120328-90-7

Upstream product

• 2491-20-5 L-alanine methyl ester hydrochloride 
• 100-52-7 benzaldehyde 
• 10065-72-2 L-Alanine methyl ester 
• 7625-53-8 rac-Ala-OMe 
• 13515-97-4 methyl 2-aminopropanoate monohydrochloride 
• 73035-89-9 methyl (2R,3R)-2-amino-3-hydroxy-2-methyl-3-phenylpropanoate 

Downstream Products

• 5424-29-3 2-amino-3-hydroxy-2-methyl-propionic acid 
• 119995-12-9 3-Hydroxy-2-methyl-2-{[1-phenyl-meth-(E)-ylidene]-amino}-propionic acid methyl ester 
• 119934-00-8 4-Methyl-2-phenyl-oxazolidine-4-carboxylic acid methyl ester 
• 119933-94-7 3-Benzoyl-2-methyl-5-phenyl-4-((E)-styryl)-pyrrolidine-2-carboxylic acid methyl ester 
• 111396-03-3 4-Benzoyl-2-methyl-5-phenyl-3-((E)-styryl)-pyrrolidine-2-carboxylic acid methyl ester 
• 64298-85-7 methyl-2-benzylideneamino-2-methyl-3-phenylpropanoate 
• 76741-27-0 (3S,4R,1'S)-1-(1'-Methoxycarbonyl)ethyl-3-azido-4-phenylazetidin-2-one 
• 76741-28-1 (3R,4S,1'S)-1-(1'-Methoxycarbonyl)ethyl-3-azido-4-phenylazetidin-2-one 
• 64298-84-6 2-Methyl-2-{[1-phenyl-meth-(E)-ylidene]-amino}-pent-4-enoic acid methyl ester 
• 64298-95-9 4-Cyano-2-methyl-2-{[1-phenyl-meth-(Z)-ylidene]-amino}-butyric acid methyl ester 
• 64298-96-0 dimethyl 2-(benzylideneamino)-2-methylpentanedioate 
• 119933-96-9 2,3-Dimethyl-5-phenyl-pyrrolidine-2,3-dicarboxylic acid dimethyl ester 
• 111396-06-6 2,4-Dimethyl-5-phenyl-pyrrolidine-2,4-dicarboxylic acid dimethyl ester 
• 120020-05-5 3-(3,4-Dimethyl-phenyl)-2-methyl-2-{[1-phenyl-meth-(E)-ylidene]-amino}-propionic acid methyl ester 

Relevant academic research and scientific papers

PEPTIDOMIMETIC N5-METHYL-N2-(NONANOYL-L-LEUCYL)-L-GLUTAMINATE DERIVATIVES, TRIAZASPIRO[4.14]NONADECANE DERIVATIVES AND SIMILAR COMPOUNDS AS INHIBITORS OF NOROVIRUS AND CORONAVIRUS REPLICATION

Peptidomimetic N5-methyl-N2-(nonanoyl-L-leucyl)-L-glutaminate derivatives, triazaspiro[4.14]nonadecane derivatives and similar compounds for use in methods of inhibiting the replication of noroviruses and coronaviruses in a biological sample or patient, for use in reducing the amount of noroviruses or coronaviruses in a biological sample or patient, and for use in treating norovirus and coronavirus in a patient, comprising administering to said biological sample or patient a safe and effective amount of a compound represented by formulae I or II, or a pharmaceutically acceptable salt thereof. The present description discloses the synthesis and characterisation of exemplary compounds as well as pharmacological data thereof (e.g. page 99 to page 271; examples 1 to 3; compounds A1 to A104 and Bl to B66; tables A to E).

INHIBITORS OF NOROVIRUS AND CORONAVIRUS REPLICATION

Compounds of Formula (I) and methods of inhibiting the replication of viruses in a biological sample or patient, of reducing the amount of viruses in a biological sample or patient, and of treating a virus infection in a patient, comprising administering to said biological sample or patient an effective amount of a compound represented by Formula (I), a compound of Table A or B or a pharmaceutically acceptable salt thereof.

Re-Engineering Organocatalysts for Asymmetric Friedel-Crafts Alkylation of Indoles through Computational Studies

The discovery of efficient organocatalysts is generally carried out by thorough experimental screening of different candidates. We recently reported an efficient organocatalyst for iminium-ion-based asymmetric Diels-Alder reactions following a rational design approach. This result encouraged us to test this optimal catalyst in the mechanistically related Friedel-Crafts alkylation of indoles, but to our surprise, almost null enantioselectivity was observed. The results did not significantly improve with structurally related catalysts, and a totally unexpected facial selectivity inversion was also noticed. Using DFT calculations by modeling the competing transition structures with ONIOM, we could unravel the origins of those findings, further employed to predict the most efficient catalyst for this new transformation. The computational results were validated experimentally (up to 92:8 er), providing another successful example of a general strategy to accelerate catalyst development which still remains underexplored.

