P. Leeson

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The influence of drug-like concepts on decision-making in medicinal chemistry

P. Leeson, B. Springthorpe, 2007, Nature Reviews Drug Discovery.

A comparison of physiochemical property profiles of development and marketed oral drugs.

P. Leeson, M. Wenlock, R. Austin, 2003, Journal of medicinal chemistry.

An analysis of the attrition of drug candidates from four major pharmaceutical companies

R. M. Owen, A. Leach, P. Leeson, 2015, Nature Reviews Drug Discovery.

The role of ligand efficiency metrics in drug discovery

A. Hopkins, G. Keserü, P. Leeson, 2014, Nature Reviews Drug Discovery.

Is There a Difference Between Leads and Drugs? A Historical Perspective.

Tudor I. Oprea, T. Oprea, P. Leeson, 2001 .

Paul D Leeson, Andrew M Davis, P. Leeson, 2004, Journal of medicinal chemistry.

Reducing the Risk of Drug Attrition Associated with Physicochemical Properties

Paul D. Leeson, P. Leeson, J. Empfield, 2010 .

Impact of ion class and time on oral drug molecular properties

Paul D. Leeson, Mark C. Wenlock, P. Leeson, 2011 .

Effect of plasma protein binding on in vivo activity and brain penetration of glycine/NMDA receptor antagonists.

P D Leeson, J. Kemp, P. Leeson, 1997, Journal of medicinal chemistry.

The influence of the 'organizational factor' on compound quality in drug discovery

Paul D. Leeson, P. Leeson, S. St-Gallay, 2011, Nature Reviews Drug Discovery.

Molecular inflation, attrition and the rule of five.

Paul D Leeson, P. Leeson, 2016, Advanced drug delivery reviews.

Substituted pyrazoles as novel selective ligands for the human dopamine D4 receptor.

P. Leeson, I. Collins, M. Rowley, 1998, Bioorganic & medicinal chemistry.

Selective thyromimetics. Cardiac-sparing thyroid hormone analogues containing 3'-arylmethyl substituents.

J. C. Emmett, P. Leeson, H. D. Prain, 1989, Journal of Medicinal Chemistry.

The Role of Ligand Efficiency Measures in Drug Discovery

A. Hopkins, P. Leeson, G. Keserű, 2014 .

4-Amido-2-carboxytetrahydroquinolines. Structure-activity relationships for antagonism at the glycine site of the NMDA receptor.

P. Leeson, A. Foster, S. Grimwood, 1992, Journal of medicinal chemistry.

Quality guidelines for oral drug candidates: dose, solubility and lipophilicity.

P. Leeson, D. Green, M. Bayliss, 2016, Drug discovery today.

Review Central & Peripheral Nervous Systems: Glycine-site NMDA receptor antagonists

P. Leeson, J. Kulagowski, 1995 .

Kynurenic acid derivatives. Structure-activity relationships for excitatory amino acid antagonism and identification of potent and selective antagonists at the glycine site on the N-methyl-D-aspartate receptor.

J. Kemp, P. Leeson, Brett Williams, 1991, Journal of medicinal chemistry.

From ATP to AZD6140: the discovery of an orally active reversible P2Y12 receptor antagonist for the prevention of thrombosis.

P. Leeson, B. Springthorpe, P. Barton, 2007, Bioorganic & medicinal chemistry letters.

[3H]L-655,708, a Novel Ligand Selective for the Benzodiazepine Site of GABAA Receptors which Contain the α5 Subunit

P. Leeson, R. Mckernan, C. Ragan, 1996, Neuropharmacology.

Synthesis of 2S-[2-2H]-kynurenine and use in kinetic isotope effect studies with kynureninase

P. Leeson, N. Botting, Fiona C. Ross, 1997 .

Two syntheses of 2S-[2-2H]-kynurenine

P. Leeson, N. Botting, Fiona C. Ross, 1996 .

Stereospecific synthesis of α-deuteriated α-amino acids: regiospecific deuteriation of chiral 3-isopropyl-2,5-dimethoxy-3,6-dihydropyrazines

P. Leeson, D. Gani, J. Rose, 1995 .

Anticonvulsant and behavioral profile of L-701,324, a potent, orally active antagonist at the glycine modulatory site on the N-methyl-D-aspartate receptor complex.

