4i11 › Citations

Structure-based design of novel dihydroisoquinoline BACE-1 inhibitors that do not engage the catalytic aspartates.

Bowers S, Xu YZ, Yuan S, Probst GD, Hom RK, Chan W, Konradi AW, Sham HL, Zhu YL, Beroza P, Pan H, Brecht E, Yao N, Lougheed J, Tam D, Ren Z, Ruslim L, Bova MP, Artis DR
Bioorg Med Chem Lett 23 2181-6 (2013)
Related entries: 4hzt, 4i0g, 4i0z, 4i10

Cited: 8 times
EuropePMC logo PMID: 23465612

Abstract

The structure-activity relationship of a series of dihydroisoquinoline BACE-1 inhibitors is described. Application of structure-based design to screening hit 1 yielded sub-micromolar inhibitors. Replacement of the carboxylic acid of 1 was guided by X-ray crystallography, which allowed the replacement of a key water-mediated hydrogen bond. This work culminated in compounds such as 31, which possess good BACE-1 potency, excellent permeability and a low P-gp efflux ratio.

Articles - 4i11 mentioned but not cited (3)

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  2. Structural model for phenylalkylamine binding to L-type calcium channels. Cheng RCK, Tikhonov DB, Zhorov BS. J Biol Chem 284 28332-28342 (2009)
  3. An In Silico Target Fishing Approach to Identify Novel Ochratoxin A Hydrolyzing Enzyme. Dellafiora L, Gonaus C, Streit B, Galaverna G, Moll WD, Vogtentanz G, Schatzmayr G, Dall'Asta C, Prasad S. Toxins (Basel) 12 E258 (2020)


Articles citing this publication (5)

  1. Biological and computational evaluation of resveratrol inhibitors against Alzheimer's disease. Koukoulitsa C, Villalonga-Barber C, Csonka R, Alexi X, Leonis G, Dellis D, Hamelink E, Belda O, Steele BR, Micha-Screttas M, Alexis MN, Papadopoulos MG, Mavromoustakos T. J Enzyme Inhib Med Chem 31 67-77 (2016)
  2. Thermodynamic and kinetic characterization of hydroxyethylamine β-secretase-1 inhibitors. Mondal K, Regnstrom K, Morishige W, Barbour R, Probst G, Xu YZ, Artis DR, Yao N, Beroza P, Bova MP. Biochem. Biophys. Res. Commun. 441 291-296 (2013)
  3. One-pot synthesis of 1H-isochromenes and 1,2-dihydroisoquinolines by a sequential isocyanide-based multicomponent/Wittig reaction. Wang L, Guan ZR, Ding MW. Org. Biomol. Chem. 14 2413-2420 (2016)
  4. Fragment Binding to β-Secretase 1 without Catalytic Aspartate Interactions Identified via Orthogonal Screening Approaches. Rombouts FJR, Alexander R, Cleiren E, De Groot A, Carpentier M, Dijkmans J, Fierens K, Masure S, Moechars D, Palomino-Schätzlein M, Pineda-Lucena A, Trabanco AA, Van Glabbeek D, Vos A, Tresadern G. ACS Omega 2 685-697 (2017)
  5. Access to 1-amino-3,4-dihydroisoquinolines via palladium-catalyzed C-H bond aminoimidoylation reaction from functionalized isocyanides. Xiong Z, Cai P, Mei Y, Wang J. RSC Adv 9 42072-42076 (2019)


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