Small-molecule BACE1 inhibitors: a patent literature review (2006 – 2011)

Structure based design of iminohydantoin BACE1 inhibitors: Identification of an orally available, centrally active BACE1 inhibitor

(2012) Jared N. Cumming et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Aminoimidazoles as BACE-1 inhibitors: The challenge to achieve in vivo brain efficacy

(2012) Britt-Marie Swahn et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

2011 Alzheimer’s disease facts and figures

(2011)   Alzheimers & Dementia

Rational design and synthesis of aminopiperazinones as β-secretase (BACE) inhibitors

(2011) Gary Tresadern et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Monosubstituted γ-lactam and conformationally constrained 1,3-diaminopropan-2-ol transition-state isostere inhibitors of β-secretase (BACE)

(2011) Kenneth M. Boy et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

New pyrazolyl and thienyl aminohydantoins as potent BACE1 inhibitors: Exploring the S2′ region

(2011) Michael S. Malamas et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Synthesis and in vivo evaluation of cyclic diaminopropane BACE-1 inhibitors

(2011) Lorin A. Thompson et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Structure based design, synthesis and SAR of cyclic hydroxyethylamine (HEA) BACE-1 inhibitors

(2011) Heinrich Rueeger et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Discovery of pyrrolidine-based β-secretase inhibitors: Lead advancement through conformational design for maintenance of ligand binding efficiency

(2011) Shawn J. Stachel et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Modes of Aβ toxicity in Alzheimer’s disease

(2011) Jürgen Götz et al.   CELLULAR AND MOLECULAR LIFE SCIENCES

Inclusion body myositis

(2011) Steven A. Greenberg   CURRENT OPINION IN RHEUMATOLOGY

γ-Secretase Substrates and their Implications for Drug Development in Alzheimer's Disease

(2011) Alberto Lleo et al.   CURRENT TOPICS IN MEDICINAL CHEMISTRY

From Fragment Screening to In Vivo Efficacy: Optimization of a Series of 2-Aminoquinolines as Potent Inhibitors of Beta-Site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE1)

(2011) Yuan Cheng et al.   JOURNAL OF MEDICINAL CHEMISTRY

Aβ-Degrading Enzymes: Potential for Treatment of Alzheimer Disease

(2011) James Scott Miners et al.   JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY

Robust Central Reduction of Amyloid-  in Humans with an Orally Available, Non-Peptidic  -Secretase Inhibitor

(2011) P. C. May et al.   JOURNAL OF NEUROSCIENCE

Alzheimer's disease

(2011) Clive Ballard et al.   LANCET

Soluble amyloid  -protein dimers isolated from Alzheimer cortex directly induce Tau hyperphosphorylation and neuritic degeneration

(2011) M. Jin et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

A Therapeutic Antibody Targeting BACE1 Inhibits Amyloid-  Production in Vivo

(2011) J. K. Atwal et al.   Science Translational Medicine

Novel pyrrolyl 2-aminopyridines as potent and selective human β-secretase (BACE1) inhibitors

(2010) Michael S. Malamas et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Design and synthesis of hydroxyethylamine (HEA) BACE-1 inhibitors: Structure–activity relationship of the aryl region

(2010) Gary D. Probst et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Design of an orally efficacious hydroxyethylamine (HEA) BACE-1 inhibitor in a preclinical animal model

(2010) Anh P. Truong et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

BACE-1 hydroxyethylamine inhibitors using novel edge-to-face interaction with Arg-296

(2010) Brian Clarke et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Rapid P1 SAR of brain penetrant tertiary carbinamine derived BACE inhibitors

(2010) Hong Zhu et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

SAR of tertiary carbinamine derived BACE1 inhibitors: Role of aspartate ligand amine pKa in enzyme inhibition

(2010) Hemaka A. Rajapakse et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Macrocyclic BACE inhibitors: Optimization of a micromolar hit to nanomolar leads

(2010) Yifang Huang et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Improving the permeability of the hydroxyethylamine BACE-1 inhibitors: Structure–activity relationship of P2′ substituents

(2010) Anh P. Truong et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Pyridinyl aminohydantoins as small molecule BACE1 inhibitors

(2010) Ping Zhou et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Design and synthesis of aminohydantoins as potent and selective human β-secretase (BACE1) inhibitors with enhanced brain permeability

