516445-83-3

Usage

Uses

Used in Pharmaceutical Industry:
N-Tricyclo[3.3.1.13,7]dec-1-yl-1H-Indazole-3-carboxamide is used as an intermediate in the synthesis of synthetic cannabinoids for the pharmaceutical industry. Its primary application is in the production of AKB48 (A450100), which mimics the effects of JWH 018 adamantyl carboxamide and STS-135. These synthetic cannabinoids are of interest due to their potential recreational use and the need for research and development in this area.
Used in Research and Development:
In the field of research and development, N-Tricyclo[3.3.1.13,7]dec-1-yl-1H-Indazole-3-carboxamide is used as a key compound in the synthesis of novel synthetic cannabinoids. This allows scientists and researchers to explore the properties, effects, and potential applications of these compounds, including their recreational use and any associated risks or benefits.
Used in Drug Synthesis:
N-Tricyclo[3.3.1.13,7]dec-1-yl-1H-Indazole-3-carboxamide is also used in the synthesis of various drugs, particularly those related to the cannabinoid receptor system. Its role in the production of synthetic cannabinoids like AKB48 (A450100) makes it an important compound in the development of new drugs that target these receptors, potentially leading to novel therapeutic applications.

Upstream product

• 665-66-7 amantadine hydrochloride 
• 4498-67-3 1H-Indazole-3-carboxylic acid 
• 768-94-5 1-Adamantanamine 

Relevant academic research and scientific papers

Synthesis and identifications of potential metabolites as biomarkers of the synthetic cannabinoid AKB-48

AKB-48 belongs to the family of synthetic cannabinoids. It has strong binding affinity to CB1 receptor and is psychoactive. It is banned in many countries including USA, Japan, Germany, New Zealand, Singapore and China etc. But the difficulty in detecting the parent compound in urine samples highlights the importance of studies of its metabolites. Here we report the synthesis of 19 potential metabolites of AKB-48, among which, compounds 2, 9, 10, 30 and 31, together with the commercially available substance 5 were identified as metabolites of AKB-48 by comparison with one authentic human urine sample and human liver microsomal data. Compounds 10 and 30 could be of use as biomarkers in detecting AKB-48 in human urine samples.

Synthesis and antitumour evaluation of indole-2-carboxamides against paediatric brain cancer cells

Paediatric glioblastomas are rapidly growing, devastating brain neoplasms with an invasive phenotype. Radiotherapy and chemotherapy, which are the current therapeutic adjuvant to surgical resection, are still associated with various toxicity profiles and only marginally improve the course of the disease and life expectancy. A considerable body of evidence supports the antitumour and apoptotic effects of certain cannabinoids, such as WIN55,212-2, against a wide spectrum of cancer cells, including gliomas. In fact, we previously highlighted the potent cytotoxic activity of the cannabinoid ligand 5 against glioblastoma KNS42 cells. Taken together, in this study, we designed, synthesised, and evaluated several indoles and indole bioisosteres for their antitumour activities. Compounds 8a, 8c, 8f, 12c, and 24d demonstrated significant inhibitory activities against the viability (IC50 = 2.34-9.06 μM) and proliferation (IC50 = 2.88-9.85 μM) of paediatric glioblastoma KNS42 cells. All five compounds further retained their antitumour activities against two atypical teratoid/rhabdoid tumour (AT/RT) cell lines. When tested against a medulloblastoma DAOY cell line, only 8c, 8f, 12c, and 24d maintained their viability inhibitory activities. The viability assay against non-neoplastic human fibroblast HFF1 cells suggested that compounds 8a, 8c, 8f, and 12c act selectively towards the panel of paediatric brain tumour cells. In contrast, compound 24d and WIN55,212-2 were highly toxic toward HFF1 cells. Due to their structural resemblance to known cannabimimetics, the most potent compounds were tested in cannabinoid 1 and 2 receptor (CB1R and CB2R) functional assays. Compounds 8a, 8c, and 12c failed to activate or antagonise both CB1R and CB2R, whereas compounds 8f and 24d antagonised CB1R and CB2R, respectively. We also performed a transcriptional analysis on KNS42 cells treated with our prototype compound 8a and highlighted a set of seven genes that were significantly downregulated. The expression levels of these genes were previously shown to be positively correlated with tumour growth and progression, indicating their implication in the antitumour activity of 8a. Overall, the drug-like and selective antitumour profiles of indole-2-carboxamides 8a, 8c, 8f, and 12c substantiate the versatility of the indole scaffold in cancer drug discovery. This journal is

