Ge Healthcare Limited

Ge Healthcare As

Nycomed Amersham Plc

Nihon Medi-physics Company, Limited

Amersham International Plc

Amersham Plc

Anthony Eamon Storey

Marivi Mendizabal

Ian Andrew Wilson

Peter Knox

Denis Raymond Christophe Bouvet

Alan Michael Forster

Gary Robert Bower

Alan Cuthbertson

Bengt Langstrom

Farhad Karimi

Anthony Leonard Riley

Alexander Mark Gibson

Steven Michael Fairway

Lorenzo Williams

Robert James Nairne

Clare Louise Jones

Susan Champion

Alex Gibson

Benedicte Guilbert

Harry John Wadsworth

Colin M Archer

Nigel Anthony Powell

Lewis Reuben Canning

Harjit Kaur Gill

Nicolas Lasbistes

Philip Duncanson

David Vaughan Griffiths

Timothy Charles Richardson

Akio Hayashi

Magne Solbakken

Henry Raphael Wolfe

Daisaku Nakamura

Duncan George Wynn

Yoshifumi Shirakami

Shigeyuki Tanifuji

Shinya Takasaki

Dagfinn Lovhaug

Koichi Hanaoka

Joseph Maduabuchi Arukwe

Yoshihito Minosako

Nicholas Lasbistes

Julie Davis

Karen Jane Barnes

Sally-Ann Ricketts

Kirsty Heywood

Michael Schafers

Stefan Wagner

Hans-Jörg Breyholz

Sudhakar Kasina

Vinay Chandrakant Desai

Edward R Bacon

Mark Dixon

Koichi Homma

Georg Brauers

The invention relates to a process for preparation of a compound of formula (I): Ris selected from Calkyl, Calkenyl, and Calkynyl;which comprises:(i) reaction with fluoride, suitably [F]fluoride, of a corresponding compound of formula (II): wherein Ris selected from hydrogen, Calkyl, Chaloalkyl, Caryl, Carylalkyl, &#x2014;(CHCHO)&#x2014;CHwherein q is an integer of from 1 to 10;Ris as defined for the compound of formula (I); andRis a leaving group. Certain novel precursors of formula (II) and radiopharmaceutical kits containing such precursors are also claimed.

Fluorination process

The invention relates to a process for preparation of a compound of formula (I): Ris selected from Calkyl, Calkenyl, and Calkynyl; which comprises: (i) reaction with fluoride, suitably [F]fluoride, of a corresponding compound of formula (II): wherein Ris selected from hydrogen, Calkyl, Chaloalkyl, Caryl, Carylalkyl, &#x2014;(CHCHO)&#x2014;CHwherein q is an integer of from 1 to 10; Ris as defined for the compound of formula (I); and Ris a leaving group. Certain novel precursors of formula (II) and radiopharmaceutical kits containing such precursors are also claimed. 

Fluorination process of anilide derivatives and benzothiazole fluorinate derivatives as in vivo imaging agents

A compound that has affinity with amyloid, exhibits sufficiently rapid clearance from normal tissues, and is suppressed in toxicity such as mutagenicity is provided, which is represented by the following formula (1): or a salt thereof,wherein Ris a group selected from hydrogen, hydroxyl group, carboxyl group, sulfate group, amino group, nitro group, cyano group, an alkyl substituent with one to 4 carbon atoms or an alkoxy substituent with one to 4 carbon atoms; Ris a radioactive halogen substituent; and m is an integer of 0 to 2, and a low-toxic diagnostic agent for Alzheimer's disease comprising a compound represented by the above formula or a salt thereof is also provided.

Compound having affinity for amyloid

The present invention relates to the field of diagnostic imaging. Specifically, the invention relates to the diagnostic imaging of diseases where specific matrix metalloproteinases are known to be involved. One embodiment of the invention is a compound having matrix metalloproteinase inhibitory activity suitable for diagnostic imaging. Also disclosed in the present invention is a pharmaceutical composition comprising the diagnostic imaging agent of the invention in a form suitable for mammalian administration. The invention furthermore discloses intermediates in the synthesis of the diagnostic imaging agents of the invention and kits for the preparation of the pharmaceutical composition of the invention. The pharmaceutical composition of the invention may be used in the diagnosis of diseases where specific matrix metalloproteinases are known to be involved.