(2010) Michael S. Malamas et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Discovery of Cyclic Acylguanidines as Highly Potent and Selective β-Site Amyloid Cleaving Enzyme (BACE) Inhibitors: Part I—Inhibitor Design and Validation∥(1)

(2010) Zhaoning Zhu et al.   JOURNAL OF MEDICINAL CHEMISTRY

Intramolecular Hydrogen Bonding in Medicinal Chemistry

(2010) Bernd Kuhn et al.   JOURNAL OF MEDICINAL CHEMISTRY

BACE1 Deficiency Causes Altered Neuronal Activity and Neurodegeneration

(2010) X. Hu et al.   JOURNAL OF NEUROSCIENCE

Oral Treatment with a  -Secretase Inhibitor Improves Long-Term Potentiation in a Mouse Model of Alzheimer's Disease

(2010) M. Townsend et al.   JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS

11C-PiB PET assessment of change in fibrillar amyloid-β load in patients with Alzheimer's disease treated with bapineuzumab: a phase 2, double-blind, placebo-controlled, ascending-dose study

(2010) Juha O Rinne et al.   LANCET NEUROLOGY

Alzheimer's disease: strategies for disease modification

(2010) Martin Citron   NATURE REVIEWS DRUG DISCOVERY

The secretases: enzymes with therapeutic potential in Alzheimer disease

(2010) Bart De Strooper et al.   Nature Reviews Neurology

Alzheimer's Disease

(2010) Henry W. Querfurth et al.   NEW ENGLAND JOURNAL OF MEDICINE

Di-substituted pyridinyl aminohydantoins as potent and highly selective human β-secretase (BACE1) inhibitors

(2009) Michael S. Malamas et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Structure-based design and synthesis of macrocyclic peptidomimetic β-secretase (BACE-1) inhibitors

(2009) Rainer Machauer et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Macrocyclic peptidomimetic β-secretase (BACE-1) inhibitors with activity in vivo

(2009) Rainer Machauer et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Second generation of BACE-1 inhibitors part 3: Towards non hydroxyethylamine transition state mimetics

(2009) Nicolas Charrier et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Discovery of aminoheterocycles as a novel β-secretase inhibitor class: pH dependence on binding activity part 1

(2009) Shawn J. Stachel et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Second generation of BACE-1 inhibitors. Part 1: The need for improved pharmacokinetics

(2009) Nicolas Charrier et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Design and synthesis of cell potent BACE-1 inhibitors: Structure–activity relationship of P1′ substituents

(2009) Jennifer M. Sealy et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Second generation of BACE-1 inhibitors part 2: Optimisation of the non-prime side substituent

(2009) Nicolas Charrier et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Discovery and initial optimization of 5,5′-disubstituted aminohydantoins as potent β-secretase (BACE1) inhibitors

(2009) Pawel Nowak et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Macrocyclic BACE-1 inhibitors acutely reduce Aβ in brain after po application

(2009) Andreas Lerchner et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Cell biology, regulation and inhibition of β-secretase (BACE-1)

(2009) Clare E. Hunt et al.   FEBS Journal

Aminoimidazoles as Potent and Selective Human β-Secretase (BACE1) Inhibitors

(2009) Michael S. Malamas et al.   JOURNAL OF MEDICINAL CHEMISTRY

Design and Synthesis of 5,5′-Disubstituted Aminohydantoins as Potent and Selective Human β-Secretase (BACE1) Inhibitors

(2009) Michael S. Malamas et al.   JOURNAL OF MEDICINAL CHEMISTRY

The  -Secretase Enzyme BACE in Health and Alzheimer's Disease: Regulation, Cell Biology, Function, and Therapeutic Potential

(2009) R. Vassar et al.   JOURNAL OF NEUROSCIENCE

APP binds DR6 to trigger axon pruning and neuron death via distinct caspases

(2009) Anatoly Nikolaev et al.   NATURE

Apolipoprotein E and its receptors in Alzheimer's disease: pathways, pathogenesis and therapy

(2009) Guojun Bu   NATURE REVIEWS NEUROSCIENCE

A phase 2 multiple ascending dose trial of bapineuzumab in mild to moderate Alzheimer disease

(2009) S. Salloway et al.   NEUROLOGY

Soluble Oligomers of Amyloid β Protein Facilitate Hippocampal Long-Term Depression by Disrupting Neuronal Glutamate Uptake

