Abstract: The present invention relates to compounds of formula I: in which R1, R2, R3 and R4 are as defined in the Summary of the Invention. Compounds of formula I are capable of disrupting the BCL-2 interations with proteins containing a BH3 domain. Disrupting this interaction can restore the anti-apoptotic function of BCL-2 in cancer cells and tumor tissue expressing BCL-2. The invention further provides a process for the preparation of compounds of the invention, pharmaceutical preparations comprising such compounds and methods of using such compounds in the treatment of cancerous diseases.

Abstract: The present invention provides a compound consisting essentially of the following elements: one or more reactive groups; and two or more cross-linked antibodies or fragments thereof; characterised in that the or each reactive group is suitable for attaching an effector molecule but does not react with any of the antibodies or fragments thereof.

Abstract: The present invention provides an albumin-binding compound essentially of the following elements: a spacer group, a water-soluble bridging group, a fatty acid chain and an acidic group characterised in that the acidic group is attached to the distal end of the fatty acid chain. The invention also provides an albumin-binding compound to which one or more biologically active moieties are attached.

Abstract: Compounds of formula (1) are described: in which X is an —O— or —S— atom or —N(R2)— group and R1 is a group Ar1L2Ar2Alk- in which Ar1 is an optionally substituted aromatic or heteroaromatic group, L2 is a covalent bond or a linker atom or group, Ar2 is an optionally substituted bicyclic heteroarylene group and Alk is a chain —CH2—CH(R)—, —CH?C(R)—, OR—CH(CH2R)— in which R is a carboxylic acid (—CO2H) or a derivative or biostere thereof. The compounds are selective inhibitors of alpha 4 integrins such as ?4?1 and are of use in modulating cell adhesion for the prophylaxis or treatment of inflammatory diseases or disorders, such as rheumatoid arthritis, in which the extravasculation of leukocytes plays a role.

Abstract: The present invention provides a compound consisting essentially of the following elements: one or more reactive groups; and two or more cross-linked antibodies or fragments thereof; characterised in that the or each reactive group is suitable for attaching an effector molecule but does not react with any of the antibodies or fragments thereof.

Abstract: Alkanoic acid derivatives of formula (1) are described: Ar1(Alka)rL1Ar2CH(R1)C(Ra)(Ra?)R??(1) Ar1 is an optionally substituted aromatic or heteroarotic group; L1 is a covalent bond or a linker atom or group; Ar2 is an optionally substituted phenylene or nitrogen-containing six-membered heteroarylene group; R is a carboxylic acid (—CO2H) or a derivative thereof; and the salts, solvates, hydrates and N-oxides thereof. The compounds are able to inhibit the binding of ?4 integrins to their ligands and are of use in the prophylaxis and treatment of immune or inflammatory disorders.

Abstract: Phenylalanine derivatives of formula (1) are described: wherein L1 is a linker atom or group; X1 is a group selected from —N(R3)CO—, —N(R3)SO2—, —N(R3)C(O)O— or —N(R3)CON(R3a)—; and R is a carboxylic acid or a derivative thereof. The compounds are able to inhibit the binding of a 4 integrins to their ligands and are of use in the prophylaxis and treatment of diseases or disorders involving inflammation.

Abstract: Compounds of formula (1) are described: in which X is an —O— or —S— atom or —N(R2)— group and R1 is a group Ar1L2Ar2Alk- in which Ar1 is an optionally substituted aromatic or heteroaromatic group, L2 is a covalent bond or a linker atom or group, Ar2 is an optionally substituted bicyclic heteroarylene group and Alk is a chain —CH2—CH(R)—, —CH═C(R)—, OR—CH(CH2R)— or which R is a carboxylic acid (—CO2H) or a derivative or biostere thereof. The compounds are selective inhibitors of alpha 4 integrins such as &agr;4&bgr;1 and are of use in modulating cell adhesion for the prophylaxis or treatment of inflammatory diseases or disorders, such as rheumatoid arthritis, in which the extravasculation of leukocytes plays a role.

Abstract: Enamine derivatives of formula (1) are described: wherein R1 is a group Ar1L2Ar2Alk- in, which Ar1 is an aromatic or heteroaromatic group, L2 is a covalent bond or a linker atom or group, Ar2 is an arylene or heteroarylene group and Alk is a chain —CH2—CH(R)—, —CH═C(R)— or in which R is a carboxylic acid or a derivative or biostere thereof; R2 is a hydrogen atom or a C1-6alkyl group; Cy is a cycloaliphatic or heterocycloaliphatic ring in which X is a N atom or a C(Rw) group; Rx is a oxo, thioxo, or imino group; Rw and Rz is each a hydrogen atom or optional substituent; provided that Cy is not a cyclobutenedione group; and the salts, solvates, hydrates and N-oxides thereof. The compounds are able to inhibit the binding of integrins to their ligands and are of use in the prophylaxis and treatment of immune or inflammatory disorders, or disorders involving the inappropriate growth or migration of cells.

