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Application of Fragment-Based Lead Generation to the Discovery of Novel, Cyclic Amidine β-Secretase Inhibitors with Nanomolar Potency, Cellular Activity, and High Ligand Efficiency

Journal of medicinal chemistry, 2007-11, Vol.50 (24), p.5912-5925

2007

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Discovery of a Novel Warhead against β-Secretase through Fragment-Based Lead Generation

Journal of medicinal chemistry, 2007-11, Vol.50 (24), p.5903-5911

2007

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Application of Fragment Screening by X-ray Crystallography to the Discovery of Aminopyridines as Inhibitors of β-Secretase

Journal of medicinal chemistry, 2007-03, Vol.50 (6), p.1124-1132

2007

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An integrated approach to fragment-based lead generation: philosophy, strategy and case studies from AstraZeneca's drug discovery programmes

Current topics in medicinal chemistry, 2007-08, Vol.7 (16), p.1600-1629

2007

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Linear non-competitive inhibition of solubilized human gamma-secretase by pepstatin A methylester, L685458, sulfonamides, and benzodiazepines

The Journal of biological chemistry, 2002-08, Vol.277 (35), p.31499-31505

2002

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Biochemical characterization and in vitro activity of AZ513, a noncovalent, reversible, and noncompetitive inhibitor of fatty acid amide hydrolase

European journal of pharmacology, 2011-09, Vol.667 (1), p.74-79

2011

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Synthesis and enzymatic evaluation of a P1 arginine aminocoumarin substrate library for trypsin-like serine proteases

Bioorganic & medicinal chemistry letters, 2000-10, Vol.10 (20), p.2291-2294

2000

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Discovery of 8-azabicyclo[3.2.1]octan-3-yloxy-benzamides as selective antagonists of the kappa opioid receptor. Part 1

Bioorganic & medicinal chemistry letters, 2010-10, Vol.20 (19), p.5847-5852

2010

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Synthesis and physical characterization of a P1 arginine combinatorial library, and its application to the determination of the substrate specificity of serine peptidases

Bioorganic & medicinal chemistry, 2002-11, Vol.10 (11), p.3637-3647

2002

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Orally Active Trifluoromethyl Ketone Inhibitors of Human Leukocyte Elastase

Journal of medicinal chemistry, 1997-09, Vol.40 (20), p.3173-3181

1997

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Design, synthesis, and kinetic evaluation of a unique class of elastase inhibitors, the peptidyl .alpha.-ketobenzoxazoles, and the x-ray crystal structure of the covalent complex between porcine pancreatic elastase and Ac-Ala-Pro-Val-2-benzoxazole

Journal of the American Chemical Society, 1992-02, Vol.114 (5), p.1854-1863

1992

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Peptidyl .alpha.-ketoheterocyclic inhibitors of human neutrophil elastase. 2. Effect of varying the heterocyclic ring on in vitro potency

Journal of medicinal chemistry, 1995-01, Vol.38 (1), p.76-85

1995

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Peptidyl .alpha.-ketoheterocyclic inhibitors of human neutrophil elastase. 3. In vitro and in vivo potency of a series of peptidyl .alpha.-ketobenzoxazoles

Journal of medicinal chemistry, 1995-09, Vol.38 (20), p.3972-3982

1995

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alpha.-Amino carbanions. Preparation, metalation, and alkylation of enamidines. Synthesis of piperidine and pyrrolidine natural products and homologation of carbonyl compounds

Journal of organic chemistry, 1985-04, Vol.50 (7), p.1019-1026

1985

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Nonpeptidic Inhibitors of Human Neutrophil Elastase. 7. Design, Synthesis, and in Vitro Activity of a Series of Pyridopyrimidine Trifluoromethyl Ketones

Journal of medicinal chemistry, 1996-03, Vol.39 (5), p.1112-1124

1996

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Design of Orally Active, Non-Peptidic Inhibitors of Human Leukocyte Elastase

Journal of medicinal chemistry, 1994-04, Vol.37 (9), p.1259-1261

1994

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Surviving the lethal triad of trauma: a case from Kosovo

Journal of the Royal Naval Medical Service, 2003, Vol.89 (2), p.67-72

2003

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C3 activation is inhibited by analogs of compstatin but not by serine protease inhibitors or peptidyl α-ketoheterocycles

Immunopharmacology, 2000-07, Vol.48 (2), p.199-212

2000

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Synthetic Inhibitors of Elastase

Medicinal research reviews, 1994-03, Vol.14 (2), p.127-194

1994

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Nonpeptidic Inhibitors of Human Leukocyte Elastase. 3. Design, Synthesis, X-ray Crystallographic Analysis, and Structure-Activity Relationships for a Series of Orally Active 3-Amino-6-phenyl-2-pyridinyl Trifluoromethyl Ketones

