Pharmacia Aktiebolag

Pharmacia Diagnostics Ab

Pharmacia Fine Chemicals Ab

Pharmacia Ab

Rolf E Axen

Jan P Carlsson

Hakan N Drevin

Goran E Lindgren

Goran L Kaj

Rune Bjorkman

Sven O Oscarsson

Bror S Rigner

Jan P Carisson

Per H Ponterius

Therapeutically active organic compound exhibiting at least one group comprising a structure --S'--S'--R, wherein the group --S'--R is defined by R being an organic group comprised in a physiologically acceptable compound H--S'--R obtainable by the splitting of the disulfide bridge --S'--S'-- in said structure, in which compound H--S'--R the sulfur atom S' is bound to a carbon atom in a heterocyclic aromatic ring in R having a configuration being such that the compound H--S'--R, while maintaining physiological acceptability, is stabilized, by tautomerism or resonance involving the sulfur atom S' bound to R, so as to be mainly excluded from reaction involving thiol disulfide exchange; S' being bound to an aliphatic carbon atom; and said compound, in addition to the group or groups comprising the structure --S'--S'--R, consisting of a residue of a therapeutically active organic base compound of non-polypeptide structure bound to S'. The invention also relates to a method of modifying a therapeutically active organic compound of non-polypeptide structure by introducing a structure --S'--S'--R according to above; a method of treating diseases by administration of a compound according to the invention and also to a pharmaceutical composition containing at least one compound according to the invention.

Therapeutically active compound and its use

Therapeutically active organic compound exhibiting at least one radical comprising a structure --S'--S'--R, where S'--R is defined by R being an organic group comprised in a physiologically acceptable compound H--S'--R obtainable by the splitting of the disulfide bridge --S'--S'-- in said structure, in which compound H--S'--R the sulfur atom S' is bound to a carbon atom in a heterocyclic aromatic ring in R having a configuration being such that the compound H--S'--R, while maintaining physiological acceptability, is stabilized, by tautomerism or resonance involving the sulfur atom S' bound to R, so as to be mainly excluded from further reaction involving thiol disulfide exchange; S' being bound to an aliphatic carbon atom; and said compound, in addition to the group or groups comprising the structure --S'--S'--R, also consisting of a residue of a therapeutically active organic base compound of polypeptide structure bound to S', for therapeutical use in mammals, including humans. The invention also relates to a pharmaceutical composition containing as an active substance the compound mentioned above.

Therapeutically active compound and pharmaceutical composition

Method and device for biospecific affinity reactions

Method for splitting di-sulphide bonds and a compound obtained thereby

Novel pyridine compounds having the formula R.sup.1 -S-S-A-Z are disclosed, in which formula R.sup.1 is 2-pyridyl, 5-nitro-2-pyridyl or 4-pyridyl, A is a hydrocarbon residue having 1-10 carbon atoms and Z is a group ##STR1## or acid addition salts of the last mentioned group, where n is 2 or 3, R.sup.1 has the same significance as R.sup.1 above and is equal thereto and R.sup.2 is methyl or ethyl. These compounds are particularly useful as bifunctional coupling agents and as thiolating agents.

Pyridine compounds modifying proteins, polypeptides or polysaccharides

In the formation of polymeric layers, especially anisotropic polymeric layers, on a solid substrate on which the layer is formed by cross-linking of an organic substance which can be cross-linked, the cross-linking is performed in a manner such that a concentration gradient of at least one of the components controlling the cross-linking reaction is formed in the boundary layer between the substrate to be coated and the surrounding solution, which concentration gradient is adjusted so that cross-linking can take place in the boundary layer but not in the surrounding solution. The concentration gradient is preferably achieved by impregnating the substrate with at least one of the components which control the cross-linking reaction and which tends to diffuse into the solution on contact therewith.

Method of forming polymeric layers

An improvement in assaying methods involving biospecific affinity reactions, in which there are used from 2 to 4 reactants, one of which, reactant (I), is labelled with at least one analytically indicatable atom or group and is soluble in the aqueous liquid in which the biospecific affinity reaction is carried out, the reactants forming, by means of biospecific reactions, a conjugate in which labelled reactant (I) is incorporated; and in which assaying methods the analytically indicatable atom or group is assayed in the conjugate and/or in labelled reactant (I), which is not bound to the conjugate. The conjugate that has been formed or labelled reactant (I) not bound to the conjugate is bound covalently to an insoluble carrier or to an insolubilizable carrier, which latter carrier is made insoluble after the covalent binding has been carried out, whereafter the assay of the analytically indicatable atom or group is carried out.

Assaying methods involving biospecific affinity reactions

A method of carrying out assaying methods involving biospecific affinity reactions in which there is used a component (I), which is labelled with at least one analytically indicatable group and is soluble in the liquid in whose presence the biospecific affinity reaction is carried out, for reaction with a counterpart (II) which exhibits biospecific affinity to (I) and optionally also one or more additional counterparts exhibiting biospecific affinity to (I) and/or (II), and forming an insoluble conjugate in which the labelled component (I) is incorporated and which conjugate is separated from the liquid phase, whereafter the analytically indicatable group is assayed in the insoluble conjugate, said method being characterized in that the analytically indicatable group is bound to the component (I) with a splittable bond of covalent nature and/or one of said counterparts is bound to a carrier, which is insoluble in said liquid, with a splittable bond of covalent nature, said splittable bonds being splittable under conditions which have practically disturbing influence on the assay method used; and in that the insoluble conjugate is split at said splittable bond or bonds, in the presence of a liquid, to form fragments which are soluble in said liquid and which contain the analytically indicatable group, which group is then assayed in the liquid phase.

Method in assaying methods involving biospecific affinity reactions and

A reagent for use in immunochemical assay methods carried out in the presence of an aqueous liquid, which reagent comprises a conjugate of one or more molecules of immunoglobulin and one or more units of an analytically indicatable group which molecules and units are bound together via bridges containing the group, --S--S--, said conjugate being soluble in said aqueous liquid.

Reagent for use in immunochemical assay methods

A novel class of reactive derivatives of polymers containing HS-groups is disclosed in which derivatives a number of the HS-groups are converted to a disulphide group of the formula -S-S-A-Z, where A is a hydrocarbon residue having 1-10 carbon atoms and Z is a group ##STR1## or acid addition salts of the last mentioned group, where n is 2 or 3, R.sup.1 is 2-pyridyl, 5-nitro-2-pyridyl or 4-pyridyl and R.sup.2 is methyl or ethyl. The novel derivatives may be used, for example, as thiolating agents or as carriers for e.g. enzymes or other proteins etc.

Growing community of inventors

Balinge, Sweden

Rolf E Axen