Abstract: The compound (W-Z-M) according to the invention comprises a component (M) chosen from the group consisting of markers and therapeutic agents possessing an intracellular active site (A.S.), linked to a ligand (W-Z) comprising an arm (Z) linked to a terminal group (W), characterized in that the linkage between the arm (Z) of the ligand (W-Z) and the component (M) prevents intracellular entry of the compound (W-Z-M) and/or inhibits expression of the marker (M), in that said linkage can be selectively cleaved by factors secreted by target cells so as to permit expression of the marker (M) or entry of the therapeutic agent (M) into said target cells, and in that the terminal group (W) provides for the stability of the compound (W-Z-M) in the serum and circulating blood.

Abstract: The compound (W-Z-M) according to the invention comprises a component (M) chosen from the group consisting of markers and therapeutic agents possessing an intracellular active site (A.S.), linked to a ligand (W-Z) comprising an arm (Z) linked to a terminal group (W), characterized in that the linkage between the arm (Z) of the ligand (W-Z) and the component (M) prevents intracellular entry of the compound (W-Z-M) and/or inhibits expression of the marker (M), in that said linkage can be selectively cleaved by factors secreted by target cells so as to permit expression of the marker (M) or entry of the therapeutic agent (M) into said target cells, and in that the terminal group (W) provides for the stability of the compound (W-Z-M) in the serum and circulating blood.

Abstract: The product of the invention is a modified form of a therapeutic agent and comprises a therapeutic agent, an oligopeptide having a plasmin peptide substrate of 2-4 amino acids and mono- or di-peptide linkage, a stabilizing group and, optionally, a linker group. The prodrug is cleavable by plasmin. Also disclosed are methods of making and using the prodrug compounds.

Abstract: Compounds are disclosed with the general formula A-B, which in the vicinity of tumor cells result in a positively charged moiety B and an uncharged or negatively charged moiety A. Moiety B is able to induce blood clotting by interacting with negatively charged heparin-like substances lining vascular endothelia and the positive charge is reversibly masked by the uncharged or negatively charged moiety A in order to prevent unspecific disseminated blood coagulation and toxicity. Moiety B is either a covalent assembly of positively charged chemical groups or a positively charged molecule, which in aqueous solutions forms non-covalent polycations due to its propensity to form intermolecular aggregates. Pharmaceutical compositions including the compound and a pharmaceutically acceptable adjuvant or excipient are also disclosed. The disclosed compounds are useful in medicine, in particular for the manufacture of a medicament and its use for the treatment of a subject.

Abstract: The invention is directed to novel prodrug compounds, compositions comprising the prodrug compounds, methods of making the prodrug compounds and methods of using the prodrug compounds. The prodrug compounds comprise a biologically active entity linked to a masking moiety via a linking moiety. The prodrug compounds are selectively activated at or near target cells and display lower toxicity and possibly a longer in vivo or serum half-life than the corresponding naked biologically active entity.

Abstract: The prodrug of the invention is a modified form of a therapeutic agent and comprises a therapeutic agent, an oligopeptide of three amino acids, a stabilizing group and, optionally, a linker group. The prodrug is cleavable by a trouase enzyme such as Thimet oligopeptidase. Also disclosed are methods of making and using the prodrug compounds.

Abstract: The compound (W—Z—M) according to the invention comprises a component (M) chosen from the group consisting of markers and therapeutic agents possessing an intracellular active site (A.S.), linked to a ligand (W—Z) comprising an arm (Z) linked to a terminal group (W), characterized in that the linkage between the arm (Z) of the ligand (W—Z) and the component (M) prevents intracellular entry of the compound (W—Z—M) and/or inhibits expression of the marker (M), in that said linkage can be selectively cleaved by factors secreted by target cells so as to permit expression of the marker (M) or entry of the therapeutic agent (M) into said target cells, and in that the terminal group (W) provides for the stability of the compound (W—Z—M) in the serum and circulating blood.

Abstract: The prodrug of the invention is a modified form of a therapeutic agent and comprises a therapeutic agent, an oligopeptide, a stabilizing group and, optionally, a linker group. The prodrug is cleavable by the enzyme Thimet oligopeptidase, or TOP. Also disclosed are methods of designing prodrugs by utilizing TOP-cleavable sequences within the conjugate and methods of treating patients with prodrugs of the invention.