P. Leeson, M. Tricklebank, L. Bristow, 1996, The Journal of pharmacology and experimental therapeutics.

THE MPTP-TREATED PRIMATE AS A MODEL FOR ASSESSING NOVEL ANTIPARKINSONUN AGENTS

S. Iversen, L. Iversen, J. Kemp, 2006 .

S. Iversen, L. Iversen, J. Kemp, 1992, Annals of the New York Academy of Sciences.

Synthesis and sar of 2- and 3-substituted 7-azaindoles as potential dopamine D4 ligands.

P. Leeson, S. Freedman, S. Patel, 1999, Bioorganic & medicinal chemistry letters.

4-Heterocyclyl tetrahydropyridines as selective ligands for the human dopamine D4 receptor

P. Leeson, S. Patel, R. Marwood, 1997 .

Is There a Difference between Leads and Drugs? A Historical Perspective

Tudor I. Oprea, Paul D. Leeson, Andrew M. Davis, 2001, J. Chem. Inf. Comput. Sci..

Transannular reactions of 5-hydroxylamino and 5-azido dibenzo[a,e]cyclo-octatrienes: regiospecific syntheses of dibenzohomotropane and pavine analogues

P. Leeson, R. Baker, K. James, 1989 .

Synthesis of iminomethano-dibenzo[a,e]cyclooctenes by transannular formation and cleavage of isoxazolidines

P. Leeson, R. Carling, 1988 .

Precipitation and 13C-NMR relaxation enhancement measurements of the interactions of bile acids with synthetic cationic bile acid derivatives, and with spin labelled fatty acids.

P. Leeson, S. Robinson, D. Reid, 1991, Chemistry and physics of lipids.

3′‐(Arylmethyl)‐ and 3′‐(Aryloxy)‐3‐phenyl‐4‐hydroxyquinolin‐2(1H)‐ ones: Orally Active Antagonists of the Glycine Site on the NMDA Receptor.

J. Kemp, P. Leeson, M. Tricklebank, 2010 .

3'-(Arylmethyl)- and 3'-(aryloxy)-3-phenyl-4-hydroxyquinolin-2(1H)-ones: orally active antagonists of the glycine site on the NMDA receptor.

P. Leeson, I. Stansfield, M. Rowley, 1994, Journal of medicinal chemistry.

The reactions of flavin analogues and other heterocycles as models for bacterial bioluminescence

P. Leeson, F. McCapra, G. Perry, 1986 .

The Time and Place for Nature in Drug Discovery

P. Leeson, N. Turner, S. Flitsch, 2022, JACS Au.

The atypical neuroleptic profile of the glycine/N-methyl-D-aspartate receptor antagonist, L-701,324, in rodents.

P. Leeson, M. Tricklebank, L. Bristow, 1996, The Journal of pharmacology and experimental therapeutics.

Mechanisms and stereochemistry of the activation of (2S)- and (2R)-serine O-sulfate as suicide inhibitors for Escherichia coli glutamic acid decarboxylase

P. Leeson, D. Gani, J. Rose, 1992 .

3-((4-(4-Chlorophenyl)piperazin-1-yl)-methyl)-1H-pyrrolo-2,3-b-pyridine: an antagonist with high affinity and selectivity for the human dopamine D4 receptor.

P D Leeson, P. Leeson, C. Ragan, 1996, Journal of medicinal chemistry.

Synthesis of thyroid hormone analogues. Part 1. Preparation of 3′heteroarylmethyl-3,5-di-iodo-L-thyronines via phenol–dinitrophenol condensation and relationships between structure and selective thyromimetic activity

J. C. Emmett, P. Leeson, 1988 .

Synthesis of thyroid hormone analogues. Part 2. Oxidative coupling approach to SK&F L-94901

P. Leeson, D. M. Hickey, S. D. Carter, 1988 .

3-Phenyl-6-(2-pyridyl)methyloxy-1,2,4-triazolo[3,4-a]phthalazines and Analogues: High-Affinity γ-Aminobutyric Acid-A Benzodiazepine Receptor Ligands with α2, α3, and α5-Subtype Binding Selectivity over α1

G. Dawson, P. Leeson, R. Mckernan, 2004 .

3-phenyl-6-(2-pyridyl)methyloxy-1,2,4-triazolo[3,4-a]phthalazines and analogues: high-affinity gamma-aminobutyric acid-A benzodiazepine receptor ligands with alpha 2, alpha 3, and alpha 5-subtype binding selectivity over alpha 1.

