612487-72-6

Basic information

• Product Name: AZD 1080
• Synonyms: AZD 1080;AZD1080;AZD-1080;2-Hydroxy-3-[5-[(morpholin-4-yl)methyl]pyridin-2-yl]-1H-indole-5-carbonitrile;2-Hydroxy-3-[5-[(morpholin-4-yl)methyl]pyridin-2-yl]-1H-indole-5-carbonitrile AZD1080;2-Hydroxy-3-(5-(morpholinomethyl)pyridin-2-yl)-1H-indole-5-carbonitrile
• CAS NO: 612487-72-6
• Molecular Formula: C19H18N4O2
• Molecular Weight: 334.37182
• Product Categories: Inhibitors;Akt;mTOR;PI3K
• Mol File: 612487-72-6.mol
• Article Data: 4

Chemical Properties

• Boiling Point: 594.0±50.0 °C(Predicted)
• Appearance: /
• Density: 1.40±0.1 g/cm3(Predicted)
• Solubility: insoluble in H2O; insoluble in EtOH; ≥16.7 mg/mL in DMSO
• PKA: 8.32±0.50(Predicted)
• CAS DataBase Reference: AZD 1080(CAS DataBase Reference)
• NIST Chemistry Reference: AZD 1080(612487-72-6)
• EPA Substance Registry System: AZD 1080(612487-72-6)

Safety Data

• Hazardous Substances Data: 612487-72-6(Hazardous Substances Data)

Usage

Description

The two isoforms of glycogen synthase kinase 3, GSK3α and GSK3β, constitutively phosphorylate and inactivate glycogen synthase, preventing glycogen synthesis. They also phosphorylate proteins that are relevant to Alzheimer’s disease and osteogenesis. AZD 1080 is a potent, brain permeable inhibitor of GSK3α and GSK3β (Kis = 6.9 and 31 nM, respectively). It shows >14-fold selectivity against several kinases, receptors, enzymes, and ion channels. AZD 1080 inhibits tau phosphorylation in cells. It shows good bioavailability after oral administration in vivo, inhibiting hippocampal tau phosphorylation and reversing cognitive deficits induced by the NMDA receptor antagonist (+)-MK-801 . In humans, oral AZD 1080 inhibits GSK3 activity in peripheral blood lymphocytes following an initial delay in response.

Uses

AZD1080 is a selective, orally active, brain permeable glycogen synthase kinase-3 (GSK3) inhibitor (1,2). AZD1080 has shown to rescue synaptic plasticity deficits in rodent brain and exhibit peripheral target engagement in humans.

references

[1] georgievska b1, sandin j, doherty j, m?rtberg a, neelissen j, andersson a, gruber s, nilsson y, sch?tt p, arvidsson pi, hellberg s, osswald g, berg s, f?lting j, bhat rv. azd1080, a novel gsk3 inhibitor, rescues synaptic plasticity deficits in rodent brain and exhibits peripheral target engagement in humans. j neurochem. 2013 may;125(3):446-56.

Upstream product

• 557-21-1 zinc(II) cyanide 
• 612488-09-2 5-bromo-3-[5-(morpholin-4-ylmethyl)pyridin-2-yl]-1H-indol-2-ol 
• 557-21-1 dicyanozinc 
• 1073614-10-4 1,2-dihydroxy-3-(5-morpholin-4-ylmethyl-pyridin-2-yl)-1H-indole-5-carbonitrile 
• 1073614-09-1 (2-amino-5-cyano-phenyl)-(5-morpholin-4-ylmethyl-pyridin-2-yl)-acetic acid ethyl ester 
• 311774-34-2 N-(6-chloropyridin-3-ylmethyl)morpholine 

Relevant articles and documents

Development of a mild and robust method for large-scale palladium-catalysed cyanation of aryl bromides: Importance of the order of addition

A mild and robust method for the large-scale palladium-catalysed cyanation of aryl bromides has been developed. The reaction is sensitive to cyanide poisoning of the catalyst, and it was found that the order of adding the reagents had a strong impact on the performance of the reaction. Addition of the cyanide source to a preheated mixture of the other reagents was critical for achieving a robust and scaleable process. This improved protocol allowed the reaction to be run to full conversion within 3 h at 50 °C on a 6.7 kg scale. Furthermore, it led to the identification of several new efficient catalysts for the reaction.

A PROCESS FOR PREPARING 2-HYDROXY-3- [5- (MORPHOLIN-4-YLMETHYL)PYRIDIN-2-YL] LH-INDOLE-5-CARBONITRILE AS A FREE BASE OR SALTS THEREOF

The present invention relates to a new process for the manufacture of the compound 2-hydroxy-3-[5-(moφholin-4-ylmethyl)pyridin-2-yl]lH'-indole-5-carbonitrile as a free base and pharmaceutically acceptable salts thereof, particularly the 2-hydroxy-3-[5- (morpholm-4-ylmethyl)pyridin-2-yl]lH-indole-5-carbonitrile citrate, to the use of said compounds for the manufacturing of a medicament for the treatment of cognitive disorders, Alzheimer disease, dementias, chronic and acute neurodegenerative diseases, bipolar disorders, schizophrenia, diabetes, hair loss etc. and to new intermediates as well as a robust condition for catalytic cyanation for the preparation of 2-hydroxy-3-[5- (moφholin-4-yhnethyl)pyridin-2-yl]lH-indole-5-carbonitrile as a free base and pharmaceutically acceptable salts thereof, and to a new intermediate prepared in said process suitable for large scale manufacturing of said compounds.The invention also relates to a new use in cyanation reaction of palladium catalysts.