(2009) Shaomin Li et al.   NEURON

The Role of Apolipoprotein E in Alzheimer's Disease

(2009) Jungsu Kim et al.   NEURON

Amyloid- 42 signals tau hyperphosphorylation and compromises neuronal viability by disrupting alkylacylglycerophosphocholine metabolism

(2009) S. D. Ryan et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Alzheimer's-related endosome dysfunction in Down syndrome is A -independent but requires APP and is reversed by BACE-1 inhibition

(2009) Y. Jiang et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

BACE-1 inhibitors part 3: Identification of hydroxy ethylamines (HEAs) with nanomolar potency in cells

(2008) Paul Beswick et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

BACE-1 inhibitors Part 1: Identification of novel hydroxy ethylamines (HEAs)

(2008) Brian Clarke et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Rational design of novel, potent piperazinone and imidazolidinone BACE1 inhibitors

(2008) J.N. Cumming et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

BACE-1 inhibitors part 2: Identification of hydroxy ethylamines (HEAs) with reduced peptidic character

(2008) Brian Clarke et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

SYMPOSIUM: Clearance of Aβ from the Brain in Alzheimer's Disease: Aβ-Degrading Enzymes in Alzheimer's Disease

(2008) James Scott Miners et al.   BRAIN PATHOLOGY

Evolution of Tertiary Carbinamine BACE-1 Inhibitors: Aβ Reduction in Rhesus CSF upon Oral Dosing

(2008) Philippe G. Nantermet et al.   ChemMedChem

Activity of γ -Secretase on Substrates Other than APP

(2008) Alberto D.   CURRENT TOPICS IN MEDICINAL CHEMISTRY

Genetic deletion of BACE1 in mice affects remyelination of sciatic nerves

(2008) Xiangyou Hu et al.   FASEB JOURNAL

Proteolytic Shedding of ST6Gal-I by BACE1 Regulates the Glycosylation and Function of α4β1 Integrins

(2008) Alencia V. Woodard-Grice et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Discovery and X-ray Crystallographic Analysis of a Spiropiperidine Iminohydantoin Inhibitor of β-Secretase‡

(2008) James C. Barrow et al.   JOURNAL OF MEDICINAL CHEMISTRY

Second Generation of Hydroxyethylamine BACE-1 Inhibitors: Optimizing Potency and Oral Bioavailability†

(2008) Nicolas Charrier et al.   JOURNAL OF MEDICINAL CHEMISTRY

First Demonstration of Cerebrospinal Fluid and Plasma A  Lowering with Oral Administration of a  -Site Amyloid Precursor Protein-Cleaving Enzyme 1 Inhibitor in Nonhuman Primates

(2008) S. Sankaranarayanan et al.   JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS

Amyloid-β protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory

(2008) Ganesh M Shankar et al.   NATURE MEDICINE

Linking Calcium to Aβ and Alzheimer's Disease

(2008) Kim N. Green et al.   NEURON

Phosphorylation of the Translation Initiation Factor eIF2α Increases BACE1 Levels and Promotes Amyloidogenesis

(2008) Tracy O'Connor et al.   NEURON

ApoE Promotes the Proteolytic Degradation of Aβ

(2008) Qingguang Jiang et al.   NEURON

Alteration of BACE1-dependent NRG1/ErbB4 signaling and schizophrenia-like phenotypes in BACE1-null mice

(2008) A. V. Savonenko et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Cerebral Amyloid Angiopathy: Progressive Disruption of the Neurovascular Unit

(2008) G. J. Zipfel et al.   STROKE

Neuronal calcium mishandling and the pathogenesis of Alzheimer's disease

(2008) Ilya Bezprozvanny et al.   TRENDS IN NEUROSCIENCES

Acylguanidine inhibitors of β-secretase: Optimization of the pyrrole ring substituents extending into the substrate binding pocket

(2007) Lee D. Jennings et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Discovery of an orally efficaceous 4-phenoxypyrrolidine-based BACE-1 inhibitor

(2007) U. Iserloh et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Acylguanidine inhibitors of β-secretase: Optimization of the pyrrole ring substituents extending into the S1 and S3 substrate binding pockets

(2007) Derek C. Cole et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Potent pyrrolidine- and piperidine-based BACE-1 inhibitors

(2007) U. Iserloh et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Alzheimer's disease-type neuronal tau hyperphosphorylation induced by Aβ oligomers

(2007) Fernanda G. De Felice et al.   NEUROBIOLOGY OF AGING