公开(公告)号：US07049313B2

公开(公告)日：2006-05-23

申请号：US10373114

申请日：2003-02-24

申请人： Graeme Cameron Murray Smith ,  Niall Morrison Barr Martin ,  Stephen Philip Jackson ,  Mark James O'Connor ,  Alan Yin Kai Lau ,  Xiao-Ling Fan Cockcroft ,  Ian Timothy Williams Matthews ,  Keith Allan Menear ,  Laurent Jean Martin Rigoreau ,  Marc Geoffery Hummersone ,  Roger John Griffin

发明人： Graeme Cameron Murray Smith ,  Niall Morrison Barr Martin ,  Stephen Philip Jackson ,  Mark James O'Connor ,  Alan Yin Kai Lau ,  Xiao-Ling Fan Cockcroft ,  Ian Timothy Williams Matthews ,  Keith Allan Menear ,  Laurent Jean Martin Rigoreau ,  Marc Geoffery Hummersone ,  Roger John Griffin

IPC分类号： A61K31/535 ,  C07D413/00 ,  A61P35/00

CPC分类号： C07D409/04 ,  C07D417/04

摘要： The application concerns a compound of formula I: wherein one of P and Q is O, and the other of P and Q is CH, where there is a double bond between whichever of Q and P is CH and the carbon atom bearing the R3 group; Y is either O or S; R1 and R2 are independently hydrogen, an optionally substituted C1-7 alkyl group, C3-20 heterocyclyl group, or C5-20 aryl group, or may together form an optionally substituted heterocyclic ring having from 4 to 8 ring atoms; R3 is a phenyl or pyridyl group, attached by a first bridge group selected from —S—, —S(═O)—, —S(═O)2—, —O—, —NRN— and CRC1RC2— to an optionally substituted C5-20 carboaryl group, the phenyl or pyridyl group and optionally substituted C5-20 carboaryl group being optionally further linked by a second bridge group, so as to form an optionally substituted C5-7 ring, the phenyl or pyridyl group being further optionally substituted.

摘要翻译： 本申请涉及式I化合物：其中P和Q中的一个为O，P和Q中的另一个为CH，其中Q和P中的任一个为CH且具有R 1的碳原子之间为双键， SUP> 3 组; Y是O或S; R 1和R 2独立地是氢，任选取代的C 1-7烷基，C 3-20 或杂环基，或C 5-20-20芳基，或者可以一起形成任选取代的具有4至8个环原子的杂环; R 3是通过选自-S - ， - S（-O） - ， - S（-O）2 N的第一桥基团连接的苯基或吡啶基） - ， - O - ， - NR N - 和CR C1 - C2 - 与任选取代的C 5-20 - 苯基或吡啶基和任选取代的C 5-20碳芳基任选地通过第二桥基进一步连接，从而形成任选取代的C 5-7 苯基或吡啶基进一步任选被取代。

公开(公告)号：US08912187B2

公开(公告)日：2014-12-16

申请号：US13179353

申请日：2011-07-08

申请人： Niall Morrison Barr Martin ,  Graeme Cameron Smith ,  Stephen Philip Jackson ,  Vincent Junior M Loh ,  Xiao-Ling Fan Cockcroft ,  Ian Timothy Williams Matthews ,  Keith Allan Menear ,  Frank Kerrigan ,  Alan Ashworth

发明人： Niall Morrison Barr Martin ,  Graeme Cameron Smith ,  Stephen Philip Jackson ,  Vincent Junior M Loh ,  Xiao-Ling Fan Cockcroft ,  Ian Timothy Williams Matthews ,  Keith Allan Menear ,  Frank Kerrigan ,  Alan Ashworth

IPC分类号： A01N43/58 ,  A61K31/50 ,  C07D237/30

CPC分类号： A61K31/502 ,  A61K31/00 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/551 ,  A61K45/06 ,  A61N5/10 ,  C07D237/32 ,  C07D243/08 ,  C07D401/10 ,  C07D401/12 ,  C07D401/14 ,  C07D403/10 ,  C07D403/12 ,  C07D403/14 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D491/04 ,  C07D495/04

