Pledpharma Ab

Rolf Andersson

Tino Kurz

Jan-Olof G Karlsson

Michael Hall

Karl Reineke

Sven Jacobsson

Jacques Näsström

Christina McLaughlin

Jan Olof G Karlsson

Jan Olof Karlsson

Jan-Olof Karlsson

A pharmaceutical composition for treatment of a pathological condition in a patient comprises, as a first component, a manganese complex of Formula I( ), and, as a second component, a non-manganese complex compound of Formula (I), optionally together with one or more physiologically acceptable carriers and/or excipients, wherein X, R, R, R, and R are as defined herein. Methods for treatment of a pathological condition in a patient, for example, a pathological condition caused by the presence of oxygen-derived free radicals, comprises administering to said patient the first component and the second component. 

Pharmaceutical compositions and therapeutic methods employing a combination of a manganese complex compound and a non-manganese complex form of the compound

Methods for treatment of a pathological condition caused by oxidative stress in a patient comprise administering to the patient a mixed metal complex of a compound of Formula I, or a salt thereof, in an amount effective to reduce the oxidative stress. Pharmaceutical compositions are formed by suspending or dissolving a mixed metal complex of a compound of Formula I, or a salt thereof, in a liquid medium, optionally with one or more physiologically acceptable excipients. The mixed metals comprise calcium and manganese in a molar ratio of calcium to manganese in the range of 1-10: wherein X, R, R, R, and Rare as defined herein.

Calmangafodipir, a new chemical entity, and other mixed metal complexes, methods of preparation, compositions, and methods of treatment

Methods for treatment of a pathological condition caused by oxidative stress in a patient comprise administering to the patient a mixed metal complex of a compound of Formula I, or a salt thereof, in an amount effective to reduce the oxidative stress. The mixed metals comprise calcium and manganese in a molar ratio of calcium to manganese in the range of 1-10: wherein X, R, R, R, and Rare as defined herein.

A mixed metal complex of a compound of Formula I, or a salt thereof, wherein the mixed metals comprise a Group III-XII transition metal and a Group II metal: wherein X, R, R, R, and Rare as defined herein, is produced in a one step crystallization from a solution of the Group III-XII transition metal, the Group II metal, and a compound of Formula I. Methods for treatment of a pathological condition in a patient, for example, a pathological condition caused by the presence of oxygen-derived free radicals, comprise administering the mixed metal complex to the patient.

Pharmaceutical compositions comprise a first compound of Formula I or a physiologically acceptable salt thereof, and a cyto-protective amount of a manganese chelate of N,N'-dipyridoxyl ethylenediamine-N,N&#x2032;-diacetic acid (MnPLED): wherein R, R, R, Rand X are defined in the specification.

Compounds for use in the treatment of cancer

Compound of Formula I or a salt thereof for treating cancer, wherein X represents CH or N; Rrepresents hydrogen or &#x2014;CHCOR; Rrepresents hydroxy, optionally hydroxylated alkoxy, amino or alkylamido; Rrepresents ZYR; Z represents a bond, or a Calkylene or oxoalkylene group optionally substituted by R; Y represents a bond, an oxygen atom or NR; Ris a hydrogen atom, COOR, an alkyl, alkenyl, cycloalkyl, aryl or aralkyl group optionally substituted by one or more selected from COOR, CONR, NR, OR, &#x2550;NR, &#x2550;O, OP(O)(OR)Rand OSOM; Ris hydroxy, an optionally hydroxylated, optionally alkoxylated alkyl or aminoalkyl group; Ris a hydrogen atom or an optionally hydroxylated, optionally alkoxylated alkyl group; M is a hydrogen atom or one equivalent of a physiologically tolerable cation; Rrepresents Calkylene, 1,2-cykloalkylene, or 1,2-arylene, optionally substituted with R; and Rrepresents hydrogen or Calkyl. 

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Vikingstad, Sweden

Rolf Andersson