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1. EP2989110 - TAMOXIFEN DERIVATIVES FOR TREATMENT OF NEOPLASTIC DISEASES, ESPECIALLY WITH HIGH HER2 PROTEIN LEVEL

Office
European Patent Office
Application Number 14721738
Application Date 07.04.2014
Publication Number 2989110
Publication Date 02.03.2016
Publication Kind B1
IPC
C07F 9/54
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
FACYCLIC, CARBOCYCLIC, OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
9Compounds containing elements of Groups 5 or 15 of the Periodic System
02Phosphorus compounds
28with one or more P-C bonds
54Quaternary phosphonium compounds
A61K 31/662
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
31Medicinal preparations containing organic active ingredients
66Phosphorus compounds
662Phosphorus acids or esters thereof having P-C bonds, e.g. foscarnet, trichlorfon
A61P 35/04
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
35Antineoplastic agents
04specific for metastasis
CPC
C07F 9/5442
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
FACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
9Compounds containing elements of Groups 5 or 15 of the Periodic System
02Phosphorus compounds
28with one or more P—C bonds
54Quaternary phosphonium compounds
5442Aromatic phosphonium compounds (P-C aromatic linkage)
C07F 9/5449
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
FACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
9Compounds containing elements of Groups 5 or 15 of the Periodic System
02Phosphorus compounds
28with one or more P—C bonds
54Quaternary phosphonium compounds
5449Polyphosphonium compounds
C09B 23/0008
CCHEMISTRY; METALLURGY
09DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
BORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES ; , e.g. PIGMENTS; MORDANTS; LAKES
23Methine or polymethine dyes, e.g. cyanine dyes
0008substituted on the polymethine chain
C09B 23/141
CCHEMISTRY; METALLURGY
09DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
BORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES ; , e.g. PIGMENTS; MORDANTS; LAKES
23Methine or polymethine dyes, e.g. cyanine dyes
14Styryl dyes
141Bis styryl dyes containing two radicals C6H5-CH=CH-
C09B 69/001
CCHEMISTRY; METALLURGY
09DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
BORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES ; , e.g. PIGMENTS; MORDANTS; LAKES
69Dyes not provided for by a single group of this subclass
001Dyes containing an onium group attached to the dye skeleton via a bridge
C09B 69/008
CCHEMISTRY; METALLURGY
09DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
BORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES ; , e.g. PIGMENTS; MORDANTS; LAKES
69Dyes not provided for by a single group of this subclass
008Dyes containing a substituent, which contains a silicium atom
Applicants SMART BRAIN SRO
BIOTECHNOLOGICKY USTAV AV CR V V I
NEUZIL JIRI
KKCG AG
Inventors NEUZIL JIRÍ
STURSA JAN
WERNER LUKÁS
Designated States
Title
(DE) TAMOXIFENDERIVATE ZUR BEHANDLUNG VON NEOPLASTISCHEN KRANKHEITEN, INSBESONDERE MIT HOHEM HER2-PROTEIN-SPIEGEL
(EN) TAMOXIFEN DERIVATIVES FOR TREATMENT OF NEOPLASTIC DISEASES, ESPECIALLY WITH HIGH HER2 PROTEIN LEVEL
(FR) DÉRIVÉS DE TAMOXIFÈNE DANS LE TRAITEMENT DE MALADIES NÉOPLASIQUES, SPÉCIALEMENT AVEC UNE TENEUR ÉLEVÉE EN PROTÉINE HER2
Abstract
(EN) The subject of the invention are new mitochondrially targeted E/Z isomers of aliphatic triphenylphosphonium derivatives of tamoxifen where the aliphatic chain is alkyl or alkenyl, and their corresponding tertiary amine salts and/or their mixture (MitoTAX). Alkyl triphenylphosphonium derivatives of tamoxifen have the general formula (I), where n=8 to 12 and where Z is selected from the group of organic salts or inorganic salts. Alkenyl triphenylphosphonium derivatives of tamoxifen have the general formula IA, where n = 6 to 10 and where Z has the above mentioned meaning. These compounds are applicable for the treatment of neoplastic disease, especially those with high HER2 protein levels. The drug for the treatment of neoplastic diseases according to the invention contains at least one E/Z isomer of aliphatic triphenylphosphonium derivatives of tamoxifen of the general formula (I) and/or IA or their corresponding salts of tertiary amine.
(FR) La présente invention a pour objet de nouveaux isomères E/Z à ciblage mitochondrial de dérivés de triphénylphosphonium aliphatiques du tamoxifen, où la chaîne aliphatique est une chaîne alkyle ou alcényle, et leurs sels d'amine tertiaire correspondants et/ou leur mélange (MitoTAX). Les dérivés d'alkyltriphénylphosphonium du tamoxifène répondent à la formule générale (I), où n = 8 à 12 et Z est choisi dans le groupe constitué par les sels organiques et inorganiques. Les dérivés d'alcényltriphénylphosphonium du tamoxifène répondent à la formule générale IA, où n = 6 à 10 et Z prend la valeur susmentionnée. Ces composés sont applicables au traitement d'une maladie néoplasique, spécialement de celles qui présentent des teneurs élevées en protéine HER2. Le médicament destiné au traitement de maladies néoplasiques selon l'invention contient au moins un isomère E/Z de dérivés de triphénylphosphonium aliphatiques du tamoxifène de formule générale (I) et/ou IA ou de leurs sels correspondants d'amine tertiaire.
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