摘要： Compounds of the formula (I): wherein A and B together represent an optionally substituted, fused aromatic ring; X can be NRX or CRXRY; if X═NRX then n is 1 or 2 and if X═CRXRY then n is 1; RX is selected from the group consisting of H, optionally substituted C1-20 alkyl, C5-20 aryl, C3-20 heterocyclyl, amido, thioamido, ester, acyl, and sulfonyl groups; RY is selected from H, hydroxy, amino; or RX and RY may together form a spiro-C3-7 cycloalkyl or heterocyclyl group; RC1 and RC2 are both hydrogen, or when X is CRXRY, RC1, RC2, RX and RY, together with the carbon atoms to which they are attached, may form an optionally substituted fused aromatic ring; and R1 is selected from H and halo.

摘要翻译： 式（I）的化合物：其中A和B一起表示任选取代的稠合芳环; X可以是NRX或CRXRY; 如果X = NRX则n为1或2，如果X = CRXRY则n为1; RX选自H，任选取代的C 1-20烷基，C 5-20芳基，C 3-20杂环基，酰氨基，硫代酰氨基，酯，酰基和磺酰基; RY选自H，羟基，氨基; 或RX和RY可以一起形成螺C 3-7环烷基或杂环基; RC1和RC2均为氢，或当X为CRXRY时，RC1，RC2，RX和RY与它们所连接的碳原子一起形成任选取代的稠合芳环; 并且R 1选自H和卤素。

公开(公告)号：US07981889B2

公开(公告)日：2011-07-19

申请号：US12109260

申请日：2008-04-24

申请人： Niall Morrison Barr Martin ,  Graeme Cameron Smith ,  Stephen Philip Jackson ,  Vincent Junior M Loh ,  Xiao-Ling Fan Cockcroft ,  Ian Timothy Williams Matthews ,  Keith Allan Menear ,  Frank Kerrigan ,  Alan Ashworth

发明人： Niall Morrison Barr Martin ,  Graeme Cameron Smith ,  Stephen Philip Jackson ,  Vincent Junior M Loh ,  Xiao-Ling Fan Cockcroft ,  Ian Timothy Williams Matthews ,  Keith Allan Menear ,  Frank Kerrigan ,  Alan Ashworth

IPC分类号： A61K31/50 ,  A61K31/495 ,  C07D487/00

CPC分类号： A61K31/502 ,  A61K31/00 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/551 ,  A61K45/06 ,  A61N5/10 ,  C07D237/32 ,  C07D243/08 ,  C07D401/10 ,  C07D401/12 ,  C07D401/14 ,  C07D403/10 ,  C07D403/12 ,  C07D403/14 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D491/04 ,  C07D495/04

摘要： Compounds of the formula (I): wherein A and B together represent an optionally substituted, fused aromatic ring; X can be NRX or CRXRY; if X═NRX then n is 1 or 2 and if X═CRXRY then n is 1; RX is selected from the group consisting of H, optionally substituted C1-20 alkyl, C5-20 aryl, C3-20 heterocyclyl, amido, thioamido, ester, acyl, and sulfonyl groups; RY is selected from H, hydroxy, amino; or RX and RY may together form a spiro-C3-7 cycloalkyl or heterocyclyl group; RC1 and RC2 are both hydrogen, or when X is CRXRY, RC1, RC2, RX and RY, together with the carbon atoms to which they are attached, may form an optionally substituted fused aromatic ring; and R1 is selected from H and halo.

