Abstract: Insulin-like Growth Factor II (IGF-II) analogues in which at least one of R37 and R38 is replaced with another amino add residue, the most preferred being IGF-II R37Q R38Q, can readily be produced in E. coli, unlike natural IGF-II, which is cleaved on secretion. The analogues retain activity on the type I and type II IGF receptors but have lower affinity for the insulin receptor; they are therefore more specific in their action.

Abstract: Compounds of general formula (I), wherein W represents a 5- or 6-membered aromatic heterocyclic ring containing one or more non-quaternised sp2 nitrogen atoms in its ring, which heterocyclic ring may be optionally fused to a benzene ring or to a further 5- or 6-membered aromatic heterocyclic ring containing one or more nitrogen atoms, wherein at least one of the said heterocyclic rings may also contain an oxygen or sulphur atom, and wherein any of the rings may be optionally substituted with one or more substituents selected from --C.sub.1 -C.sub.6 alkyl, --OC.sub.1 -C.sub.6 alkyl, halo, --CF.sub.3 and --CN; Z represents a) a divalent alkanediyl group from 1 to 8 carbon atoms which may be a straight or branched-chain, wherein the said group is either unsubstituted or substituted by one or more substituents selected from hydroxy, --OC.sub.1 -C.sub.6 alkyl, --SC.sub.1 -C.sub.

Abstract: Compounds of general formula I: ##STR1## wherein: R.sup.1 represents a C.sub.1 -C.sub.6 alkyl, phenyl, thiophenyl, substituted phenyl, phenyl(C.sub.1 -C.sub.6)alkyl, heterocyclyl, (C.sub.1 -C.sub.6)alkylcarbonyl phenacyl or substituted phenacyl group; or, when n=O, R.sup.1 represents SR.sup.x, wherein R.sup.x represents a group: ##STR2## R.sup.2 represents a hydrogen atom or a C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkenyl, phenyl(C.sub.1 -C.sub.6)alkyl, cycloalkyl(C.sub.1 -C.sub.6)alkyl or cycloalkenyl(C.sub.1 -C.sub.6)alkyl group;R.sup.3 represents an amino acid residue with R or S stereochemistry or a C.sub.1 -C.sub.6 alkyl, benzyl, (C.sub.1 -C.sub.6 alkoxy)benzyl or benzyloxy(C.sub.1 -C.sub.6 alkyl) group;R.sup.4 represents a hydrogen atom or a C.sub.1 -C.sub.6 alkyl group;R.sup.5 represents a hydrogen atom or a methyl group;n is an integer having the value 0, 1 or 2; andA represents a C.sub.1 -C.sub.6 hydrocarbon chain, optionaly substituted with one or more C.sub.1 -C.sub.

Abstract: Hydroxamic acid derivatives of formula (I): ##STR1## wherein R.sup.1 represents hydrogen or an (C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.6)alkoxycarbonyl(C.sub.1 -C.sub.6)alkyl, phenyl, substituted phenyl, phenyl(C.sub.1 -C.sub.6)alkyl, heterocyclyl, (C.sub.1 -C.sub.6)alkylcarbonyl, phenacyl or substituted phenacyl group;R.sup.2 represents hydrogen or a (C.sub.1 -C.sub.6)alkyl, (C.sub.2 -C.sub.6)alkenyl, phenyl(C.sub.1 -C.sub.6)alkyl, cycloalkyl(C.sub.1 -C.sub.6)alkyl or cycloalkenyl(C.sub.1 -C.sub.6)alkyl group,R.sup.3 represents a group --CH.sub.2 CO.sub.2 (C.sub.1 -C.sub.4)alkyl or --CH.sub.2 CH.sub.2 CO.sub.2 (C.sub.1 -C.sub.4)alkyl;R.sup.4 represents hydrogen or a (C.sub.1 -C.sub.6)alkyl or phenyl(C.sub.1 -C.sub.6)alkyl group;R.sup.5 represents hydrogen or a methyl group;n is 0, 1 or 2;and A represents a (C.sub.1 -C.sub.6)hydrocarbon chain optionally substituted with one or more (C.sub.1 -C.sub.

Abstract: Relatively inactive fusion proteins are activatable by enzymes of the clotting cascade to have fibrinolytic and/or clot formation inhibition activity. For example, a fusion protein comprising two hirudin or streptokinase molecules, linked by a cleavable linkage sequence, may be cleaved to yield anti-thrombotic hirudin or fibrinolytic streptokinase by thrombin or Factor Xa. Fibrinolytic or clot formation inhibition activity is therefore directed to the site of clot formation. Cleavable streptokinase/hirudin heterodimers are claimed.

Abstract: Compounds of general formula I: ##STR1## Wherein: R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, and R.sup.6 are variables. These compounds have collagenase inhibition activity and are useful in the management of disease involving collagen degradation. Its uses include rheumatoide arthritis, corneal ulceration, osteoporosis, periodontitis, gingivitis and tumor invasion.

