90725-68-1

Usage

Uses

Used in Pharmaceutical Industry:
Methyl 2-bromomethyl-5-nitrobenzoate is used as a synthetic intermediate for the preparation of novel and reversible inhibitors targeting the papain-like protease enzyme in severe acute respiratory syndrome-coronaviruses (SARS-CoV). These inhibitors play a crucial role in the development of potential antiviral therapies to combat SARS-CoV infections and mitigate the severity of respiratory symptoms associated with the disease.

InChI:InChI=1/C9H8BrNO4/c1-15-9(12)8-4-7(11(13)14)3-2-6(8)5-10/h2-4H,5H2,1H3

Upstream product

• 77324-87-9 methyl 2-methyl-5-nitrobenzoate 
• 128-08-5 N-Bromosuccinimide 
• 118-90-1 ortho-methylbenzoic acid 
• 89-71-4 2-Methyl-benzoic acid methyl ester 
• 1975-52-6 5-nitro-o-toluic acid 

Downstream Products

• 129229-77-2 2-phenoxymethyl-5-nitrobenzoic acid methyl ester 
• 129229-79-4 2-phenoxymethyl-5-nitrobenzoyl chloride 
• 129229-78-3 2-phenoxymethyl-5-nitrobenzoic acid 
• 129229-82-9 (2-{2-[2-(5-Amino-2-phenoxymethyl-benzoylamino)-acetylamino]-acetylamino}-acetylamino)-acetic acid ethyl ester 
• 129229-68-1 (S)-4-Benzyl-20-chloromethyl-2,5,8,11,14,17-hexaaza-bicyclo[17.3.1]tricosa-1⁽²³⁾,19,21-triene-3,6,9,12,15,18-hexaone 
• 129229-67-0 (S)-4-Benzyl-20-bromomethyl-2,5,8,11,14,17-hexaaza-bicyclo[17.3.1]tricosa-1⁽²³⁾,19,21-triene-3,6,9,12,15,18-hexaone 
• 138965-45-4 (S)-4-Benzyl-20-hydroxymethyl-2,5,8,11,14,17-hexaaza-bicyclo[17.3.1]tricosa-1⁽²³⁾,19,21-triene-3,6,9,12,15,18-hexaone 
• 129229-80-7 (2-{2-[2-(5-Nitro-2-phenoxymethyl-benzoylamino)-acetylamino]-acetylamino}-acetylamino)-acetic acid ethyl ester 
• 129229-76-1 Acetic acid (S)-4-benzyl-3,6,9,12,15,18-hexaoxo-2,5,8,11,14,17-hexaaza-bicyclo[17.3.1]tricosa-1⁽²³⁾,19,21-trien-20-ylmethyl ester 
• 131918-93-9 (S)-4-Benzyl-20-phenoxymethyl-2,5,8,11,14,17-hexaaza-bicyclo[17.3.1]tricosa-1⁽²³⁾,19,21-triene-3,6,9,12,15,18-hexaone 
• 138965-42-1 Boc-Phe-m-aB<Φ>-Gly4-OEt 
• 138965-43-2 {(S)-1-[3-({[({[(Hydrazinocarbonylmethyl-carbamoyl)-methyl]-carbamoyl}-methyl)-carbamoyl]-methyl}-carbamoyl)-4-phenoxymethyl-phenylcarbamoyl]-2-phenyl-ethyl}-carbamic acid tert-butyl ester 
• 138965-44-3 5-((S)-2-Amino-3-phenyl-propionylamino)-N-{[({[(hydrazinocarbonylmethyl-carbamoyl)-methyl]-carbamoyl}-methyl)-carbamoyl]-methyl}-2-phenoxymethyl-benzamide; hydrochloride 
• 668262-51-9 methyl 2-{[bromo(triphenyl)phosphoranyl]methyl}-5-nitrobenzoate 

Relevant academic research and scientific papers

COMPOUNDS AND USES THEREOF

The present disclosure features compounds and methods useful for the treatment of BAF complex-related disorders.

Copper-promoted direct amidation of isoindolinone scaffolds by sodium persulfate

Isoindolinones are ubiquitous structural motifs in natural products and pharmaceuticals. Establishing an efficient method for structural modification of isoindolinones could significantly facilitate new drug development. Herein, we describe copper-promoted direct amidation of isoindolinone scaffolds mediated by sodium persulfate. The method exhibits mild reaction conditions and high site-selectivity, and enables the structural modification of the drug indobufen ester with various amides with yields of 49 to 98%. It is also gram-scalable. Additionally, the reaction mechanism appears to involve a radical and a carbocationic pathway.

DIMERIC IMMUNO-MODULATORY COMPOUNDS AGAINST CEREBLON-BASED MECHANISMS

Disclosed are small molecules against cereblon to enhance effector T cell function. Methods of making these molecules and methods of using them to treat various disease states are also disclosed.

Antibody Conjugation of a Chimeric BET Degrader Enables in vivo Activity

The ability to selectively degrade proteins with bifunctional small molecules has the potential to fundamentally alter therapy in a variety of diseases. However, the relatively large size of these chimeric molecules often results in challenging physico-chemical properties (e. g., low aqueous solubility) and poor pharmacokinetics which may complicate their in vivo applications. We recently discovered an exquisitely potent chimeric BET degrader (GNE-987) which exhibited picomolar cell potencies but also demonstrated low in vivo exposures. In an effort to improve the pharmacokinetic properties of this molecule, we discovered the first degrader-antibody conjugate by attaching GNE-987 to an anti-CLL1 antibody via a novel linker. A single IV dose of the conjugate afforded sustained in vivo exposures that resulted in antigen-specific tumor regressions. Enhancement of a chimeric protein degrader with poor in vivo properties through antibody conjugation thereby expands the utility of directed protein degradation as both a biological tool and a therapeutic possibility.

