137686-07-8

Upstream product

• 24424-99-5 di-tert-butyl dicarbonate 
• 13433-00-6 diethyl aminomalonate hydrochloride 
• 102831-44-7 diethyl tert-butoxycarbonylaminomalonate 

Downstream Products

• 222979-06-8 2-tert-butoxycarbonylamino-N-(1-tert-butoxycarbonyl-2-phenyl-ethyl)-malonamic acid ethyl ester 
• 321658-32-6 (R)-4-((E)-4-tert-Butoxycarbonylamino-4-ethoxycarbonyl-3-oxo-but-1-enyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid benzyl ester 
• 607358-20-3 3-(4-acetoxy-phenyl)-2-tert-butoxycarbonylamino-3-oxo-propionic acid ethyl ester 
• 607358-36-1 (2S,3S)-2-tert-Butoxycarbonylamino-3-hydroxy-3-(4-hydroxy-phenyl)-propionic acid 
• 607358-38-3 (2R,3R)-2-tert-Butoxycarbonylamino-3-hydroxy-3-(4-hydroxy-phenyl)-propionic acid ethyl ester 
• 607358-40-7 2-tert-butoxycarbonylamino-3-hydroxy-3-(4-hydroxy-phenyl)-thiopropionic acid S-(2-acetylamino-ethyl) ester 
• 607358-42-9 2-tert-butoxycarbonylamino-3-hydroxy-3-(4-hydroxy-phenyl)-thiopropionic acid S-(2-acetylamino-ethyl) ester 
• 1255203-06-5 (2S,3S)-ethyl 2-(tert-butoxycarbonylamino)-3-hydroxy-3-(2-methoxyphenyl)propanoate 
• 1255203-08-7 (2S,3S)-ethyl 3-(2-bromophenyl)-2-(tert-butoxycarbonylamino)-3-hydroxypropanoate 
• 1255203-09-8 (2S,3S)-ethyl 2-(tert-butoxycarbonylamino)-3-(4-fluorophenyl)-3-hydroxypropanoate 
• 1255203-10-1 (2S,3S)-ethyl-3-(4-bromophenyl)-2-((tert-butoxycarbonyl)amino)-3-hydroxypropanoate 
• 1255203-11-2 (2S, 3S)-ethyl 3-(3-bromophenyl)-2-(tert-butoxycarbonylamino)-3-hydroxypropanoate 
• 1255203-12-3 (2S,3S)-ethyl 2-(tert-butoxycarbonylamino)-3-(3-chlorophenyl)-3-hydroxypropanoate 

Relevant academic research and scientific papers

Design, synthesis and antimalarial activity of novel, quinoline-based, zinc metallo-aminopeptidase inhibitors

PfA-M1, a neutral zinc aminopeptidase of Plasmodium falciparum, is a new potential target for the discovery of antimalarials. The design and synthesis of a library of 45 quinoline-based inhibitors of PfA-M1 is reported. The best inhibitor displays an IC50 of 854 nM. The antimalarial activity on a CQ-resistant strain and the specificity towards mammalian aminopeptidase N are also discussed.

Demonstrating Ligandability of the LC3A and LC3B Adapter Interface

Autophagy is the common name for a number of lysosome-based degradation pathways of cytosolic cargos. The key components of autophagy are members of Atg8 family proteins involved in almost all steps of the process, from autophagosome formation to their selective fusion with lysosomes. In this study, we show that the homologous members of the human Atg8 family proteins, LC3A and LC3B, are druggable by a small molecule inhibitor novobiocin. Structure-activity relationship (SAR) studies of the 4-hydroxy coumarin core scaffold were performed, supported by a crystal structure of the LC3A dihydronovobiocin complex. The study reports the first nonpeptide inhibitors for these protein interaction targets and will lay the foundation for the development of more potent chemical probes for the Atg8 protein family which may also find applications for the development of autophagy-mediated degraders (AUTACs).

