公开(公告)号：US08691806B2

公开(公告)日：2014-04-08

申请号：US13536174

申请日：2012-06-28

申请人： Valerio Berdini ,  Gordon Saxty ,  Marinus Leendert Verdonk ,  Steven John Woodhead ,  Paul Graham Wyatt ,  Robert George Boyle ,  Hannah Fiona Sore ,  David Winter Walker ,  Ian Collins ,  Robert Downham ,  Robin Arthur Ellis Carr

发明人： Valerio Berdini ,  Gordon Saxty ,  Marinus Leendert Verdonk ,  Steven John Woodhead ,  Paul Graham Wyatt ,  Robert George Boyle ,  Hannah Fiona Sore ,  David Winter Walker ,  Ian Collins ,  Robert Downham ,  Robin Arthur Ellis Carr

IPC分类号： A61K31/397 ,  C07D231/12

CPC分类号： A61K31/415 ,  A61K9/0019 ,  A61K9/20 ,  A61K9/48 ,  A61K31/4155 ,  A61K31/4178 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/4545 ,  A61K31/496 ,  A61K31/497 ,  A61K31/5377 ,  A61K31/551 ,  A61K45/06 ,  C07D231/12 ,  C07D401/04 ,  C07D401/10 ,  C07D401/12 ,  C07D401/14 ,  C07D403/10 ,  C07D403/12 ,  C07D405/04 ,  C07D413/10

摘要： The invention provides compounds of the formula (I) having protein kinase B inhibiting activity: Also provided are pharmaceutical compositions containing the compounds, methods for preparing the compounds and their use as anticancer agents.

摘要翻译： 本发明提供具有蛋白激酶B抑制活性的式（I）化合物：还提供含有化合物的药物组合物，制备化合物的方法及其作为抗癌剂的用途。

公开(公告)号：US08546407B2

公开(公告)日：2013-10-01

申请号：US11577963

申请日：2005-10-25

申请人： Valerio Berdini ,  Robert George Boyle ,  Gordon Saxty ,  David Winter Walker ,  Steven John Woodhead ,  Paul Graham Wyatt ,  Alastair Donald ,  John Caldwell ,  Ian Collins ,  Tatiana Faria Da Fonseca

发明人： Valerio Berdini ,  Robert George Boyle ,  Gordon Saxty ,  David Winter Walker ,  Steven John Woodhead ,  Paul Graham Wyatt ,  Alastair Donald ,  John Caldwell ,  Ian Collins ,  Tatiana Faria Da Fonseca

IPC分类号： C07D487/04 ,  A61K31/519 ,  A61P35/00

CPC分类号： C07D471/04 ,  A61K31/4545 ,  A61K31/519 ,  A61K31/52 ,  A61K31/522 ,  C07D473/34 ,  C07D487/04

摘要： The invention provides a compound for use as a protein kinase B inhibitor, the compound being a compound of the formula (Ic) or salts, tautomers or N-oxides thereof.

摘要翻译： 本发明提供了用作蛋白激酶B抑制剂的化合物，该化合物是式（Ic）化合物或其盐，互变异构体或N-氧化物。

公开(公告)号：US08247576B2

公开(公告)日：2012-08-21

申请号：US10596788

申请日：2004-12-23

申请人： Valerio Berdini ,  Gordon Saxty ,  Marinus Leendert Verdonk ,  Steven John Woodhead ,  Paul Graham Wyatt ,  Robert George Boyle ,  Hannah Fiona Sore ,  David Winter Walker ,  Ian Collins ,  Robert Downham ,  Robin Arthur Ellis Carr

发明人： Valerio Berdini ,  Gordon Saxty ,  Marinus Leendert Verdonk ,  Steven John Woodhead ,  Paul Graham Wyatt ,  Robert George Boyle ,  Hannah Fiona Sore ,  David Winter Walker ,  Ian Collins ,  Robert Downham ,  Robin Arthur Ellis Carr

IPC分类号： C07D231/12

CPC分类号： A61K31/415 ,  A61K9/0019 ,  A61K9/20 ,  A61K9/48 ,  A61K31/4155 ,  A61K31/4178 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/4545 ,  A61K31/496 ,  A61K31/497 ,  A61K31/5377 ,  A61K31/551 ,  A61K45/06 ,  C07D231/12 ,  C07D401/04 ,  C07D401/10 ,  C07D401/12 ,  C07D401/14 ,  C07D403/10 ,  C07D403/12 ,  C07D405/04 ,  C07D413/10

