1428640-42-9

Basic information

• Product Name: C₁₅H₁₇BrN₄
• CAS NO: 1428640-42-9
• Molecular Weight: 333.231
• Mol File: 1428640-42-9.mol
• Article Data: 3

Chemical Properties

• CAS DataBase Reference: C₁₅H₁₇BrN₄(CAS DataBase Reference)
• NIST Chemistry Reference: C₁₅H₁₇BrN₄(1428640-42-9)
• EPA Substance Registry System: C₁₅H₁₇BrN₄(1428640-42-9)

Safety Data

• Hazardous Substances Data: 1428640-42-9(Hazardous Substances Data)

Upstream product

• 32064-67-8 tert-butylhydrazine 
• 1364226-31-2 2-(methoxy-(3-bromobenzyl)methylene)malononitrile 
• 7400-27-3 tertbutylhydrazine hydrochloride 
• 98288-51-8 2-(3-bromophenyl)acetyl chloride 
• 1878-67-7 3-Bromophenylacetic acid 

Downstream Products

• 956025-99-3 3-(3-bromobenzyl)-1-tert-butyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine 

Relevant articles and documents

Discovery of a potent protein kinase D inhibitor: insights in the binding mode of pyrazolo[3,4-d]pyrimidine analogues

In this study, we set out to rationally optimize PKD inhibitors based on the pyrazolo[3,4-d]pyrimidine scaffold. The lead compound for this study was 1-NM-PP1, which was previously found by us and others to inhibit PKD. In our screening we identified one compound (3-IN-PP1) displaying a 10-fold increase in potency over 1-NM-PP1, opening new possibilities for specific protein kinase inhibitors for kinases that show sensitivity towards pyrazolo[3,4-d]pyrimidine derived compounds. Interestingly the observed SAR was not in complete agreement with the commonly observed binding mode where the pyrazolo[3,4-d]pyrimidine compounds are bound in a similar fashion as PKD's natural ligand ATP. Therefore we suggest an alternate binding mode where the compounds are flipped 180 degrees. This possible alternate binding mode for pyrazolo[3,4-d]pyrimidine based compounds could pave the way for a new class of specific protein kinase inhibitors for kinases sensitive towards pyrazolo[3,4-d]pyrmidines.

A small molecule inhibitor selective for a variant ATP-binding site of the chaperonin GroEL

The chaperonin GroEL is a megadalton-sized molecular machine that plays an essential role in the bacterial cell assisting protein folding to the native state through actions requiring ATP binding and hydrolysis. A combination of medicinal chemistry and genetics has been employed to generate an orthogonal pair, a small molecule that selectively inhibits ATPase activity of a GroEL ATP-binding pocket variant. An initial screen of kinase-directed inhibitors identified an active pyrazolo-pyrimidine scaffold that was iteratively modified and screened against a collective of GroEL nucleotide pocket variants to identify a cyclopentyl carboxamide derivative, EC3016, that specifically inhibits ATPase activity and protein folding by the GroEL mutant, I493C, involving a side chain positioned near the base of ATP. This orthogonal pair will enable in vitro studies of the action of ATP in triggering activation of GroEL-mediated protein folding and might enable further studies of GroEL action in vivo. The approach originated for studying kinases by Shokat and his colleagues may thus also be used to study large macromolecular machines.