G. Dawson, P. Leeson, R. Mckernan, 2004, Journal of medicinal chemistry.

Anticonvulsant activity of glycine-site NMDA antagonists. 2. trans 2-carboxy-4-substituted tetrahydroquinolines.

J. Kemp, P. Leeson, M. Tricklebank, 1993 .

2-Carboxytetrahydroquinolines. Conformational and stereochemical requirements for antagonism of the glycine site on the NMDA receptor.

J. Kemp, P. Leeson, A. Foster, 1992, Journal of medicinal chemistry.

3-Nitro-3,4-dihydro-2(1H)-quinolones. Excitatory amino acid antagonists acting at glycine-site NMDA and (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors.

J. Kemp, P. Leeson, C. Moyes, 1993, Journal of medicinal chemistry.

4-Heterocyclylpiperidines as selective high-affinity ligands at the human dopamine D4 receptor.

P D Leeson, P. Leeson, C. Ragan, 1997, Journal of medicinal chemistry.

5-(4-Chlorophenyl)-4-methyl-3-(1-(2-phenylethyl)piperidin-4-yl)isoxazole: a potent, selective antagonist at human cloned dopamine D4 receptors.

P. Leeson, C. Ragan, H. Broughton, 1996, Journal of medicinal chemistry.

An efficient solid phase synthetic route to 1,3-disubstituted 2,4(1H,3H)-Quinazolinediones suitable for combinatorial synthesis

P. Leeson, C. Thomson, A. Smith, 1996 .

Enantiomers of HA-966 (3-amino-1-hydroxypyrrolid-2-one) exhibit distinct central nervous system effects: (+)-HA-966 is a selective glycine/N-methyl-D-aspartate receptor antagonist, but (-)-HA-966 is a potent gamma-butyrolactone-like sedative.

S. Iversen, L. Iversen, J. Kemp, 1990, Proceedings of the National Academy of Sciences of the United States of America.

Drug discovery: Chemical beauty contest

P. Leeson, Paul Leeson, 2012, Nature.

Routes to 4-substituted analogues of the glycine/NMDA antagonist HA-996. Enantioselective synthesis of (3R,4R) 3-amino-1-hydroxy-4-methyl-2-pyrrolidinone (L-687, 414).

P. Leeson, M. Rowley, B. Williams, 1992 .

The glycine site of the NMDA receptor--five years on.

J. Kemp, P. Leeson, 1993, Trends in pharmacological sciences.

Tetramic acids as novel glycine site antagonists

P. Leeson, S. Grimwood, G. Marshall, 1995 .

Amino acid bioisosteres: design of 2-quinolone derivatives as glycine-site N-methyl-D-aspartate receptor antagonists

J. Kemp, P. Leeson, I. Stansfield, 1993 .

Derivatives of 1-hydroxy-3-aminopyrrolidin-2-one (HA-966). Partial agonists at the glycine site of the NMDA receptor

J. Kemp, P. Leeson, Brett Williams, 1993 .

2-carboxy indolines and indoles as potential glycine/NMDA antagonists: effect of five-membered ring conformation on affinity.

P. Leeson, M. Rowley, A. Foster, 1992 .

Kynurenic acid analogues with improved affinity and selectivity for the glycine site on the N-methyl-D-aspartate receptor from rat brain.

J. Kemp, P. Leeson, A. Foster, 1992, Molecular pharmacology.

Characterization of the binding of [3H]L-689,560, an antagonist for the glycine site on the N-methyl-D-aspartate receptor, to rat brain membranes.

P. Leeson, A. Foster, S. Grimwood, 1992, Molecular pharmacology.

Binding of 2,4-disubstituted morpholines at human D4 dopamine receptors.

P D Leeson, P. Leeson, D. O'connor, 1998, Bioorganic & medicinal chemistry.

