公开(公告)号：US09290478B2

公开(公告)日：2016-03-22

申请号：US13990193

申请日：2011-11-29

申请人： Gordon Saxty ,  Christopher William Murray ,  Valerio Berdini ,  Gilbert Ebai Besong ,  Christopher Charles Frederick Hamlett ,  Steven John Woodhead ,  Yannick Aime Eddy Ligny ,  Patrick René Angibaud

发明人： Gordon Saxty ,  Christopher William Murray ,  Valerio Berdini ,  Gilbert Ebai Besong ,  Christopher Charles Frederick Hamlett ,  Steven John Woodhead ,  Yannick Aime Eddy Ligny ,  Patrick René Angibaud

IPC分类号： A61K31/498 ,  C07D241/40 ,  C07D403/04 ,  C07D401/14 ,  C07D403/14

CPC分类号： C07D403/04 ,  C07D401/14 ,  C07D403/14

摘要： The invention relates to new quinoxaline derivative compounds of formula (I), to pharmaceutical compositions comprising said compounds, to processes for the preparation of said compounds and to the use of said compounds in the treatment of diseases, e.g. cancer.

摘要翻译： 本发明涉及式（I）的新的喹喔啉衍生物化合物，包含所述化合物的药物组合物，所述化合物的制备方法和所述化合物在治疗疾病中的用途。 癌症。

公开(公告)号：US08895745B2

公开(公告)日：2014-11-25

申请号：US12520481

申请日：2007-12-21

申请人： Valerio Berdini ,  Gilbert Ebai Besong ,  Owen Callaghan ,  Maria Grazia Carr ,  Miles Stuart Congreve ,  Adrian Liam Gill ,  Charlotte Mary Griffiths-Jones ,  Andrew Madin ,  Christopher William Murray ,  Rajdeep Kaur Nijjar ,  Michael Alistair O'Brien ,  Andrew Pike ,  Gordon Saxty ,  Richard David Taylor ,  Emma Vickerstaffe

发明人： Valerio Berdini ,  Gilbert Ebai Besong ,  Owen Callaghan ,  Maria Grazia Carr ,  Miles Stuart Congreve ,  Adrian Liam Gill ,  Charlotte Mary Griffiths-Jones ,  Andrew Madin ,  Christopher William Murray ,  Rajdeep Kaur Nijjar ,  Michael Alistair O'Brien ,  Andrew Pike ,  Gordon Saxty ,  Richard David Taylor ,  Emma Vickerstaffe

IPC分类号： C07D471/04 ,  A61K31/437 ,  C07D487/04

CPC分类号： C07D487/04 ,  A61K31/437 ,  C07D471/04

摘要： The invention relates to new bicyclic heterocyclic derivative compounds, to pharmaceutical compositions comprising said compounds and to the use of said compounds in the treatment of diseases, e.g. cancer.

摘要翻译： 本发明涉及新的双环杂环衍生物化合物，包含所述化合物的药物组合物和所述化合物在治疗疾病中的用途。 癌症。

公开(公告)号：US08722687B2

公开(公告)日：2014-05-13

申请号：US13264596

申请日：2010-04-15

申请人： Gordon Saxty ,  Valerio Berdini ,  Christopher William Murray ,  Eddy Jean Edgard Freyne ,  Yannick Aimé Eddy Ligny ,  Pascal Ghislain André Bonnet ,  Berthold Wroblowski ,  Alexandra Papanikos

发明人： Gordon Saxty ,  Valerio Berdini ,  Christopher William Murray ,  Eddy Jean Edgard Freyne ,  Yannick Aimé Eddy Ligny ,  Pascal Ghislain André Bonnet ,  Berthold Wroblowski ,  Alexandra Papanikos

IPC分类号： C07D239/42 ,  C07D401/04 ,  A61K31/44 ,  A01N43/42 ,  C07D513/02 ,  C07D515/02 ,  C07D401/00 ,  C07D403/00 ,  C07D405/00 ,  C07D409/00 ,  C07D411/00 ,  C07D413/00

CPC分类号： C07D471/04

摘要： The invention relates to new bicyclic heterocyclyl derivatives of formula (I), to pharmaceutical compositions comprising said compounds and to the use of said compounds in the treatment of diseases, e.g. cancer.

