852714-84-2

Upstream product

• 589-15-1 1-bromomethyl-4-bromobenzene 
• 100-39-0 benzyl bromide 
• 259529-54-9 (4S)-3-(1-oxo-2-propen-1-yl)-4-phenyl-1,3-oxazolidin-2-one 
• 852714-83-1 Benzyl-{4-[(E)-3-oxo-3-((S)-2-oxo-4-phenyl-oxazolidin-3-yl)-propenyl]-benzyl}-phosphinic acid tert-butyl ester 
• 1826-67-1 vinyl magnesium bromide 

Downstream Products

• 852714-87-5 (3S,4S)-4-[4-(Benzyl-tert-butoxy-phosphinoylmethyl)-phenyl]-3-(1-{(S)-2-carbamoyl-1-[(R)-2-(5-methyl-indol-1-ylmethyl)-pent-4-enylcarbamoyl]-ethylcarbamoyl}-cyclohexylcarbamoyl)-hex-5-enoic acid tert-butyl ester 
• 852714-88-6 [(E)-(9S,10S,14R,18S)-10-[4-(Benzyl-tert-butoxy-phosphinoylmethyl)-phenyl]-18-carbamoylmethyl-14-(5-methyl-indol-1-ylmethyl)-8,17,20-trioxo-7,16,19-triaza-spiro[5.14]icos-11-en-9-yl]-acetic acid tert-butyl ester 
• 852714-86-4 2-{1-[4-(benzyl-tert-butoxy-phosphinoylmethyl)-phenyl]-allyl}-succinic acid 4-tert-butyl ester 
• 852714-85-3 4-[4-(benzyl-tert-butoxy-phosphinoylmethyl)-phenyl]-3-(2-oxo-4-phenyl-oxazolidine-3-carbonyl)-hex-5-enoic acid tert-butyl ester 

Relevant academic research and scientific papers

Examination of phosphoryl-mimicking functionalities within a macrocyclic Grb2 SH2 domain-binding platform

Reported herein are the design, synthesis, and Grb2 SH2 domain-binding affinities of several phosphoryl-mimicking groups displayed within the context of a conformationally constrained macrocyclic platform. With use of surface plasmon resonance techniques, single-digit nanomolar affinities were exhibited by phosphonic acid and malonyl-containing diacidic phosphoryl mimetics (for 4h and 4g, KD = 1.47 and 3.62 nM, respectively). Analogues containing monoacidic phosphoryl mimetics provided affinities of KD = 16-67 nM. Neutral phosphoryl-mimicking groups did not show appreciable binding.

SH2 domain binding inhibitors

Disclosed are compounds represented by the formula: [image] or a pharmaceutically acceptable salt or isomer thereof, wherein R1-R6 are as defined in the specification. These compounds are targeted for use as inhibitors of SH2 domain binding with a phosphoprotein, and are contemplated for use in a number of diseases including cancer. Also disclosed are pharmaceutical compositions comprising a compound of the invention and a pharmaceutically acceptable carrier.