摘要翻译： 式（I）的化合物：其中A和B一起表示任选取代的稠合芳环; X可以是NRX或CRXRY; 如果X = NRX则n为1或2，如果X = CRXRY则n为1; RX选自H，任选取代的C 1-20烷基，C 5-20芳基，C 3-20杂环基，酰氨基，硫代酰氨基，酯，酰基和磺酰基; RY选自H，羟基，氨基; 或RX和RY可以一起形成螺C 3-7环烷基或杂环基; RC1和RC2均为氢，或当X为CRXRY时，RC1，RC2，RX和RY与它们所连接的碳原子一起形成任选取代的稠合芳环; 并且R 1选自H和卤素。

公开(公告)号：US20120010204A1

公开(公告)日：2012-01-12

申请号：US13179353

申请日：2011-07-08

申请人： Niall Morrison Barr Martin ,  Graeme Cameron Smith ,  Stephen Philip Jackson ,  Vincent M. Loh, JR. ,  Xiao-Ling Fan Cockcroft ,  Ian Timothy Williams Matthews ,  Keith Allan Menear ,  Frank Kerrigan ,  Alan Ashworth

发明人： Niall Morrison Barr Martin ,  Graeme Cameron Smith ,  Stephen Philip Jackson ,  Vincent M. Loh, JR. ,  Xiao-Ling Fan Cockcroft ,  Ian Timothy Williams Matthews ,  Keith Allan Menear ,  Frank Kerrigan ,  Alan Ashworth

IPC分类号： A61K31/502 ,  A61P35/00 ,  A61K31/5377

CPC分类号： A61K31/502 ,  A61K31/00 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/551 ,  A61K45/06 ,  A61N5/10 ,  C07D237/32 ,  C07D243/08 ,  C07D401/10 ,  C07D401/12 ,  C07D401/14 ,  C07D403/10 ,  C07D403/12 ,  C07D403/14 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D491/04 ,  C07D495/04

摘要： Compounds of the formula (I): wherein A and B together represent an optionally substituted, fused aromatic ring; X can be NRX or CRXRY; if X═NRX then n is 1 or 2 and if X═CRXRY then n is 1; RX is selected from the group consisting of H, optionally substituted C1-20 alkyl, C5-20 aryl, C3-20 heterocyclyl, amido, thioamido, ester, acyl, and sulfonyl groups; RY is selected from H, hydroxy, amino; or RX and RY may together form a spiro-C3-7 cycloalkyl or heterocyclyl group; RC1 and RC2 are both hydrogen, or when X is CRXRY, RC1, RC2, RX and RY, together with the carbon atoms to which they are attached, may form an optionally substituted fused aromatic ring; and R1 is selected from H and halo.

摘要翻译： 式（I）的化合物：其中A和B一起表示任选取代的稠合芳环; X可以是NRX或CRXRY; 如果X = NRX则n为1或2，如果X = CRXRY则n为1; RX选自H，任选取代的C 1-20烷基，C 5-20芳基，C 3-20杂环基，酰氨基，硫代酰氨基，酯，酰基和磺酰基; RY选自H，羟基，氨基; 或RX和RY可以一起形成螺C 3-7环烷基或杂环基; RC1和RC2均为氢，或当X为CRXRY时，RC1，RC2，RX和RY与它们所连接的碳原子一起形成任选取代的稠合芳环; 并且R 1选自H和卤素。

公开(公告)号：US07449464B2

公开(公告)日：2008-11-11

申请号：US10876080

申请日：2004-06-24

申请人： Niall Morrison Barr Martin ,  Graeme Cameron Smith ,  Stephen Philip Jackson ,  Vincent Junior M Loh ,  Xiao-Ling Fan Cockcroft ,  Ian Timothy Williams Matthews ,  Keith Allan Menear ,  Frank Kerrigan ,  Alan Ashworth

发明人： Niall Morrison Barr Martin ,  Graeme Cameron Smith ,  Stephen Philip Jackson ,  Vincent Junior M Loh ,  Xiao-Ling Fan Cockcroft ,  Ian Timothy Williams Matthews ,  Keith Allan Menear ,  Frank Kerrigan ,  Alan Ashworth

