公开(公告)号：US08343955B2

公开(公告)日：2013-01-01

申请号：US13477587

申请日：2012-05-22

申请人： Nicole Blaquiere ,  Steven Do ,  Danette Dudley ,  Adrian Folkes ,  Robert Heald ,  Timothy Heffron ,  Mark Jones ,  Aleksandr Kolesnikov ,  Chudi Ndubaku ,  Alan G. Olivero ,  Stephen Price ,  Steven Staben ,  Lan Wang

发明人： Nicole Blaquiere ,  Steven Do ,  Danette Dudley ,  Adrian Folkes ,  Robert Heald ,  Timothy Heffron ,  Mark Jones ,  Aleksandr Kolesnikov ,  Chudi Ndubaku ,  Alan G. Olivero ,  Stephen Price ,  Steven Staben ,  Lan Wang

IPC分类号： A61K31/553

CPC分类号： C07D498/04 ,  A61K31/553 ,  A61K45/06 ,  C07D491/044 ,  C07D498/14 ,  C07D519/00

摘要： Benzoxazepin compounds of Formula I, including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, wherein: Z1 is CR1 or N; Z2 is CR2 or N; Z3 is CR3 or N; Z4 is CR4 or N; and B is a pyrazolyl, imidazolyl, or triazolyl ring fused to the benzoxepin ring, are useful for inhibiting lipid kinases including p110 alpha and other isoforms of PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

公开(公告)号：US20110076292A1

公开(公告)日：2011-03-31

申请号：US12890812

申请日：2010-09-27

申请人： Nicole Blaquiere ,  Steven Do ,  Danette Dudley ,  Adrian Folkes ,  Robert Heald ,  Timothy Heffron ,  Mark Jones ,  Aleksandr Kolesnikov ,  Chudi Ndubaku ,  Alan G. Olivero ,  Stephen Price ,  Steven Staben ,  Lan Wang

发明人： Nicole Blaquiere ,  Steven Do ,  Danette Dudley ,  Adrian Folkes ,  Robert Heald ,  Timothy Heffron ,  Mark Jones ,  Aleksandr Kolesnikov ,  Chudi Ndubaku ,  Alan G. Olivero ,  Stephen Price ,  Steven Staben ,  Lan Wang

IPC分类号： A61K31/553 ,  C07D498/04 ,  C07D491/044 ,  C07D498/14 ,  A61K31/4196 ,  A61K31/496 ,  A61K31/454 ,  A61K39/00 ,  A61P35/00 ,  A61P35/02 ,  A61P29/00 ,  A61P9/00 ,  A61P1/16 ,  A61P31/12 ,  A61P7/00 ,  A61P3/10

CPC分类号： C07D498/04 ,  A61K31/553 ,  A61K45/06 ,  C07D491/044 ,  C07D498/14 ,  C07D519/00

摘要： Benzoxazepin compounds of Formula I, including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, wherein: Z1 is CR1 or N; Z2 is CR2 or N; Z3 is CR3 or N; Z4 is CR4 or N; and B is a pyrazolyl, imidazolyl, or triazolyl ring fused to the benzoxepin ring, are useful for inhibiting lipid kinases including p110 alpha and other isoforms of PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

摘要翻译： 式I的苯并氧氮杂化合物，包括立体异构体，几何异构体，互变异构体，溶剂合物，代谢物及其药学上可接受的盐，其中：Z1是CR1或N; Z2为CR2或N; Z3为CR3或N; Z4是CR4或N; B是与苯并氧杂环环稠合的吡唑基，咪唑基或三唑基环，可用于抑制脂质激酶，包括p110α和PI3K的其他同种型，并用于治疗由脂质激酶介导的癌症等疾病。 公开了使用式I化合物在体外，原位和体内诊断，预防或治疗哺乳动物细胞或相关病理状况中的这种病症的方法。

公开(公告)号：US4959488A

公开(公告)日：1990-09-25

申请号：US353371

申请日：1989-05-17

申请人： James M. Renga ,  Alan G. Olivero ,  Mark Bosse

发明人： James M. Renga ,  Alan G. Olivero ,  Mark Bosse

IPC分类号： C07C33/26 ,  C07C63/307

CPC分类号： C07C63/307 ,  C07C33/26

摘要： Polyfunctional hexasubstituted benzene derivatives wherein at least three of the substituents are saturated carbon chains having from 1 to 21 carbon atoms and functional groups containing hetero functionalities at the ends of the carbon chains and the remainder of the 6 substituents are either saturated carbon chains containing from 1 to 21 carbon atoms or saturated carbon chains containing from 1 to 21 carbon atoms having a functional group including a hetero functional group containing N, O, S, P, or Si at the end of the chains. These derivatives are made by reacting a disubstituted alkyne wherein one or both of the substituents are saturated carbon chains having 1 to 21 carbon atoms to which hetero functional groups are attached with a palladium catalyst and isolating the resulting hexasubstituted benzene derivative.

