Abstract: Compounds of general formula (1) are described: wherein ═W— is (1) ═C(Y)— where Y is a halogen atom, or an alkyl or —XRa group where X is —O—, —S(O)m— [where m is zero or an integer of value 1 or 2], or —N(Rb)— [where Rb is a hydrogen atom or an optionally substituted alkyl group] and Ra is a hydrogen atom or an optionally substituted alkyl group or, (2) ═N—; L is (1) a —C(R)═C(R1)(R2) or [—CH(R)]nCH(R1)(R2) group; is (2) a —(Xa)nAlk′Ar′, or Alk′XaAr′ group; or is (3) XaR1; Z is a group (A), (B), (C) or (D):  wherein Ar is a monocyclic or bicyclic aryl group optionally containing one or more heteroatoms selected from oxygen, sulphur or nitrogen atoms; Z1is a group —NR12C(O)— [where R12 is a hydrogen atom or an optionally substituted alkyl or (Alk)tAr group], —C(O)NR12—, —NR12

Abstract: Compounds of general formula (1) are described: wherein R1 is a hydrogen or halogen atom or an optionally substituted straight or branched chain alkyl, alkenyl or alkynyl group or a group selected from hydroxyl (—OH), substituted hydroxyl, thiol (—SH), substituted thiol, amino (—NH2), or substituted amino; R2 and R3, which may be the same or different, is each an optionally substituted straight or branched chain alkyl, alkenyl or alkynyl group; R4 is a hydrogen atom or a straight or branched chain alkyl group; R5 is a hydrogen atom or an optionally substituted straight or branched chain alkyl, alkenyl or alkynyl group; R6 is a hydrogen or halogen atom or an amino (—NH2), substituted amino, nitro, carboxyl (—CO2H) or esterified carboxyl group or a group —X1—R6a where X1 is a direct bond or a linker atom or group and R6a is an optionally substituted straight or branched chain alkyl, alkenyl or alkynyl group; X is a direct bond or a linker atom or

Abstract: This invention relates to whole antibodies of neutral isotype having specificity for E-selectin, process for their preparation (using vectors), pharmaceutical compositions containing them, and their use in therapy and diagnosis. Said antibodies are variants of natural antibodies altered in the Fc region, especially in the CH2 domain, so that the interactions with antibodies Fc receptors and complement are very low.

Abstract: Phenylalanine derivatives of formula (1) are described: in which L1 is a linker atom or group; A is a chain —[C(R7)(R8)]pY[C(R9)(R10)]q— in which Y is a sulphur atom or a —S(O)— or —S(O)2— group, R7, R8, R9 and R10, which may be the same or different, is each a hydrogen atom or a straight or branched alkyl or optionally substituted aromatic group, or R7 and R8 together with the carbon atom to which they are attached, or R9 and R10 together with the carbon atom to which they are attached, each forms a C3-7cycloalkyl group, and p and q, which may be the same or different, is each zero or an integer 1 or 2, provided that when one of p or q is zero the other is an integer 1 or 2; L2 is a linker group selected from —C(O)—, —C(O)O—, —C(S)—, —S(O)2—, —CON(R11)—, [where R11 is a hydrogen atom or a straight or branched alkyl group], —CSN(R11)—, —SON(R11)&m

Abstract: Compounds of the general formula (1) wherein: ═W— is ═N—; Y is halogen or an alkyl or —XRa group; X is —O—, —S(O)m— or —N(Ra)—, where m is zero or an integer 1 or 2; Ra is hydrogen or an optionally substituted alkyl group; R2 is an optionally substituted cycloalkyl or cycloalkenyl group; R3 is R13 or —L1R13, where R13 is a halogen atom, an optionally substituted straight or branched chain C2-6alkenyl group or an optionally substituted C6-12 monocyclic or bicyclic aryl group and L1 is an optionally substituted straight or branched chain C1-6alkylene, C2-6alkenylene or C2-6alkynylene group; R4 is a hydrogen atom or a group —(CH2)nAr where Ar is an optionally substituted monocyclic aryl group and n is zero or an integer 1, 2 or 3; R5 is hydrogen; R6 is an optionally substituted 2-, 3- or 4-pyridyl group; and each of R7 and R8 is independently hydrogen or an optionally substituted straight or branched alkyl group.

Abstract: The invention describes humanized antibodies having specificity for the epitope recognised by the murine monoclonal antibody L243. Also described are processes for preparing said antibodies and pharmaceutical compositions and medical uses of said antibodies.