摘要： The invention provides compounds of the formula: (I) having protein kinase B inhibiting activity: wherein A is a saturated hydrocarbon linker group containing from 1 to 7 carbon atoms, the linker group having a maximum chain length of 5 atoms extending between R1 and NR2R3 and a maximum chain length of 4 atoms extending between E and NR2R3, wherein one of the carbon atoms in the linker group may optionally be replaced by an oxygen or nitrogen atom; and wherein the carbon atoms of the linker group A may optionally bear one or more substituents selected from oxo, fluorine and hydroxy, provided that the hydroxy group when present is not located at a carbon atom a with respect to the NR2R3 group and provided that the oxo group when present is located at a carbon atom a with respect to the NR2R3 group; E is a monocyclic or bicyclic carbocyclic or heterocyclic group; R1 is an aryl or heteroaryl group; and R2, R3, R4 and R5 are as defined in the claims. Also provided are pharmaceutical compositions containing the compounds, methods for preparing the compounds and their use as anticancer agents.

摘要翻译： 本发明提供下式的化合物：（I）具有蛋白激酶B抑制活性：其中A是含有1至7个碳原子的饱和烃连接基团，连接基团在R1和NR2R3之间延伸的最大链长为5个原子 并且在E和NR2R3之间延伸的4个原子的最大链长度，其中连接基团中的一个碳原子可以任选地被氧或氮原子替代; 并且其中连接基团A的碳原子可以任选地具有一个或多个选自氧代，氟和羟基的取代基，条件是当存在的羟基不相对于NR 2 R 3基团位于碳原子a时， 存在时的氧代基相对于NR 2 R 3基团位于碳原子a; E是单环或双环碳环或杂环基; R1是芳基或杂芳基; 并且R 2，R 3，R 4和R 5如权利要求中所定义。 还提供含有化合物的药物组合物，制备化合物的方法及其作为抗癌剂的用途。

公开(公告)号：US20090247538A1

公开(公告)日：2009-10-01

申请号：US11577963

申请日：2005-10-25

申请人： Valerio Berdini ,  Robert George Boyle ,  Gordon Saxty ,  David Winter Walker ,  Steven John Woodhead ,  Paul Graham Wyatt ,  Alastair Donald ,  John Caldwell ,  Ian Collins ,  Tatiana Faria Da Fonseca

发明人： Valerio Berdini ,  Robert George Boyle ,  Gordon Saxty ,  David Winter Walker ,  Steven John Woodhead ,  Paul Graham Wyatt ,  Alastair Donald ,  John Caldwell ,  Ian Collins ,  Tatiana Faria Da Fonseca

IPC分类号： A61K31/52 ,  C07D473/34 ,  C07D487/04 ,  A61K31/519 ,  C12N9/99 ,  C12Q1/48

CPC分类号： C07D471/04 ,  A61K31/4545 ,  A61K31/519 ,  A61K31/52 ,  A61K31/522 ,  C07D473/34 ,  C07D487/04

摘要： The invention provides a compound for use as a protein kinase B inhibitor, the compound being a compound of the formula (I) or salts, solvates, tautomers or N-oxides thereof, wherein T is N or CR5; J1-J2 is N═C(R6), (R7)C═N, (R8)N—C(O), (R8)2C—C(O), N═N or (R7)C═C(R6); E is a monocyclic carbocyclic or heterocyclic group of 5 or 6 ring members, the heterocyclic group containing up to 3 heteroatoms selected from O, N and S; Q1 is a bond or a saturated C1-3 hydrocarbon linker group, one of the carbon atoms in the linker group being optionally be replaced by an oxygen or nitrogen atom, or an adjacent pair of carbon atoms may be replaced by CONRq or NRqCO where Rq is hydrogen or methyl, or Rq is a C1-4 alkylene chain linked to R1 or a carbon atom of Q1 to form a cyclic moiety; and wherein the carbon atoms of the linker group Q1 may optionally bear one or more substituents selected from fluorine and hydroxy; Q2 is a bond or a saturated hydrocarbon linker group containing from 1 to 3 carbon atoms, wherein one of the carbon atoms in the linker group may optionally be replaced by an oxygen or nitrogen atom; and wherein the carbon atoms of the linker group may optionally bear one or more substituents selected from fluorine and hydroxy, provided that the hydroxy group when present is not located at a carbon atom a with respect to the G group; and provided that when E is aryl or heteroaryl, then Q2 is other than a bond; G is hydrogen, NR2R, OH or SH provided that when E is aryl or heteroaryl and Q2 is a bond, then G is hydrogen; R1 is hydrogen or an aryl or heteroaryl group, with the proviso that when R1 is hydrogen and G is NR2R3, then Q2 is a bond; and R2, R3, R4, R6 and R8 are as defined in the claims.

