1009298-09-2

Usage

References

1) Chresta et al. (2010), AZD8055 is a potent, selective, and orally bioavailable ATP-competitive mammalian target of rapamycin kinase inhibitor with in vitro and in vivo antitumor activity; Cancer Res. 70 288 2) Pike et al. (2013), Optimization of potent an selective dual mTORC1 and mTORC2 inhibitors: the discovery of AZD8055 and AZD2014; Bioorg. Med. Chem. Lett. 23 1212 3) Holt et al. (2012), Enhanced apoptosis and tumor growth suppression elicited by combination of MEK (selumetinib) and mTOR kinase inhibitors (AZD8055); Cancer Res. 72 1804 4) Willems et al. (2012), The dual mTORC1 and mTORC2 inhibitor AZD8055 has anti-tumor activity in acute myeloid leukemia; Leukemia 26 1195 5) Li et al. (2013),The mTOR inhibitor AZD8055 inhibits proliferation and glycolysis in cervical cancer cells; Oncol. Lett. 5 717 6) Li et al. (2013), The dual mTORC1 and mTORC2 inhibitor AZD8055 inhibits head and neck squamous cell carcinoma cell growth in vivo and in vitro; Biochem. Biophys. Res. Commun. 440 701 7) Hu et al. (2014), AZD8055 induces cell death associated with autophagy and activation of AMPK in hepatocellular carcinoma; Oncol. Rep. 31 649

Upstream product

• 1009303-44-9 (3S)-4-[7-chloro-2-[(3S)-3-methylmorpholin-4-yl]pyrido[2,3-d] pyrimidin-4-yl] 3-methyl-morpholine 
• 1009303-77-8 [2-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methanol 
• 1009303-42-7 (S)-4-(2,7-dichloropyrido[2,3-d]pyrimidin-4-yl)-3-methylmorpholine 
• 58584-92-2 2-amino-6-chloronicotinic acid 
• 938443-20-0 2,4,7-trichloropyrido[2,3-d]pyrimidine 
• 938443-19-7 7-chloropyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione 
• 64321-24-0 2-amino-6-chloro-pyridine-3-carboxamide 
• 38496-18-3 2,6-dichloropyridine-3-carboxylic acid 
• 1201798-98-2 5-{2,4-bis[(3S)-3-methylmorpholin-4-yl]pyrido[2,3-d]pyrimidin-7-yl}-2-methoxybenzyl pivalate 
• 1009298-82-1 methyl 5-{2,4-bis[(3S)-3-methylmorpholin-4-yl]pyrido[2,3-d]pyrimidin-7-yl}-2-methoxybenzoate 

Relevant academic research and scientific papers

Optimization of potent and selective dual mTORC1 and mTORC2 inhibitors: The discovery of AZD8055 and AZD2014

The optimization of a potent and highly selective series of dual mTORC1 and mTORC2 inhibitors is described. An initial focus on improving cellular potency whilst maintaining or improving other key parameters, such as aqueous solubility and margins over hERG IC50, led to the discovery of the clinical candidate AZD8055 (14). Further optimization, particularly aimed at reducing the rate of metabolism in human hepatocyte incubations, resulted in the discovery of the clinical candidate AZD2014 (21).

COMPOSITION AND PROCESS - 356

There is provided a process for the preparation of a compound of Formula 1, the use of said process in the preparation of a compound of Formula 5 or a phosphate, sulphate, hydrogensulphate, malate, citrate, tartrate or fumarate salt thereof, and the use of the fumarate salt in a composition for use in therapy.

2-METHYLMORPHOLINE PYRIDO-, PYRAZO- AND PYRIMIDO-PYRIMIDINE DERIVATIVES AS MTOR INHIBITORS

There is provided a compound of Formula (I), or a pharmaceutically acceptable salt thereof. There are also provided processes for the manufacture of a compound of Formula (1), and the use of a compound of Formula (1) as a medicament and in the treatment of cancer