5219-05-6

Upstream product

• 121-98-2 methyl 4-methoxybenzoate 
• 104-47-2 p-methoxybenzylnitrile 

Downstream Products

• 199987-17-2 3-amino-2-(4-methoxyphenyl)-5-methoxy-1-indenone 

Relevant academic research and scientific papers

Pyrazolo[1,5-a]pyrimidines as estrogen receptor ligands: Defining the orientation of a novel heterocyclic core

We investigated the pyrazolo[1,5-a]pyrimidine system as a novel heterocyclic scaffold for the development of estrogen receptor (ER) ligands. By altering the pattern of hydroxyl substitution, we established the orientation that is most favorable for ER bin

Fragment-Based Approaches to the Development of Mycobacterium tuberculosis CYP121 Inhibitors

The essential enzyme CYP121 is a target for drug development against antibiotic resistant strains of Mycobacterium tuberculosis. A triazol-1-yl phenol fragment 1 was identified to bind to CYP121 using a cascade of biophysical assays. Synthetic merging and optimization of 1 produced a 100-fold improvement in binding affinity, yielding lead compound 2 (KD = 15 μM). Deconstruction of 2 into its component retrofragments allowed the group efficiency of structural motifs to be assessed, the identification of more LE scaffolds for optimization and highlighted binding affinity hotspots. Structure-guided addition of a metal-binding pharmacophore onto LE retrofragment scaffolds produced low nanomolar (KD = 15 nM) CYP121 ligands. Elaboration of these compounds to target binding hotspots in the distal active site afforded compounds with excellent selectivity against human drug-metabolizing P450s. Analysis of the factors governing ligand potency and selectivity using X-ray crystallography, UV-vis spectroscopy, and native mass spectrometry provides insight for subsequent drug development.

Pyrazolo[1,5-α]pyrimidines: Estrogen receptor ligands possessing estrogen receptor β antagonist activity

In our search for novel subtype-selective estrogen receptor (ER) ligands, we have examined various heterocyclic units as core structural elements. Here, we have investigated the fused, bicyclic pyrazolo[1,5-a]pyrimidine core, which is a system that allows

Enolate Ions as ss-Activators of ortho-metalation: Direct Synthesis of 3-Aminoindenones

ss-Ketonitriles derived from a Claisen condensation of benzoate esters with alkyl- or phenylacetonitriles lead to 3-aminoindenones in the presence of excess LDA. This new reaction is also applicable to pyridine carboxylic esters. All of the 3-aminoindenones and their aza analogues can be hydrolyzed by acid to give the corresponding 1,3-indandiones. The mechanism of the reaction falls into the directed-ortho-metalation class in which the initial enolate ion of the keto-nitrile directs self-metalation at an ortho position. The new anion then cyclizes onto the nitrile group to generate an aminoindenone. Surprisingly the simplest member of the series, benzoylacetonitrile, does not undergo cyclization. Mechanistic isotope studies revealed that this substance preferentially and directly forms a dianion on the side chain, which is not further deprotonated at the ortho position of the aromatic ring.

A new anionic cyclization reaction: Condensation of benzoate esters with nitriles to give 3-amino-2-inden-1-ones

A new type of anionic cyclization has been discovered in which the condensation of alkyl benzoates with simple nitriles, induced by an excess of LDA, leads directly to substituted-3-amino-1-ones. The corresponding intermediate β-oxonitriles undergo cyclization to give, in most instances, superior yields of the same compounds. Acid hydrolysis of these indenones leads in high yield to the corresponding biologically active (anticoagulant) indandiones.