Abstract: Compounds of general formula I: ##STR1## wherein: each of R.sup.1 -R.sup.8, k, and V represent disclosed functional groups that have been chosen such that all disclosed variations of compound I and their pharmaceutically and veterinarily acceptable acid addition salts and hydrates are antagonists of platelet activating factor (PAF) and as such are useful in the treatment or amelioration of various diseases or disorders mediated by PAF.

Abstract: Compounds of general formula I: ##STR1## wherein: R.sup.1 represents a C.sub.1 -C.sub.6 alkyl, phenyl, thiophenyl, substituted phenyl, phenyl(C.sub.1 -C.sub.6)alkyl, heterocyclyl, (C.sub.1 -C.sub.6)alkylcarbonyl phenacyl or substituted phenacyl group; or, when n=O, R.sup.1 represents SR.sup.x, wherein R.sup.x represents a group: ##STR2## R.sup.2 represents a hydrogen atom or a C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkenyl, phenyl(C.sub.1 -C.sub.6)alkyl, cycloalkyl(C.sub.1 -C.sub.6)alkyl or cycloalkenyl(C.sub.1 -C.sub.6)alkyl group;R.sup.3 represents an amino acid residue with R or S stereochemistry or a C.sub.1 -C.sub.6 alkyl, benzyl, (C.sub.1 -C.sub.6 alkoxy)benzyl or benzyloxy(C.sub.1 -C.sub.6 alkyl) group;R.sup.4 represents a hydrogen atom or a C.sub.1 -C.sub.6 alkyl group;R.sup.5 represents a hydrogen atom or a methyl group;n is an integer having the value 0, 1 or 2; andA represents a C.sub.1 -C.sub.6 hydrocarbon chain, optionaly substituted with one or more C.sub.1 -C.sub.

Abstract: Compounds of either of general formulae (I) and (II), wherein: R.sup.1 represents a C.sub.1-8 alkyl, C.sub.3-8 cycloalkyl, C.sub.3-8 cycloalkyl(C.sub.1-8)alkyl, C.sub.2-8 alkenyl, or C.sub.1-6 alkyl substituted phenyl group; R.sup.2 represents a C.sub.1-8 alkyl, C.sub.2-8 alkenyl, C.sub.2-8 alkynyl group or a C.sub.1-5 alkyl, C.sub.2-5 alkenyl or C.sub.2-5 alkynyl group substituted with a substituted phenyl group; R.sup.3 represents a hydrogen atom or a substituent R.sup.4 or M; R.sup.4 represents a C.sub.1-5 alkyl group, or C.sub.1-5 alkyl group substituted with a group chosen from substituted phenyl, dimethylamino and acetylamino; R.sup.5 represents a hydrogen atom or a methyl or ethyl group except that when R.sup.2 is methyl then R.sup.5 is not methyl; M represents a cation capable of forming a pharmaceutically acceptable salt; Q represents C.dbd.

Abstract: Compounds of general formula I: ##STR1## wherein: R.sup.1 represents a hydrogen atom or a C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkenyl, phenyl, phenyl(C.sub.1 -C.sub.6)alkyl, C.sub.1 -C.sub.6 alkylthiomethyl, phenylthiomethyl, substituted phenylthiomethyl, phenyl(C.sub.1 -C.sub.6)alkylthiomethyl or heterocyclylthiomethyl group; or R.sup.1 represents --SR.sup.x wherein R.sup.x represents a group ##STR2## R.sup.2 represents a hydrogen atom or a C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkenyl, phenyl(C.sub.1 -C.sub.6)alkyl, cycloalkyl(C.sub.1 -C.sub.6)alkyl, or cycloalkenyl(C.sub.1 -C.sub.6)alkyl;R.sup.3 represents an amino acid residue with R or S stereochemistry or a C.sub.1 -C.sub.6 alkyl, benzyl, (C.sub.1 -C.sub.6)alkoxybenzyl or benzyloxy(C.sub.1 -C.sub.6)alkyl group;R.sup.4 represents a hydrogen atom or a methyl group;n is an integer from 1 to 6; andA represents the group --NH.sub.

Abstract: Compounds of general formula I; ##STR1## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, and R.sup.7 are variables.These compounds are antagonists of platelet activating factor (PAF) and as such are useful in the treatment or amelioration of various diseases or disorders mediated by PAF.

Abstract: Compounds of general formula I: ##STR1## Wherein: R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, and R.sup.6 are variables.These compounds have collagenase inhibition activity and are useful in the management of disease involving collagen degradation. Its uses include rheumatoide arthritis, corneal ulceration, osteoporosis, periodontitis, gingivitis and tumour invasion.

Abstract: Compounds of general formula I; ##STR1## wherein: A.sup.1 is .dbd.N--, .dbd.CH-- or .dbd.CR.sup.1 --;A.sup.2 is .dbd.N--, .dbd.CH-- or .dbd.CR.sup.2 --;provided that, when one of A.sup.1 and A.sup.2 is a nitrogen atom, the other of A.sup.1 and A.sup.2 is other than a nitrogen atom; wherein the rest of the variables are defined in the specification;and their pharmaceutically and veterinarily acceptable acid addition salts and hydrates are antagonists of platelet activating factor (PAF) and as such are useful in the treatment or amelioration of various diseases or disorders mediated by PAF.

