1215867-37-0

Basic information

• Product Name: (S)-7-(2-fluoropyridin-3-yl)-3-(p-tolyl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-2'-amine
• Synonyms: (S)-7-(2-fluoropyridin-3-yl)-3-(p-tolyl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-2'-amine
• CAS NO: 1215867-37-0
• Molecular Weight: 438.461
• Mol File: 1215867-37-0.mol

Chemical Properties

• CAS DataBase Reference: (S)-7-(2-fluoropyridin-3-yl)-3-(p-tolyl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-2'-amine(CAS DataBase Reference)
• NIST Chemistry Reference: (S)-7-(2-fluoropyridin-3-yl)-3-(p-tolyl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-2'-amine(1215867-37-0)
• EPA Substance Registry System: (S)-7-(2-fluoropyridin-3-yl)-3-(p-tolyl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-2'-amine(1215867-37-0)

Safety Data

• Hazardous Substances Data: 1215867-37-0(Hazardous Substances Data)

Upstream product

• 1215867-39-2 (S)-2'-amino-3-(p-tolyl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-7-ol 
• 1215867-38-1 (S)-2'-amino-3-bromo-5'H-spiro[chromeno[2,3-b]pyridin-5,4'-oxazol]-7-ol 
• 1215867-40-5 (S)-2′-amino-3-(p-tolyl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-7-yl trifluoromethanesulfonate 
• 174669-73-9 (2-fluoro-pyridin-3-yl)boronic acid 
• 5720-05-8 4-methylphenylboronic acid 

Relevant articles and documents

Inhibitors of β-site amyloid precursor protein cleaving enzyme (BACE1): Identification of (S)-7-(2-fluoropyridin-3-yl)-3-((3-methyloxetan-3-yl)ethynyl)-5′ H -spiro[chromeno[2,3- b ]pyridine-5,4′-oxazol]-2′-amine (AMG-8718)

We have previously shown that the aminooxazoline xanthene scaffold can generate potent and orally efficacious BACE1 inhibitors although certain of these compounds exhibited potential hERG liabilities. In this article, we describe 4-aza substitution on the xanthene core as a means to increase BACE1 potency while reducing hERG binding affinity. Further optimization of the P3 and P2′ side chains resulted in the identification of 42 (AMG-8718), a compound with a balanced profile of BACE1 potency, hERG binding affinity, and Pgp recognition. This compound produced robust and sustained reductions of CSF and brain Aβ levels in a rat pharmacodynamic model and exhibited significantly reduced potential for QTc elongation in a cardiovascular safety model.

SPIRO-TETRACYCLIC RING COMPOUNDS AS BETA - SECRETASE MODULATORS

The present invention comprises a new class of compounds useful for the modulation of Beta-secretase enzyme activity and for the treatment of Beta-secretase mediated diseases, including Alzheimer's disease (AD) and other related conditions. In one embodiment, the compounds have a general Formula (I) wherein A1, A2, A3, A4, A5, A6, R2, R7, X and Y of Formula I are defined herein. The invention also includes use of these compounds in pharmaceutical compositions for treatment, prophylactic or therapeutic, of disorders and conditions related to the activity of beta-secretase protein. Such disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairment, schizophrenia and other central nervous system conditions related to and/or caused by the formation and/or deposition of plaque on the brain. The invention also comprises further embodiments of Formula I, intermediates and processes useful for the preparation of compounds of Formula I.