IPC分类号： A01N43/60 ,  A01N43/58 ,  A61K31/50 ,  A61K31/495 ,  C07D487/00

CPC分类号： A61K31/00 ,  C07D237/32 ,  C07D401/10 ,  C07D401/12 ,  C07D401/14 ,  C07D403/10 ,  C07D403/12 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D491/04 ,  C07D495/04

摘要： Compounds of the formula (I): wherein A and B together represent an optionally substituted, fused aromatic ring; X can be NRX or CRXRY; if X=NRX then n is 1 or 2 and if X=CRXRY then n is 1; RX is selected from the group consisting of H, optionally substituted C1-20 alkyl, C5-20 aryl, C3-20 heterocyclyl, amido, thioamido, ester, acyl, and sulfonyl groups; RY is selected from H, hydroxy, amino; or RX and RY may together form a spiro-C3-7 cycloalkyl or heterocyclyl group; RC1 and RC2 are both hydrogen, or when X is CRXRY, RC1, RC2, RX and RY, together with the carbon atoms to which they are attached, may form an optionally substituted fused aromatic ring; and R1 is selected from H and halo.

摘要翻译： 式（I）的化合物：其中A和B一起表示任选取代的稠合芳环; X可以是NR X或X X R O Y; 如果X = NR X，则n为1或2，并且如果X = CR X R Y Y，则n为1; R X选自H，任选取代的C 1-20烷基，C 5-20-20芳基，C 1〜 酰胺基，磺酰基，磺酰基，酰基和磺酰基; R Y选自H，羟基，氨基; 或R X和R Y可以一起形成螺C 3-7环烷基或杂环基; R C1和R C2都是氢，或者当X是CR X R Y，R O， C 1，R 2，R 2，X和R Y以及它们所连接的碳原子可以形成 任选取代的稠合芳环; R 1和R 2选自H和卤素。

公开(公告)号：US07662818B2

公开(公告)日：2010-02-16

申请号：US11318155

申请日：2005-12-23

申请人： Niall Morrison Barr Martin ,  Graeme Cameron Smith ,  Stephen Philip Jackson ,  Vincent Junior M Loh ,  Xiao-Ling Fan Cockcroft ,  Ian Timothy Williams Matthews ,  Keith Allan Menear ,  Frank Kerrigan ,  Alan Ashworth

发明人： Niall Morrison Barr Martin ,  Graeme Cameron Smith ,  Stephen Philip Jackson ,  Vincent Junior M Loh ,  Xiao-Ling Fan Cockcroft ,  Ian Timothy Williams Matthews ,  Keith Allan Menear ,  Frank Kerrigan ,  Alan Ashworth

IPC分类号： A01N43/60 ,  C07D221/02 ,  C07D237/30

CPC分类号： A61K31/00 ,  C07D237/32 ,  C07D401/10 ,  C07D401/12 ,  C07D401/14 ,  C07D403/10 ,  C07D403/12 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D491/04 ,  C07D495/04

摘要： Compounds of the formula (I): wherein A and B together represent an optionally substituted, fused aromatic ring; X can be NRX or CRXRY; if X=NRX then n is 1 or 2 and if X=CRXRY then n is 1; RX is selected from the group consisting of H, optionally substituted C1-20 alkyl, C5-20 aryl, C3-20 heterocyclyl, amido, thioamido, ester, acyl, and sulfonyl groups; RY is selected from H, hydroxy, amino; or RX and RY may together form a spiro-C3-7 cycloalkyl or heterocyclyl group; RC1 and RC2 are both hydrogen, or when X is CRXRY, RC1, RC2, RX and RY, together with the carbon atoms to which they are attached, may form an optionally substituted fused aromatic ring; and R1 is selected from H and halo.