Abstract: Compounds of general formula I; ##STR1## wherein: A.sup.1 is .dbd.N--, .dbd.CH-- or .dbd.CR.sup.1 --;A.sup.2 is --N.dbd., --CH.dbd. or --CR.sup.2 .dbd.;provided that, when one of A.sup.1 and A.sup.2 is a nitrogen atom, the other of A.sup.1 and A.sup.2 is other than a nitrogen atom; wherein the rest of the variables are defined in the specification; and their pharmaceutically and veterinarily acceptable acid addition salts and hydrates are antagonists of platelet activating factor (PAF) and as such are useful in the treatment of amelioration of various diseases or disorders mediated by PAF.

Abstract: compounds of formula I ##STR1## wherein R.sup.1 represents a C.sub.1-8 alkyl, C.sub.2-8 alkenyl, C.sub.2-8 alkynyl, C.sub.3-8 cycloalkyl(C.sub.1-8)alkyl, C.sub.1-8 hydroxyalkyl, C.sub.1-8 alkylthio, phenyl or substituted phenyl;R.sup.3 represents a C.sub.1-8 alkyl, C.sub.2-8 alkenyl, C.sub.2-8 alkynyl, CO2(C.sub.1-8)alkyl, CO.sub.2 (C.sub.2-8) alkenyl, C.sub.1-8 alkylthio, (C.sub.1-2)alkyl CO.sub.2 (C.sub.1-8) alkyl or C.sub.1-8 aldehydroalkyl where the aldehyde function is protected by a suitable protecting group (for example, an acetal such as a dimethyl acetal);R.sup.4 represents a hydrogen atom, C.sub.1-8 alkyl or C.sub.2-8 alkenyl;Z represents a group (CH.sub.2).sub.n or a branched alkyl chain;n is 1 to 8;and each of a, b and c is independently a single or a double bond;can be prepared relatively easily and in good xxx at room temperature by reacting a compound of general formula II ##STR2## wherein R.sup.2, R.sup.3, R.sup.

Abstract: Compounds of general formula I: ##STR1## wherein: R.sup.1 represents a C.sub.1 -C.sub.6 alkyl, phenyl, thiophenyl, substituted phenyl, phenyl(C.sub.1 -C.sub.6)alkyl, heterocyclyl, (C.sub.1 -C.sub.6)alkylcarbonyl phenacyl or substituted phenacyl group; or, when n=O, R.sup.1 represents SR.sup.x, wherein R.sup.x represents a group: ##STR2## R.sup.2 represents a hydrogen atom or a C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkenyl, phenyl (C.sub.1 -C.sub.6) alkyl, cycloalkyl(C.sub.1 -C.sub.6)alkyl or cycloalkenyl(C.sub.1 -C.sub.6)alkyl group;R.sup.3 represents an amino acid residue with R or S stereochemistry or a C.sub.1 -C.sub.6 alkyl, benzyl, (C.sub.1 -C.sub.6 alkoxy)benzyl or benzyloxy(C.sub.1 -C.sub.6 alkyl) group;R.sup.4 represents a hydrogen atom or a C.sub.1 -C.sub.6 alkyl group;R.sup.5 represents a hydrogen atom or a methyl group;n is an integer having the value 0, 1 or 2; andA represents a C.sub.1 -C.sub.6 hydrocarbon chain, optionaly substituted with one or more C.sub.1 -C.sub.

Abstract: Tissue plasminogen activator (t-PA) analogues have at least one substitution in the growth factor (GF) domain that at least partially reduces hepatic receptor binding without substantially jeopardising physico-chemical stability in blood or fibrinolytic activity. This results in a longer plasma half life. Substitutions in the beta-sheet encompassing residues 63-72, especially at Leu 66 and/or Tyr 67 and/or Phe 68, are particularly preferred.

Abstract: Compounds of either of general formulae I and II: ##STR1## wherein: R.sup.1, R.sup.2, R.sup.3, R.sup.5, R.sup.6, a, b, c, and d are variables.These compounds are useful in the treatment of hypercholesterolaemia in general and arteriosclerosis, familial hypercholesterolaemia or hyperlipidaemia in particular.

Abstract: Compounds of general formula I; ##STR1## wherein: A.sup.1 is .dbd.N--, .dbd.CH-- or .dbd.CR.sup.1 --;A.sup.2 is --N.dbd., --CH.dbd. or --CR.sup.2 .dbd.;provided that, when one of A.sup.1 and A.sup.2 is a nitrogen atom, the other of A.sup.1 and A.sup.2 is other than a nitrogen atom;the rest of the variables are described in the specification;and their pharmaceutically and veterinarily acceptable acid addition salts and hydrates are antagonists of platelet activating factor (PAF) and as such are useful in the treatment or amelioration of various diseases or disorders mediated by PAF.

Abstract: Synthetic DNA coding for horseradish peroxidase includes the following sequence: ##STR1## and incorporates useful restriction sites at frequent intervals to facilitate the cassette mutagenesis of selected regions. Also included are flanking restriction sites to simplify the incorporation of the gene into any desired expression system.