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New aminopyridine derivatives that have a selective inhibitory action on Aurora A

机译:对Aurora A具有选择性抑制作用的新氨基吡啶衍生物

摘要

A compound of general Formula I: ** Formula ** where: R1 is F, CN, COORa1, CONRa2Ra2 ', NRa3CORa3', CONRa4ORa4 ', NRa5CONRa5'Ra5 ", NRa6COORa6', SO2NRa7Ra7 ', NRa8SO2Ra7, , NO2, ORa11, NRa12Ra12 ', a lower alkyl that can be substituted or a heterocyclic group that can be substituted, where: Ra1 Ra3, Ra4, Ra5, Ra6 and Ra8 are each independently a hydrogen atom or lower alkyl that can be substituted; Ra2, Ra2 ', Ra5', Ra5 ", Ra7, Ra7 ', Ra12 and Ra12' are each independently a hydrogen or lower alkyl atom that may be substituted, provided, however, that Ra2 and Ra2 '; Ra5 'and Ra5 "; Ra7 and Ra7'; and Ra12 and Ra12 'each, together with the nitrogen atom to which they are attached, can form a heterocyclic group that may be substituted; Ra3', Ra4 ', Ra6', Ra8 ', Ra9, Ra10 and Ra11 are each independently a hydrogen or lower alkyl atom that may be substituted; R2 is CO, SO2, or CHRx where Rx is CF3, CN, CORx1, COORx2, CONRx3Rx3', SO2Rx4 or SO2NRx5Rx5 '; and Rx1, Rx2 and Rx4 are each independently a hydrogen or lower alkyl atom that can be substituted; and Rx3, Rx3', Rx5 and Rx5 'are each independently a hydrogen or lower alkyl atom that can be substituted , provided, however, that Rx3 and Rx3 '; and Rx5 and Rx5', each independently, together with the nitrogen atom to which they are attached, may form a heterocyclic group which may be substituted; R3 is a phenyl which may be substituted; X1 is CH, CX1a or N where X1a is lower alkyl that it may be substituted; X2 is CH, CX2a, or N where: X2a is lower alkyl; or X2a is a substituent selected from group of substituents A1, or lower alkyl which is substituted by one or more of the same or different substituents selected from group of substituents A1, wherein group of substituents A1 it is a halogen atom; cyano; hydroxy; lower alkylamino; di-lower alkylamino; lower alkoxy which may be substituted with one or more hydroxy: lower alkylthio groups; lower alkylsulfonyl; and phenyl which may be substituted; or X2a is COORx10, CONRx20Rx30, NHCORx10, NHCONRx20Rx30, NHSO2NRx20Rx30, NRx40Rx50 or CH2NRx40Rx50, where: Rx10 is a hydrogen or lower alkyl atom that may be substituted; Rx20 and Rx30, which may be the same or different, are each a hydrogen atom, lower alkyl that can be substituted or cycloalkyl that can be substituted; or alternatively Rx20 and Rx30, together with the nitrogen atom to which they are attached, form a 5- or 6-membered aliphatic heterocyclic group containing at least one atom selected from N, O and S and which may be substituted; and Rx40 and Rx50, which may be the same or different, are a hydrogen atom, lower alkyl that can be substituted or cycloalkyl that can be