发明名称 Heteroalkyl linked pyrimidine derivatives
摘要 The present invention relates to pyrimidine compounds that are useful as anti-proliferative agents. More particularly, the present invention relates to heteroalkyl linked and substituted pyrimidine compounds, methods for their preparation, pharmaceutical compositions containing these compounds and uses of these compounds in the treatment of proliferative disorders. These compounds may be useful as medicaments for the treatment of a number of proliferative disorders including tumors and cancers as well as other conditions or disorders associated with kinases.
申请公布号 US9133214(B2) 申请公布日期 2015.09.15
申请号 US201213371837 申请日期 2012.02.13
申请人 S*BIO Pte Ltd 发明人 Blanchard Stéphanie;Ethirajulu Kantharaj;Lee Cheng Hsia Angeline;Nagaraj Harish Kumar Mysore;Poulsen Anders;Sun Eric T.;Tan Yee Ling Evelyn;Teo Ee Ling;William Anthony Deodaunia
分类号 C07D498/06;C07D498/08;C07D498/16;C07D498/18;C07D515/16;C07D515/18;A61K31/519 主分类号 C07D498/06
代理机构 Novak Druce Connolly Bove + Quigg LLP 代理人 Novak Druce Connolly Bove + Quigg LLP
主权项 1. A method of inhibiting one or more protein kinase(s) selected from the group consisting of CDK2, FLT3 and JAK2, the method including exposing the one or more protein kinase(s) and/or co-factor(s) thereof to an effective amount of a compound according to a compound of formula I: wherein: R1 and R2 are each independently selected from the group consisting of: H, halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, heteroalkyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, arylalkyl, heteroarylalkyl, arylalkenyl, cycloalkylheteroalkyl, heterocycloalkylheteroalkyl, heteroarylheteroalkyl, arylheteroalkyl, hydroxy, hydroxyalkyl, alkoxy, alkoxyalkyl, alkoxyaryl, alkenyloxy, alkynyloxy, cycloalkylkoxy, heterocycloalkyloxy, aryloxy, arylalkyloxy, phenoxy, benzyloxy, heteroaryloxy, amino, alkylamino, aminoalkyl, acylamino, arylamino, sulfonylamino, sulfinylamino, —COOH, —COR3, —COOR3, —CONHR3, —NHCOR3, —NHCOOR3, —NHCONHR3, alkoxycarbonyl, alkylaminocarbonyl, sulfonyl, alkylsulfonyl, alkylsulfinyl, arylsulfonyl, arylsulfinyl, aminosulfonyl, —SR3, R4S(O)R6—, R4S(O)2R6—, R4C(O)N(R5)R6—, R4SO2N(R5)R6—, R4N(R5)C(O)R6—, R4N(R5)SO2R6—, R4N(R5)C(O)N(R5)R6— and acyl, each of which may be optionally substituted;each R3, R4, and R5 is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, haloalkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, arylalkyl, heteroarylalkyl and acyl, each of which may be optionally substituted;each R6 is independently selected from the group consisting of a bond, alkyl, alkenyl, alkynyl, haloalkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, arylalkyl, heteroarylalkyl and acyl, each of which may be optionally substituted;Z2 is selected from the group consisting of a bond, O, S, —N(R7)—, —N(R7)C1-2alkyl-, and —C1-2alkylN(R7)—;each R7 is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, haloalkyl, hetero alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, arylalkyl, heteroarylalkyl and acyl, each of which may be optionally substituted;Ar1 and Ar2 are independently selected from the group consisting of aryl and heteroaryl, each of which may be optionally substituted;L is a group of formula: —X1—Y—X2—wherein X1 is attached to Ar1 and X2 is attached to Ar2, and wherein X1, X2 and Y are selected such that the group L has between 5 and 15 atoms in the normal chain,X1 and X2 are each independently an optionally substituted heteroalkyl group such that X1 and X2 are not both heteroalkyl groups containing at least one oxygen atom in the normal chain,Y is a group of formula —CRa═CRb- or an optionally substituted cycloalkyl group,wherein Ra and Rb are each independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, haloalkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, arylalkyl, heteroarylalkyl and acyl, each of which may be optionally substituted, orRa and Rb may be joined such that when taken together with the carbon atoms to which they are attached they form a cycloalkenyl or cycloheteroalkenyl group; or a pharmaceutically acceptable salt, or N-oxide, thereof.
地址 Singapore Science Park II SG