摘要翻译： 本发明提供用作蛋白激酶B抑制剂的化合物，该化合物为式（I）化合物或其盐，溶剂合物，互变异构体或N-氧化物，其中T为N或CR 5; J1-J2是N-C（R6），（R7）C-N，（R8）N-C（O），（R8）2C-C（O），N-N或（R7）C-C（R6） E是5或6个环成员的单环碳环或杂环基，杂环基含有至多3个选自O，N和S的杂原子; Q1是键或饱和的C 1-3烃连接基团，连接基团中的一个碳原子任选被氧或氮原子代替，或者相邻的一对碳原子可被CONRq或NRqCO代替，其中Rq 是氢或甲基，或Rq是与R1或Q1的碳原子连接的C 1-4亚烷基链，形成环状部分; 并且其中所述连接基团Q1的碳原子可任选地具有一个或多个选自氟和羟基的取代基; Q2是含有1至3个碳原子的键或饱和烃连接基团，其中连接基团中的一个碳原子可任选被氧或氮原子取代; 并且其中所述连接基团的碳原子可以任选地具有一个或多个选自氟和羟基的取代基，条件是当存在的羟基不相对于G基团位于碳原子a时; 并且条件是当E是芳基或杂芳基时，则Q2不是键; G为氢，NR2R，OH或SH，条件是当E为芳基或杂芳基且Q2为键时，则G为氢; R 1是氢或芳基或杂芳基，条件是当R 1是氢且G是NR 2 R 3时，则Q2是一个键; 并且R 2，R 3，R 4，R 6和R 8如权利要求中所定义。

公开(公告)号：US20080275029A1

公开(公告)日：2008-11-06

申请号：US11718943

申请日：2005-11-09

申请人： Valerio Berdini ,  Robert George Boyle ,  Gordon Saxty ,  Marinus Leendert Verdonk ,  Steven John Woodhead ,  Paul Graham Wyatt ,  Hannah Fiona Sore ,  David Winter Walker ,  John Caldwell ,  Ian Collins

发明人： Valerio Berdini ,  Robert George Boyle ,  Gordon Saxty ,  Marinus Leendert Verdonk ,  Steven John Woodhead ,  Paul Graham Wyatt ,  Hannah Fiona Sore ,  David Winter Walker ,  John Caldwell ,  Ian Collins

IPC分类号： A61K31/517 ,  C07D239/88 ,  C07D401/12 ,  C07D401/04 ,  A61K31/496 ,  A61K31/551 ,  A61P35/00 ,  C12N5/06 ,  A61K31/5377 ,  C07D401/06 ,  C07D403/12 ,  C07D413/14

CPC分类号： C07D403/12 ,  A61K31/505 ,  C07D239/88 ,  C07D239/91 ,  C07D239/96 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D403/04

摘要： The invention provides a compound of the formula (I) or a salt, solvate, tautomer or N-oxide thereof for use in the treatment or prophylaxis of a disease state or condition mediated by protein kinase A and/or protein kinase B; wherein the ring Q is a benzene ring; J2-J1 is N═CR7 or R1aN—CO; G is OH or NR5R6; E is CONR7, NR7CO, C(R8)═C(R8) or (X)m(CR8R8a)n where X is O, S or NR7; provided that when J2-J1 is R1aN—CO, E is other than NR7CO; m and n are each 0 or 1, where m+n=1 or 2; A is a bond and R4 and R4a are absent or A is a saturated optionally substituted C1-7 hydrocarbon linker group having a maximum chain length of 5 atoms extending between E and G, one carbon atom in the linker group A being optionally replaced by O or N; R1, R1a, R2, and R3 are each H; halogen; C1-6 hydrocarbyl optionally substituted by halogen, OH or C1-2 alkoxy; CN; CONHR8; NH2; NHCOR10 or NHCONHR10; R4 is H or C1-4 alkyl; R4a is H, C1-4 alkyl or a group R9; R5 and R6 are each selected from H, R9 and C1-4 hydrocarbyl optionally substituted by halogen, C1-2 alkoxy or R9; or NR5R6 forms a saturated 4-7 membered monocyclic heterocyclic group; R7 is H or C1-4 alkyl; R8 and R8a each H or saturated C1-4 hydrocarbyl optionally substituted by fluorine; R9 is a monocyclic or bicyclic carbocyclic or heterocyclic group containing up to 3 ring heteroatoms selected from N, O and S; or R4, R4a and A together form a saturated monocyclic 4-7 membered heterocycle; or NR5R6, R4 and A form a saturated 4-7 membered monocyclic heterocycle; or R4, together with R7 or R8 and A and E form a 4-7 membered saturated monocyclic heterocycle; or NR5R6 and R7 or R8 together with A and E form a 4-7 membered saturated monocyclic heterocycle; and R10 is optionally substituted phenyl or benzyl.

