Porphyrins and metalloporphyrins for inhibiting heme iron...

C - Chemistry – Metallurgy – 07 – D

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C07D 487/22 (2006.01) A61K 31/555 (2006.01) A61P 3/00 (2006.01) A61P 7/00 (2006.01)

Patent

CA 2528090

The present invention provides a class of porphyrins and metal chelated porphyrins for use as inhibitors of heme iron uptake. The porphyrin/metal chelated porphyrin molecules of the invention are tetra-positively charged porphyrins based on meso-tetra (4-pyridyl) porphines. Several such agents are shown herein to cause inhibition of iron uptake in vivo and in vitro. The invention further provides therapeutic compositions including the porphyrins and/or metalloporphyrins of the invention. In addition, methods of inhibition of heme iron uptake in vivo are taught, as well as methods of treatment of diseases characterized by iron-overload. These methods include the administration of a porphyrin or metalloporphyrin in a therapeutic composition of the invention to prevent uptake of heme iron, thus preventing replenishment of a patient's iron stores.

L'invention concerne une classe de porphyrines et de métalloporphyrines à chélation métallique destinées à être utilisées comme inhibiteurs de l'absorption de fer hémique. Les molécules des porphyrines et des métalloporphyrines à chélation métallique selon l'invention sont des porphyrines à charge tétra-positive à base de méso-tétra(4-pyridyl)porphines. Plusieurs agents de ce type décrits dans le présent descriptif causent l'inhibition de l'absorption de fer in vivo et in vitro. L'invention concerne également des compositions thérapeutiques qui contiennent les porphyrines et les métalloporphyrines à chélation métallique selon l'invention. L'invention concerne en outre des méthodes permettant d'inhiber l'absorption de fer hémique in vivo ainsi que des méthodes permettant de traiter des maladies caractérisées par une surcharge de fer. Ces méthodes consistent à administrer une porphyrine ou une métalloporphyrine dans une composition thérapeutique selon l'invention afin de prévenir l'absorption de fer hémique et, ainsi, de prévenir le réapprovisionnement des stocks de fer d'un patient.

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