摘要翻译： 式（I）的化合物：其中A和B一起表示任选取代的稠合芳环; X可以是NRX或CRXRY; 如果X = NRX，则n为1或2，如果X = CRXRY，则n为1; RX选自H，任选取代的C 1-20烷基，C 5-20芳基，C 3-20杂环基，酰氨基，硫代酰氨基，酯，酰基和磺酰基; RY选自H，羟基，氨基; 或RX和RY可以一起形成螺C 3-7环烷基或杂环基; RC1和RC2均为氢，或当X为CRXRY时，RC1，RC2，RX和RY与它们所连接的碳原子一起形成任选取代的稠合芳环; 并且R 1选自H和卤素。

公开(公告)号：US20080200469A1

公开(公告)日：2008-08-21

申请号：US12109260

申请日：2008-04-24

申请人： Niall Morrison Barr Martin ,  Graeme Cameron Smith ,  Stephen Philip Jackson ,  Vincent Junior M Loh ,  Xiao-Ling Fan Cockcroft ,  Ian Timothy Williams Matthews ,  Keith Allan Menear ,  Frank Kerrigan ,  Alan Ashworth

发明人： Niall Morrison Barr Martin ,  Graeme Cameron Smith ,  Stephen Philip Jackson ,  Vincent Junior M Loh ,  Xiao-Ling Fan Cockcroft ,  Ian Timothy Williams Matthews ,  Keith Allan Menear ,  Frank Kerrigan ,  Alan Ashworth

IPC分类号： A61K31/502 ,  C07D403/08 ,  A61P35/04

CPC分类号： A61K31/502 ,  A61K31/00 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/551 ,  A61K45/06 ,  A61N5/10 ,  C07D237/32 ,  C07D243/08 ,  C07D401/10 ,  C07D401/12 ,  C07D401/14 ,  C07D403/10 ,  C07D403/12 ,  C07D403/14 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D491/04 ,  C07D495/04

摘要： Compounds of the formula (I): wherein A and B together represent an optionally substituted, fused aromatic ring; X can be NRX or CRXRY; if X=NRX then n is 1 or 2 and if X=CRXRY then n is 1; RX is selected from the group consisting of H, optionally substituted C1-20 alkyl, C5-20 aryl, C3-20 heterocyclyl, amido, thioamido, ester, acyl, and sulfonyl groups; RY is selected from H, hydroxy, amino; or RX and RY may together form a spiro-C3-7 cycloalkyl or heterocyclyl group; RC1 and RC2 are both hydrogen, or when X is CRXRY, RC1, RC2, RX and RY, together with the carbon atoms to which they are attached, may form an optionally substituted fused aromatic ring; and R1 is selected from H and halo.

摘要翻译： 式（I）的化合物：其中A和B一起表示任选取代的稠合芳环; X可以是NR X或X X R O Y; 如果X = NR X，则n为1或2，并且如果X = CR X R Y Y，则n为1; R X选自H，任选取代的C 1-20烷基，C 5-20-20芳基，C 1〜 酰胺基，磺酰基，磺酰基，酰基和磺酰基; R Y选自H，羟基，氨基; 或R X和R Y可以一起形成螺C 3-7环烷基或杂环基; R C1和R C2都是氢，或者当X是CR X R Y，R O， C 1，R 2，R 2，X和R Y以及它们所连接的碳原子可以形成 任选取代的稠合芳环; R 1和R 2选自H和卤素。

公开(公告)号：US07138236B1

公开(公告)日：2006-11-21

申请号：US09462962

申请日：1998-07-16

申请人： Stephen Philip Jackson ,  Nicholas David Lakin ,  Graeme Cameron Murray Smith

发明人： Stephen Philip Jackson ,  Nicholas David Lakin ,  Graeme Cameron Murray Smith

IPC分类号： G01N33/53

CPC分类号： G01N33/6842 ,  A61K38/00 ,  C07K14/4746 ,  C12N9/1205 ,  C12Q1/48 ,  G01N33/574 ,  G01N33/68 ,  G01N33/6896 ,  G01N2333/91205

摘要： The interaction of ATM and related protein kinases such as ATR and DNA-PK with p53 is disclosed, in particular the phosphorylation of Ser15 and Thr18 by these proteins. The activity of the proteins is shown to increase in the presence of DNA. Assays for modulators of phosphorylation by the interaction between the proteins and p53 or other proteins having similar phosphorylation sites are provided. Methods of purifying ATM or ATR employing DNA or NTA are also disclosed.

