41955-11-7

Basic information

• Product Name: benzyl ((2R)-(3R)-3-(tert-butoxy)-1-hydroxybutan-2-yl)carbamate
• Synonyms: benzyl ((2R)-(3R)-3-(tert-butoxy)-1-hydroxybutan-2-yl)carbamate
• CAS NO: 41955-11-7
• Molecular Weight: 295.379
• Mol File: 41955-11-7.mol
• Article Data: 9

Chemical Properties

• CAS DataBase Reference: benzyl ((2R)-(3R)-3-(tert-butoxy)-1-hydroxybutan-2-yl)carbamate(CAS DataBase Reference)
• NIST Chemistry Reference: benzyl ((2R)-(3R)-3-(tert-butoxy)-1-hydroxybutan-2-yl)carbamate(41955-11-7)
• EPA Substance Registry System: benzyl ((2R)-(3R)-3-(tert-butoxy)-1-hydroxybutan-2-yl)carbamate(41955-11-7)

Safety Data

• Hazardous Substances Data: 41955-11-7(Hazardous Substances Data)

Upstream product

• 10068-65-2 Z-Thr(Bu^t)-ONSu 
• 16966-07-7 (2S,3R)-2-(((benzyloxy)carbonyl)amino)-3-(tert-butoxy)butanoic acid dicyclohexylammonium salt 
• 543-27-1 isobutyl chloroformate 
• 501-53-1 benzyl chloroformate 
• 57224-63-2 methyl (2S,3R)-2-(benzyloxycarbonylamino)-3-hydroxybutyrate 
• 16966-09-9 N-benzyloxycarbonyl-O-t-butyl-L-threonine 
• 27981-26-6 (R)-2-[(1R,2S)-2-((2S,3R)-2-Benzyloxycarbonylamino-3-tert-butoxy-butyryloxy)-1-(3-methyl-butyryloxy)-propyl]-hexanoic acid tert-butyl ester 

Downstream Products

• 85308-84-5 ((1S,2R)-2-tert-Butoxy-1-formyl-propyl)-carbamic acid benzyl ester 
• 285124-39-2 (1R,2R)-N-(benzyloxycarbonyl)-1-(methanesulfonyloxymethyl)-2-(tert-butoxy)propanamine 
• 1628805-46-8 IDH-305 

Relevant articles and documents

2-AMINOPYRIMIDINE DERIVATIVE, PREPARATION METHOD AND USE THEREOF

The disclosure provides an aminopyrimidine derivative for preventing and treating diseases related to IDH mutation, a preparation method and use thereof. Specifically, the disclosure provides a compound of Formula I, a stereoisomer, racemate thereof, or pharmaceutically acceptable salt thereof. The compound of the general Formula I has isocitrate dehydrogenase 1 (IDH1) inhibitory activity and can treat cancer induced by IDH1 mutation.

Discovery of new small molecule inhibitors targeting isocitrate dehydrogenase 1 (IDH1) with blood-brain barrier penetration

Isocitrate dehydrogenase 1 (IDH1), which catalyzes the conversion of isocitrate to α-ketoglutarate, is one of key enzymes in the tricarboxylic acid cycle (TCA). Hotspot mutation at Arg132 in IDH1 that alters the function of IDH1 by further converting the α-ketoglutarate(α-KG) to 2-hydroxyglutarate (2-HG) have been identified in a variety of cancers. Because the IDH1 mutations occur in a significant portion of gliomas and glioblastomas, it is important that IDH1 inhibitors have to be brain penetrant to treat IDH1-mutant brain tumors. Here we report the efforts to design and synthesize a novel serial of mutant IDH1 inhibitors with improved activity and the blood-brain barrier (BBB) penetration. We show that compound 5 exhibits good brain exposure and potent 2-HG inhibition in a HT1080-derived mouse xenograft model, which makes it a potential preclinical candidate to treat IDH1-mutant brain tumors.

Discovery and Evaluation of Clinical Candidate IDH305, a Brain Penetrant Mutant IDH1 Inhibitor

Inhibition of mutant IDH1 is being evaluated clinically as a promising treatment option for various cancers with hotspot mutation at Arg132. Having identified an allosteric, induced pocket of IDH1R132H, we have explored 3-pyrimidin-4-yl-oxazolidin-2-ones as mutant IDH1 inhibitors for in vivo modulation of 2-HG production and potential brain penetration. We report here optimization efforts toward the identification of clinical candidate IDH305 (13), a potent and selective mutant IDH1 inhibitor that has demonstrated brain exposure in rodents. Preclinical characterization of this compound exhibited in vivo correlation of 2-HG reduction and efficacy in a patient-derived IDH1 mutant xenograft tumor model. IDH305 (13) has progressed into human clinical trials for the treatment of cancers with IDH1 mutation.