally comparing our hit compound with the endogenous ligand LPC. Further optimization to improve the pharmacokinetic profile and enhance the ATX inhibitory activity in human plasma resulted in the identification of ONO-8430506 (20), which enhanced the antitumor effect of paclitaxel in a breast cancer model.

Virtual screening-driven discovery of dual 5-HT6/5-HT2A receptor ligands with pro-cognitive properties

A virtual screening campaign aimed at finding structurally new compounds active at 5-HT6R provided a set of candidates. Among those, one structure, 4-(5-{[(2-{5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl}ethyl)amino]methyl}furan-2-yl)phenol (1, 5-HT6R Ki = 91 nM), was selected as a hit for further optimization. As expected, the chemical scaffold of selected compound was significantly different from all the serotonin receptor ligands published to date. Synthetic efforts, supported by molecular modelling, provided 43 compounds representing different substitution patterns. The derivative 42, 4-(5-{[(2-{5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl}ethyl)amino]methyl}furan-2-yl)phenol (5-HT6R Ki = 25, 5-HT2AR Ki = 32 nM), was selected as a lead and showed a good brain/plasma concentration profile, and it reversed phencyclidine-induced memory impairment. Considering the unique activity profile, the obtained series might be a good starting point for the development of a novel antipsychotic or antidepressant with pro-cognitive properties.

Facile in Vitro Biocatalytic Production of Diverse Tryptamines

Tryptamines are a medicinally important class of small molecules that serve as precursors to more complex, clinically used indole alkaloid natural products. Typically, tryptamine analogues are prepared from indoles through multistep synthetic routes. In the natural world, the desirable tryptamine synthon is produced in a single step by l-tryptophan decarboxylases (TDCs). However, no TDCs are known to combine high activity and substrate promiscuity, which might enable a practical biocatalytic route to tryptamine analogues. We have now identified the TDC from Ruminococcus gnavus as the first highly active and promiscuous member of this enzyme family. RgnTDC performs up to 96 000 turnovers and readily accommodates tryptophan analogues with substituents at the 4, 5, 6, and 7 positions, as well as alternative heterocycles, thus enabling the facile biocatalytic synthesis of >20 tryptamine analogues. We demonstrate the utility of this enzyme in a two-step biocatalytic sequence with an engineered tryptophan synthase to afford an efficient, cost-effective route to tryptamines from commercially available indole starting materials.

Synthesis and SAR of the antistaphylococcal natural product nematophin from Xenorhabdus nematophila

The repeated and improper use of antibiotics had led to an increased number of multiresistant bacteria. Therefore, new lead structures are needed. Here, the synthesis and an expanded structure–activity relationship of the simple and antistaphylococcal amide nematophin from Xenorhabdus nematophila and synthetic derivatives are described. Moreover, the synthesis of intrinsic fluorescent derivatives, incorporating azaindole moieties was achieved for the first time.

Characterization of the properties of a selective, orally bioavailable autotaxin inhibitor in preclinical models of advanced stages of liver fibrosis

Background and Purpose: Autotaxin (ATX) is a secreted phospholipase which hydrolyses lysophosphatidylcholine to generate lysophosphatidic acid (LPA). The extracellular signalling molecule LPA exerts its biological actions through activation of six GPCRs expressed in various cell types including fibroblasts. Multiple preclinical studies using knockout animals, LPA receptor antagonists or ATX inhibitors have provided evidence for a potential role of the ATX/LPA axis in tissue fibrosis. Despite growing evidence for a correlation between ATX levels and the degree of fibrosis in chronic liver diseases, including viral hepatitis and hepatocellular carcinoma, the role of ATX in non-alcoholic steatohepatitis (NASH) remains unclear. Experimental Approach: The relevance of ATX in the pathogenesis of liver fibrosis was investigated by oral administration of Ex_31, a selective ATX inhibitor, in a 10?week model of carbon tetrachloride-induced liver injury and in a 14?week model of choline-deficient amino acid-defined diet-induced liver injury in rats. Key Results: Oral administration of Ex_31, a selective ATX inhibitor, at 15?mg·kg?1 twice daily in therapeutic intervention mode resulted in efficient ATX inhibition and more than 95% reduction in plasma LPA levels in both studies. Treatment with Ex_31 had no effect on biomarkers of liver function, inflammation, or fibrosis and did not result in histological improvements in diseased animals. Conclusions and Implications: Our findings question the role of ATX in the pathogenesis of hepatic fibrosis and the potential of small molecule ATX inhibitors for the treatment of patients with NASH and advanced stages of liver fibrosis.

TETRAHYDROCARBOLINE DERIVATIVE

An object of the present invention is to provide a drug having the inhibitory activity on ENPP2 which is a different target from that of the existing drug, as a medicament useful in a urinary excretion disorder patient for whom the existing drug has the insufficient effect. The present invention provides a compound represented by the general formula (I): (wherein definition of each group is as defined in the description) having the ENPP2 inhibitory activity, a salt thereof or a solvate thereof or a prodrug thereof, and an agent for preventing or treating urinary excretion disorder and/or improving symptoms thereof, containing them as an active ingredient.

Optimization of the in vitro cardiac safety of hydroxamate-based histone deacetylase inhibitors

Histone deacetylase (HDAC) inhibitors have shown promise in treating various forms of cancer. However, many HDAC inhibitors from diverse structural classes have been associated with QT prolongation in humans. Inhibition of the human ether a-go-go related gene (hERG) channel has been associated with QT prolongation and fatal arrhythmias. To determine if the observed cardiac effects of HDAC inhibitors in humans is due to hERG blockade, a highly potent HDAC inhibitor devoid of hERG activity was required. Starting with dacinostat (LAQ824), a highly potent HDAC inhibitor, we explored the SAR to determine the pharmacophores required for HDAC and hERG inhibition. We disclose here the results of these efforts where a high degree of pharmacophore homology between these two targets was discovered. This similarity prevented traditional strategies for mitigating hERG binding/modulation from being successful and novel approaches for reducing hERG inhibition were required. Using a hERG homology model, two compounds, 11r and 25i, were discovered to be highly efficacious with weak affinity for the hERG and other ion channels.

A facile chemoenzymatic approach: One-step syntheses of monoterpenoid indole alkaloids

Facile chemoenzymatic syntheses of cytotoxic monoterpenoid indole alkaloids with novel skeletons and multiple chiral centers are described. Synthesis of these alkaloids was achieved by a simple one-step reaction using strictosidine and 12-aza-strictosidine as the key intermediates. Strictosidines were prepared by coupling of secologanin with tryptamine and 7-aza-tryptamine, respectively, using the immobilized recombinant Rauvolfia strictosidine synthase. A detailed stereochemical analysis is presented herein. The results provide an opportunity for a chemoenzymatic approach that leads to an increased diversification of complex alkaloids with improved structures and activities.

Azaindolylalkylamine derivatives as 5-hydroxytryptamine-6 ligands

The present invention provides a compound of formula I and the use thereof for the therapeutic treatment of disorders relating to or affected by the 5-HT6 receptor.

Azaindole-ethylamine derivatives as nicotine acetylchlorine receptor binding agents

Compounds of formula I are useful in treatment of conditions associated with depletion of nicotine receptors in mammals.