712-97-0

Usage

Uses

Used in Chemical Synthesis:
6-NITROPIPERONAL is used as a synthetic intermediate for the production of various compounds, including 6-[18F]fluoro-L-dopa, which is an essential component in the study and treatment of neurological disorders such as Parkinson's disease. Its chemical properties make it a valuable building block in the synthesis of complex molecules.
Used in Pharmaceutical Research:
In the pharmaceutical industry, 6-NITROPIPERONAL is used as a key compound in the study of the mechanism of aromatic nucleophilic substitution reactions. Understanding these reactions is crucial for the development of new drugs and the improvement of existing ones, as it helps researchers predict and control the outcomes of chemical reactions involving aromatic compounds.
Used in Radiochemistry:
6-NITROPIPERONAL is used as a precursor in the production of radiolabeled compounds, specifically in the synthesis of 6-[18F]fluoro-L-dopa. Radiolabeled compounds are essential tools in medical imaging and diagnostic procedures, allowing researchers and medical professionals to track the movement and distribution of molecules within the body. This application is particularly important in the field of nuclear medicine and molecular imaging.

InChI:InChI=1/C8H5NO5/c10-3-5-1-7-8(14-4-13-7)2-6(5)9(11)12/h1-3H,4H2

Upstream product

• 120-57-0 piperonal 
• 96806-57-4 (E)-4,5-dihydroxy-2,β-dinitrostyrene 
• 7697-37-2 nitric acid 
• 4543-59-3 1,2-bis(3,4-dioxymethylenephenyl)ethane-1,2-diol 
• 56-23-5 tetrachloromethane 
• 64-19-7 acetic acid 
• 133-03-9 sesamin 
• 15341-08-9 (6-nitrobenzo[d][1,3]dioxol-5-yl)methanol 
• 500284-46-8 (6-nitro-1,3-benzodioxol-5-yl)methylene diacetate 
• 15862-98-3 5-(chloromethyl)-6-nitrobenzo[d][1,3]dioxole 
• 136-72-1 piperic acid 

Downstream Products

• 21873-12-1 4-((Z)-6-nitro-benzo[1,3]dioxol-5-ylmethylene)-2-phenyl-4H-oxazol-5-one 
• 39531-38-9 4',5'-methylenedioxy-2'-nitro-cis-stilbene-α-carboxylic acid 
• 1195185-88-6 cis-α-Phenyl-2-nitro-4,5-methylendioxy-cinnamylsaeure 
• 341541-01-3 2-cyano-3ξ-(6-nitro-benzo[1,3]dioxol-5-yl)-acrylic acid anilide 
• 6315-90-8 3-(3,4-methylenedioxy-6-nitrophenyl)propenoic acid 
• 855164-88-4 3ξ-(6-nitro-benzo[1,3]dioxol-5-yl)-acrylic acid anilide 
• 857778-88-2 5-(3,4-dimethoxy-phenyl)-3-((Ξ)-6-nitro-benzo[1,3]dioxol-5-ylmethylene)-3H-furan-2-one 
• 6315-90-8 4',5'-(methylenedioxy)-2-nitrocinnamic acid 
• 2501-04-4 4-methyl-N-[(1E)-(6-nitro-1,3-benzodioxol-5-yl)methylene]aniline 
• 2620-44-2 5-nitro-1,3-benzodioxole 

Relevant academic research and scientific papers

Synthesis, pharmacological evaluation and electrochemical studies of novel 6-nitro-3,4-methylenedioxyphenyl-N-acylhydrazone derivatives: Discovery of LASSBio-881, a new ligand of cannabinoid receptors

We describe herein the discovery of LASSBio-881 (3c) as a novel in vivo antinociceptive, anti-inflammatory, and in vitro antiproliferative and antioxidant compound, with a cannabinoid ligand profile. We observed that LASSBio-881 (3c) was able to bind to CB1 receptors (71% at 100 μM) and also to inhibit T-cell proliferation (66% at 10 μM) probably by binding to CB2 receptors, in a non-proapoptotic manner, different from anandamide (1). It was also demonstrated that LASSBio-881 (3c) had an important antioxidant profile toward free radicals (DPPH and hydroxyl), probably due to its particular redox behavior, which reflects the presence of both nitro and 3,5-di-tert-butyl-4-hydroxyphenyl sub-units, as demonstrated by cyclic voltammetry studies. In addition, we showed that these structural sub-units are essential for the observed pharmacological activity.

