1227923-94-5

Basic information

• Product Name: 6-((6-chloropyridin-3-yl)methyl)-3-((1S,2S)-2-hydroxycyclohexyl)benzo[h]quinazolin-4(3H)-one
• Synonyms: 6-((6-chloropyridin-3-yl)methyl)-3-((1S,2S)-2-hydroxycyclohexyl)benzo[h]quinazolin-4(3H)-one
• CAS NO: 1227923-94-5
• Molecular Weight: 419.911
• Mol File: 1227923-94-5.mol
• Article Data: 5

Chemical Properties

• CAS DataBase Reference: 6-((6-chloropyridin-3-yl)methyl)-3-((1S,2S)-2-hydroxycyclohexyl)benzo[h]quinazolin-4(3H)-one(CAS DataBase Reference)
• NIST Chemistry Reference: 6-((6-chloropyridin-3-yl)methyl)-3-((1S,2S)-2-hydroxycyclohexyl)benzo[h]quinazolin-4(3H)-one(1227923-94-5)
• EPA Substance Registry System: 6-((6-chloropyridin-3-yl)methyl)-3-((1S,2S)-2-hydroxycyclohexyl)benzo[h]quinazolin-4(3H)-one(1227923-94-5)

Safety Data

• Hazardous Substances Data: 1227923-94-5(Hazardous Substances Data)

Upstream product

• 1227924-43-7 1-amino-4-bromo-N-[(1S,2S)-2-hydroxycyclohexyl]-2-naphthamide 
• 1227924-42-6 1-amino-4-bromo-2-naphthoic acid 
• 1268515-63-4 methyl 1-amino-4-bromo-2-naphthoate hydrobromide 
• 35092-83-2 methyl 1-amino-2-naphthoate 
• 78508-71-1 methyl 1-nitro-2-naphthoate 
• 103987-83-3 1-nitro-2-naphthoic acid 
• 881-03-8 1-nitro-2-methylnaphthalene 
• 352530-36-0 ((6-chloropyridin-3-yl)methyl)zinc(II) chloride 
• 1227924-44-8 6-bromo-3-[(1S,2S)-2-hydroxycyclohexyl]benzo[h]quinazolin-4(3H)-one 
• 4637-24-5 N,N-dimethyl-formamide dimethyl acetal 
• 931-15-7 (1S,2S)-trans-2-aminocyclohexanol 

Downstream Products

• 1227924-25-5 3-((1S,2S)-2-hydroxycyclohexyl)-6-((6-isopropenylpyridin-3-yl)methyl)benzo[h]quinazolin-4(3H)-one 
• 1227923-91-2 3-((1S,2S)-2-hydroxycyclohexyl)-6-((6-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)methyl)benzo-[h]quinazolin-4(3H)-one 
• 1227924-28-8 3-((1S,2S)-2-hydroxycyclohexyl)-6-((6-methoxypyridin-3-yl)methyl)benzo[h]quinazolin-4(3H)-one 
• 1227924-20-0 3-((1S,2S)-2-hydroxycyclohexyl)-6-((6-(methylthio)pyridin-3-yl)methyl)benzo[h]quinazolin-4(3H)-one 
• 1371535-87-3 3-((1S,2S)-2-((tert-butyldimethylsilyl)oxy)cyclohexyl)-6-((6-methylpyridin-3-yl)methyl)-2,3-dihydrobenzo[h]quinazolin-4(1H)-one 
• 1371535-86-2 3-((1S,2S)-2-((tert-butyldimethylsilyl)oxy)cyclohexyl)-6-((6-methylpyridin-3-yl)methyl)benzo[h]quinazolin-4(3H)-one 
• 1227923-29-6 3-[(1S,2S)-2-hydroxycyclohexyl]-6-[(6-methylpyridin-3-yl)methyl]benzo[h]quinazolin-4(3H)-one 

Relevant articles and documents

MK-7622: A First-in-Class M1 Positive Allosteric Modulator Development Candidate

Identification of ligands that selectively activate the M1 muscarinic signaling pathway has been sought for decades to treat a range of neurological and cognitive disorders. Herein, we describe the optimization efforts focused on addressing key physicochemical and safety properties, ultimately leading to the clinical candidate MK-7622, a highly selective positive allosteric modulator of the M1 muscarinic receptor that has entered Phase II studies in patients with Alzheimer's disease.

Novel Fused Arylpyrimidinone Based Allosteric Modulators of the M1 Muscarinic Acetylcholine Receptor

Benzoquinazolinone 1 is a positive allosteric modulator (PAM) of the M1 muscarinic acetylcholine receptor (mAChR), which is significantly more potent than the prototypical PAM, 1-(4-methoxybenzyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (BQCA). In this study, we explored the structural determinants that underlie the activity of 1 as a PAM of the M1 mAChR. We paid particular attention to the importance of the tricyclic scaffold of compound 1, for the activity of the molecule. Complete deletion of the peripheral fused benzene ring caused a significant decrease in affinity and binding cooperativity with acetylcholine (ACh). This loss of affinity was rescued with the addition of either one or two methyl groups in the 7- and/or 8-position of the quinazolin-4(3H)-one core. These results demonstrate that the tricyclic benzo[h]quinazolin-4(3H)-one core could be replaced with a quinazolin-4(3H)-one core and maintain functional affinity. As such, the quinazolin-4(3H)-one core represents a novel scaffold to further explore M1 mAChR PAMs with improved physicochemical properties.

ARYL METHYL BENZOQUINAZOLINONE M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS

The present invention is directed to benzoquinazilinone compounds of formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimer's disease, schizophrenia, pain or sleep disorders. The invention is also directed to pharmaceutical compositions comprising the compounds, and to the use of the compounds and compositions in the treatment of diseases mediated by the M1 receptor.