Abstract: Fused polycyclic 2-aminopyrimidines of formula (1) are described: whereinR.sup.1 is a group --L.sup.1 R.sup.2 where L.sup.1 is a covalent bond or a linker atom or group and R.sup.2 is a group --(Alk).sub.m L.sup.2 R.sup.3 where Alk is an optionally substituted aliphatic or heteroaliphatic chain, m is zero or the integer 1, L.sup.2 is a covalent bond or a linker atom or group and R.sup.3 is an optionally substituted cycloaliphatic or heterocycloaliphatic group provided that when m is zeroL.sup.2 is a covalent bond;Ar is an aryl or heteroaryl group;X is a carbon or nitrogen atom;Y is a carbon or nitrogen atom;Z is a linker group;A together with X and Y forms an optionally substituted monocyclic or bicyclic aromatic or heteroaromatic group;and the salts, solvates, hydrates and N-oxides thereof.

Abstract: Aromatic amines of formula (1) are described: ##STR1## wherein Az is an optionally substituted monocyclic six-membered nitrogen-containing aromatic group;L.sup.1 is a linker atom or group;R is a carboxylic acid or a derivative thereof;and R.sup.5 is a group --L.sup.2 (CH.sub.2).sub.t R.sup.6 in which L.sup.2 is a --N(R.sup.7)CO-- or --N(R.sup.7)CS-- group.The compounds are able to inhibit the binding of .alpha..sub.4 integrins to their ligands and are of use in the prophylaxis and treatment of immune or inflammatory disorders.

Abstract: Compounds of general formula (1): ##STR1## are described wherein Het is an optionally substituted heteroaromatic group; R.sup.1 is a hydrogen atom or a straight or branched chain alkyl group; R.sup.2 is a hydrogen or halogen atom or a group --X.sup.1 --R.sup.2a where X.sup.1 is a direct bond or a linker atom or group, and R.sup.2a is an optionally substituted straight or branched chain alkyl, alkenyl or alkynyl group; R.sup.3 is an optionally substituted aromatic or heteroaromatic group; and the salts, solvates, hydrates and N-oxides thereof. The compounds are selective protein kinase inhibitors, particularly the kinases p56.sup.lck, ZAP-70 and protein kinase C and are of use in the prophylaxis and treatment of immune diseases, hyperproliferative disorders and other diseases in which inappropriate protein kinase action is believed to have a role.

Abstract: Tyrosine derivatives of formula (1) are described: ##STR1## in which R is (1) a group R.sup.1 X.sup.1 -- where R.sup.1 is an optionally substituted alkyl or aromatic group, and X.sup.1 is a covalent bond or a --(CH.sub.2).sub.n -- [where n is an integer 1 or 2], --C(O)--, --CH.sub.2 C(O)--, --NHC(O)--, --CH.sub.2 NHC(O)--, or --SO.sub.2 -- group, or (2) a group (Hal.sup.1).sub.3 CSO.sub.2 --, where Hal.sup.1 is a fluorine or chlorine atom;R.sup.2 and R.sup.3, which may be the same or different, is each a hydrogen or halogen atom or an alkyl, alkoxy, hydroxyl or nitro group;Alk is an alkylene chain;m is zero or an integer 1;R.sup.4 is a hydrogen atom or a methyl group;R.sup.5 is a group --(CH.sub.2).sub.p CO.sub.2 R.sup.8 where p is zero or an integer 1 and R.sup.8 is a hydrogen atom or an alkyl group;R.sup.6 is a hydrogen atom or an alkyl group;Y is a sulphur atom or a --S(O).sub.q -- group where q is an integer 1 or 2;X.sup.2 is a --C(O)--, --C(O)O--, --CONH-- or --S(O).sub.2 -- group;R.sup.

Abstract: Compounds of formula (1) ##STR1## are described wherein Y represents a halogen atom or a group --OR.sup.1, where R.sup.1 is an optionally substituted alkyl group; R.sup.2 represents an optionally substituted cycloalkyl or cycloalkenyl group; R.sup.3 is a monocyclic or bicyclic aryl group optionally containing one or more heteroatoms selected from oxygen or sulphur atoms or a group --N(R.sup.4)-- where R.sup.4 is a hydrogen atom or an alkyl group; X is --O--, --S--, or --N(R.sup.5)--, where R.sup.5 is a hydrogen or an alkyl group; with the proviso that when X is --O-- then R.sup.3 is not a 3-cyanamino-6-pyridazinyl or a 3-chloro-6-pyridazinyl group; and the salts, solvates, hydrates and N-oxides thereof.The compounds are selective and potent inhibitors of phosphodiesterase IV and are useful for the prophylaxis and treatment of inflammatory diseases and the alleviation of conditions associated with central nervous malfunction.