摘要翻译： 多官能六取代苯衍生物，其中至少三个取代基是具有1至21个碳原子的饱和碳链和在碳链末端含有杂官能团的官能团，并且6个取代基的其余部分是含有1个 至21个碳原子或含有1至21个碳原子的饱和碳链，其具有在链末端包含含有N，O，S，P或Si的杂官能团的官能团。 这些衍生物通过二取代炔反应制得，其中一个或两个取代基是具有1至21个碳原子的饱和碳链，其中杂官能团与钯催化剂连接，并分离得到的六取代苯衍生物。

公开(公告)号：US08673952B2

公开(公告)日：2014-03-18

申请号：US13568707

申请日：2012-08-07

申请人： Nicole Blaquiere ,  Steven Do ,  Danette Dudley ,  Adrian Folkes ,  Richard Goldsmith ,  Robert Heald ,  Timothy Heffron ,  Aleksandr Kolesnikov ,  Chudi Ndubaku ,  Alan G. Olivero ,  Stephen Price ,  Steven Staben ,  BinQing Wei

发明人： Nicole Blaquiere ,  Steven Do ,  Danette Dudley ,  Adrian Folkes ,  Richard Goldsmith ,  Robert Heald ,  Timothy Heffron ,  Aleksandr Kolesnikov ,  Chudi Ndubaku ,  Alan G. Olivero ,  Stephen Price ,  Steven Staben ,  BinQing Wei

IPC分类号： A61K31/41 ,  C07D249/14

CPC分类号： C07D495/04 ,  A61K31/381 ,  A61K31/41 ,  A61K31/4196 ,  A61K31/4245 ,  A61K31/429 ,  A61K31/4365 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/4545 ,  A61K31/496 ,  A61K31/4985 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/541 ,  A61K31/551 ,  A61K45/06 ,  C07D249/14 ,  C07D495/14 ,  C07D513/04 ,  C07D513/14

摘要： Benzoxepin compounds of Formula I, and including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting lipid kinases including p110 alpha and other isoforms of PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

摘要翻译： 式I的苯并氧杂多磷化合物，包括立体异构体，几何异构体，互变异构体，溶剂合物，代谢产物及其药学上可接受的盐可用于抑制脂质激酶，包括p110α和PI3K的其他同种型，并用于治疗诸如由脂质激酶介导的癌症 。 公开了使用式I化合物在体外，原位和体内诊断，预防或治疗哺乳动物细胞或相关病理状况中的这种病症的方法。

公开(公告)号：US20130012488A1

公开(公告)日：2013-01-10

申请号：US13568707

申请日：2012-08-07

申请人： Nicole Blaquiere ,  Steven Do ,  Danette Dudley ,  Adrian Folkes ,  Richard Goldsmith ,  Robert Heald ,  Timothy Heffron ,  Aleksandr Kolesnikov ,  Chudi Ndubaku ,  Alan G. Olivero ,  Stephen Price ,  Steven Staben ,  BinQing Wei

发明人： Nicole Blaquiere ,  Steven Do ,  Danette Dudley ,  Adrian Folkes ,  Richard Goldsmith ,  Robert Heald ,  Timothy Heffron ,  Aleksandr Kolesnikov ,  Chudi Ndubaku ,  Alan G. Olivero ,  Stephen Price ,  Steven Staben ,  BinQing Wei

IPC分类号： A61K31/429 ,  C07D495/04 ,  A61P35/00 ,  C07D495/14 ,  A61K31/4365 ,  A61K31/5377 ,  C07D513/04 ,  A61K31/381

CPC分类号： C07D495/04 ,  A61K31/381 ,  A61K31/41 ,  A61K31/4196 ,  A61K31/4245 ,  A61K31/429 ,  A61K31/4365 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/4545 ,  A61K31/496 ,  A61K31/4985 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/541 ,  A61K31/551 ,  A61K45/06 ,  C07D249/14 ,  C07D495/14 ,  C07D513/04 ,  C07D513/14

摘要： Benzoxepin compounds of Formula I, and including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting lipid kinases including p110 alpha and other isoforms of PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

摘要翻译： 式I的苯并氧杂多磷化合物，包括立体异构体，几何异构体，互变异构体，溶剂合物，代谢产物及其药学上可接受的盐可用于抑制脂质激酶，包括p110α和PI3K的其他同种型，并用于治疗诸如由脂质激酶介导的癌症 。 公开了使用式I化合物在体外，原位和体内诊断，预防或治疗哺乳动物细胞或相关病理状况中的这种病症的方法。

