4r93 › Citations

Discovery of potent iminoheterocycle BACE1 inhibitors.

Caldwell JP, Mazzola RD, Durkin J, Chen J, Chen X, Favreau L, Kennedy M, Kuvelkar R, Lee J, McHugh N, McKittrick B, Orth P, Stamford A, Strickland C, Voigt J, Wang L, Zhang L, Zhang Q, Zhu Z
Bioorg Med Chem Lett 24 5455-9 (2014)
Related entries: 4r8y, 4r91, 4r92, 4r95

Cited: 5 times
EuropePMC logo PMID: 25455483

Abstract

The synthesis of a series of iminoheterocycles and their structure-activity relationships (SAR) as inhibitors of the aspartyl protease BACE1 will be detailed. An effort to access the S3 subsite directly from the S1 subsite initially yielded compounds with sub-micromolar potency. A subset of compounds from this effort unexpectedly occupied a different binding site and displayed excellent BACE1 affinities. Select compounds from this subset acutely lowered Aβ40 levels upon subcutaneous and oral administration to rats.

Reviews citing this publication (2)

  1. Development and Structural Modification of BACE1 Inhibitors. Gu T, Wu WY, Dong ZX, Yu SP, Sun Y, Zhong Y, Lu YT, Li NG. Molecules 22 (2016)
  2. Synthesis of amino heterocycle aspartyl protease inhibitors. Chambers RK, Khan TA, Olsen DB, Sleebs BE. Org. Biomol. Chem. 14 4970-4985 (2016)

Articles citing this publication (3)

  1. Effect of sampling on BACE-1 ligands binding free energy predictions via MM-PBSA calculations. Chéron N, Shakhnovich EI. J Comput Chem 38 1941-1951 (2017)
  2. In silico screening of potential β-secretase (BACE1) inhibitors from VIETHERB database. Nhung NT, Duong N, Phung HTT, Vo QV, Tam NM. J Mol Model 28 60 (2022)
  3. The preparation of (4H)-imidazol-4-ones and their application in the total synthesis of natural products. Keel KL, Tepe J. Org Chem Front 7 3284-3311 (2020)


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