摘要翻译： 本发明涉及式（I）的新的双环杂环基衍生物，包含所述化合物的药物组合物和所述化合物在治疗疾病中的用途，例如， 癌症。

公开(公告)号：US08288368B2

公开(公告)日：2012-10-16

申请号：US10469094

申请日：2002-02-25

申请人： Marcello Allegretti ,  Riccardo Bertini ,  Valerio Berdini ,  Cinzia Bizzarri ,  Maria Candida Cesta ,  Vito Di Cioccio ,  Gianfranco Caselli ,  Fracesco Colotta ,  Carmelo Gandolfi ,  Janete Peloia Barroso Gandolfi, legal representative ,  Giulio Agostino Gandolfi, legal representative ,  Maria Carla Gandolfi, legal representative ,  Arrigo Aldo Gandolfi, legal representative

发明人： Marcello Allegretti ,  Riccardo Bertini ,  Valerio Berdini ,  Cinzia Bizzarri ,  Maria Candida Cesta ,  Vito Di Cioccio ,  Gianfranco Caselli ,  Fracesco Colotta ,  Carmelo Gandolfi

IPC分类号： A61K31/397 ,  A61K31/55 ,  A61K31/445 ,  A61K31/40 ,  A61K31/165 ,  A61K31/195

CPC分类号： C07C233/51 ,  A61K31/165 ,  A61K31/198 ,  A61K31/445 ,  A61K31/4453 ,  A61K31/5375 ,  C07B2200/07 ,  C07C231/02 ,  C07C231/16 ,  C07C233/40 ,  C07C233/44 ,  C07C235/34 ,  C07C235/70 ,  C07C235/78 ,  C07C237/20 ,  C07C237/22 ,  C07C279/12 ,  C07C281/16 ,  C07D211/04 ,  C07D211/58 ,  C07D233/24 ,  C07D233/46 ,  C07D295/13 ,  C07D451/04

摘要： (R)-2-Arylpropionamide compounds of formula (I) are described. The process for their preparation and pharmaceutical preparations thereof are also described. The 2-Arylpropionamides of the invention are useful in the prevention and treatment of tissue damage due to the exacerbate recruitment of polymorphonuclear leukocytes (leukocytes PMN) and of monocytes at the inflammatory sites. In particular, the invention relates to the R enantiomers of omega-aminoalkylamides of 2-aryl propionic acids, of formula (I), for use in the inhibition of the chemotaxis of neutrophils and monocytes induced by the C5a fraction of the complement and by other chemotactic proteins whose biological activity is associated with activation of a 7-TD receptor.Selected compounds of formula (I) are dual inhibitors of both the C5a-induced chemotaxis of neutrophils and monocytes and the IL-8-induced chemotaxis of PMN leukocytes.The compounds of the invention are used in the treatment of psoriasis, ulcerative cholitis, glomerular nephritis, acute respiratory insufficiency, idiopathic fibrosis, rheumatoid arthritis and in the prevention and the treatment of injury caused by ischemia and reperfusion.

摘要翻译： 描述了式（I）的（R）-2-芳基丙酰胺化合物。 还描述了其制备方法及其制备药物。 本发明的2-芳基丙酰胺可用于预防和治疗由于多发性白细胞（白细胞PMN）和单核细胞在炎症部位的加剧性募集引起的组织损伤。 特别地，本发明涉及式（I）的2-芳基丙酸的ω-氨基烷基酰胺的R对映异构体，其用于抑制由补体的C5a部分诱导的嗜中性粒细胞和单核细胞的趋化性和其它 其生物活性与7-TD受体激活相关的趋化蛋白。 选择的式（I）化合物是C5a诱导的嗜中性粒细胞和单核细胞的趋化性和IL-8诱导的PMN白细胞趋化性的双重抑制剂。 本发明的化合物用于治疗牛皮癣，溃疡性胆囊炎，肾小球肾炎，急性呼吸功能不全，特发性纤维化，类风湿性关节炎，以及预防和治疗由缺血和再灌注引起的损伤。

公开(公告)号：US08080666B2

公开(公告)日：2011-12-20

申请号：US12877499

申请日：2010-09-08

申请人： Valerio Berdini ,  Michael Alistair O'Brien ,  Maria Grazia Carr ,  Theresa Rachel Early ,  Adrian Liam Gill ,  Gary Trewartha ,  Alison Jo-Anne Woolford ,  Andrew James Woodhead ,  Paul Graham Wyatt

