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Dive into the research topics where Harry John Wadsworth is active.

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Featured researches published by Harry John Wadsworth.


Bioorganic & Medicinal Chemistry Letters | 2012

[18F]GE-180: A novel fluorine-18 labelled PET tracer for imaging Translocator protein 18 kDa (TSPO)

Harry John Wadsworth; Paul A. Jones; Wai-Fung Chau; Clare Durrant; Naghmeh Fouladi; Joanna Passmore; Dennis O’Shea; Duncan Wynn; Veronique Morisson-Iveson; Amanda Ewan; Mikkel Thaning; Dimitrios Mantzilas; Ingvil Gausemel; Imtiaz Khan; Andrew Black; Michelle Avory; William Trigg

A series of tricyclic compounds have been synthesised and evaluated in vitro for affinity against Translocator protein 18 kDa (TSPO) and for preferred imaging properties. The most promising of the compounds were radiolabelled and evaluated in vivo to determine biodistribution and specificity for high expressing TSPO regions. Metabolite profiling in brain and plasma was also investigated. Evaluation in an autoradiography model of neuroinflammation was also carried out for the best compound, 12a ([(18)F]GE-180).


Bioorganic & Medicinal Chemistry Letters | 2013

Exploration of the structure-activity relationship of a novel tetracyclic class of TSPO ligands-potential novel positron emitting tomography imaging agents.

Dennis O’Shea; Rabia Ahmad; Erik Arstad; Michelle Avory; Wai-Fung Chau; Clare Durrant; Ella Hirani; Paul A. Jones; Imtiaz Khan; Sajinder K. Luthra; Dimitrios Mantzilas; Veronique Morisson-Iveson; Joanna Passmore; Edward Robins; Bo Shan; Harry John Wadsworth; Sarah Walton; Yongjun Zhao; William Trigg

A series of novel TSPO ligands based on the tetracyclic class of translocator protein (TSPO) ligands first described by Okubo et al. was synthesised and evaluated as potential positron emitting tomography (PET) ligands for imaging TPSO in vivo. Fluorine-18 labelling of the molecules was achieved using direct radiolabelling or synthon based labelling approaches. Several of the ligands prepared have promising profiles as potential TSPO PET imaging ligands.


Bioorganic & Medicinal Chemistry Letters | 2012

Exploration of the structure-activity relationship of the diaryl anilide class of ligands for translocator protein--potential novel positron emitting tomography imaging agents.

Harry John Wadsworth; Paul A. Jones; Wai-Fung Chau; Clare Durrant; Veronique Morisson-Iveson; Joanna Passmore; Dennis O’Shea; Duncan Wynn; Imtiaz Khan; Andrew Black; Michelle Avory; William Trigg

A series of novel ligands based on the diaryl anilide (DAA) class of translocator protein (TSPO) ligands was synthesised and evaluated as potential positron emitting tomography (PET) ligands for imaging TPSO in vivo. Fluorine-18 labelling of the molecules was achieved using direct radiolabelling or synthon based labelling approaches. Several of the ligands prepared have promising profiles as potential TSPO PET imaging ligands and will be evaluated further as potential clinical imaging agents.


Bioorganic & Medicinal Chemistry Letters | 1997

2-[(substituted)phenyl]-5-[1-(2-phenylazacycloheptyl)methyl]-1H-pyrroles with high affinity and selectivity for the dopamine D3 receptor

David Bolton; Martyn C. Coldwell; Michael S. Hadley; Amanda Johns; Christopher Norbert Johnson; Roger Edward Markwell; David John Nash; Graham J. Riley; Emma E. Scott; Stephen A. Smith; Geoffrey Stemp; Harry John Wadsworth; Eric Alfred Watts

Abstract A series of 2-[(substituted)phenyl]-5-[1-(2-phenylazacycloheptyl)methyl]-1 H -pyrroles ( 8 – 15 ) has been prepared to investigate the effect on affinity and selectivity for the dopamine D 3 receptor of modifying the substituent in the phenyl ring at the 2-position of the pyrrole. Sulfonate 7 and sulfonamides 12 , 14 , 15 were shown to have high affinities (pKis 8.0 – 8.7) and selectivities (100 – 150-fold) for the D 3 over the D 2 receptor.


