1436711-72-6

Basic information

• Product Name: C₁₈H₂₀N₂OS
• Synonyms: C₁₈H₂₀N₂OS
• CAS NO: 1436711-72-6
• Molecular Weight: 312.436
• Mol File: 1436711-72-6.mol

Chemical Properties

• CAS DataBase Reference: C₁₈H₂₀N₂OS(CAS DataBase Reference)
• NIST Chemistry Reference: C₁₈H₂₀N₂OS(1436711-72-6)
• EPA Substance Registry System: C₁₈H₂₀N₂OS(1436711-72-6)

Safety Data

• Hazardous Substances Data: 1436711-72-6(Hazardous Substances Data)

Upstream product

• 75-75-2 methanesulfonic acid 
• 1436711-69-1 C₁₈H₂₀N₂OS 
• 10365-98-7 3-methoxyphenylboronic acid 
• 893734-63-9 1-(3'-methoxy[1,1'-biphenyl]-3-yl)ethan-1-one 
• 2142-63-4 1-(3-Bromophenyl)ethanone 

Relevant articles and documents

Synthesis of a carbon-11 radiolabeled BACE1 inhibitor

Beta-secretase (BACE1), a transmembrane aspartyl protease, can cleave membrane-bound β-amyloid precursor proteins (APPs) to initiate the accumulation of amyloid-β (Aβ). The inhibition of BACE-1 to limit the accumulation of neurotoxic Aβ peptides could offer a potential treatment for Alzheimer’s Disease (AD). However, little is known about the distribution and density of BACE1 in the central nervous system. As a step toward filling this gap in knowledge, we have evaluated a potential radiotracer for the imaging of BACE1 using positron emission tomography (PET). A BACE1 inhibitor, 5, is reported with blood-brain barrier (BBB) permeability and high binding affinity. To characterize the pharmacokinetics and distribution of 5 in the brain, we radiolabeled 5 with carbon-11. Using PET, we found that [11C]5 shows moderate uptake in the brain when administered intravenously to rodents and further work will be performed in animal models to test its application as a PET imaging probe for the central nervous system. Our study demonstrates the effectiveness of PET at providing brain pharmacokinetic data for BACE1 inhibitors, crucial for the development of treatments for AD where CNS penetration is critical.

Core refinement toward permeable β-secretase (BACE-1) inhibitors with low hERG activity

By use of iterative design aided by predictive models for target affinity, brain permeability, and hERG activity, novel and diverse compounds based on cyclic amidine and guanidine cores were synthesized with the goal of finding BACE-1 inhibitors as a treatment for Alzheimer's disease. Since synthesis feasibility had low priority in the design of the cores, an extensive synthesis effort was needed to make the relevant compounds. Syntheses of these compounds are reported, together with physicochemical properties and structure-activity relationships based on in vitro data. Four crystal structures of diverse amidines binding in the active site are deposited and discussed. Inhibitors of BACE-1 with 3 μM to 32 nM potencies in cells are shown, together with data on in vivo brain exposure levels for four compounds. The results presented show the importance of the core structure for the profile of the final compounds.