发明人： Valerio Berdini ,  Michael Alistair O'Brien ,  Maria Grazia Carr ,  Theresa Rachel Early ,  Adrian Liam Gill ,  Gary Trewartha ,  Alison Jo-Anne Woolford ,  Andrew James Woodhead ,  Paul Graham Wyatt

IPC分类号： C07D401/02

CPC分类号： C07D231/38 ,  A61K31/415 ,  A61K31/4152 ,  A61K31/4155 ,  A61K31/416 ,  A61K31/4178 ,  A61K31/4196 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/541 ,  A61K45/06 ,  C04B35/632 ,  C07D231/14 ,  C07D231/40 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/12 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14 ,  C07D453/02 ,  C07D471/04

摘要： The invention provides compounds of the formula (0) or salts or tautomers or N-oxides or solvates thereof for use in the prophylaxis or treatment of disease states and conditions such as cancers mediated by cyclin-dependent kinase and glycogen synthase kinase-3. In formula (0): X is a group R1-A-NR4— or a 5- or 6-membered carbocyclic or heterocyclic ring; A is a bond, SO2, C═O, NRg(C═O) or O(C═O) wherein Rg is hydrogen or C1-4 hydrocarbyl optionally substituted by hydroxy or C1-4 alkoxy; Y is a bond or an alkylene chain of 1, 2 or 3 carbon atoms in length; R1 is hydrogen; a carbocyclic or heterocyclic group having from 3 to 12 ring members; or a C1-8 hydrocarbyl group optionally substituted by one or more substituents selected from halogen (e.g. fluorine), hydroxy, C1-4 hydrocarbyloxy, amino, mono- or di-C1-4 hydrocarbylamino, and carbocyclic or heterocyclic groups having from 3 to 12 ring members, and wherein 1 or 2 of the carbon atoms of the hydrocarbyl group may optionally be replaced by an atom or group selected from O, S, NH, SO, SO2; R2 is hydrogen; halogen; C1-4 alkoxy (e.g. methoxy); or a C1-4 hydrocarbyl group optionally substituted by halogen (e.g. fluorine), hydroxyl or C1-4 alkoxy (e.g. methoxy); R3 is selected from hydrogen and carbocyclic and heterocyclic groups having from 3 to 12 ring members; and R4 is hydrogen or a C1-4 hydrocarbyl group optionally substituted by halogen (e.g. fluorine), hydroxyl or C1-4 alkoxy (e.g. methoxy).

摘要翻译： 本发明提供式（O）的化合物或其盐或互变异构体或N-氧化物或溶剂合物，用于预防或治疗疾病状态和病症，例如由细胞周期蛋白依赖性激酶和糖原合酶激酶-3介导的癌症。 在式（0）中：X为基团R 1 -A-NR 4 - 或5或6元碳环或杂环; A是键，SO 2，C = O，NR g（C = O）或O（C = O），其中R g是氢或任选被羟基或C 1-4烷氧基取代的C 1-4烃基; Y是长度为1,2或3个碳原子的键或亚烷基链; R1是氢; 具有3至12个环成员的碳环或杂环基; 或任选被一个或多个选自卤素（例如氟），羟基，C 1-4烃氧基，氨基，单或二-C 1-4烃基氨基的取代基取代的C 1-8烃基，以及具有3至 12个环成员，并且其中烃基的1或2个碳原子可以任选地被选自O，S，NH，SO，SO 2的原子或基团取代; R2是氢; 卤素; C 1-4烷氧基（如甲氧基）; 或任选被卤素（例如氟），羟基或C 1-4烷氧基（例如甲氧基）取代的C 1-4烃基; R 3选自具有3至12个环成员的氢和碳环和杂环基; 和R 4是氢或任选被卤素（例如氟），羟基或C 1-4烷氧基（例如甲氧基）取代的C 1-4烃基。

公开(公告)号：US08076354B2

公开(公告)日：2011-12-13

申请号：US12682508

申请日：2008-10-10

申请人： Gordon Saxty ,  Valerio Berdini ,  Christopher William Murray ,  Charlotte Mary Griffiths-Jones ,  Emma Vickerstaffe ,  Gilbert Ebai Besong ,  Maria Grazia Carr

发明人： Gordon Saxty ,  Valerio Berdini ,  Christopher William Murray ,  Charlotte Mary Griffiths-Jones ,  Emma Vickerstaffe ,  Gilbert Ebai Besong ,  Maria Grazia Carr

IPC分类号： A01N43/42 ,  A61K31/44 ,  C07D491/02 ,  C07D498/02

CPC分类号： C07D471/04 ,  C07D487/04

摘要： The invention relates to new bicyclic heterocyclic derivative compounds of formula (I): wherein R1, A, X1, X2, X3, X4, X5 and R2 are as defined herein, to pharmaceutical compositions comprising said compounds and to the use of said compounds in the treatment of diseases, e.g. cancer.