Bioorganic & Medicinal Chemistry Letters | 1996

Novel 2,5-disubstituted-1H-pyrroles with high affinity for the dopamine D3 receptor

David Bolton; Martyn C. Coldwell; Michael S. Hadley; Maureen A.M. Healy; Christopher Norbert Johnson; Roger Edward Markwell; David John Nash; Graham J. Riley; Geoffrey Stemp; Harry John Wadsworth

Abstract A series of 2,5-disubstituted-1H-pyrroles (4–18) has been prepared based on replacement of the amide of sultopride 1 by a pyrrole ring. Subsequent modification of the basic side chain gave compounds with high affinity for the dopamine D3 receptor. In addition, 12 and 17 were shown to be D3 antagonists with 30-fold selectivity for the D3 receptor over the D2 receptor.


Chemistry: A European Journal | 2013

A Resin-linker-vector approach to radiopharmaceuticals containing 18F: application in the synthesis of O-(2-[18F]-Fluoroethyl)-L-tyrosine

Amy C. Topley; Valerio Isoni; Thomas A. Logothetis; Duncan Wynn; Harry John Wadsworth; Alex Gibson; Imtiaz Khan; Neil J. Wells; Cécile Perrio; Richard C. D. Brown

A Resin-linker-vector (RLV) strategy is described for the radiosynthesis of tracer molecules containing the radionuclide (18)F, which releases the labelled vector into solution upon nucleophilic substitution of a polystyrene-bound arylsulfonate linker with [(18)F]-fluoride ion. Three model linker-vector molecules 7a-c containing different alkyl spacer groups were assembled in solution from (4-chlorosulfonylphenyl)alkanoate esters, exploiting a lipase-catalysed chemoselective carboxylic ester hydrolysis in the presence of the sulfonate ester as a key step. The linker-vector systems were attached to aminomethyl polystyrene resin through amide bond formation to give RLVs 8a-c with acetate, butyrate and hexanoate spacers, which were characterised by using magic-angle spinning (MAS) NMR spectroscopy. On fluoridolysis, the RLVs 8a,b containing the longer spacers were shown to be more effective in the release of the fluorinated model vector (4-fluorobutyl)phenylcarbamic acid tert-butyl ester (9) in NMR kinetic studies and gave superior radiochemical yields (RCY≈60%) of the (18) F-labelled vector. The approach was applied to the synthesis of the radiopharmaceutical O-(2-[(18)F]-fluoroethyl)-L-tyrosine ([(18) F]-FET), delivering protected [(18) F]-FET in >90% RCY. Acid deprotection gave [(18)F]-FET in an overall RCY of 41% from the RLV.


Tetrahedron Letters | 1991

Synthesis of ethyl 1-azabicyclo[2.2.1]hept-4-yl carboxylate

Barry Sidney Beecham Pharmaceuticals Orlek; Harry John Wadsworth; Paul Adrian Wyman; Frank King

Abstract The dipolar cycloaddition reaction of α-methylene butyrolactone and N-benzyl azomethine ylid (5) affords the spirolactone (2) which rearranges to give ethyl 1-zabicyclo[2.2.1]hept-4-yl carboxylate (1) in excellent overall yield.


Biochemical Journal | 1999

INHIBITION OF FIBRIL FORMATION IN BETA -AMYLOID PEPTIDE BY A NOVEL SERIES OF BENZOFURANS

David R. Howlett; Amanda E. Perry; Fiona Godfrey; Jane E. Swatton; Kevin H. Jennings; Claus Spitzfaden; Harry John Wadsworth; Stephen J. Wood; Roger Edward Markwell


Journal of Medicinal Chemistry | 1991

Comparison of azabicyclic esters and oxadiazoles as ligands for the muscarinic receptor

Barry Sidney Beecham Pharmaceuticals Orlek; Frank E. Blaney; Frank Brown; Michael S.G. Clark; Michael S. Hadley; John M. Hatcher; Graham J. Riley; Howard Elliott Rosenberg; Harry John Wadsworth; Paul Adrian Wyman


Journal of Medicinal Chemistry | 1992

Synthesis and muscarinic activities of quinuclidin-3-yltriazole and -tetrazole derivatives.

Harry John Wadsworth; Sarah Margaret Jenkins; Barry Sidney Orlek; Frederick Cassidy; Michael S.G. Clark; Frank Brown; Graham J. Riley; Diane Graves; Julie Hawkins; Christopher B. Naylor

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