58620-63-6

Upstream product

• 100-69-6 2-vinylpyridine 
• 623-73-4 diazoacetic acid ethyl ester 
• 186581-53-3 diazomethane 
• 1121-60-4 pyridine-2-carbaldehyde 
• 140-88-5 ethyl acrylate 
• 274-59-9 triazolopyridine 
• 91496-20-7 ethyl 2-(phenylsulfanyl)cyclopropane-1-carboxylate 
• 109-04-6 2-bromo-pyridine 
• 1774-47-6 trimethylsulfoxonium iodide 
• 7340-23-0 ethyl 3-(pyridin-2-yl)acrylate 

Downstream Products

• 90563-75-0 (±)-trans-2-(pyridin-2-yl)cyclopropanecarboxylic acid 
• 90563-75-0 (+/-)-cis-2-[2]pyridyl-cyclopropanecarboxylic acid 

Relevant academic research and scientific papers

Structure-based design and synthesis of potent benzothiazole inhibitors of interleukin-2 inducible T cell kinase (ITK)

Inhibition of the non-receptor tyrosine kinase ITK, a component of the T-cell receptor signalling cascade, may represent a novel treatment for allergic asthma. Here we report the structure-based optimization of a series of benzothiazole amides that demons

Cobalt(II)-based Metalloradical Activation of 2-(Diazomethyl)pyridines for Radical Transannulation and Cyclopropanation

A new catalytic method for the denitrogenative transannulation/cyclopropanation of in-situ-generated 2-(diazomethyl)pyridines is described using a cobalt-catalyzed radical-activation mechanism. The method takes advantage of the inherent properties of a CoIII-carbene radical intermediate and is the first report of denitrogenative transannulation/cyclopropanation by a radical-activation mechanism, which is supported by various control experiments. The synthetic benefits of the metalloradical approach are showcased with a short total synthesis of (±)-monomorine.

Divergent Synthesis of Cyclopropane-Containing Lead-Like Compounds, Fragments and Building Blocks through a Cobalt Catalyzed Cyclopropanation of Phenyl Vinyl Sulfide

Cyclopropanes provide important design elements in medicinal chemistry and are widely present in drug compounds. Here we describe a strategy and extensive synthetic studies for the preparation of a diverse collection of cyclopropane-containing lead-like compounds, fragments and building blocks exploiting a single precursor. The bifunctional cyclopropane (E/Z)-ethyl 2-(phenylsulfanyl)-cyclopropane-1-carboxylate was designed to allow derivatization through the ester and sulfide functionalities to topologically varied compounds designed to fit in desirable chemical space for drug discovery. A cobalt-catalyzed cyclopropanation of phenyl vinyl sulfide affords these scaffolds on multigram scale. Divergent, orthogonal derivatization is achieved through hydrolysis, reduction, amidation and oxidation reactions as well as sulfoxide–magnesium exchange/functionalization. The cyclopropyl Grignard reagent formed from sulfoxide exchange is stable at 0 °C for > 2 h, which enables trapping with various electrophiles and Pd-catalyzed Negishi cross-coupling reactions. The library prepared, as well as a further virtual elaboration, is analyzed against parameters of lipophilicity (ALog P), MW and molecular shape by using the LLAMA (Lead-Likeness and Molecular Analysis) software, to illustrate the success in generating lead-like compounds and fragments.

CAFFEINE INHIBITORS OF MTHFD2 AND USES THEREOF

The present invention provides compounds, compositions thereof, and methods of using the same.

Reactivity of [1,2,3]Triazolo[1,5-a]pyridines as 1,3-dipoles

We have studied the reactions between [1,2,3]Triazolo[1,5-a]pyridines 1a,b,c and electron-deficient ethylenes in different conditions. Compounds 1a and 1b react with ethyl propiolate, and dimethyl acetylene dicarboxylate giving a new class of biaryl compounds pyridyl pyrazoles, and with ethyl acrylate giving pyridyl cyclopropanes. Compound 1c did not give any product in the studied conditions. A proposal of mechanism of these reactions is done in which the triazolopyridines act as 1,3-dipoles giving 1,3-dipolar cycloadditions.

Discovery of pyrazolopyrimidine phosphodiesterase 10A inhibitors for the treatment of schizophrenia

Herein, we present the identification of a novel class of pyrazolopyrimidine phosphodiesterase 10A (PDE10A) inhibitors. Beginning with a lead molecule (1) identified through a fragment-based drug discovery (FBDD) effort, lead optimization was enabled by rational design, X-ray crystallography, metabolic and off-target profiling, and fragment scaffold-hopping. We highlight the discovery of PyP-1, a potent, highly selective, and orally bioavailable pyrazolopyrimidine inhibitor of PDE10A. PyP-1 exhibits sub-nanomolar potency (PDE10A Ki = 0.23 nM), excellent pharmacokinetic (PK) and physicochemical properties, and a clean off-target profile. It displays dose-dependent efficacy in numerous pharmacodynamic (PD) assays that measure potential for anti-psychotic activity and cognitive improvement. PyP-1 also has a clean preclinical profile with respect to cataleptic potential in rats, prolactin secretion, and weight gain, common adverse events associated with currently marketed therapeutics. Further, PyP-1 displays in vivo preclinical target engagement as measured by PET enzyme occupancy in concert with [11C]MK-8193, a novel PDE10A PET tracer.

PYRIMIDINE PDE10 INHIBITORS

The present invention is directed to pyrimidine compounds which are useful as therapeutic agents for the treatment of central nervous system disorders associated with phosphodiesterase 10 (PDE10). The present invention also relates to the use of such compounds for treating neurological and psychiatric disorders, such as schizophrenia, psychosis or Huntington's disease, and those associated with striatal hypofunction or basal ganglia dysfunction.

One-pot approach for the synthesis of trans-cyclopropyl compounds from aldehydes. Application to the synthesis of GPR40 receptor agonists

A novel multicatalytic one-pot process providing trans-cyclopropyl compounds from corresponding aldehydes has been developed and applied to the synthesis of GPR40 small molecule agonists. The Royal Society of Chemistry.