substituted; or X2a is a 5- to 6-membered aliphatic heterocyclic group containing at least one atom selected from N, O, and S and which may be substituted, in which two hydrogen atoms that are bonded to the same carbon atom of the aliphatic heterocyclic group they can be substituted with oxo and two adjacent carbon atoms that make up the aliphatic heterocyclic ring can form a double bond; or a lower alkyl that is substituted with the aliphatic heterocyclic group; or X2a is a 5- to 6-membered aromatic heterocyclic group containing at least one atom selected from N, O, and S and which may be substituted; or a lower alkyl that is substituted with the aromatic heterocyclic group; X3 is CH, CX3a, or N where X3a is a lower alkyl that may be substituted; provided, however, that between X1, X2 and X3, the number of nitrogens is 0 or 1; W is the following residue: ** Formula ** in which: W2 is CH, CW2a, N, NW2b, O or S, in which W2a and W2b are each independently a hydrogen atom, a halogen atom, cyano , lower alkyl having one to two carbon atoms, cycloalkyl having three to five carbon atoms, or lower alkyl having one to two carbon atoms that may be substituted with one or more halogen atoms; W3 is C or N; at least one of W1, W2 and W3 is a carbon atom; however, two of W1, W2, and W3 are not simultaneously O or S.
机译:通式I的化合物:** **其中R1为F,CN,COORa1,CONRa2Ra2',NRa3CORa3',CONRa4ORa4',NRa5CONRa5'Ra5',NRa6COORa6',SO2NRa7Ra7',NRa8SO2Ra7,,NO2,ORa11, ',可以被取代的低级烷基或可以被取代的杂环基,其中:Ra1 Ra3,Ra4,Ra5,Ra6和Ra8各自独立地是氢原子或可以被取代的低级烷基; Ra2,Ra2',Ra5 ',Ra5',Ra7,Ra7',Ra12和Ra12'各自独立地是氢或可被取代的低级烷基原子,但前提是Ra2和Ra2'; Ra5′和Ra5″; Ra7和Ra7′;以及Ra12和Ra12′,以及它们所连接的氮原子,可以形成可以被取代的杂环基; Ra3′,Ra4′,Ra6′,Ra8′。 ,R a9,R a10和R a11各自独立地是氢或可以被取代的低级烷基原子; R 2是CO,SO 2或CHR x,其中R x是CF 3,CN,CORx1,COORx2,CONRx3Rx3',SO2Rx4或SO2NRx5Rx5';和Rx1 Rx2和Rx4各自独立地为氢或可被取代的低级烷基原子;并且Rx3,Rx3',Rx5和Rx5'各自独立地为可被取代的氢或低级烷基原子,但是前提是Rx3和Rx3' ;并且Rx5和Rx5'分别独立地与它们所连接的氮原子一起形成可以被取代的杂环基; R3是可以被取代的苯基; X1是CH,CX1a或N,其中X1a是它可以被取代的低级烷基; X2是CH,CX2a或N,其中:X2a是低级烷基;或X2a是选自取代基A1>或被选自<取代基A1>的组中的一个或多个相同或不同取代基取代的低级烷基,其中<取代基A1的组>是卤素原子;氰基;羟基低级烷基氨基;二低级烷基氨基;可被一个或多个羟基取代的低级烷氧基:低级烷硫基;低级烷基磺酰基;和可以被取代的苯基; X2a是COORx10,CONRx20Rx30,NHCORx10,NHCONRx20Rx30,NHSO2NRx20Rx30,NRx40Rx50或CH2NRx40Rx50,其中:Rx10是氢或可被取代的低级烷基原子;或Rx20和Rx30可以相同或不同,分别为氢原子,可被取代的低级烷基或可被取代的环烷基。或者Rx20和Rx30与它们所连接的氮原子一起形成5或6元脂族杂环基,该脂族杂环基含有至少一个选自N,O和S的原子并且可以被取代; Rx40和Rx50可以相同或不同,是氢原子,可以被取代的低级烷基或可以被取代的环烷基。或X 2a是含有至少一个选自N,O和S的原子并且可以被取代的5至6元脂族杂环基,其中两个与该脂族杂环基的相同碳原子键合的氢原子它们可以被氧代取代,构成脂族杂环的两个相邻碳原子可以形成双键。或被脂族杂环基取代的低级烷基;或X 2a为含有至少一个选自N,O和S的原子且可以被取代的5至6元芳香族杂环基。或被芳族杂环基取代的低级烷基;或X3是CH,CX3a或N,其中X3a是可以被取代的低级烷基;但是,假设在X1,X2和X3之间,氮的数目为0或1; W是以下残基:**式**,其中:W 2是CH,CW 2a,N,NW 2b,O或S,其中W 2a和W 2b各自独立地是氢原子,卤素原子,氰基,具有一个的低级烷基。至两个碳原子,具有三个至五个碳原子的环烷基或具有一个至两个碳原子的可被一个或多个卤素原子取代的低级烷基; W3是C或N; W1,W2和W3中的至少一个是碳原子;但是,W1,W2和W3中的两个不同时为O或S。

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