4-substituted-3-phenylquinolin-2(1H)-ones: acidic and nonacidic glycine site N-methyl-D-aspartate antagonists with in vivo activity.

J. Kemp, P. Leeson, M. Hudson, 1997, Journal of medicinal chemistry.

3-Acyl-4-hydroxyquinolin-2(1H)-ones. Systemically active anticonvulsants acting by antagonism at the glycine site of the N-methyl-D-aspartate receptor complex.

J. Kemp, P. Leeson, I. Stansfield, 1993, Journal of medicinal chemistry.

Molecular Property Design: Does Everyone Get It?

Paul D Leeson, Robert J Young, P. Leeson, 2015, ACS medicinal chemistry letters.

The glycine site on the NMDA receptor: structure-activity relationships and therapeutic potential.

L. Iversen, P. Leeson, 1994, Journal of medicinal chemistry.

Effects of five-membered ring conformation on bioreceptor recognition: identification of 3R-amino-1-hydroxy-4R-methylpyrrolidin-2-one (L-687,414) as a potent glycine/N-methyl-D-aspartate receptor antagonist

P. Leeson, M. Rowley, B. Williams, 1990 .

Synthesis and SAR of diiodotyrosine-derived glycine-site N-methyl-D-aspartate receptor ligands

P. Leeson, M. Rowley, S. Grimwood, 1996 .

The dephosphorylation of inositol 1,4-bisphosphate to inositol in liver and brain involves two distinct Li+-sensitive enzymes and proceeds via inositol 4-phosphate.

P. Leeson, C. Ragan, R. Barnaby, 1988, The Biochemical journal.

Target-based evaluation of ‘drug-like’ properties and ligand efficiencies

A. Leach, A. Hersey, P. Leeson, 2021, Journal of medicinal chemistry.

4-N-linked-heterocyclic piperidine derivatives with high affinity and selectivity for human dopamine D4 receptors.

P. Leeson, M. Rowley, S. Patel, 1999, Bioorganic & medicinal chemistry letters.

L-745,870, a subtype selective dopamine D4 receptor antagonist, does not exhibit a neuroleptic-like profile in rodent behavioral tests.

P. Leeson, C. Ragan, M. Tricklebank, 1997, The Journal of pharmacology and experimental therapeutics.

The anticonvulsant and behavioural profile of L‐687,414, a partial agonist acting at the glycine modulatory site on the N‐methyl‐D‐aspartate (NMDA) receptor complex

P. Leeson, Brett Williams, M. Tricklebank, 1994, British journal of pharmacology.

Resolution and synthesis of the individual enantiomers of the glycine antagonist 3-amino-1-hydroxypyrrolidin-2-one (HA-966)

P. Leeson, B. Williams, R. Baker, 1989 .

Mapping the Efficiency and Physicochemical Trajectories of Successful Optimizations.

P. Leeson, R. Young, 2018, Journal of medicinal chemistry.

NMDA)receptor complex

P. Leeson, M. Tricklebank, M. Rowley, 1994 .

Resolution and Synthesis of the Individual Enantiomers of the Glycine Antagonist 3-Amino-1-hydroxypyrrolidin-2-one (HA-966).

P. Leeson, B. Williams, R. Baker, 1990 .

A thyromimetic that decreases plasma cholesterol levels without increasing cardiac activity

J. C. Emmett, S. B. Flynn, P. Leeson, 1986, Nature.

3'-Acetyl-3,5-diiodo-L-thyronine: a novel highly active thyromimetic with low receptor affinity.

J. C. Emmett, P. Leeson, D. Ellis, 1984, Biochemical pharmacology.

Allosteric modulation of the glutamate site on the NMDA receptor by four novel glycine site antagonists.

P. Leeson, M. Rowley, A. Foster, 1995, European journal of pharmacology.

7-Chlorokynurenic acid is a selective antagonist at the glycine modulatory site of the N-methyl-D-aspartate receptor complex.

L. Iversen, J. Kemp, P. Leeson, 1988, Proceedings of the National Academy of Sciences of the United States of America.

1-(3-Cyanobenzylpiperidin-4-yl)-5-methyl-4-phenyl-1, 3-dihydroimidazol-2-one: a selective high-affinity antagonist for the human dopamine D(4) receptor with excellent selectivity over ion channels.

