Imperial Chemical Industries Limited

Schering Corporation

Zeneca Limited

Ici Pharma

David Huw Davies

Alan K Mallams

Francis Thomas Boyle

Geoffrey L Norris

Peter R Marsham

James Michael Wardleworth

David Charles Blakey

Colin J Strawson

Frederick H Jung

Jean C Arnould

Dominique Boucherot

Anthony Michael Slater

John Frederick Hennam

Zbigniew Stanely Matusiak

Peter Wedderburn Kenny

David G Acton

Peter Beverley Scholes

Jeffrey P Poyser

Laurent Francois Andre Hennequin

Michael J Smithers

Robert I Dowell

David William Heaton

Laurent Francois Hennequin

Brian Robert Rabin

Antonio Tarragona-Fiol

Hendrikus Johannes Eggelte

Christopher John Taylorson

Richard W Tkach

Richard J Ernill

Pharmaceutical compositions comprising an inhibitor of ras farnesylation of formula (I) wherein, R is for example H and further values as defined in the specification; R is for example H and further values as defined in the specification; R is for example H or a substituent having values as defined in the specification; p is 0-3 in which R values can be the same or different; L is a linking moiety for example &mdash;CO&mdash;NH &mdash; and further values as defined in the specification; A is selected from phenyl; naphthyl; a 5-10 membered monocyclic or bicyclic heteroaryl ring containing up to 5 heteroatoms where the heteroatoms are independently selected from O, N and S; or a &mdash;S&mdash;S-dimer thereof when R &equals;H; or an enantiomer, diastereoisomer, pharmaceutically acceptable salt, prodrug or solvate thereof together with a pharmaceutically acceptable diluent or carrier. A particular use is cancer therapy.

4-mercaptopyrrolidine derivatives as farnesyl transferase inhibitors

Antibody Directed Enzyme Prodrug Therapy (ADEPT) systems for use in cancer based on mutated carboxypeptidase B (CPB) enzymes. Enzyme conjugates for ADEPT are substantially non-immunogenic in humans comprising a targeting moiety (for example an antibody) capable of binding with a tumor associated antigen, the targeting moiety being linked to a mutated form of a CPB enzyme capable of converting a prodrug into an antineoplastic drug wherein the prodrug is not significantly convertible into antineoplastic drug in humans by natural unmutated enzyme. A preferred enzyme mutant is human pancreatic CPB comprising a Lys or Arg residue at position 253. Suitable mustard prodrugs are disclosed in the specification.

Chemical compounds

Pharmaceutical compositions comprising an inhibitor of ras farnesylation of formula (I) wherein, R,is for example H and further values as defined in the specification; R,is for example H and further values as defined in the specification; R,is for example H or a substituent having values as defined in the specification; p is 0-3 in which R,values can be the same or different; L is a linking moiety for example &mdash;CO&mdash;NH,&mdash; and further values as defined in the specification; A is selected from phenyl; naphthyl; a 5-10 membered monocyclic or bicyclic heteroaryl ring containing up to 5 heteroatoms where the heteroatoms are independently selected from O, N and S; or a &mdash;S&mdash;S&mdash; dimer thereof when R,&equals;H; or an enantiomer, diastereoisomer, pharmaceutically acceptable salt, prodrug or solvate thereof together with a pharmaceutically acceptable diluent or carrier. A particular use is cancer therapy.

4-Mercaptopyrrolidine derivatives as farnesyl transferase inhibitors

Cephalosporin derivatives having a 3-position substituent of formula I are described: ##STR1## wherein R.sup.1 is hydrogen, alkenyl or optionally substituted alkyl, Het is a 5- or 6-membered heterocyclic ring bonded via a carbon atom to the amide linkage, wherein Het is selected from a group of the formulae II-III: ##STR2## wherein A is CH or a nitrogen atom; B is oxygen, sulphur or a group NR.sup.4 ; one or two of D, E, F and G are nitrogen atoms and the remainder are CH groups: or Het is a pyrazinone, pyridinone, pyridazinone or pyrimidinone ring, or is a thione equivalent of such a ring, said rings having a substituent R.sup.4 on one nitrogen atom, or is pyranone, or pyranthione; the ring Het being fused by any two adjacent carbon atoms to the benzene ring; and Het being attached to the --CH.sub.2 NR.sup.1 CO-- group via a carbon atom;

Cephalosporin derivatives

Cephalosporin antibiotics having a 3-position substituent of the formula: ##STR1## are described; wherein R.sup.1 is hydrogen or certain substituted alkyl groups, Z is CH or N, R.sup.2 and R.sup.3 are hydroxy or in vivo hydrolysable esters thereof, (R.sup.12).sub.n represents various optional substituents and X=Y is an olefin, oxime, azo or related group. Processes for their preparation and use are described.