Diagnostic imaging agents with MMP inhibitory activity

A stabilized radiopharmaceutical composition, a kit including same, and a method for making same, where the radiopharmaceutical is (i) susceptible to either reductive degradation or radiolysis and which includes a metal complex of a radionuclide with a ligand, (ii) a first stabilizer for the radiopharmaceutical which is an amino-substituted aromatic carboxylic acid or a salt, ester or amide thereof, and (iii) a second stabilizer for the radiopharmaceutical which is a diphosphonic acid or salt thereof. The first and second stabilizers are present in an amount effective to stabilize the radiopharmaceutical, and the radiopharmaceutical is not a metal complex of the diphosphonic acid.

Stabiliser for radiopharmaceuticals

The present invention provides tetra-amine chelator conjugates with biological targeting moieties, linked via a linker group and technetium complexes thereof as radiopharmaceuticals. The linker group is such that the chelator is mono-functionalized at the bridgehead position and provides both flexibility and a lack or aryl groups, to minimize lipophilicity and steric hulk. Protected versions of the chelators are provided which permit conjugation with a wide range of targeting molecules without interfering reactions with the amine nitrogens of the tetra-amine chelator. Syntheses of the functionalised chelators are described, together with bifunctional chelate precursors. Radiopharmaceutical compositions comprising the technetium metal complexes of the invention are described, together with non-radioactive kits for the preparation of such radiopharmaceuticals.

N4 chelator conjugates

A peptide-chelate conjugate with affinity for the ST receptor is disclosed, wherein the chelate is tetradentate. The peptide-chelate conjugate of the invention may be labelled with a radiometal to provide a metal complex. A radiopharmaceutical composition comprising the metal complex is provided. which is suitable for the diagnostic imaging of colorectal cancer. Also provided for in the invention is a kit for the preparation of the radiopharmaceutical preparation.

Peptide-chelate conjugates

A contrast agent of formula I: V-L-R (I) where V is an organic group having binding affinity for an angiotensin II receptor site, L is a linear or branched amino acid-comprising biomodifier or linker moiety, and R is a reporter moiety detectable in in vivo imaging of a human or animal body.

Contrast agent

Synthetic analogues of lysine and glutamine are provided which function as substrates for the fibrin-stabilising enzyme Factor XIIIa even when labelled with a detectable moiety. The use of suitable protecting groups provides compounds which possess reduced susceptibility to in vivo metabolism especially by peptidases, and are hence useful agents for the diagnosis of thrombosis, embolism, atherosclerosis, inflammation or cancer.

Labelled glutamine and lysine analogues

A complex of a radiometal or paramagnetic metal ion with a metal chelating agent such as a diaminedioxime has attached thereto a substituent of formula (Y)-A-NHR)can function as a substrate for the fibrin-stabilizing Factor XIIIa. The complex is useful for the diagnosis or therapy of thrombosis, embolism, atherosclerosis, inflammation or cancer.

Labelled factor XIIIa substrates

A complex of a radiometal or paramagnetic metal ion with a metal chelating agent such as a diaminedioxime has attached thereto a substituent of formula &mdash;(Y) &mdash;A&mdash;NHR, can function as a substrate for the fibrin-stabilizing Factor XIIIa. The complex is useful for the diagnosis or therapy of thrombosis, embolism, atherosclerosis, inflammation or cancer.

A human leucocyte elastase (HLE) inhibitor labelled with a detector moiety where the inhibitor is synthetic and has a molecular weight of less than 2000, is useful for the diagnostic imaging of sites of inflammation of infection in vivo, for labelling leucocytes in vitro, or for radiotherapy of rthritis. The HLE inhibitor is preferably a &bgr;-lactam or an azetidinone.

Labelled elastase inhibitors

Ligands for radiopharmaceutical use are capable of chelating radiometal species and of being bound to biological targeting molecules. The ligands have formula (a) and (b), where A, A'=--SZ or Y, B.dbd.O or S, Y.dbd. (c), Z.dbd.H or a thiol protecting group, m=2 or 3, n=2 or 3, q=0 or 1, R.dbd.H or unsubstituted or substituted hydrocarbon and pharmaceutically acceptable salts, provided that at least one CR.sub.2 group represents CO and forms, together with an adjacent N atom, a --CONR-- amide group. ##STR1##

Metal chelating compounds having an SNNN donor set

Ligands for radiopharmaceutical use are capable of chelating radiometal species and of being bound to biological targeting molecules. The ligands have the formula (a) and (b), where A, A'=--SZ or Y, B=O or S, Y=(c), Z=H or a thiol protecting group, m=2 or 3, n=2 or 3, q=0 or 1, R=H or unsubstituted or substituted hydrocarbon and pharmaceutically acceptable salts, provided that at least one CR.sub.2 group represents CO and forms, together with an adjacent N atom; a --CONR-- amide group. ##STR1##

Thioether-containing metal chelating compounds

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Lincs, United Kingdom

Anthony Eamon Storey