P. Leeson, A. Pike, C. Moyes, 1999, Journal of medicinal chemistry.

Biological profile of L-745,870, a selective antagonist with high affinity for the dopamine D4 receptor.

P. Leeson, M. Knowles, G. Mcallister, 1997, The Journal of pharmacology and experimental therapeutics.

Thyroid hormone analogues. Synthesis of 3'-substituted 3,5-diiodo-L-thyronines and quantitative structure-activity studies of in vitro and in vivo thyromimetic activities in rat liver and heart.

J. C. Emmett, P. Leeson, D. Ellis, 1988, Journal of medicinal chemistry.

Inhibitors of myo-inositol monophosphatase unrelated to the enzyme substrate

P. Leeson, C. Ragan, E. Harley, 1992 .

Design and synthesis of 6α-substituted 2β,4α-dihydroxy-1β-phosphoryloxycyclohexanes, potent inhibitors of inositol monophosphatase

P. Leeson, N. Liverton, R. Baker, 1991 .

Validity of ligand efficiency metrics.

Nicola J. Richmond, Andrew L Hopkins, Paul D Leeson, 2014, ACS medicinal chemistry letters.

Chapter 2:Drug-Like Physicochemical Properties

Tudor I. Oprea, Paul D. Leeson, P. Leeson, 2011 .

3-(1-piperazinyl)-4,5-dihydro-1H-benzo[g]indazoles: high affinity ligands for the human dopamine D4 receptor with improved selectivity over ion channels.

P. Leeson, I. Collins, M. Rowley, 1998, Bioorganic & medicinal chemistry.

Drug-like properties: guiding principles for design - or chemical prejudice?

John Steele, Paul D Leeson, Andrew M Davis, 2004, Drug discovery today. Technologies.

Ask the experts: past, present and future of the rule of five.

M. Congreve, P. Leeson, J. Baell, 2013, Future medicinal chemistry.

Overview: Excitatory Amino Acid Antagonists

P. Leeson, M. Rowley, 1992 .

Identification and pharmacological characterization of [125I]L-750,667, a novel radioligand for the dopamine D4 receptor.

P. Leeson, S. Freedman, S. Patel, 1996, Molecular pharmacology.

The discovery of novel, potent and highly selective inhibitors of inducible nitric oxide synthase (iNOS).

Glen Andrews, Paul D Leeson, Anders Åberg, 2011, Bioorganic & medicinal chemistry letters.

Identification of (1S)-phosphoryloxy-(2R,4S)-dihydroxycyclohexane as a potent inhibitor of inositol monophosphatase

P. Leeson, N. Liverton, J. Kulagowski, 1990 .

Synthesis of 2- and 6-deoxyinositol 1-phosphate and the role of the adjacent hydroxy groups in the mechanism of inositol monophosphatase

P. Leeson, N. Liverton, D. Billington, 1989 .

Anticonvulsant activity of glycine-site NMDA antagonists: 1. 2-Carboxyl prodrugs of 5,7-dichlorokynurenic acid

P. Leeson, R. Carling, K. Moore, 1993 .

Role of hydrogen bonding in ligand interaction with the N-methyl-D-aspartate receptor ion channel.

E. Wong, P. Leeson, R. Carling, 1990, Journal of Medicinal Chemistry.

Impact of Physicochemical Properties on Dose and Hepatotoxicity of Oral Drugs.

P. Leeson, 2018, Chemical research in toxicology.

Strategies to improve in vivo toxicology outcomes for basic candidate drug molecules.

Niklas Blomberg, Britt-Marie Swahn, Paul D Leeson, 2011, Bioorganic & medicinal chemistry letters.

The Design of Leadlike Combinatorial Libraries.

Tudor I. Oprea, P. Leeson, A. Davis, 1999, Angewandte Chemie.

Lessons learned from candidate drug attrition.

Paul D Leeson, P. Leeson, J. Empfield, 2010, IDrugs : the investigational drugs journal.

Drug-like properties: guiding principles for design - or chemical prejudice?

P. Leeson, A. Davis, J. Steele, 2004, Drug discovery today. Technologies.