377727-87-2

Usage

Uses

Used in Pharmaceutical Industry:
Unii-950o97nupo is used as a potent and selective antagonist at the adenosine A2A receptor for its potential therapeutic applications in treating Parkinson's disease. It has shown promise in reducing catalepsy induced by haloperidol in rats and increasing the efficacy of L-DOPA when used in combination with eltoprazine in a 6-OHDA rat lesion model of Parkinson’s disease dyskinesia.

References

1)?Hodgson?et al.?(2009), Characterization of the potent and selective A2A receptor antagonists preladenant and SCH 412348 [7-[2-[4-2,4-difluorophenyl]-1-piperazinyl]ethyl]-2-(2-furanyl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimodin-5-amine] in rat models of movement disorders and depression;?J.Pharmacol.Exp.Ther.?330294 2)?Hodgson?et al.?(2010), Preladenant, a selective A(2A) receptor antagonist, is active in primate models of movement disorders;?Exp.Neurol.?225384 3)?Pinna?et al.?(2016), Antidyskinetic effect of A2A and 5HT1A/B receptor ligands in two animal models of Parkinson’s disease;?Mov.Disord.?31501 4)?Beavis?et al.?(2013), Blockade of A2A receptors potently suppresses the metastasis of CD73+ tumors;?Proc.Natl.Acad.Sci USA.?11014711 5)?Hatfield and Sitkovsky (2016), A2A adenosine receptor antagonist to weaken the hypoxia-HIF-1a driven immunosuppression and improve immunotherapies of cancer;?Curr.Opin.Pharmacol.?2990 6)?Ohta?et al.?(2016), A metabolic immune checkpoint: adenosine in the tumor microenvironment;?Front.Immunol.?71 7)?NCT03099161

Upstream product

• 377729-85-6 C₁₂H₁₀BrN₇O 
• 515160-72-2 1-(4-(2-methoxyethoxy)phenyl)piperazine 
• 929884-33-3 tert-butyl 2-(6-amino-1-(2-(4-(4-(2-methoxyethoxy) phenyl) piperazin-1-yl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)hydrazine carboxylate 
• 1401067-78-4 4-(2-(furan-2-ylmethylene)hydrazinyl)-1-(2-(4-(4-(2-methoxy-ethoxy)phenyl)piperazin-1-yl)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine 
• 1401067-81-9 5-amino-7-chloro-2-(furan-2-yl)-[1,2,4]triazolo[1,5-c]pyrimidine-8-carbaldehyde 
• 1401067-82-0 1-(2-hydrazinylethyl)-4-(4-(2-methoxyethoxy)phenyl)piperazine 
• 1401067-77-3 C₂₀H₂₆ClN₇O₂ 
• 377729-86-7 C₁₂H₁₃N₇O₃ 
• 387358-27-2 1-{4-[4-(2-methoxy-ethoxy)-phenyl]-piperazin-1-yl}-ethanone 
• 67914-60-7 N-acetyl-N'-(4-hydroxyphenyl)piperazine 
• 850648-62-3 C₂₄H₃₀N₈O₃*ClH 
• 506-68-3 bromocyane 
• 377729-81-2 furan-2-carboxylic acid N-(6-amino-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-hydrazide 
• 377729-80-1 furan-2-carboxylic acid N-(2-amino-6-chloro-5-formylpyrimidin-4-yl)-hydrazide 

Downstream Products

• 377729-89-0 C₁₆H₁₉N₉O 
• 1245905-29-6 C₂₃H₂₇N₉O₃ 
• 1245905-32-1 C₂₅H₂₉N₉O₅ 
• 1245905-31-0 C₂₅H₂₉N₉O₅ 
• 1245905-33-2 C₁₂H₁₂N₈O 
• 1245905-34-3 C₂₅H₂₇N₉O₄ 
• 377727-88-3 C₂₄H₂₅N₉O₃ 

Relevant academic research and scientific papers

Fluorinated adenosine A2A receptor antagonists inspired by preladenant as potential cancer immunotherapeutics

Antagonism of the adenosine A2A receptor on T cells blocks the hypoxia-adenosinergic pathway to promote tumor rejection. Using an in vivo immunoassay based on the Concanavalin A mouse model, a series of A2A antagonists were studied and identified preladenant as a potent lead compound for development.Molecular modeling was employed to assist drug design and subsequent synthesis of analogs and those of tozadenant, including fluorinated polyethylene glycol PEGylated derivatives. The efficacy of the analogs was evaluated using two in vitro functional bioassays, and compound 29, a fluorinated triethylene glycol derivative of preladenant, was confirmed as a potential immunotherapeutic agent.

PROCESS AND INTERMEDIATES FOR THE PREPARATION OF PRELADENANT AND RELATED COMPOUNDS

The present invention describes processes for the synthesis of 2-(furan-2-yl)-7-[2-[4-[4-(2-methoxyethoxy)phenyl]piperazin-l-yl] ethyl]-7H-pyrazolo[ 4,3-e ][1,2,4]- triazolo[1,5c] pyrimidin-5-amine (Preladenant) represented by the structure of formula (1

Potent, selective, and orally active adenosine A2A receptor antagonists: Arylpiperazine derivatives of pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidines

Antagonism of the adenosine A2A receptor offers great promise in the treatment of Parkinson's disease. Employing the known pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine A2A antagonist SCH 58261 as a starting point, we identified the potent and selective (vs. A1) antagonist 11 h, orally active in the rat haloperidol-induced catalepsy model. We further optimized this lead to the methoxyethoxyethyl ether 12a (SCH 420814), which shows broad selectivity, good pharmacokinetic properties, and excellent in vivo activity.

Process for preparing substituted 5-amino-pyrazolo-[4,3-e]-1,2,4-triazolo-[1,5-c]-pyrimidine

A process for preparing substituted 5-amino-pyrazolo[4,3-e]-1,2,4-triazolo-[1,5-c]pyrimidine compounds having an aminoalkyl substituent at the 7-position is disclosed, wherein the pyrimidine ring is cyclized using a cyanating agent.

PROCESS FOR PREPARING SUBSTITUTED 5-AMINO-PYRAZOLO-[4,3-E]-1,2,4-TRIAZOLO[1,5-C]PYRIMIDINES

A process for preparing substituted 5-amino-pyrazolo[4,3-e]-1,2,4-triazolo-[1,5-c]pyrimidine compounds having an aminoalkyl substituent at the 7-position is disclosed.