Preparation of 1,4-disubstituted piperazines, 1-naphthylsulfonamide and 1,8-naphthalimide derivatives as antiangiogenic agents, their pharmaceutical compositions containing them, and their use for treating particularly cancers.

The invention is related to the prepn. of title compds., e.g., tert-Bu [3-[4-[3-[[[5-(dimethylamino)naphthalen-1-yl]sulfonyl]amino]propyl]piperazin-1-yl]propyl]carbamate (I), having antiangiogenic and/or antitumor activity, to pharmaceutical compns. contg. them, and to their use in the treatment and/or prevention of angiogenesis-dependent diseases such as cancer, macular degeneration, diabetic retinopathy, psoriasis and rheumatoid arthritis. Thus, reaction of dansyl chloride with [3-[4-[3-[(tert-butoxycarbonyl)amino]propyl]piperazin-1-yl]propyl]ami ne in DCM for 15 h at room temp. gave I. I inhibited the migration of HMEC-1 cells with an EC50 of 5 $μ$M while its EC50 was 25 $μ$M on wound closure in 3T3 cells in a screening of antiangiogenic mols. from a library. The effect of I in a series of in vitro angiogenesis tests and on tumor formation in vivo was studied. I inhibited the phosphorylation of MAP kinases induced by FGF-2 and to a lesser extent by the VEGF-A. [on SciFinder(R)]

Références

Titre
Preparation of 1,4-disubstituted piperazines, 1-naphthylsulfonamide and 1,8-naphthalimide derivatives as antiangiogenic agents, their pharmaceutical compositions containing them, and their use for treating particularly cancers.
Type de publication
Brevet
Année de publication
2012
Patent Number
WO 2012104788 A2
Soumis le 23 mai 2018