Abstract: A pharmaceutical, cosmetic, and/or food composition containing a pyrazine derivative useful for preparing a medicament for preventing and/or treating pathologies related to the activity of oxygen promoters or for treating cancer tumors. The pathologies which can be treated include inflammatory diseases, carcinogenic diseases, atherosclerosis, or cancerous tumors. The pyrazine may be coelenteramine or its derivatives.

Abstract: The compound (W-Z-M) according to the invention comprises a component (M) chosen from the group consisting of markers and therapeutic agents possessing an intracellular active site (A.S.), linked to a ligand (W-Z) comprising an arm (Z) linked to a terminal group (W), characterized in that the linkage between the arm (Z) of the ligand (W-Z) and the component (M) prevents intracellular entry of the compound (W-Z-M) and/or inhibits expression of the marker (M), in that said linkage can be selectively cleaved by factors secreted by target cells so as to permit expression of the marker (M) or entry of the therapeutic agent (M) into said target cells, and in that the terminal group (W) provides for the stability of the compound (W-Z-M) in the serum and circulating blood.

Abstract: The compound (W-Z-M) according to the invention comprises a component (M) chosen from the group consisting of markers and therapeutic agents possessing an intracellular active site (A.S.), linked to a ligand (W-Z) comprising an arm (z) linked to a terminal group (W), characterized in that the linkage in the arm (Z) of the ligand (W-Z) and the component (M) prevents intracellular entry of the compound (W-Z-M) and/or inhibits expression of the marker (M), in that said linkage can be selectively cleaved by factors secreted by target cells so as to permit expression of the marker (M) or entry of the therapeutic agent (M) into said target cells, and in that the terminal group (W) provides for the stability of the compound (W-Z-M) in the serum and the circulating blood.

Abstract: The invention relates to new quinoline derivatives containing a free amine group and having antimalarial properties, in particular new primaquine derivatives or their addition salts with acids, and to a method for preparing them.According to the invention, these new derivatives are represented schematically by the formula:PQ-Xin which PQ denotes quinolines containing a free amine group and having antimalarial properties, in particular primaquine; X denotes an amino acid or a peptide of 2 to 4 amino acids; and the PQ-X bond being a covalent peptide bond between the free amine group of PQ and the carboxyl group of X, the PQ-X covalent bond being stable in serum and resistant to lysosomal hydrolases.In an embodiment of the invention, the amino acid or the first amino acid of a peptide linked to PQ is gamma-L-glutamic acid or beta-aspartic acid linked to PQ via their beta- or gamma-carboxyl group, or L-pyroglutamic acid or aspartic acid linked to PQ via their alpha-carboxyl group.

Abstract: The present invention relates to a process for preparing lipid microparticles of microcrystalline appearance, of a water-insoluble substance possessing an affinity for phospholipids and of at least one phospholipid, the microparticles being stable in suspension in an aqueous solution, characterized in that:a) the said substance and the said phospholipid or phospholipids are dissolved in a common organic solvent for the said substance and for the said phospholipid or phospholipids,b) the solution of said substance and of the said phospholipid or phospholipids is mixed with an aqueous solution in an amount such that an insolubilization takes place in the form of a precipitate, andc) the organic solution is removed to recover an aqueous solution containing the microparticles in the form of microsuspensions.

Abstract: The subject of the present invention is conjugates of vinca (indole-dihydroindole) derivatives carrying a detergent chain of at least 7 aliphatic carbon atoms in the C-3 position bonded via a covalent bond to a macromolecular carrier of polypeptide character, and also pharmaceutical compositions containing these conjugates and a process of preparation.

Abstract: The invention relates to vinca (indole-dihydroindole) alkaloid derivatives, in which a fatty chain containing at least 7 aliphatic carbon atoms is present at least at the C.sup.3 /C.sup.4 -position.The derivatives according to the present invention are useful as drugs.

Abstract: A complex of deoxyribonucleic acids (DNA) with an ester derived from daunorubicine of the formula ##STR1## in which R.sub.1 represents a radical of the formula ##STR2## in which each X represents oxygen or sulfur and each R.sub.3 represents alkyl, phenyl or both R.sub.3 form together with one another an alkylene group, R.sub.4 is hydrogen, alkyl or phenyl and R.sub.2 is hydrogen or trifluoracetyl.Said complexes are usable for treating cancerous tumors.