Investigation of Novel Primary and Secondary Pharmacophores and 3-Substitution in the Linking Chain of a Series of Highly Selective and Bitopic Dopamine D3 Receptor Antagonists and Partial Agonists

Dopamine D3 receptors (D3R) play a critical role in neuropsychiatric conditions including substance use disorders (SUD). Recently, we reported a series of N-(3-hydroxy-4-(4-phenylpiperazin-1-yl)butyl)-1H-indole-2-carboxamide analogues as high affinity and selective D3R lead molecules for the treatment of opioid use disorders (OUD). Further optimization led to a series of analogues that replaced the 3-OH with a 3-F in the linker between the primary pharmacophore (PP) and secondary pharmacophore (SP). Among the 3-F-compounds, 9b demonstrated the highest D3R binding affinity (Ki = 0.756 nM) and was 327-fold selective for D3R over D2R. In addition, modification of the PP or SP with a 3,4-(methylenedioxy)phenyl group was also examined. Further, an enantioselective synthesis as well as chiral HPLC methods were developed to give enantiopure R- and S-enantiomers of the four lead compounds. Off-target binding affinities, functional efficacies, and metabolic profiles revealed critical structural components for D3R selectivity as well as drug-like features required for development as pharmacotherapeutics.

Docking, synthesis and pharmacological activity of novel urea-derivatives designed as p38 MAPK inhibitors

p38 mitogen-activated protein kinase (p38 MAPK) is an important signal transducing enzyme involved in many cellular regulations, including signaling pathways, pain and inflammation. Several p38 MAPK inhibitors have been developed as drug candidates to treatment of autoimmune disorders, such as rheumatoid arthritis. In this paper we reported the docking, synthesis and pharmacological activity of novel urea-derivatives (4a-e) designed as p38 MAPK inhibitors. These derivatives presented good theoretical affinity to the target p38 MAPK, standing out compound 4e (LASSBio-998), which showed a better score value compared to the prototype GK-00687. This compound was able to reduce in vitro TNF-α production and was orally active in a hypernociceptive murine model sensible to p38 MAPK inhibitors. Otherwise, compound 4e presented a dose-dependent analgesic effect in a model of antigen (mBSA)-induced arthritis and anti-inflammatory profile in carrageenan induced paw edema, indicating its potential as a new antiarthritis prototype.

Non-alkylator anti-glioblastoma agents induced cell cycle G2/M arrest and apoptosis: Design, in silico physicochemical and SAR studies of 2-aminoquinoline-3-carboxamides

Malignant gliomas are the most common brain tumors, with generally dismal prognosis, early clinical deterioration and high mortality. Recently, 2-aminoquinoline scaffold derivatives have shown pronounced activity in central nervous system disorders. We herein reported a series of 2-aminoquinoline-3-carboxamides as novel non-alkylator anti-glioblastoma agents. The synthesized compounds showed comparable activity to cisplatin against glioblastoma cell line U87 MG in vitro. Among them, we found that 6a displayed good inhibitory activity against A172 and U118 MG glioblastoma cell lines and induced cell cycle arrest in the G2/M phase and apoptosis in U87 MG by flow cytometry analysis. Additionally, 6a displayed low cytotoxicity to several normal human cell lines. In silico study showed 6a had promising physicochemical properties and was predicted to cross the blood–brain barrier. Moreover, preliminary structure–activity relationships are also investigated, shedding light on further modifications towards more potent agents on this series of compounds. Our results suggest this compound has a promising potential as an anti-glioblastoma agent with a differential effect between tumor and non-malignant cells.

Synthesis of Azepino[1,2-a]indole-10-amines via [6+1] Annulation of Ynenitriles with Reformatsky Reagent

Lewis acid-catalyzed [6+1] annulation reactions of 2-cyano-1-propargyl- and 2-alkynyl-1-cyanomethyl-indoles with Reformatsky reagent are described. 8-Aryl, 8-alkyl-, 8-hetaryl-, 9-aryl, and 9-alkyl-azepino[1,2-a]indole amines were obtained through a 7-endo-mode cyclization of the β-aminoacrylate intermediates. The antiproliferative activity of the azepino[1,2-a]indoles analogs against the HCT-116 cells were also examined.

DOPAMINE D3 RECEPTOR SELECTIVE ANTAGONISTS/PARTIAL AGONISTS AND USES THEREOF

Disclosed herein are novel methods of treating pain in a patient in need thereof by providing to the patient a selective dopamine D3 receptor antagonist/partial agonist which when used with an opioid analgesic, can mitigate the development of opioid dependence, by preventing the need for dose escalation while either maintaining the opioid analgesic effect or providing analgesia with a lower dose of the opioid. In addition, the D3 antagonists/partial agonists described herein may be used to augment the effectiveness of current Medication Assisted Treatment regimens (e.g. methadone or buprenorphine) for the treatment of opioid use disorders.