Discovery of CRBN E3 Ligase Modulator CC-92480 for the Treatment of Relapsed and Refractory Multiple Myeloma

Many patients with multiple myeloma (MM) initially respond to treatment with modern combination regimens including immunomodulatory agents (lenalidomide and pomalidomide) and proteasome inhibitors. However, some patients lack an initial response to therapy (i.e., are refractory), and although the mean survival of MM patients has more than doubled in recent years, most patients will eventually relapse. To address this need, we explored the potential of novel cereblon E3 ligase modulators (CELMoDs) for the treatment of patients with relapsed or refractory multiple myeloma (RRMM). We found that optimization beyond potency of degradation, including degradation efficiency and kinetics, could provide efficacy in a lenalidomide-resistant setting. Guided by both phenotypic and protein degradation data, we describe a series of CELMoDs for the treatment of RRMM, culminating in the discovery of CC-92480, a novel protein degrader and the first CELMoD to enter clinical development that was specifically designed for efficient and rapid protein degradation kinetics.

Study of 1,3-dipolar cycloaddition of amino-acid azomethines and Juglone

Novel 2,3,4,9-tetrahydro- and 4,9-dihydro-1H-benzo[f]isoindole derivatives were synthesized from Juglone and amino-acid azomethines in 74–85% yields via 1,3-dipolar cycloaddition. The stereo- and regioselectivity of cycloaddition was confirmed by NMR spec

Synthesis of novel multi-functionalized pyrrolidines by [3 + 2] dipolar cycloaddition of azomethine ylides and vinyl ketones

Abstract: An efficient and easy synthetic route to substituted pyrrolidine derivatives has been established through [3 + 2] dipolar cycloaddition of vinyl ketones and azomethine ylides. The reactions proceed smoothly, under mild conditions, affording mode

Utilization of fluoroform for difluoromethylation in continuous flow: A concise synthesis of α-difluoromethyl-amino acids

Fluoroform (CHF3) can be considered as an ideal reagent for difluoromethylation reactions. However, due to the low reactivity of fluoroform, only very few applications have been reported so far. Herein we report a continuous flow difluoromethyl

Synthesis and Deployment of an Elusive Fluorovinyl Cation Equivalent: Access to Quaternary α-(1′-Fluoro)vinyl Amino Acids as Potential PLP Enzyme Inactivators

Developing specific chemical functionalities to deploy in biological environments for targeted enzyme inactivation lies at the heart of mechanism-based inhibitor development but also is central to other protein-tagging methods in modern chemical biology including activity-based protein profiling and proteolysis-targeting chimeras. We describe here a previously unknown class of potential PLP enzyme inactivators; namely, a family of quaternary, α-(1′-fluoro)vinyl amino acids, bearing the side chains of the cognate amino acids. These are obtained by the capture of suitably protected amino acid enolates with β,β-difluorovinyl phenyl sulfone, a new (1′-fluoro)vinyl cation equivalent, and an electrophile that previously eluded synthesis, capture and characterization. A significant variety of biologically relevant AA side chains are tolerated including those for alanine, valine, leucine, methionine, lysine, phenylalanine, tyrosine, and tryptophan. Following addition/elimination, the resulting transoid α-(1′-fluoro)-β-(phenylsulfonyl)vinyl AA-esters undergo smooth sulfone-stannane interchange to stereoselectively give the corresponding transoid α-(1′-fluoro)-β-(tributylstannyl)vinyl AA-esters. Protodestannylation and global deprotection then yield these sterically encumbered and densely functionalized quaternary amino acids. The α-(1′-fluoro)vinyl trigger, a potential allene-generating functionality originally proposed by Abeles, is now available in a quaternary AA context for the first time. In an initial test of this new inhibitor class, α-(1′-fluoro)vinyllysine is seen to act as a time-dependent, irreversible inactivator of lysine decarboxylase from Hafnia alvei. The enantiomers of the inhibitor could be resolved, and each is seen to give time-dependent inactivation with this enzyme. Kitz-Wilson analysis reveals similar inactivation parameters for the two antipodes, L-α-(1′-fluoro)vinyllysine (Ki = 630 ± 20 μM; t1/2 = 2.8 min) and D-α-(1′-fluoro)vinyllysine (Ki = 470 ± 30 μM; t1/2 = 3.6 min). The stage is now set for exploration of the efficacy of this trigger in other PLP-enzyme active sites.

Ag2CO3/CA-AA-amidphos multifunctional catalysis in the enantioselective 1,3-dipolar cycloaddition of azomethine ylides

The new Ag2CO3/CA-AA-amidphos complexes have been demonstrated as highly efficient multifunctional catalysts in the asymmetric 1,3-dipolar cycloaddition of azomethine ylides. Under optimal conditions, highly functionalized endo-4 pyrrolidines were obtained with excellent yields (up to 99% yield) and enantioselectivities (up to 96% ee).

Biology-oriented synthesis of benzopyrano[3,4-c]pyrrolidines

A natural product inspired synthesis of 6,6,5-tricyclic compounds via a silver(I)-catalyzed formal 1,3-dipolar cycloaddition of coumarins with α-iminoesters was developed. The reaction proceeds in a stepwise reaction course under formation of the trans-su