Tony Johnson

AstraZeneca (United Kingdom)

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Martin Quibell

The Francis Crick Institute

Theodore Colton

Boston University

Laurence S. Freedman

Sheba Medical Center

Mark Liley

Grand Valley State University

David Hlachin

MRC Biostatistics Unit

Douglas Altnian

MRC Biostatistics Unit

Gauri Deshmukh

Genentech

Janusz J. Kulagowski

Harlow College

Michael Tucker

AstraZeneca (United Kingdom)

Mark Zak

Nurix (United States)

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AstraZeneca (United Kingdom)

100

AstraZeneca (United States)

Royal College of Physicians and Surgeons of Canada

Folkestone College

Sunonwealth Electric Machine Industry (Taiwan)

AstraZeneca (Brazil)

Genentech

Royal College of Psychiatrists

University of Cambridge

University of Manchester

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Masthead

Statistics in Medicine (1993)

Theodore Colton Laurence S. Freedman Tony Johnson David Hlachin Douglas Altnian

10.1002/sim.4780121401

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N,O‐bisFmoc derivatives of N‐(2‐hydroxy‐4‐methoxybenzyl)‐amino acids: Useful intermediates in peptide synthesis

Journal of Peptide Science (1995)

Tony Johnson Martin Quibell R. C. Sheppard

Abstract 2‐Hydroxy‐4‐methoxybenzyl‐amino acid residues inhibit interchain association in solid phase peptide synthesis. They are easily introduced through their N , O ‐bisFmoc derivatives. Preparation of a range of these derivatives is described.

Peptide Synthesis

Solid-Phase Synthesis

10.1002/psc.310010104

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Citations (93)

PREFACE

Statistics in Medicine (1996)

Ted Colton Tony Johnson DAVID MACHIN

Biostatistics

10.1002/(sici)1097-0258(19961230)15:24<2633::aid-sim1444>3.0.co;2-j

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Citations (0)

Masthead

Statistics in Medicine (1993)

Theodore Colton Laurence S. Freedman Tony Johnson David Hlachin Douglas Altnian

10.1002/sim.4780120701

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Citations (0)

Reversible modification of the acid labile 2-hydroxy-4-methoxybenzyl(Hmb) amide protecting group: A simple scheme yielding backbone substituted free peptides

Tetrahedron Letters (1994)

Martin Quibell William G. Turnell Tony Johnson

Trifluoroacetic acid

Amide

Lability

Piperidine

Protecting group

10.1016/s0040-4039(00)76807-9

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Citations (24)

Novel triazolo-pyrrolopyridines as inhibitors of Janus kinase 1

Bioorganic & Medicinal Chemistry Letters (2013)

Christopher A. Hurley Wade Blair Richard J. Bull Christine Chang Peter H. Crackett

Janus kinase inhibitor

Janus kinase 2

10.1016/j.bmcl.2013.04.018

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Citations (18)

A new generation of reversible backbone-amide protection for the solid phase synthesis of difficult sequences

Tetrahedron Letters (2000)

Jo Howe Martin Quibell Tony Johnson

Solid-Phase Synthesis

Amide

10.1016/s0040-4039(00)00537-2

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Citations (20)

Problems in the synthesis of cyclic peptides through use of the Dmab protecting group †

Perkin 1 (2000)

Tony Johnson Mark Liley Timothy J. Cheeseright Farida Begum

The preparation of side-chain-to-side-chain-cyclised peptides through lactam bridge formation requires orthogonal protecting groups for side-chain amino and carboxylate functionalities. Use of the 4-{N-[1-(4,4-dimethyl-2,6-dioxocyclohexylidene)-3-methylbutyl]amino}benzyl ester (Dmab) group for this role in the protection of the glutamyl side-chain resulted in the formation of unexpected side-products. During synthesis of fully protected peptide targets, Nα-pyroglutamyl chain-terminated peptides were observed. Pyroglutamyl peptides were not observed in analogous peptides synthesised using the traditional tert-butyl ester protecting group. Selective removal of the Dmab group proceeds through a two-stage procedure, hydrazinolytic cleavage of the dimedone moiety followed by 1,6-elimination of the resulting peptide-glutamyl 4-aminobenzyl ester. The latter reaction is sufficiently slow to allow isolation of the transiently stable glutamyl derived 4-aminobenzyl ester peptide. Attempted side-chain-to-side-chain cyclisation (through orthogonally protected Glu and Lys residues) of peptides prepared via Glu(ODmab) failed and led to modification of the Lys Nε-amino group when 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU) was used as carboxy-activating reagent. Analogous peptides prepared utilising allyl side-chain protection for glutamyl residues were successfully cyclised using HBTU.

Side chain

Protecting group

Moiety

Cleavage (geology)

10.1039/b001694m

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Citations (21)

Synthesis of azapeptides by the Fmoc/tert-butyl/polyamide technique

Journal of the Chemical Society. Perkin transactions I/Journal of the Chemical Society. Perkin transactions. I (1993)

Martin Quibell William G. Turnell Tony Johnson

A new synthesis of azapeptides for use in the study of a proteolytic enzyme associated with Alzheimer's disease is described. The method utilizes fluoren-9-ylmethoxycarbonyl (Fmoc) amino acid carbazates and hydrazides in the Fmoc/tert-butyl/polyamide technique. The preparation of these compounds is presented. Reaction of Fmoc-amino acid hydrazides with an appropriate aldehyde, followed by reduction, gave fully protected amino acid carbazate dipeptide synthon. These derivatives were used to prepare aza amino acid peptide analogues by reaction with a resin-bound amino group, activated with bis-2,4-dinitrophenyl carbonate in the presence of a base. With this activation of the amino group, hydantoin is formed in a major side-reaction, but the cyclisation could be virtually eliminated by omission of the base from the activation procedure. Upon final trifluoroacetic acid-mediated cleavage of the azapeptide, trifluoroacetylation of the N-terminal serine residue was observed.

Synthon

Trifluoroacetic acid

Tripeptide

Residue (chemistry)

Cleavage (geology)

Peptide Synthesis

10.1039/p19930002843

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Citations (53)

Identification of Imidazo-Pyrrolopyridines as Novel and Potent JAK1 Inhibitors

Journal of Medicinal Chemistry (2012)

Janusz J. Kulagowski Wade Blair Richard J. Bull Christine Chang Gauri Deshmukh

A therapeutic rationale is proposed for the treatment of inflammatory diseases, such as rheumatoid arthritis (RA), by specific targeting of the JAK1 pathway. Examination of the preferred binding conformation of clinically effective, pan-JAK inhibitor 1 led to identification of a novel, tricyclic hinge binding scaffold 3. Exploration of SAR through a series of cycloamino and cycloalkylamino analogues demonstrated this template to be highly tolerant of substitution, with a predisposition to moderate selectivity for the JAK1 isoform over JAK2. This study culminated in the identification of subnanomolar JAK1 inhibitors such as 22 and 49, having excellent cell potency, good rat pharmacokinetic characteristics, and excellent kinase selectivity. Determination of the binding modes of the series in JAK1 and JAK2 by X-ray crystallography supported the design of analogues to enhance affinity and selectivity.

Structure–activity relationship

Tricyclic

10.1021/jm300438j

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Citations (85)