Self-assembling nanoparticles of dually hydrophobic prodrugs constructed from camptothecin analogue for cancer therapy

Nanomedicines have shown success in cancer therapy in recent years because of their excellent solubility in aqueous solution and drug accumulation through controlled release in tumor tissues, but the preparation of most nanomedicines still requires ionic materials, surfactants or the amphiphilic structure to maintain nanoparticle stability and function. In this study, we developed a couple of novel dually hydrophobic prodrugs (DHPs) by combining two hydrophobic compounds through different linkers and elaborated their self-assembly mechanisms by virtue of computational simulation. Importantly, without using any excipients, FL-2 NPs exhibited significantly prolonged retention in blood circulation and displayed a remarkable anti-tumor effect at very low concentration in vivo. Both DHPs consisted of camptothecin structural analogue(FL118) and a marine natural product (ES-285). Comparative experiments proved that these compounds could quickly form nanoparticles by way of simple preparation and remained relatively stable for long periods in PBS. FL-2 NPs linked with a disulphide bond could rapidly release bioactive FL118 after being triggered by endogenous reductive stimulus to exert anti-cancer effects. Overall, this study provides a new strategy for design of therapeutic nanomedicines consisting of dually hydrophobic molecules for cancer therapy.

Synthesis of new quinoline-piperonal hybrids as potential drugs against Alzheimer’s disease

Six quinoline-piperonal hybrids were synthesized and evaluated as potential drugs against Alzheimer’s disease (AD). Theoretical analysis of the pharmacokinetic and toxicological properties of the compounds suggest that they present good oral bio-availability and are also capable of penetrating the blood–brain barrier, qualifying as leads for new drugs against AD. Evaluation of their inhibitory capacity against acetyl-and butyrilcholinesterases (AChE and BChE) through Ellmann’s test showed that three compounds present promising results with one of them being capable of inhibiting both enzymes. Further docking studies of the six compounds synthesized helped to elucidate the main interactions that may be responsible for the inhibitory activities observed.

Pyrrolo[2,1-c][1,4] benzodiazepine-3,11-diones protect SHSY-5Y cells from Cd-induced apoptosis involving suppression of endoplasmic reticulum stress

Cadmium (Cd) is a potent toxic heavy metal, some studies showed that Cd-induced apoptosis is through ER stress pathway. Compounds of pyrrolo[2,1–c][1,4]benzodiazepine (PBD)-3,11-diones were discovered as potent neuroprotective agents against Cd-induced toxicity in SH-SY5Y cells for the first time. In this study, twenty-six PBD-3,11-dione derivatives were synthesized and evaluated for their neuroprotective activity against Cd-induced toxicity by CCK-8 assay. Their preliminary SARs studies indicated that various substituents were tolerated on the benzene ring, and alkyl heterocycles groups at the N10-position of the PBD-3,11-dione scaffold were important for the activities. Among them, compound 13c exhibited the best activity (cell viability = 68.6%, 25 μM). Furthermore, we found that the compound 13c could inhibit cadmium-induced cell apoptosis with the downregulation of the ER stress markers GRP78, CHOP, cleaved-caspase12 and cleaved-caspase3 through western blotting. The results of in silico evaluation of ADME/T properties showed that 13c exhibited medium BBB penetration level and promising toxicity profiles. These results proved the potential of 13c as a promising lead compound against Cd-induced neurotoxicity.

Novel 3,4-methylenedioxyde-6-X-benzaldehyde-thiosemicarbazones: Synthesis and antileishmanial effects against Leishmania amazonensis

A series of eleven 3,4-methylenedioxyde-6-X-benzaldehyde-thiosemicarbazones (16-27) was synthesised as part of a study to search for potential new drugs with a leishmanicidal effect. The thiosemicarbazones, ten of which are new compounds, were prepared in good yields (85-98%) by the reaction of 3,4-methylenedioxyde-6-benzaldehydes (6-X-piperonal), previously synthesised for this work by several methodologies, and thiosemicarbazide in ethanol with a few drops of H2SO4. These compounds were evaluated against Leishmania amazonensis promastigotes, and derivatives where X = I (22) and X = CN (23) moieties showed impressive results, having IC50 = 20.74 μM and 16.40 μM, respectively. The intracellular amastigotes assays showed IC50 = 22.00 μM (22) and 17.00 μM (23), and selectivity index >5.7 and >7.4, respectively, with a lower toxicity compared to pentamidine (positive control, SI = 4.5). The results obtained from the preliminary QSAR study indicated the hydrophobicity (log P) as a fundamental parameter for the 2D-QSAR linear model. A molecular docking study demonstrated that both compounds interact with flavin mononucleotide (FMN), important binding site of NO synthase.