C - Chemistry – Metallurgy – 07 – C
Patent
C - Chemistry, Metallurgy
07
C
C07C 49/683 (2006.01) A61K 31/122 (2006.01) A61K 31/19 (2006.01) A61P 35/00 (2006.01) C07C 49/697 (2006.01) C07C 49/747 (2006.01) C07D 213/50 (2006.01) C07F 9/38 (2006.01)
Patent
CA 2309617
A new family of inadone and tetralone tubulin-binding compounds (TBs) is disclosed. Unlike classical TBs, which inhibit mitosis among affected dividing cells, the TBs of the invention possess two unique properties: (1) they induce apoptosis among stationary phase (non-dividing) malignant cells, yet do not impair the viability of normal nonproliferating cells; and (2) they affect cells which have acquired MDR more powerfully than they affect cells without MDR. Thus, the TBs of the invention provide means to target malignant cells for chemotherapy, even after previous therapies have failed, without affecting normal cells and tissues in the host.
L'invention concerne une nouvelle famille de composés à base d'inadone et de tétralone liant la tubuline qui, contrairement aux composés classiques de ce type inhibant la mitose parmi les cellules en voie de division affectées, possèdent les deux caractéristiques uniques suivantes : (1) ils induisent l'apoptose dans les cellules malignes en phase stationnaire (qui ne sont pas en voie de division), mais sans nuire à la viabilité des cellules normales non proliférantes; et (2) ils affectent les cellules ayant acquis la multirésistance médicamenteuse, en agissant plus puissamment que sur les cellules dépourvues de cette résistance. Ainsi, les composés considérés donnent la possibilité de cibler les cellules malignes en chimiothérapie, même après l'échec de thérapies antérieures, sans affecter les cellules et les tissus normaux chez le sujet.
Carson Dennis A.
Cottam Howard B.
Leoni Lorenzo
Shih Hsien C.
Smart & Biggar
The Regents Of The University Of California
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