公开(公告)号：US08293767B2

公开(公告)日：2012-10-23

申请号：US13188887

申请日：2011-07-22

申请人： Paul Graham Wyatt ,  David Charles Rees ,  Mladen Vinkovic ,  Gary Trewartha

发明人： Paul Graham Wyatt ,  David Charles Rees ,  Mladen Vinkovic ,  Gary Trewartha

IPC分类号： A61K31/445 ,  C07D401/00

CPC分类号： C07D231/40 ,  C07D401/12

摘要： The invention provides an acid addition salt of 4-(2,6-dichloro-benzoylamino)-1H-pyrazole-3-carboxylic acid piperidin-4-ylamide and crystals thereof, the salt being formed with an acid selected from methanesulphonic acid and acetic acid and mixtures thereof.Also provided are the novel uses of salts of 4-(2,6-dichloro-benzoylamino)-1H-pyrazole-3-carboxylic acid piperidin-4-ylamide, processes for the preparation of 4-(2,6-dichloro-benzoylamino)-1H-pyrazole-3-carboxylic acid piperidin-4-ylamide and its salts and novel chemical intermediates.

摘要翻译： 本发明提供4-（2,6-二氯 - 苯甲酰基氨基）-1H-吡唑-3-羧酸哌啶-4-基酰胺及其晶体的酸加成盐，该盐由选自甲磺酸和乙酸的酸形成 酸及其混合物。 还提供了4-（2,6-二氯 - 苯甲酰基氨基）-1H-吡唑-3-羧酸哌啶-4-基酰胺的盐的新用途，制备4-（2,6-二氯 - 苯甲酰基氨基 ）-1H-吡唑-3-羧酸哌啶-4-基酰胺及其盐和新的化学中间体。

公开(公告)号：US20090012124A1

公开(公告)日：2009-01-08

申请号：US11814458

申请日：2006-01-20

申请人： Paul Graham Wyatt ,  David Charles Rees ,  Mladen Vinkovic ,  Gary Trewartha

发明人： Paul Graham Wyatt ,  David Charles Rees ,  Mladen Vinkovic ,  Gary Trewartha

IPC分类号： A61K31/454 ,  C07D401/02 ,  A61P35/00

CPC分类号： C07D231/40 ,  C07D401/12

摘要： The invention provides an acid addition salt of 4-(2,6-dichloro-benzoylamino)-1H-pyrazole-3-carboxylic acid piperidin-4-ylamide and crystals thereof, the salt being formed with an acid selected from methanesulphonic acid and acetic acid and mixtures thereof. Also provided are the novel uses of salts of 4-(2,6-dichloro-benzoylamino)-1H-pyrazole-3-carboxylic acid piperidin-4-ylamide, processes for the preparation of 4-(2,6-dichloro-benzoylamino)-1H-pyrazole-3-carboxylic acid piperidin-4-ylamide and its salts and novel chemical intermediates.

摘要翻译： 本发明提供4-（2,6-二氯 - 苯甲酰基氨基）-1H-吡唑-3-羧酸哌啶-4-基酰胺及其晶体的酸加成盐，该盐由选自甲磺酸和乙酸的酸形成 酸及其混合物。 还提供了4-（2,6-二氯 - 苯甲酰基氨基）-1H-吡唑-3-羧酸哌啶-4-基酰胺的盐的新用途，制备4-（2,6-二氯 - 苯甲酰基氨基 ）-1H-吡唑-3-羧酸哌啶-4-基酰胺及其盐和新的化学中间体。

公开(公告)号：US08013163B2

公开(公告)日：2011-09-06

申请号：US11814458

申请日：2006-01-20

申请人： Paul Graham Wyatt ,  David Charles Rees ,  Mladen Vinkovic ,  Gary Trewartha

发明人： Paul Graham Wyatt ,  David Charles Rees ,  Mladen Vinkovic ,  Gary Trewartha

IPC分类号： C07D401/00 ,  A61K31/445

CPC分类号： C07D231/40 ,  C07D401/12

摘要： The invention provides an acid addition salt of 4-(2,6-dichloro-benzoylamino)-1H-pyrazole-3-carboxylic acid piperidin-4-ylamide and crystals thereof, the salt being formed with an acid selected from methanesulphonic acid and acetic acid and mixtures thereof. Also provided are the novel uses of salts of 4-(2,6-dichloro-benzoylamino)-1H-pyrazole-3-carboxylic acid piperidin-4-ylamide, processes for the preparation of 4-(2,6-dichloro-benzoylamino)-1H-pyrazole-3-carboxylic acid piperidin-4-ylamide and its salts and novel chemical intermediates.