Abstract: Squaric acid derivatives of formula (1) are described: wherein Het is an optionally substituted bicyclic fused ring heteroaromatic group; L2 is a covalent bond or an atom or group —O—, —S—, —C(O)—, —C(S)—, —S(O)—, —S(O)2, —N(R8)— or —C(R8)(R8a)—; Ar2 is an optionally substituted aromatic or heteroaromatic group; Alk is a chain  in which R is a carboxylic acid (—CO2H) or a derivative or biostere thereof; R1 is a hydrogen atom or a C1-6alkyl group; L1 is a covalent bond or a linker atom or group; Alk1 is an optionally substituted aliphatic chain; n is zero or the integer 1; R2 is a hydrogen atom or an optionally substituted heteroaliphatic, cycloaliphatic, heterocycloaliphatic, polycycloalphatic, heteropolycycloaliphatic, aromatic or heteroaromatic group other than a 2,6-naphthyridin-1-yl, isoquinolin-1-yl, 2,7-naphthyridin-1-yl or quinazolin-4-yl group; and the salt

Abstract: Phenylalanine derivatives of formula (1) are described: in which: Ar1 is an aromatic or heteroaromatic group; L1 is a linker atom or group; R is a carboxylic acid or a derivative thereof; Ar2 is an optionally substituted aromatic or heteroaromatic group; and the salts, solvates, hydrates and N-oxides thereof. The compounds are able to inhibit the binding of &agr;4 integrins to their ligands and are of use in the prophylaxis and treatment of immune or inflammatory disorders.

Abstract: Enamine derivatives of formula (1) are described: 1

Abstract: Phenylalanine derivatives of formula (1) are described: 1

Abstract: Squaric acid Derivatives of formula (1) are described: 1

Abstract: Enamine derivatives of formula (1) are described: wherein R1 is a group Ar1 L2Ar2Alk- in which Ar1 is an aromatic or heteroaromatic group, L2 is a covalent bond or a linker atom or group, Ar2 is an arylene or heteroarylene group and Alk is a chain —CH2—CH(R)—, —CH═C(R)— or in which R is a carboxylic acid or a derivative or biostere thereof; R2 is a hydrogen atom or a C1-6alkyl group; Cy is a cycloaliphatic or heterocycloaliphatic ring in which X is a N atom or a C(Rw) group; Rx is a oxo, thioxo, or imino group; Rw and Rz is each a hydrogen atom or optional substituent; provided that Cy is not a cyclobutenedione group; and the salts, solvates, hydrates and N-oxides thereof. The compounds are able to inhibit the binding of integrins to their ligands and are of use in the prophylaxis and treatment of immune or inflammatory disorders, or disorders involving the inappropriate growth or migration of cells.

Abstract: Enamide derivatives of formula (1) are described: wherein R1 is a group Ar1L2Ar2Alk- in which Ar1 is an optionally substituted aromatic or heteroaromatic group, L2 is a covalent bond or a linker atom or group, Ar2 is an optionally substituted arylene or heteroarylene group and Alk is a chain —CH2—CH(R)—, —CH═C(R)— or  in which R is a carboxylic acid (—CO2H) or a derivative or biostere thereof; R2 is a hydrogen atom or a C1-6alkyl group; X is an O or S atom or the group NR30 group; j and k is each zero or the integer 1 or 2 provided that the sum of j and k is zero or the integer 1 or 2; Cy1 is an optionally substituted cycloaliphatic, heterocycloaliphatic, aromatic or heteroaromatic group; and the salts, solvates, hydrates and N-oxides thereof.

Abstract: 3-Substituted 2,7-naphthyridine derivatives of formula (1) are described: wherein L1 and L1 is each a covalent bond or a linker atom or group; Alk1 is an optionally substituted aliphatic chain; R2 is a hydrogen atom or an optionally substituted heteroaliphatic, cycloaliphatic, heterocycloaliphatic, polycycloaliphatic, heteropolycycloaliphatic, aromatic or heteroaromatic group; Alk is a chain in which R is a carboxylic acid (—CO2H) or a derivative or biostere thereof; Ar2 is an optionally substituted aromatic or heteroaromatic linking group; R16 is the group —L3(Alk2)tL4R20 in which L3 and L4 which may be the same or different is each a covalent bond or a linker atom or group, t is zero or the integer 1, Alk2 is an optionally substituted aliphatic or heteroaliphatic chain and R20 is an optionally substituted aromatic or heteroaromatic group; and the salts, solvates, hydrates and N-oxides thereof.

Abstract: Compounds of formula (1): 1

Abstract: Phenylalanine derivatives of formula (1) are described: wherein R is a carboxylic acid or a derivative thereof; L1 is a linker atom or group; Ar is an optionally substituted aromatic group; and the salts, solvates, hydrates and N-oxides thereof. The compounds are able to inhibit the binding of alpha4 integrins to their ligands and are of use in the prophylaxis and treatment of immune or inflammatory disorders.

Abstract: 2,7-Naphthyridine containing squaric acids of formula (1) are described: wherein Ar1 is an optionally substituted 2,7-naphthridin-1-yl group; L2 is a covalent bond or a linker atom or group; Ar2 is an optionally substituted aromatic or heteroaromatic chain; Alk is a chain —CH2CH(R)—, —CH═C(R)—,  in which R is a carboxylic acid (—CO2H) or a derivative or biostere thereof; R1 is a hydrogen atom or a C1-6alkyl group; L1 is a covalent bond or a linker atom or group; Alk1 is an optionally substituted aliphatic chain; n is zero or the integer 1; R2 is a hydrogen atom or an optionally substituted heteroaliphatic, cycloaliphatic, heterocycloaliphatic, polycycloalphatic, heteropoly-cycloaliphatic, aromatic or heteroaromatic group; and the salts, solvates, hydrates and N-oxides thereof.