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
- Auteurs
- Feige, Jean-Jacques, Castan Agnes, Quelard Delphine, Demeunynck Martine, Constant Jean-François, and Barette Caroline.
- Patent Number
- WO 2012104788 A2
Soumis le 23 mai 2018