摘要翻译： 公开了ATM和相关蛋白激酶如ATR和DNA-PK与p53的相互作用，特别是这些蛋白质对Ser15和Thr18的磷酸化。 显示蛋白质的活性在DNA的存在下增加。 提供了通过蛋白质与p53或具有相似磷酸化位点的其它蛋白质之间的相互作用的磷酸化调节剂的测定。 还公开了使用DNA或NTA纯化ATM或ATR的方法。

公开(公告)号：US06753158B1

公开(公告)日：2004-06-22

申请号：US09341505

申请日：1999-07-12

申请人： Stephen Philip Jackson ,  Susan Elizabeth Critchlow

发明人： Stephen Philip Jackson ,  Susan Elizabeth Critchlow

IPC分类号： A61K3853

CPC分类号： G01N33/502 ,  G01N33/5008 ,  G01N33/5091 ,  G01N33/68 ,  G01N33/6842 ,  G01N2333/9015 ,  G01N2333/912

摘要： A yeast homologue of mammalian DNA ligase IV is provided and a role for DNA ligase IV established in the Ku-associated DNA repair pathway. Additionally interactions between DNA ligase IV and XRCC4, and interaction between XRCC4 and DNA-PKcs/Ku are established, providing for assays for agents which modulate such interactions and therefore cellular DNA repair activity. Such agents are useful in treatment of cancers, retroviral infections, immune system disorders and other conditions in which cellular DNA repair activity plays a role. Individuals with a predisposition to a disorder in which DNA repair plays a role may be diagnosed, by screening for the presence or absence of a defect in XRCC4 and/or DNA ligase IV activity.

摘要翻译： 提供了哺乳动物DNA连接酶IV的酵母同系物，并且在Ku相关DNA修复途径中建立了DNA连接酶IV的作用。 另外建立DNA连接酶IV和XRCC4之间的相互作用以及XRCC4和DNA-PKcs / Ku之间的相互作用，为调节这种相互作用并因此调节细胞DNA修复活性的试剂提供了测定。 这样的药剂可用于治疗癌症，逆转录病毒感染，免疫系统疾病和其中细胞DNA修复活性起作用的其它病症。 通过筛选XRCC4和/或DNA连接酶IV活性中缺陷的存在或不存在可以诊断患有DNA修复起作用的病症倾向的个体。

公开(公告)号：US06242175B1

公开(公告)日：2001-06-05

申请号：US09341515

申请日：1999-07-12

申请人： Stephen Philip Jackson ,  Jessica Anne Downs

发明人： Stephen Philip Jackson ,  Jessica Anne Downs

IPC分类号： C12Q170

CPC分类号： G01N33/502 ,  G01N33/5008 ,  G01N33/68 ,  G01N2333/9015 ,  G01N2333/912

摘要： Ku(Ku70 and Ku80) of yeast and mammalian cells and other components of the Ku-associated DNA repair pathway are involved in retrotransposon and retroviral integration into cellular nucleic acids. Agents which inhibit activity of the pathway are useful for inhibition of retroviruses. Such agents are obtainable using assays involving the Ku-associated DNA repair pathway and one or more components thereof.

摘要翻译： 酵母和哺乳动物细胞的Ku（Ku70和Ku80）以及与Ku相关的DNA修复途径的其他组分参与反转录转座子和逆转录病毒整合到细胞核酸中。 抑制途径活性的药物可用于抑制逆转录病毒。 可以使用涉及Ku-相关DNA修复途径的测定及其一种或多种组分获得这些试剂。