Abstract: Tri-substituted phenyl derivatives and processes for their preparation. In a preferred embodiment, the compounds have the general formula (1) ##STR1## wherein L may be --OR; Z may be --C(R.sup.3)(R.sup.4)--C(R.sup.5)(R.sup.6)(R.sup.7); R may be an optionally substituted cycloalkyl group; R.sup.3, R.sup.6 and R.sup.7 may be hydrogen; R.sup.4 may be --(CH.sub.2).sub.t --Ar--(L.sup.1).sub.n --Ar'; R.sup.5 may be --(CH.sub.2).sub.t Ar; Ar may be a monocyclic or bicyclic aryl or heteroaryl group; L.sup.1 may be a divalent linking group; and Ar' is Ar or an Ar containing group. Compounds of the invention may be potent and selective phosphodiesterase type IV inhibitors and are useful in the prophylaxis and treatment of various diseases, such as asthma, which are associated with an unwanted inflammatory response or muscular spasm.

Abstract: Fused polycyclic 2-aminopyrimidines of formula (1): ##STR1## wherein Ar is an optionally substituted aromatic or heteroaromatic group;X is a carbon or nitrogen atom;Y is a carbon or nitrogen atom;Z is a linker group;A together with X and Y forms an optionally substituted monocyclic or bicyclic aromatic or heteroaromatic group;and the salts, solvates, hydrates and N-oxides thereof are described. The compounds are potent and selective inhibitors of the protein tyrosine kinases p56.sup.lck and p59.sup.fyn and are of use in the prophylaxis and treatment of immune diseases, hyperproliferative disorders and other diseases in which inappropriate p56.sup.lck and/or p59.sup.fyn activity is believed to have a role.

Abstract: Compounds of formula (1) are described: ##STR1## and the salts, solvates, hydrates and N-oxides thereof, in which R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6 and R.sup.7 have the meanings given in claim 1. The compounds are selective inhibitors of protein kinases, especially src-family protein kinases and are of use in the prophylaxis and treatment of immune diseases, hyperproliferative disorders and other diseases in which inappropriate protein kinase action is believed to have a role.

Abstract: This invention provides a DNA sequence coding for a cleavage site which is specifically cleaved by blood coagulation Factor Xa, a vector containing such a sequence, and a host organism transformed with such a vector. Preferably, in the vector, the Factor Xa cleavage site coding sequence is fused at one end to a product and at its other end to an ATG codon or a sequence coding for at least part of a host protein.This invention also provides a process, for the production of a desired protein or peptide product in native form, comprising:transforming a host organism with a vector as described above;expressing the desired protein or peptide product as a fusion protein comprising the desired protein or peptide product fused to a Factor Xa cleavage site; anda cleaving the fusion protein with Factor Xa to yield the foreign gene product in native form.

Abstract: An effective anti-IL-5 recombinant antibody molecule comprising heavy and/or light chain antigen-binding residues from a donor antibody.

Abstract: Recombinant, in particular humanised, e.g. humanised chimeric and CDR-grafted humanised, antibody molecules having specificity for human TNF.alpha., are provided for use in diagnosis and therapy. In particular, the antibody molecules have antigen binding sites derived from murine monoclonal antibodies CB0006, CB0010, hTNF3 or 101.4. Preferred CDR-grafted humanised anti-hTNF.alpha. antibodies comprise variable region domains comprising human acceptor framework and donor antigen binding regions and wherein the frameworks comprise donor residues at specific positions. The antibody molecules may be used for therapeutic treatment of human patients suffering from or at risk of disorders associated with undesirably high levels of TNF, in particular for treatment of immunoregulatory and inflammatory disorders or of septic, endotoxic or cardiovascular shock.

Abstract: A human metalloproteinase is described together with nucleic acids coding therefor and corresponding antisense DNA and RNA. The metalloproteinase may be used to generate antibodies therefor and to obtain compounds capable of regulating the action of the metalloproteinase in vivo.

Abstract: Compounds of general formula (1) ##STR1## are described wherein Y is a halogen atom or a group --OR.sup.1, where R.sup.1 is an optionally substituted alkyl group; X is --O--, --S-- or --N(R.sup.7)--, where R.sup.7 is a hydrogen atom or an alkyl group; R.sup.2 is an optionally substituted cycloalkyl or cycloalkenyl group; R.sup.3 and R.sup.4, which may be the same or different, is each a hydrogen atom or an alkyl, --CO.sub.2 R.sup.8 (where R.sup.8 is a hydrogen atom or an alkyl, aryl, or aralkyl group), --CONR.sup.9 R.sup.10 (where R.sup.9 and R.sup.10 which may be the same or different is each a hydrogen atom or an alkyl, aryl or aralkyl group), --CSNR.sup.9 R.sup.10, --CN, --CH.sub.2 CN group; Z is --(CH.sub.2).sub.n -- (where n is zero or an integer 1, 2 or 3; R.sup.5 is an optionally substituted monocyclic or bicyclic aryl group optionally containing one or more heteroatoms selected from oxygen, sulphur or nitrogen atoms; R.sup.