1251156-08-7

Basic information

• Product Name: XL-388
• Synonyms: Methanone, [7-(6-amino-3-pyridinyl)-2,3-dihydro-1,4-benzoxazepin-4(5H)-yl][3-fluoro-2-methyl-4-(methylsulfonyl)phenyl]-;[7-(6-Amino-3-pyridinyl)-2,3-dihydro-1,4-benzoxazepin-4(5H)-yl][3-fluoro-2-methyl-4-(methylsulfonyl)phenyl]-methanone XL388;XL388, >=98%;(7-(6-Aminopyridin-3-yl)-2,3-dihydrobenzo[f][1,4]oxazepin-4(5H)-yl)(3-fluoro-2-methyl-4-(methy;XL 388;XL388;XL-388;[7-(6-Amino-3-pyridinyl)-2,3-dihydro-1,4-benzoxazepin-4(5H)-yl][3-fluoro-2-methyl-4-(methylsulfonyl)phenyl]-methanone
• CAS NO: 1251156-08-7
• Molecular Formula: C₂₃H₂₂FN₃O₄S
• Molecular Weight: 455.5018832
• Product Categories: Inhibitors;Akt;mTOR;PI3K;PI3K/Akt/mTOR
• Mol File: 1251156-08-7.mol

Chemical Properties

• Boiling Point: 738.6±60.0 °C(Predicted)
• Appearance: /
• Density: 1.354±0.06 g/cm3(Predicted)
• Storage Temp.: Keep in dark place,Inert atmosphere,Store in freezer, under -20°C
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 6.22±0.13(Predicted)
• Stability: Hygroscopic
• CAS DataBase Reference: XL-388(CAS DataBase Reference)
• NIST Chemistry Reference: XL-388(1251156-08-7)
• EPA Substance Registry System: XL-388(1251156-08-7)

Safety Data

• Hazardous Substances Data: 1251156-08-7(Hazardous Substances Data)

Upstream product

• 1251164-88-1 3-fluoro-2-methyl-4-(methylsulfonyl)benzoyl chloride 
• 1251165-18-0 5-(2,3,4,5-tetrahydrobenzo[f][1,4]oxazepin-7-yl)pyridin-2-amine 
• 1217862-54-8 tert-butyl N-(5-bromo-2-hydroxybenzyl)-N-(2-hydroxyethyl)carbamate 
• 847502-81-2 1-bromo-3,4-difluoro-2-methyl-benzene 
• 3828-49-7 1,2-difluoro-3-methyl-benzene 
• 157652-31-8 3,4-difluoro-2-methyl benzoic acid 
• 118287-06-2 3-fluoro-2-methyl-4-(thiomethyl)benzoic acid 
• 703-51-5 2,3-dihydro-1,4-benzoxazepin-5(4H)-one 
• 5755-05-5 7-bromo-3,4-dihydrobenzo[f][1,4]oxazepin-5(2H)-one 
• 740842-71-1 7-bromo-2,3,4,5-tetrahydrobenzo[f][1,4]oxazepine 
• 491-37-2 2,3-dihydro-4H-1-benzopyran-4-one 
• 740842-72-2 7-bromo-2,3,4,5-tetrahydrobenzo[f ][1,4]oxazepine hydrochloride 
• 6329-74-4 5-bromo-2-hydroxybenzamide 
• 118939-18-7 3-fluoro-2-methyl-4-(methylsulfonyl)benzoic acid 

Relevant articles and documents

Process Development and Scale-Up of a Benzoxazepine-Containing Kinase Inhibitor

The benzoxazepine core is present in several kinase inhibitors, including the mTOR inhibitor 1. The process development for a scalable synthesis of 7-bromobenzoxazepine and the telescoped synthesis of 1 are reported. Compound 1 consists of three chemicall

Discovery of a novel class of highly potent, selective, ATP-competitive, and orally bioavailable inhibitors of the mammalian target of rapamycin (mTOR)

A series of novel, highly potent, selective, and ATP-competitive mammalian target of rapamycin (mTOR) inhibitors based on a benzoxazepine scaffold have been identified. Lead optimization resulted in the discovery of inhibitors with low nanomolar activity and greater than 1000-fold selectivity over the closely related PI3K kinases. Compound 28 (XL388) inhibited cellular phosphorylation of mTOR complex 1 (p-p70S6K, pS6, and p-4E-BP1) and mTOR complex 2 (pAKT (S473)) substrates. Furthermore, this compound displayed good pharmacokinetics and oral exposure in multiple species with moderate bioavailability. Oral administration of compound 28 to athymic nude mice implanted with human tumor xenografts afforded significant and dose-dependent antitumor activity.

BENZOXAZEPIN-4- (5H) -YL DERIVATIVES AND THEIR USE TO TREAT CANCER

The invention is directed to Compounds of Formula I: and pharmaceutically acceptable salts or solvates thereof, as well as methods of making and using the compounds.