Novel renin inhibitors: synthesis of aminostatine and comparison with statine-containing analogues

Arrowsmith, R. J.; Carter, Keith D.; Dann, J. G.; Davies, D. E.; Harris, Christopher; Morton, J. J.; Lister, Philip; Robinson, John A.; Williams, David J.

doi:10.1039/c39860000755

Cited by 26 publications

(4 citation statements)

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“…An additional illustrative example is the transformation of adduct 6x into compound 13 , which is an orthogonally protected form of 3-aminodeoxystatine, an isosterically modified statine analogue . Configuration of adducts 12 and 13 , and therefore of their immediate precursors 6k and 6x , was determined by comparison of chiroptic and chromatographic data with published values ,. For the remaining syn aza-Henry adducts 6m − w , it was assumed on the basis of an uniform reaction mechanism.…”

Section: Resultsmentioning

confidence: 99%

Asymmetric Aza-Henry Reaction Under Phase Transfer Catalysis: An Experimental and Theoretical Study

et al. 2008

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An efficient catalytic asymmetric aza-Henry reaction under phase transfer conditions is presented. The method is based on the reaction of the respective nitroalkane with alpha-amido sulfones effected by CsOH x H2O base in toluene as solvent and in the presence of cinchone-derived ammonium catalysts. This direct aza-Henry reaction presents as interesting features its validity for both nonenolizable and enolizable aldehyde-derived azomethines and the tolerance of nitroalkanes, other than nitromethane, for the production of beta-nitroamines. The synthetic value of the methodology described is demonstrated by providing (a) a direct route for the asymmetric synthesis of differently substituted 1,2-diamines and (b) a new asymmetric synthesis of gamma-amino alpha,beta-unsaturated esters through a catalytic, highly enantioselective formal addition of functionalized alkenyl groups to azomethines. Finally, a preferred TS that nicely fits the observed enantioselectivity has been identified. Most remarkable, an unusual hydrogen bond pattern for the catalyst-nitrocompound-imine complex is predicted, where the catalyst OH group interacts with the NO2 group of the nitrocompound.

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Section: Resultsmentioning

confidence: 99%

Asymmetric Aza-Henry Reaction Under Phase Transfer Catalysis: An Experimental and Theoretical Study

et al. 2008

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“…Renin inhibitors containing the corresponding deoxyaminostatine residue [-CH(NH2)-CH2-CO-NH-] have also been shown to bind tightly to human renin (Jones et al, 1985;Arrowsmith et al, 1986), as have inhibitors containing the amino alcohol analogue [-CH(OH)-CH2-NH2] (Dann et al, 1986).…”

Section: Inhibitors Of Reninmentioning

confidence: 99%

On the rational design of renin inhibitors: x-ray studies of aspartic proteinases complexed with transition-state analogs

Blundell

Cooper²,

Foundling³

et al. 1987

Biochemistry

118

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“…13, which scores an interaction with a positively charged N-H group and a negatively charged CO0 group higher than an O-H..OOC interaction. Indeed, potent inhibitors of aspartic proteases are known that interact with the catalytic aspartates via charged amino groups [32,33]. The second run, using the targeted mode, took 52 min and retrieved 21 candidate structures.…”

Section: Hiv Proteasementioning

confidence: 99%

On the use of LUDI to search the Fine Chemicals Directory for ligands of proteins of known three-dimensional structure

Böhm¹

1994

J Computer-Aided Mol Des

127

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It is shown that the computer program LUDI can be used to search large database of three-dimensional structures for putative ligands of proteins with known 3D structure. As an example, a subset of approximately 30,000 small molecules (with less than 40 atoms and 0-2 rotatable bonds) from the Fine Chemicals Directory has been used in the search for possible novel ligands for four different proteins (trypsin, streptavidin, purine nucleoside phosphorylase and HIV protease). For trypsin and streptavidin, known ligands or substructures of known ligands are retrieved as top-scoring hits. In addition, a number of new interesting structures are found in all considered cases. Therefore, the method holds promise to retrieve automatically protein ligands from a 3D database if the 3D structure of the target protein is known.

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Novel renin inhibitors: synthesis of aminostatine and comparison with statine-containing analogues

Cited by 26 publications

References 0 publications

Asymmetric Aza-Henry Reaction Under Phase Transfer Catalysis: An Experimental and Theoretical Study

Asymmetric Aza-Henry Reaction Under Phase Transfer Catalysis: An Experimental and Theoretical Study

On the rational design of renin inhibitors: x-ray studies of aspartic proteinases complexed with transition-state analogs

On the use of LUDI to search the Fine Chemicals Directory for ligands of proteins of known three-dimensional structure

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