Azaindole derivative and preparation method and application thereof

The invention belongs to the technical field of medicines, and discloses an azaindole derivative shown as a formula (I) and/or a medicinal salt and a preparation method thereof. The preparation methodcomprises the following steps: carrying out amidation reaction on a compound shown as a formula (II) and amantadine to obtain a compound shown as a formula (III); and carrying out nucleophilic substitution reaction on the compound shown in the formula (III) and halogenated R1 to obtain the compound shown in the formula (I). The azaindole-2-formamide derivative is an agonist with high selectivity,high affinity and high activity on a cannabinoid type 2 receptor (CB2), and the structural formula of the azaindole-2-formamide derivative is shown in the specification. The active prevention and treatment effects can be achieved on multiple sclerosis, autoimmune diseases, osteoporosis, neurodegeneration, organ transplantation immunological rejection, tumor resistance and other various cannabinoid receptor related diseases.

IMMUNOASSAY FOR SYNTHETIC CANNABINOIDS OF THE 3-ADAMANTANYL INDAZOLE/INDOLE-3-CARBOXAMIDE FAMILY

An immunoassay method for detecting and determining adamantane substituted indazole and indole synthetic cannabinoids is described. Also described are components for use in implementing the method, namely, antibodies, detection agents, solid state devices and kits as well as immunogens used to raise the antibodies.

Synthesis and evaluation of fluorescent heterocyclic aminoadamantanes as multifunctional neuroprotective agents

A series of fluorescent heterocyclic adamantane amines were synthesised with the goal to develop novel fluorescent ligands for neurological assay development. These derivatives demonstrated multifunctional neuroprotective activity through inhibition of the N-methyl-d-aspartate receptor/ion channel, calcium channels and the enzyme nitric oxide synthase. It also exhibited a high degree of free radical scavenging potential. N-(1-adamantyl)-2-oxo-chromene-3- carboxamide (8), N-adamantan-1-yl-5-dimethyl-amino-1-naphthalenesulfonic acid (11) and N-(1-cyano-2H-isoindol-2-yl) adamantan-1-amine (12) were found to possess a high degree of multifunctionality with favourable physical-chemical properties for bioavailability and blood-brain barrier permeability. The ability of these heterocyclic adamantane amine derivatives as nitric oxide synthase inhibitors, calcium channel modulators, NMDAR inhibitors and effective antioxidants, indicate that they may find application as multifunctional drugs in neuroprotection.

Fluorescent polycyclic ligands for nitric oxide synthase (NOS) inhibition

In recent years polycyclic compounds have been shown to exhibit pharmacological profiles of importance in the symptomatic and proposed curative treatment of neurodegenerative diseases (e.g., Parkinson's and Alzheimer's disease). These structures also show modification and improvement of the pharmacokinetic and pharmacodynamic properties of drugs in current use. Nitric oxide (NO) is a molecular messenger involved in a number of physiological processes in mammals. It is synthesised by nitric oxide synthase (NOS) from l-arginine and its overproduction could lead to a number of neurological disorders. The aim of this study was to synthesise a series of novel indazole, indole and other fluorescent derivatives conjugated to polycyclic structures for evaluation in NOS assays. NOS is a target system where fluorescent techniques and fluorescently labelled NOS inhibitors can be used for detecting the biophysical properties of enzyme-ligand interactions and thus facilitate development of novel inhibitors of neurodegeneration. This could lead to a greater insight into the neuroprotective mechanism and a possible cure/treatment for neurodegenerative diseases. A series of compounds incorporating polycyclic structures such as 3-hydroxy-4-aza-8-oxoheptacyclo[9.4.1.0.2,100.3,140.4,90.9,13012,15]tetradecane and amantadine as well as suitable fluorescent moieties were selected for synthesis. In the biological evaluation the oxyhaemoglobin (oxyHb) assay was employed to determine the activity of the novel compounds at an enzymatic level of NOS. IC50 values of the novel fluorescent compounds were compared to that of aminoguanidine (AG) and 7-nitroindazole (7-NI), two known NOS inhibitors, and showed moderate to high affinity (IC50 values ranging from 7.73 μM to 0.291 μM) for the NOS enzyme.