Onyx Scientific Ltd

Sunderland, United Kingdom

Onyx Scientific Ltd

Sunderland, United Kingdom

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Colgin N.,Durham University | Flinn T.,Onyx Scientific Ltd | Cobb S.L.,Durham University
Organic and Biomolecular Chemistry | Year: 2011

Herein, we report the synthesis of novel phenylalanine and tyrosine derivatives containing a N-methyliminodiacetic acid boronate group. These compounds can be prepared enantiomerically pure, they are stable to column chromatography and they can be stored in air for two months without degradation occurring. This new class of boronate containing aromatic amino acids has potential applications in both peptide chemistry and natural product synthesis. © 2011 The Royal Society of Chemistry.


Day J.E.H.,Astex | Frederickson M.,Astex | Hogg C.,Onyx Scientific Ltd | Johnson C.N.,Astex | And 4 more authors.
Synlett | Year: 2015

A range of azaindolines was prepared in three steps from heterocyclic amines using halogenation, alkylation with 3-bromo-2-methylpropene, and a palladium-catalysed reductive cyclisation. The chemistry proved applicable to a multigram-scale operation. © 2015 Georg Thieme Verlag Stuttgart.


Lindhagen M.,Astrazeneca | Klingstedt T.,Astrazeneca | Andersen S.M.,Astrazeneca | Mulholland K.R.,Astrazeneca | And 3 more authors.
Organic Process Research and Development | Year: 2016

A chemoenzymatic route to (R)-allyl-(3-amino-2-(2-methylbenzyl)propyl)carbamate (1-(R)) has been developed on a kilogram scale. The key intermediate, 2-(2-methylbenzyl)propane-1,3-diamine 4, was isolated as a tartrate salt in a three-step sequence starting from 2-methylbenzyl chloride. The subsequent lipase-catalyzed desymmetrization was optimized, and 1-(R) was isolated as the d-tartrate salt. © 2015 American Chemical Society.


Wong C.,Northumbria University | Griffin R.J.,Northumbria University | Hardcastle I.R.,Northumbria University | Northen J.S.,Onyx Scientific Ltd | And 2 more authors.
Organic and Biomolecular Chemistry | Year: 2010

The attenuated SN2 reactivity of the 2,2,2-trifluoroethyl group has been exploited for the synthesis of a series of 6-cyclohexylmethoxy-2- arylaminopurines in which a sulfonamide moiety was attached to the aryl ring via a methylene group. These were required as potential inhibitors of serine-threonine kinases of interest for the treatment of cancer. 3-Nitrophenylmethanesulfonyl chloride was converted into the corresponding 2,2,2-trifluoroethoxysulfonyl ester by reaction with 2,2,2-trifluoroethanol in the presence of triethylamine/4-dimethylaminopyridine. Catalytic hydrogenation of the nitro group employing 2,2,2-trifluoroethanol as solvent gave 2,2,2-trifluoroethyl 3-aminophenylmethanesulfonate, which was reacted with 6-cyclohexylmethoxy-2-fluoropurine in 2,2,2-trifluoroethanol/trifluoroacetic acid to afford 2,2,2-trifluoroethyl 3-(6-cyclohexylmethoxy-9H-purin-2-ylamino) phenylmethanesulfonate. 3-(6-Cyclohexylmethoxy-9H-purin-2-ylamino) phenylmethanesulfonamides were synthesised by microwave heating of the trifluoroethoxysulfonate with an amine and 1,8-diazabicycloundec-7-ene in tetrahydrofuran. The mechanism of this process was shown to involve an intermediate sulfene by a deuterium-labelling experiment. 3-(6- Cyclohexylmethoxy-9H-purin-2-ylamino)phenylmethanesulfonamide derivatives were assayed as inhibitors of human cyclin-dependent kinase 2. Previous structure-activity studies demonstrated that relocating the sulfonamide group of O6-cyclohexylmethoxy-2-(4′-sulfamoylanilino)purine from the 4- to the 3-position on the 2-arylamino ring resulted in a 40-fold reduction in potency against CDK2. In the present study, no further loss of activity was observed on introducing a methylene group between the sulfonamide and the aryl ring, 3-(6-cyclohexylmethoxy-9H-purin-2-ylamino)phenylmethanesulfonamide proving equipotent with O6-cyclohexylmethoxy-2-(3′-sulfamoylanilino) purine (IC50 = 0.21 μM). N-Alkylation of the sulfonamide reduced CDK-2 inhibitory activity, while a substituted benzyl or 3-phenylpropyl group on the sulfonamide resulted in a loss of potency compared with 3-(6-cyclohexylmethoxy-9H-purin-2-ylamino)phenylmethanesulfonamide. The dimethylaminopropyl derivative, 1-[3-(6-cyclohexylmethoxy-9H-purin-2-ylamino) phenyl]-N-(3-dimethylaminopropyl)methanesulfonamide was only 2-fold less potent than 3-(6-cyclohexylmethoxy-9H-purin-2-ylamino)phenylmethanesulfonamide, suggesting an interaction between the basic dimethylamino group and the kinase. The presence of alicyclic groups on the pendant sulfonamide showed IC 50 values in the 0.5-1.5 μM range. N-(4-tert-Butylphenyl)-1-[3-(6- cyclohexylmethoxy-9H-purin-2-ylamino)phenyl]methanesulfonamide was markedly less active (IC50 = 34 μM), suggesting a steric effect within the ATP-binding domain. © 2010 The Royal Society of Chemistry.


Malik V.,Northumbria University | Zhang M.,Northumbria University | Dover L.G.,Northumbria University | Northen J.S.,Onyx Scientific Ltd | And 3 more authors.
Molecular BioSystems | Year: 2013

The main objectives of this work were to characterise a range of purified recombinant sterol 3β-glucosyltransferases and show that rational sampling of the diversity that exists within sterol 3β-glucosyltransferase sequence space can result in a range of enzyme selectivities. In our study the catalytically active domain of the Saccharomyces cerevisiae 3β- glucosyltransferase was used to mine putative sterol 3β- glucosyltransferases from the databases. Selected diverse sequences were expressed in and purified from Escherichia coli and shown to have different selectivities for the 3β-hydroxysteroids ergosterol and cholesterol. Surprisingly, three enzymes were also selective for testosterone, a 17β-hydroxysteroid. This study therefore reports for the first time sterol 3β-glucosyltransferases with selectivity for both 3β- and 17β-hydroxysteroids and is also the first report of recombinant 3β-glucosyltransferases with selectivity for steroids with a hydroxyl group at positions other than C-3. These enzymes could therefore find utility in the pharmaceutical industry for the green synthesis of a range of glycosylated compounds of medicinal interest. © 2013 The Royal Society of Chemistry.


Trademark
Onyx Scientific Inc. | Date: 2010-07-13

Digital file encryption software.


Trademark
Onyx Scientific Inc. | Date: 2010-07-08

Digital image compression software.


Trademark
Onyx Scientific Inc. | Date: 2010-07-08

Digital video compression software.


Trademark
Onyx Scientific Inc. | Date: 2010-07-29

Digital video compression software.


Trademark
Onyx Scientific Inc. | Date: 2010-07-29

Digital image compression software.

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