Journal of medicinal chemistry, 1994-09, Vol.37 (20), p.3313-3326

1994

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Nonpeptidic Inhibitors of Human Leukocyte Elastase. 2. Design, Synthesis, and in vitro Activity of a Series of 3-Amino-6-aryl-2-oxopyridyl Trifluoromethyl Ketones

Journal of medicinal chemistry, 1994-09, Vol.37 (20), p.3303-3312

1994

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Synthesis and physical characterization of a P 1 arginine combinatorial library, and its application to the determination of the substrate specificity of serine peptidases

Bioorganic & medicinal chemistry, 2002-11, Vol.10 (11), p.3637-3647

2002

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Synthesis and enzymatic evaluation of a P 1 arginine aminocoumarin substrate library for trypsin-like serine proteases

Bioorganic & medicinal chemistry letters, 2000-10, Vol.10 (20), p.2291-2294

2000

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Discovery and Biological Activity of Orally Active Peptidyl Trifluoromethyl Ketone Inhibitors of Human Neutrophil Elastase

Journal of medicinal chemistry, 1997-06, Vol.40 (12), p.1876-1885

1997

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A method for the stereoselective synthesis of peptidyl trifluoromethyl ketones

Tetrahedron letters, 1992-07, Vol.33 (30), p.4279-4282

Edwards, Philip D.

1992

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Application of Fragment-Based Lead Generation to the Discovery of Novel, Cyclic Amidine β-Secretase Inhibitors with Nanomolar Potency, Cellular Activity, and High Ligand Efficiency

Discovery of a Novel Warhead against β-Secretase through Fragment-Based Lead Generation

Application of Fragment Screening by X-ray Crystallography to the Discovery of Aminopyridines as Inhibitors of β-Secretase

An integrated approach to fragment-based lead generation: philosophy, strategy and case studies from AstraZeneca's drug discovery programmes

Linear non-competitive inhibition of solubilized human gamma-secretase by pepstatin A methylester, L685458, sulfonamides, and benzodiazepines

Biochemical characterization and in vitro activity of AZ513, a noncovalent, reversible, and noncompetitive inhibitor of fatty acid amide hydrolase

Synthesis and enzymatic evaluation of a P1 arginine aminocoumarin substrate library for trypsin-like serine proteases

Discovery of 8-azabicyclo[3.2.1]octan-3-yloxy-benzamides as selective antagonists of the kappa opioid receptor. Part 1

Synthesis and physical characterization of a P1 arginine combinatorial library, and its application to the determination of the substrate specificity of serine peptidases

Orally Active Trifluoromethyl Ketone Inhibitors of Human Leukocyte Elastase

Design, synthesis, and kinetic evaluation of a unique class of elastase inhibitors, the peptidyl .alpha.-ketobenzoxazoles, and the x-ray crystal structure of the covalent complex between porcine pancreatic elastase and Ac-Ala-Pro-Val-2-benzoxazole

Peptidyl .alpha.-ketoheterocyclic inhibitors of human neutrophil elastase. 2. Effect of varying the heterocyclic ring on in vitro potency

Peptidyl .alpha.-ketoheterocyclic inhibitors of human neutrophil elastase. 3. In vitro and in vivo potency of a series of peptidyl .alpha.-ketobenzoxazoles

alpha.-Amino carbanions. Preparation, metalation, and alkylation of enamidines. Synthesis of piperidine and pyrrolidine natural products and homologation of carbonyl compounds

Nonpeptidic Inhibitors of Human Neutrophil Elastase. 7. Design, Synthesis, and in Vitro Activity of a Series of Pyridopyrimidine Trifluoromethyl Ketones

Design of Orally Active, Non-Peptidic Inhibitors of Human Leukocyte Elastase

Surviving the lethal triad of trauma: a case from Kosovo

C3 activation is inhibited by analogs of compstatin but not by serine protease inhibitors or peptidyl α-ketoheterocycles

Synthetic Inhibitors of Elastase

Nonpeptidic Inhibitors of Human Leukocyte Elastase. 3. Design, Synthesis, X-ray Crystallographic Analysis, and Structure-Activity Relationships for a Series of Orally Active 3-Amino-6-phenyl-2-pyridinyl Trifluoromethyl Ketones

Nonpeptidic Inhibitors of Human Leukocyte Elastase. 2. Design, Synthesis, and in vitro Activity of a Series of 3-Amino-6-aryl-2-oxopyridyl Trifluoromethyl Ketones

Synthesis and physical characterization of a P 1 arginine combinatorial library, and its application to the determination of the substrate specificity of serine peptidases

Synthesis and enzymatic evaluation of a P 1 arginine aminocoumarin substrate library for trypsin-like serine proteases

Discovery and Biological Activity of Orally Active Peptidyl Trifluoromethyl Ketone Inhibitors of Human Neutrophil Elastase

A method for the stereoselective synthesis of peptidyl trifluoromethyl ketones

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