Intermediates for cephalosporin compounds

Cephalosporin compounds

Cephalosporin derivatives having a 3-position substituent of the formula I are described: ##STR1## wherein R.sup.1 is hydrogen, alkenyl or optionally substituted alkyl, Het us a 5- or 6-membered heterocyclic ring bonded via a carbon atom to the amide linkage, wherein Het is selected from a group of the formulae II-III: ##STR2## wherein A is CH or a nitrogen atom; B is oxygen, sulphur or a group NR.sup.4 ; one or two of D, E, F and G are nitrogen atoms and the remainder are CH groups: or Het is a pyrazinone, pyridinone, pyridazinone or pyrimidinone ring, or is a thione equivalent of such a ring, said rings having a substituent R.sup.4 on one nitrogen atom, or is pyranone, or pyranthione; the ring Het being fused by any adjacent carbon atoms to the benzene ring; and Het being attached to the --CH.sub.2 NR.sup.1 CO-- group via a carbon atom;

Novel ether, ester, urethane, thiourethane and carbonate derivatives of the ruminant growth promoters, M.139,603, M.139,603-adlehyde and oxime etc. derivatives thereof, all of which are effective in reducing the proportion of methane produced by ruminal fermentation, and increasing the proportion of propionic acid at the expense of acetic acid in the rumen contents; together with processes for their manufacture, compositions containing them, and their use in increasing growth and/or feed efficiency in ruminant animals.

Derivatives of M.139,603 useful as growth promoters

The invention relates to a novel metabolite, M.139603, of the empirical formula C.sub.35 H.sub.53 O.sub.8 Na, which is obtained from the aerobic fermentation of a novel Streptomyces species, NCIB 11426, and to the corresponding free acid form thereof, C.sub.35 H.sub.54 O.sub.8. M.139,603 reduces the proportion of methane produced by the 'digestion' of food in the rumen of ruminant animals and increases the proportion of propionate to acetate in the rumen contents. The compound is therefore useful for increasing the growth rate of ruminant animals, and/or for increasing their efficiency of food conversion. The compound also possesses activity against Gram positive micro-organisms, and against coccidia, for example Eimeria tenella.

Streptomyces metabolite

This invention relates to the use of aplasmomycin, boromycin and acylated and hydrogenated derivatives thereof for modifying rumen metabolism in domestic ruminant animals, by reducing the proportion of methane formed, and increasing the proportion of propionate at the expense of methane and/or acetate. This modification of rumen metabolism is believed to improve growth in ruminant animals. The disclosure also describes compositions which may be used in the claimed method, an improved process for the production of aplasmomycin, and novel analogs of aplasmomycin and boromycin together with processes for their manufacture.

Growth promotion

Novel 1-N-aminoalkyl (oxycarbonyl or carboxamido or thiocarboxamido) derivatives of 4,6-di-O-(aminoglycosyl)-1,3-diaminocyclitols, useful as antibacterial agents, are described.

1-N-substituted derivatives of

The disclosure relates to a method for use in the practice of animal husbandry which comprises the oral administration to meat producing animals a compound of the aureolic acid group. Solid and liquid compositions for use in the method are also disclosed, together with a novel process for the manufacture of mixed mithramycins, and an improved process for their purification.

Veterinary method employing certain aureolic acid compounds

This invention relates to the preparation of novel 1-epi-aminoglycosides, useful as antibacterial agents, and also relates to the process for the preparation of known as well as novel 1-N-substituted aminoglycoside antibacterial agents.

Process for preparing 4,6-di-O-(aminoglycosyl)-1,3-diaminocyclitols and

This invention relates to the preparation of novel 1-desamino-1-oxo-aminoglycosides and their use as intermediates in the preparation of novel 1-desamino-1-hydroxy and 1-desamino-1-epi-hydroxyaminoglycoside antibacterial agents.

Growing community of inventors

Macclesfield, United Kingdom

David Huw Davies