摘要翻译： 本发明涉及式（I）的新的双环杂环衍生物化合物：其中R1，A，X1，X2，X3，X4，X5和R2如本文所定义，包含所述化合物的药物组合物和所述化合物在 疾病的治疗，例如 癌症。

公开(公告)号：US08071614B2

公开(公告)日：2011-12-06

申请号：US12682478

申请日：2008-10-10

申请人： Gordon Saxty ,  Valerio Berdini ,  Christopher William Murray ,  Charlotte Mary Griffiths-Jones ,  Emma Vickerstaffe ,  Gilbert Ebai Besong

发明人： Gordon Saxty ,  Valerio Berdini ,  Christopher William Murray ,  Charlotte Mary Griffiths-Jones ,  Emma Vickerstaffe ,  Gilbert Ebai Besong

IPC分类号： A01N43/42 ,  A61K31/44 ,  C07D491/02 ,  C07D498/02

CPC分类号： C07D471/04

摘要： The invention relates to new bicyclic heterocyclic derivative compounds of formula (I): wherein R1, q, A, B, X1, X2, X3, X4, X5 and R2 are as defined herein, to pharmaceutical compositions comprising said compounds and to the use of said compounds in the treatment of diseases, e.g. cancer.

摘要翻译： 本发明涉及式（I）的新的双环杂环衍生物化合物：其中R1，q，A，B，X1，X2，X3，X4，X5和R2如本文所定义，包含所述化合物的药物组合物和使用 的所述化合物治疗疾病，例如 癌症。

公开(公告)号：US07977477B2

公开(公告)日：2011-07-12

申请号：US10564166

申请日：2004-07-05

申请人： Valerio Berdini ,  Michael Alistair O'Brien ,  Maria Grazia Carr ,  Theresa Rachel Early ,  Eva Figueroa Navarro ,  Adrian Liam Gill ,  Steven Howard ,  Gary Trewartha ,  Alison Jo-Anne Woolford ,  Andrew James Woodhead ,  Paul Wyatt

发明人： Valerio Berdini ,  Michael Alistair O'Brien ,  Maria Grazia Carr ,  Theresa Rachel Early ,  Eva Figueroa Navarro ,  Adrian Liam Gill ,  Steven Howard ,  Gary Trewartha ,  Alison Jo-Anne Woolford ,  Andrew James Woodhead ,  Paul Wyatt

IPC分类号： A61K31/5377 ,  A61K31/4184 ,  C07D413/14

CPC分类号： A61K31/5377 ,  A61K31/00 ,  A61K31/4184 ,  A61K45/06 ,  C07D401/14 ,  C07D403/04 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D471/04 ,  C07D513/04

摘要： The invention provides compounds of the formula (I): The compounds have activity against cyclin dependent kinases, glycogen synthase kinase and Auroa kinases and are therefore useful to treat cancer and viral diseases.

摘要翻译： 本发明提供式（I）化合物：该化合物具有抗细胞周期蛋白依赖性激酶，糖原合成酶激酶和Auroa激酶的活性，因此可用于治疗癌症和病毒性疾病。

公开(公告)号：US20110144080A1

公开(公告)日：2011-06-16

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 ,  Hanna 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 ,  Hanna Fiona Sore ,  David Winter Walker ,  Ian Collins ,  Robert Downham ,  Robin Arthur Ellis Carr

IPC分类号： A61K31/415 ,  C07D231/12 ,  C07D401/10 ,  A61K31/454 ,  A61K31/4439 ,  C07D413/10 ,  A61K31/5377 ,  C07D403/10 ,  A61K31/4155 ,  A61K31/496 ,  A61K31/497 ,  A61K31/551 ,  C07D401/04 ,  C07D401/14 ,  A61K31/4545 ,  A61P35/00