摘要翻译： 本发明提供4-（2,6-二氯 - 苯甲酰基氨基）-1H-吡唑-3-羧酸哌啶-4-基酰胺及其晶体的酸加成盐，该盐由选自甲磺酸和乙酸的酸形成 酸及其混合物。 还提供了4-（2,6-二氯 - 苯甲酰基氨基）-1H-吡唑-3-羧酸哌啶-4-基酰胺的盐的新用途，制备4-（2,6-二氯 - 苯甲酰基氨基 ）-1H-吡唑-3-羧酸哌啶-4-基酰胺及其盐和新的化学中间体。

公开(公告)号：US07514437B2

公开(公告)日：2009-04-07

申请号：US10499177

申请日：2002-12-20

申请人： Alan David Borthwick ,  Richard Jonathan Hatley ,  Deirdre Mary Bernadette Hickey ,  John Liddle ,  David George Hubert Livermore ,  Andrew McMurtrie Mason ,  Neil Derek Miller ,  Fabrizio Nerozzi ,  Steven Leslie Sollis ,  Anna Katrin Szardenings ,  Paul Graham Wyatt

发明人： Alan David Borthwick ,  Richard Jonathan Hatley ,  Deirdre Mary Bernadette Hickey ,  John Liddle ,  David George Hubert Livermore ,  Andrew McMurtrie Mason ,  Neil Derek Miller ,  Fabrizio Nerozzi ,  Steven Leslie Sollis ,  Anna Katrin Szardenings ,  Paul Graham Wyatt

IPC分类号： A61K31/497 ,  A61K31/4965 ,  C07D241/00 ,  C07D241/02

CPC分类号： C07D241/08 ,  A61K38/00 ,  C07D401/10 ,  C07D403/06 ,  C07D413/10 ,  C07D417/06 ,  C07K5/06078 ,  C07K5/06191

摘要： A method of treating or preventing diseases or conditions mediated through the action of oxytocin which comprises administering to a mammal in need thereof of an effective amount of a compound of the formula (I) and/or a physiologically acceptable derivative thereof, wherein the substituents have the meaning given in the description. Disclosed are also novel compounds of formula (I) and processes for their preparation.

摘要翻译： 一种治疗或预​​防通过催产素作用介导的疾病或病症的方法，其包括向有需要的哺乳动物施用有效量的式（I）化合物和/或其生理上可接受的衍生物，其中所述取代基具有 说明中给出的含义。 公开了式（I）的新化合物及其制备方法。

公开(公告)号：US20090186867A1

公开(公告)日：2009-07-23

申请号：US12412837

申请日：2009-03-27

申请人： Alan David Borthwick ,  Richard Jonathan Hatley ,  Deirdre Mary Bernadette Hickey ,  John Liddle ,  David George Hubert Livermore ,  Andrew McMurtrie Mason ,  Neil Derek Miller ,  Fabrizio Nerozzi ,  Steven Leslie Sollis ,  Anna Katrin Szardenings ,  Paul Graham Wyatt

发明人： Alan David Borthwick ,  Richard Jonathan Hatley ,  Deirdre Mary Bernadette Hickey ,  John Liddle ,  David George Hubert Livermore ,  Andrew McMurtrie Mason ,  Neil Derek Miller ,  Fabrizio Nerozzi ,  Steven Leslie Sollis ,  Anna Katrin Szardenings ,  Paul Graham Wyatt

IPC分类号： A61K31/496 ,  A61K31/4965 ,  A61K31/5377 ,  A61K31/541 ,  A61K31/551 ,  A61P15/00

CPC分类号： C07D241/08 ,  A61K38/00 ,  C07D401/10 ,  C07D403/06 ,  C07D413/10 ,  C07D417/06 ,  C07K5/06078 ,  C07K5/06191

摘要： A method of treating or preventing diseases or conditions mediated through the action of oxytocin which comprises administering to a human in need thereof of an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof.

摘要翻译： 一种治疗或预​​防通过催产素作用介导的疾病或病症的方法，其包括向有需要的人施用有效量的式（I）化合物或其药学上可接受的盐。