890324-84-2

Basic information

• Product Name: N-([3-(4-METHYLPHENYL)-1,2,4-OXADIAZOL-5-YL]METHYL)ETHANAMINE HYDROCHLORIDE
• Synonyms: N-([3-(4-METHYLPHENYL)-1,2,4-OXADIAZOL-5-YL]METHYL)ETHANAMINE HYDROCHLORIDE;N-{[3-(4-methylphenyl)-1,2,4-oxadiazol-5-yl]methyl}ethanamine hydrochloride(SALTDATA: FREE)
• CAS NO: 890324-84-2
• Molecular Formula: C₁₂H₁₅N₃O
• Molecular Weight: 217.27
• Mol File: 890324-84-2.mol

Chemical Properties

• Boiling Point: 344.2°C at 760 mmHg
• Flash Point: 161.9°C
• Appearance: /
• Density: 1.095g/cm³
• Vapor Pressure: 6.71E-05mmHg at 25°C
• Refractive Index: 1.536
• CAS DataBase Reference: N-([3-(4-METHYLPHENYL)-1,2,4-OXADIAZOL-5-YL]METHYL)ETHANAMINE HYDROCHLORIDE(CAS DataBase Reference)
• NIST Chemistry Reference: N-([3-(4-METHYLPHENYL)-1,2,4-OXADIAZOL-5-YL]METHYL)ETHANAMINE HYDROCHLORIDE(890324-84-2)
• EPA Substance Registry System: N-([3-(4-METHYLPHENYL)-1,2,4-OXADIAZOL-5-YL]METHYL)ETHANAMINE HYDROCHLORIDE(890324-84-2)

Safety Data

• Hazardous Substances Data: 890324-84-2(Hazardous Substances Data)

Usage

InChI:InChI=1/C12H15N3O/c1-3-13-8-11-14-12(15-16-11)10-6-4-9(2)5-7-10/h4-7,13H,3,8H2,1-2H3

Upstream product

• 19227-13-5 (Z)-N'-hydroxy-4-methylbenzimidamide 
• 75-04-7 ethylamine 
• 50737-29-6 3-(4-methylphenyl)-5-(chloromethyl)-1,2,4-oxadiazole 
• 93335-40-1 (Z)-N'-(2-chloroacetoxy)-4-methylbenzimidamide 

Downstream Products

• 1004392-23-7 N-ethyl-N-((3-p-tolyl-1,2,4-oxadiazol-5-yl)methyl)-2-(p-tolyloxy)acetamide 

Relevant articles and documents

Oxadiazole-isopropylamides as potent and noncovalent proteasome inhibitors

Screening of the 50 000 ChemBridge compound library led to the identification of the oxadiazole-isopropylamide 1 (PI-1833) which inhibited chymotrypsin-like (CT-L) activity (IC50 = 0.60 μM) with little effects on the other two major proteasome proteolytic activities, trypsin-like (T-L) and postglutamyl-peptide-hydrolysis-like (PGPH-L). LC-MS/MS and dialysis show that 1 is a noncovalent and rapidly reversible CT-L inhibitor. Focused library synthesis provided 11ad (PI-1840) with CT-L activity (IC50 = 27 nM). Detailed SAR studies indicate that the amide moiety and the two phenyl rings are sensitive toward modifications. Hydrophobic residues, such as propyl or butyl in the para position (not ortho or meta) of the A-ring and a m-pyridyl group as B-ring, significantly improve activity. Compound 11ad (IC50 = 0.37 μM) is more potent than 1 (IC50 = 3.5 μM) at inhibiting CT-L activity in intact MDA-MB-468 human breast cancer cells and inhibiting their survival. The activity of 11ad warrants further preclinical investigation of this class as noncovalent proteasome inhibitors.

PROTEASOME CHYMOTRYPSIN-LIKE INHIBITION USING PI-1833 ANALOGS

Focused library synthesis and medicinal chemistry on an oxadiazole- isopropylamide core proteasome inhibitor provided the lead compound that strongly inhibits CT-L activity. Structure activity relationship studies indicate the amide moiety and two phenyl rings are sensitive toward synthetic modifications. Only para-substitution in the A-ring was important to maintain potent CT-L inhibitory activity. Hydrophobic residues in the A-ring?s para-position and meta-pyridyl group at the B- ring significantly improved inhibition. The meta-pyridyl moiety improved cell permeability. The length of the aliphatic chain at the para position of the A-ring is critical with propyl yielding the most potent inhibitor, whereas shorter (i.e. ethyl, methyl or hydrogen) or longer (i.e. butyl, propyl and hexyl) chains demonstrating progressively less potency. Introduction of a stereogenic center next to the ether moiety (i.e. substitution of one of the hydrogens by methyl) demonstrated chiral discrimination in proteasome CT-L activity inhibition (the S-enantiomer was 35-40 fold more potent than the R-enantiomer)