S-Adenosyl Methionine Cofactor Modifications Enhance the Biocatalytic Repertoire of Small Molecule C-Alkylation

A tandem enzymatic strategy to enhance the scope of C-alkylation of small molecules via the in situ formation of S-adenosyl methionine (SAM) cofactor analogues is described. A solvent-exposed channel present in the SAM-forming enzyme SalL tolerates 5′-chloro-5′-deoxyadenosine (ClDA) analogues modified at the 2-position of the adenine nucleobase. Coupling SalL-catalyzed cofactor production with C-(m)ethyl transfer to coumarin substrates catalyzed by the methyltransferase (MTase) NovO forms C-(m)ethylated coumarins in superior yield and greater substrate scope relative to that obtained using cofactors lacking nucleobase modifications. Establishing the molecular determinants that influence C-alkylation provides the basis to develop a late-stage enzymatic platform for the preparation of high value small molecules.

Access to Anti or Syn 2-Amino-1,3-diol Scaffolds from a Common Decarboxylative Aldol Adduct

A straightforward synthetic pathway allowing the access to anti or syn 2-amino-1,3-diol scaffolds is presented. The strategy relies on a diastereoselective organocatalyzed decarboxylative aldol reaction of a N-Boc-hemimalonate that is easily formed from commercial N-Boc-diethyl malonate. Although this method has been optimized previously with the N-Bz-hemimalonate analogue, this key step was reinvestigated with the N-Boc derivative to improve the required reaction time, the yield, and the diastereoselectivity. The new conditions enhance this transformation, and quantitative yields and anti/syn ratios up to 96:4 can be obtained. The anti aldol product was easily isolated in pure form and then taken forward as the key precursor in the preparation of both a set of ten N-/O-alkylated anti 2-amino-1,3-diol derivatives and the syn congeners.

PYRAZOLO[3,4-b]PYRIDINES AND IMIDAZO[1,5-b]PYRIDAZINES AS PDE1 INHIBITORS

The present invention provides compounds of formula (I) that are PDE1 enzyme inhibitors and their use as a medicament, in particular for the treatment of neurodegenerative disorders and psychiatric disorders. The present invention also provides pharmaceutical compositions comprising compounds of the invention and methods of treating disorders using the compounds of the invention.

Synthesis of 1-benzyloxypyrazin-2(1H)-one derivatives

Different approaches for the synthesis of 1-benzyloxypyrazin-2(1H)-one derivatives from simple amino acids have been investigated. A library of 33 precursors for the preparation of N-hydroxy pyrazinones was obtained in moderate to good yields.

HYDANTOIN AND THIOHYDANTOIN DERIVATIVES AS ANTIVIRAL DRUGS

The present invention relates to a compound of the following formula (I), or a salt, solvate, tautomer, enantiomer, diastereoisomer or racemic mixture thereof: as well as its use as a drug, notably in the treatment of hepatitis C, its preparation process, and the pharmaceutical compositions containing such a compound.

Enantioselective synthesis of anti-β-hydroxy-α-amido esters by asymmetric transfer hydrogenation in emulsions

Herein, we present two methods for an asymmetric transfer hydrogenation through the dynamic kinetic resolution of α-amido-β-ketoesters. These procedures yield the corresponding anti-β-hydroxy-α-amido esters in good yields and with good diastereo- and enantioselectivities. First, the scope of the reduction of α-amido-β-ketoesters by using triethylammonium formate azeotrope is examined. Then, an emulsion technology with sodium formate is explored, which allows for broader substrate scope, faster reaction times, and lower catalyst loading. Furthermore, these reactions are operationally simple and can be set up in air.

Biocatalytic Friedel-Crafts alkylation using non-natural cofactors

A novel biocatalytic protocol for C -C bond formation is described and is an equivalent to Friedel-Crafts alkylation. S-Adenosyl-L-methionine (SAM), the major Chemical Equation Presentation methyl donor for biological methylation catalyzed by methyltransferases (Mtases), can perform alkylations (see scheme). These enzymes can accept non-natural cofactors and transfer functionalities other than methyl onto aromatic substrates

POLYBASIC BACTERIAL EFFLUX PUMP INHIBITORS AND THERAPEUTIC USES THEREOF

Disclosed are compounds having polybasic functionalities. The compounds inhibit bacterial efflux pump inhibitors and are used in combination with an anti-bacterial agent to treat or prevent bacterial infections. These combinations can be effective against bacterial infections that have developed resistance to anti-bacterial agents through an efflux pump mechanism.