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：US07825140B2

公开(公告)日：2010-11-02

申请号：US11875482

申请日：2007-10-19

申请人： Valerio Berdini ,  Michael Alistair O'Brien ,  Maria Grazia Carr ,  Theresa Rachel Early ,  Adrian Liam Gill ,  Gary Trewartha ,  Alison Jo-Anne Woolford ,  Andrew James Woodhead ,  Paul Graham Wyatt

发明人： Valerio Berdini ,  Michael Alistair O'Brien ,  Maria Grazia Carr ,  Theresa Rachel Early ,  Adrian Liam Gill ,  Gary Trewartha ,  Alison Jo-Anne Woolford ,  Andrew James Woodhead ,  Paul Graham Wyatt

IPC分类号： A61K31/4465 ,  C07D211/56

CPC分类号： C07D231/38 ,  A61K31/415 ,  A61K31/4152 ,  A61K31/4155 ,  A61K31/416 ,  A61K31/4178 ,  A61K31/4196 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/541 ,  A61K45/06 ,  C04B35/632 ,  C07D231/14 ,  C07D231/40 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/12 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14 ,  C07D453/02 ,  C07D471/04

摘要： The invention provides compounds of the formula (0) or salts or tautomers or N-oxides or solvates thereof for use in the prophylaxis or treatment of disease states and conditions such as cancers mediated by cyclin-dependent kinase and glycogen synthase kinase-3. In formula (0): X is a group R1-A-NR4— or a 5- or 6-membered carbocyclic or heterocyclic ring; A is a bond, SO2, C═O, NRg(C═O) or O(C═O) wherein Rg is hydrogen or C1-4 hydrocarbyl optionally substituted by hydroxy or C1-4 alkoxy; Y is a bond or an alkylene chain of 1, 2 or 3 carbon atoms in length; R1 is hydrogen; a carbocyclic or heterocyclic group having from 3 to 12 ring members; or a C1-8 hydrocarbyl group optionally substituted by one or more substituents selected from halogen (e.g. fluorine), hydroxy, C1-4 hydrocarbyloxy, amino, mono- or di-C1-4 hydrocarbylamino, and carbocyclic or heterocyclic groups having from 3 to 12 ring members, and wherein 1 or 2 of the carbon atoms of the hydrocarbyl group may optionally be replaced by an atom or group selected from O, S, NH, SO, SO2; R2 is hydrogen; halogen; C1-4 alkoxy (e.g. methoxy); or a C1-4 hydrocarbyl group optionally substituted by halogen (e.g. fluorine), hydroxyl or C1-4 alkoxy (e.g. methoxy); R3 is selected from hydrogen and carbocyclic and heterocyclic groups having from 3 to 12 ring members; and R4 is hydrogen or a C1-4 hydrocarbyl group optionally substituted by halogen (e.g. fluorine), hydroxyl or C1-4 alkoxy (e.g. methoxy).

摘要翻译： 本发明提供式（O）的化合物或其盐或互变异构体或N-氧化物或溶剂合物，用于预防或治疗疾病状态和病症，例如由细胞周期蛋白依赖性激酶和糖原合酶激酶-3介导的癌症。 在式（0）中：X为基团R 1 -A-NR 4 - 或5或6元碳环或杂环; A是键，SO 2，C = O，NR g（C = O）或O（C = O），其中R g是氢或任选被羟基或C 1-4烷氧基取代的C 1-4烃基; Y是长度为1,2或3个碳原子的键或亚烷基链; R1是氢; 具有3至12个环成员的碳环或杂环基; 或任选被一个或多个选自卤素（例如氟），羟基，C 1-4烃氧基，氨基，单或二-C 1-4烃基氨基的取代基取代的C 1-8烃基，以及具有3至 12个环成员，并且其中烃基的1或2个碳原子可以任选地被选自O，S，NH，SO，SO 2的原子或基团取代; R2是氢; 卤素; C 1-4烷氧基（如甲氧基）; 或任选被卤素（例如氟），羟基或C 1-4烷氧基（例如甲氧基）取代的C 1-4烃基; R 3选自具有3至12个环成员的氢和碳环和杂环基; 和R 4是氢或任选被卤素（例如氟），羟基或C 1-4烷氧基（例如甲氧基）取代的C 1-4烃基。