4-amino-2-pyrido-bicyclic pyrimidines and use thereof as topoisomerase ii inhibitors
AssigneesFondazione Istituto Italiano Di Tecnologia, Alma Mater Studiorum - Università di Bologna, Universita' Degli Studi Di Padova
InventorsMarco DE VIVO, Jose Antonio ORTEGA MARTINEZ, Jose Manuel ARENCIBIA JIMENEZ, Anna MINARINI, Claudia SISSI
Life of this patent
Estimating the term…
Abstract
The present invention concerns 4-amino-2-pyrido-bicyclic pyrimidines as type II topoisomerase inhibitors and use thereof as medicaments especially in the treatment of cancer. The invention also provides a method for the manufacture of 4-amino-2-pyrido bicyclic pyrimidines.
Claims20
A compound of formula (I)
- an enantiomer, or a pharmaceutically acceptable salt thereof,
- wherein
- R═H, halogen, C1-6 alkyl, C1-6 alkoxy, OH, CF3, NR″R′″;
- R′ H, C1-6 alkyl,
- X is H, C1-6 alkyl, C1-6 alkoxy, NR″R′″, C1-6 alkylalkoxy, C1-C6 alkylamide;
- R″R′″ are, independently, H, C1-6 alkyl, C1-6 alkylalkoxy or may form a 4 to 7-membered heterocyclic ring together with the nitrogen atom to which they are connected,
- for use in treating cancer.
A compound of Formula (Ia)
- wherein R═H, C1-6 alkyl, C1-6 alkoxy, OH, NR″R′″ and
- R′═H, C1-6 alkyl;
- R″R′″ are, independently, H, C1-6 alkyl, C1-C6 alkylalkoxy or may form a 4 to 7-membered heterocyclic ring together with the nitrogen atom to which they are connected.
A compound of Formula (Ib)
- wherein R═H, Cl, C1-6 alkyl, OH, CF3, NR″R′″,
- R′═H, C1-6 alkyl;
- X═H, C1-6 alkyl, C1-6 alkoxy, NR″R′″, C1-6 alkylalkoxy, C1-C6 alkylamide.
A method for the manufacture of a compound of formula E3 comprising the steps C to E according to the following reaction scheme
- wherein
- step A comprises the addition of urea
- step B comprises the addition of PCl5 in POCl3
- step C comprises the addition of 3-fluoroaniline, diisopropylethylamine
- step D comprises the addition of PdCl2(dppf) dichloromethane complex and K2CO3 aqueous solution in 1,4-dioxane
- step E comprises the addition of ammonium formate (4 mmol), Pd(OH)2—C.
Dependencies are inferred from the claim text.