TERT-BUTYL (S)-2-(4-(PHENYL)-6H-THIENO[3,2-F][1,2,4]TRIAZOLO[4,3-A] [1,4]DIAZEPIN-6-YL) ACETATE DERIVATIVES AND RELATED COMPOUNDS AS BROMODOMAIN BRD4 INHIBITORS FOR TREATING CANCER

The present disclosure relates to te rt-butyl (S)-2-(4-(phenyl)-6H-thieno[3,2-f][l,2,4]triazolo[4,3-a] [l,4]diazepin-6-yl) acetate derivatives and related compounds as bromodomain BRD4 inhibitors for treating cancer. Exemplary compounds are e.g. tert-butyl (S)-2-(4-(4-(3-aminoprop-l-yn-l-yl)phenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][l,2,4]triazolo[4,3-a][l,4]diazepin-6-yl)acetate (example 1, compound la), tert-butyl(S,E)-2-(4-(4-(3-aminoprop-l-en-l-yl)phenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][l,2,4]triazolo[4,3-a][l,4]diazepin-6-yl)acetate (example 6, compound 6a) or tert-butyl(S)-2-(4-(4-(3-(hydroxyamino)prop-l-yn-l-yl)phenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][l,2,4]triazolo[4,3-a] [l,4]diazepin-6-yl)acetate (example 8, compound 8a).Results of biological assays, such as e.g. BRD4 BD1 and BD2 binding (table 2), cell proliferation assays (table 6) and inhibition of MYC expression in MV-4-11 cells (table 7) are disclosed.

THIENODIAZEPINE DERIVATIVES AND APPLICATION THEREOF

The present invention relates to a class of thienodiazepine derivatives and an application thereof in the preparation of a drug for the treatment of diseases associated with bromodomain and extra-terminal (BET) Bromodomain inhibitors. Specifically, the present invention relates to compounds represented by formulas (I) and (II), as well as pharmaceutically acceptable salts thereof.

(4-HYDROXYPYRROLIDIN-2-YL)-HYDROXAMATE COMPOUNDS AND METHODS OF USE THEREOF

The present disclosure relates to bifunctional compounds, which can be used as modulators of targeted ubiquitination. In particular, the present disclosure is directed to compounds which contain on one end a VHL ligand moiety, which binds to the VHL E3 ubiquitin ligase, and on the other end a moiety that binds a target protein such that degradation of the target protein/polypeptide is effectuated. Also disclosed are VHL ligands.

(4-HYDROXYPYRROLIDIN-2-YL)-HETEROCYCLIC COMPOUNDS AND METHODS OF USE THEREOF

The present disclosure relates to bifunctional compounds of formula (I), which can be used as modulators of targeted ubiquitination. In particular, the present disclosure is directed to compounds which contain on one end a VHL ligand moiety, which binds to the VHL E3 ubiquitin ligase, and on the other end a moiety that binds a target protein such that degradation of the target protein/polypeptide is effectuated. Also disclosed are VHL ligands of formula (III).

Water-soluble, stable and azide-reactive strained dialkynes for biocompatible double strain-promoted click chemistry

The Sondheimer dialkyne is extensively used in double strain-promoted azide-alkyne cycloadditions. This reagent suffers with poor water-solubility and rapidly decomposes in aqueous solutions. This intrinsically limits its application in biological systems, and no effective solutions are currently available. Herein, we report the development of novel highly water-soluble, stable, and azide-reactive strained dialkyne reagents. To demonstrate their extensive utility, we applied our novel dialkynes to a double strain-promoted macrocyclisation strategy to generate functionalised p53-based stapled peptides for inhibiting the oncogenic p53-MDM2 interaction. These functionalised stapled peptides bind MDM2 with low nanomolar affinity and show p53 activation in a cellular environment. Overall, our highly soluble, stable and azide-reactive dialkynes offer significant advantages over the currently used Sondheimer dialkyne, and could be utilised for numerous biological applications.

Synthesis, computational, and spectroscopic analysis of tunable highly fluorescent BN-1,2-azaborine derivatives containing the N-BOH moiety

Nine new polycyclic aromatic BN-1,2-azaborine analogues containing the N-BOH moiety were synthesized using a convenient two-step, one-pot procedure. Characterization of the prepared compounds show the luminescence wavelength and the quantum yields of the azaborines were tunable by controlling the power and location of the donor and acceptor substituents on the chromophore. UV-visible spectroscopy and density functional theory (DFT) computations revealed that the addition of electron-donating moieties to the isoindolinone hemisphere raised the energy of the HOMO, resulting in the reduction of the HOMO-LUMO gap. The addition of an electron-accepting moiety to the isoindolinone hemisphere and an electron-donating group to the boronic acid hemisphere decreased the HOMO-LUMO gap considerably, leading to emission properties from partial intramolecular charge transfer (ICT) states. The combined effect of an acceptor on the isoindolinone side and a donor on the boronic acid side (strong acceptor-π-donor) gave the most red-shifted absorption. The polycyclic aromatic BN-1,2-azaborines emitted strong fluorescence in solution and in the solid-state with the largest red-shifted emission at 640 nm and a Stokes shift of Δλ = 218 nm, or Δν = 8070 cm-1.