870070-55-6

Basic information

• Product Name: 4-Hydroxy-N-[4-methoxy-7-(4-morpholinyl)-2-benzothiazolyl]-4-methyl-1-piperidinecarboxamide
• Synonyms: 4-Hydroxy-N-[4-methoxy-7-(4-morpholinyl)-2-benzothiazolyl]-4-methyl-1-piperidinecarboxamide;SYN-115;4-Hydroxy-N-[4-methoxy-7-...;Tozadenant;4-hydroxy-N-(4-methoxy-7-morpholinobenzo[d]thiazol-2-yl)-4-methylpiperidine-1-carboxamide;Tozadenant (SYN-115);SYN-115 (Tozadenant);1-Piperidinecarboxamide, 4-hydroxy-N-[4-methoxy-7-(4-morpholinyl)-2-benzothiazolyl]-4-methyl-
• CAS NO: 870070-55-6
• Molecular Formula: C₁₉H₂₆N₄O₄S
• Molecular Weight: 406.49914
• Mol File: 870070-55-6.mol
• Article Data: 3

Chemical Properties

• Appearance: /
• Density: 1.374
• Solubility: insoluble in EtOH; insoluble in H2O; ≥20.35 mg/mL in DMSO
• PKA: 14.95±0.20(Predicted)
• CAS DataBase Reference: 4-Hydroxy-N-[4-methoxy-7-(4-morpholinyl)-2-benzothiazolyl]-4-methyl-1-piperidinecarboxamide(CAS DataBase Reference)
• NIST Chemistry Reference: 4-Hydroxy-N-[4-methoxy-7-(4-morpholinyl)-2-benzothiazolyl]-4-methyl-1-piperidinecarboxamide(870070-55-6)
• EPA Substance Registry System: 4-Hydroxy-N-[4-methoxy-7-(4-morpholinyl)-2-benzothiazolyl]-4-methyl-1-piperidinecarboxamide(870070-55-6)

Safety Data

• Hazardous Substances Data: 870070-55-6(Hazardous Substances Data)

Usage

Description

4-Hydroxy-N-[4-methoxy-7-(4-morpholinyl)-2-benzothiazolyl]-4-methyl-1-piperidinecarboxamide, also known as Tozadenant, is an adenosine A2A receptor antagonist with high affinity for both human and rhesus monkey receptors. It exhibits neuroprotective and symptomatic benefits in animal models of Parkinson's disease, making it a promising candidate for the treatment of this neurodegenerative disorder.

Uses

Used in Pharmaceutical Industry:
4-Hydroxy-N-[4-methoxy-7-(4-morpholinyl)-2-benzothiazolyl]-4-methyl-1-piperidinecarboxamide is used as a therapeutic agent for the treatment of Parkinson's disease. It acts as an adenosine A2A receptor antagonist, which helps to increase the distance traveled and reduce contralateral asymmetry in the open field test in a rat model of Parkinson's disease induced by 6-OHDA when administered at a dose of 30 mg/kg.
Additionally, Tozadenant (150 mg/kg) reverses locomotor deficits and restores novel object-stimulated locomotion in a marmoset model of MPTP-induced Parkinson's disease, demonstrating its potential to improve motor function and alleviate symptoms associated with the disorder.

references

hauser ra, olanow cw, kieburtz kd et al. tozadenant (syn115) in patients with parkinson's disease who have motor fluctuations on levodopa: a phase 2b, double-blind, randomised trial. lancet neurol. 2014 aug;13(8):767-76.

Upstream product

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Relevant articles and documents

Design, synthesis and biological evaluation of Tozadenant analogues as adenosine A2A receptor ligands

With the aim to obtain potent adenosine A2A receptor (A2AR) ligands, a series of eighteen derivatives of 4-hydroxy-N-(4-methoxy-7-morpholin-4-yl-1,3-benzo[d]thiazol-2-yl)-4-methylpiperidine-1-carboxamide (SYN-115, Tozadenant) were designed and synthesized. The target compounds were obtained by a chemical building block principle that involved reaction of the appropriate aminobenzothiazole phenyl carbamates with either commercially available or readily synthesized functionalized piperidines. Their affinity and subtype selectivity with regard to human adenosine A1-and A2A receptors were determined using radioligand binding assays. Ki values for human A2AR ranged from 2.4 to 38 nM, with more than 120-fold selectivity over A1 receptors for all evaluated compounds except 13k which had a Ki of 361 nM and 18-fold selectivity. The most potent fluorine-containing derivatives 13e, 13g and 13l exhibited Ki values of 4.9 nM, 3.6 nM and 2.8 nM for the human A2AR. Interestingly, the corresponding values for rat A2AR were found to be four to five times higher. Their binding to A2AR was further confirmed by radiolabeling with 18F and in vitro autoradiography in rat brain slices, which showed almost exclusive striatal binding and complete displacement by the A2AR antagonist ZM 241385. We conclude that these compounds represent potential candidates for the visualization of the A2A receptor and open pathways to novel therapeutic treatments of neurodegenerative disorders or cancer.

4-Hydroxy-4-methyl-piperidine-1-carboxylic acid (4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-amide

The present invention relates to the compound of formula which is 4-hydroxy-4-methyl-piperidine-1-carboxylic acid(4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-amide, and to pharmaceutically acceptable acid addition salts thereof. It has been found that the compound is useful for the treatment or prevention of Alzheimer's disease, Parkinson's disease, Huntington's disease, neuroprotection, schizophrenia, anxiety, pain, respiration deficits, depression, ADHD (attention deficit hyper-activity disorder), drug addiction to amphetamines, cocaine, opioids, ethanol, nicotine, or cannabinoids, or for the treatment of asthma, allergic responses, hypoxia, ischemia, seizure, substance abuse, or for use as muscle relaxants, antipsychotics, antiepileptics, anticonvulsants and cardioprotective agents.