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US 8,138,194 B2Granted
Fused bicyclic pyrimidine compounds as aurora kinase inhibitors
AssigneeNational Health Research Institutes
InventorsHsing-Pang Hsieh, Selvaraj Mohane Coumar, Tsu-An Hsu, Su-Ying Wu, Yu-Sheng Chao
Life of this patent
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Abstract
Fused bicyclic pyrimidine compounds of formula (I): wherein R1, R3, R4, X1, X2, Y, Z, A, B, C, D, n, and the two bonds are defined herein. Also disclosed are a method for inhibiting Aurora kinase activity and a method for treating cancer with these compounds.
Claims34
A compound of formula (I):
- wherein
- one of the two bonds is a single bond and the other is a double bond;
- X1 is NRa and X2 is CR2, in which Ra is H, alkyl, alkenyl, alkynyl, aryl, or heteroaryl;
- each of Y and Z, independently, is O, S, or NRb, in which Rb is H, alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, cyano, or NO2;
- each of R1 and R2, independently, is H, alkyl, alkenyl, alkynyl, aryl, heteroaryl, halo, C(O)ORc, or C(O)NRcRd, in which each of Rc and Rd, independently, is H, alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl;
- each of R3 and R4, independently, is H, halo, nitro, cyano, amino, hydroxy, alkoxy, aryloxy, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, aryl, or heteroaryl;
- A is arylene or heteroarylene;
- B is O, S, or NRe, in which Re is H, alkyl, alkenyl, or alkynyl;
- C is O, S, alkylene, or NRf, in which Rf is H, alkyl, alkenyl, or alkynyl;
- or B and C, together with the carbon atom to which they are bonded, are heterocycloalkyl or heterocycloalkenyl;
- D is H, alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl;
- or C and D together are heterocycloalkyl, heterocycloalkenyl, aryl or heteroaryl;
- and
- n is 1, 2, 3, or 4.
11 more elements
A compound of formula (I):
- wherein
- one of the two bonds is a single bond and the other is a double bond;
- X1 is S and X2 is CR2, or X1 is CR2 and X2 is S;
- each of Y and Z, independently, is O, S, or NRb, in which Rb is H, alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, or cyano;
- R1 and R2, together with the carbon atoms to which they are bonded, are cycloalkenyl, heterocycloalkenyl, aryl, or heteroaryl;
- each of R3 and R4, independently, is H, halo, nitro, cyano, amino, hydroxy, alkoxy, aryloxy, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, aryl, or heteroaryl;
- A is arylene or heteroarylene;
- B is O, S or NRe, in which Re is H, alkyl, alkenyl, or alkynyl;
- C is O, S, alkylene, or NRf, in which Rf is H, alkyl, alkenyl, or alkynyl;
- or B and C, together with the carbon atom to which they are bonded, are heterocycloalkyl or heterocycloalkenyl;
- D is H, alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl;
- or C and D together are heterocycloalkyl, heterocycloalkenyl, aryl, or heteroaryl;
- and
- n is 1, 2, 3, or 4.
11 more elements
A compound of formula (I):
- wherein
- one of the two bonds is a single bond and the other is a double bond;
- X1 is O or NH and X2 is CR2;
- Y is O, S, or NRb, in which Rb is H, alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, cyano, or NO2;
- Z is O;
- R1 is phenyl optionally substituted with hydroxyl or alkoxy, or heteroaryl;
- R2 is H, alkyl, alkenyl, alkynyl, aryl, heteroaryl, halo, C(O)ORc, or C(O)NRcRd, in which each of Rc and Rd, independently, is H, alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl;
- each of R3 and R4, independently, is H, halo, nitro, cyano, amino, hydroxy, alkoxy, aryloxy, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, aryl, or heteroaryl;
- A is arylene or heteroarylene;
- each of B and C is NH;
- D is H, alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl;
- or C and D together are heterocycloalkyl, heterocycloalkenyl, aryl or heteroaryl;
- and
- n is 1, 2, 3, or 4.
11 more elements
Dependencies are inferred from the claim text.