公开(公告)号：US20110076291A1

公开(公告)日：2011-03-31

申请号：US12890810

申请日：2010-09-27

申请人： Nicole Blaquiere ,  Steven Do ,  Danette Dudley ,  Adrian Folkes ,  Richard Goldsmith ,  Robert Heald ,  Timothy Heffron ,  Aleksandr Kolesnikov ,  Chudi Ndubaku ,  Alan G. Olivero ,  Stephen Price ,  Steven Staben ,  BinQing Wei

发明人： Nicole Blaquiere ,  Steven Do ,  Danette Dudley ,  Adrian Folkes ,  Richard Goldsmith ,  Robert Heald ,  Timothy Heffron ,  Aleksandr Kolesnikov ,  Chudi Ndubaku ,  Alan G. Olivero ,  Stephen Price ,  Steven Staben ,  BinQing Wei

IPC分类号： A61K31/429 ,  C07D513/04 ,  C07D495/04 ,  C07D495/14 ,  A61K31/381 ,  A61K31/4365 ,  A61K31/4245 ,  A61K31/454 ,  A61K31/4439 ,  A61K31/5377 ,  A61K31/496 ,  A61K39/00 ,  A61P35/00 ,  A61P35/02 ,  A61P29/00 ,  A61P9/00 ,  A61P3/10 ,  A61P31/12 ,  A61P7/00 ,  A61P1/16

CPC分类号： C07D495/04 ,  A61K31/381 ,  A61K31/41 ,  A61K31/4196 ,  A61K31/4245 ,  A61K31/429 ,  A61K31/4365 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/4545 ,  A61K31/496 ,  A61K31/4985 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/541 ,  A61K31/551 ,  A61K45/06 ,  C07D249/14 ,  C07D495/14 ,  C07D513/04 ,  C07D513/14

摘要： Benzoxepin compounds of Formula I, and including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, wherein: Z1 is CR1 or N; Z2 is CR2 or N; Z3 is CR3 or N; Z4 is CR4 or N; and where (i) X1 is N and X2 is S, (ii) X1 is S and X2 is N, (iii) X1 is CR7 and X2 is S, (iv) X1 is S and X2 is CR7; (v) X1 is NR8 and X2 is N, (vi) X1 is N and X2 is NR8, (vii) X1 is CR7 and X2 is O, (viii) X1 is O and X2 is CR7, (ix) X1 is CR7 and X2 is C(R7)2, (x) X1 is C(R7)2 and X2 is CR7; (xi) X1 is N and X2 is O, or (xii) X1 is O and X2 is N, are useful for inhibiting lipid kinases including p110 alpha and other isoforms of PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

摘要翻译： 式I的苯并氧杂环己烯化合物，包括立体异构体，几何异构体，互变异构体，溶剂合物，代谢物及其药学上可接受的盐，其中：Z1是CR1或N; Z2为CR2或N; Z3为CR3或N; Z4是CR4或N; 并且其中（i）X1为N且X2为S，（ii）X1为S且X2为N，（iii）X1为CR7，X2为S，（iv）X1为S且X2为CR7; （ⅴ）X1为NR8，X2为N，（vi）X1为N，X2为NR8，i X1为CR7，X2为O，（ii）X1为O，X2为CR7，ix为CR7 X2为C（R7）2，（x）X1为C（R7）2，X2为CR7; （xi）X1是N，X2是O，或（xii）X1是O，X2是N，可用于抑制脂质激酶包括p110α和PI3K的其他同种型，并用于治疗由脂质激酶介导的癌症等疾病。 公开了使用式I化合物在体外，原位和体内诊断，预防或治疗哺乳动物细胞或相关病理状况中的这种病症的方法。

公开(公告)号：US07109326B2

公开(公告)日：2006-09-19

申请号：US10854388

申请日：2004-05-25

申请人： Brent Blackburn ,  Alan G. Olivero ,  Kirk Robarge

发明人： Brent Blackburn ,  Alan G. Olivero ,  Kirk Robarge

IPC分类号： C07D243/24

CPC分类号： C07D223/16 ,  C07D243/14 ,  C07D243/24

摘要： Halo-alkoxycarbonyl derivatives are provided as prodrug moieties for pharmaceutical agents containing a basic or polar nitrogen containing functionality. The prodrugs are provided as pharmaceutical compositions as well as in methods of treatment.

摘要翻译： 提供卤代 - 烷氧基羰基衍生物作为含有碱性或极性含氮官能团的药物的前药部分。 前药作为药物组合物以及治疗方法提供。

公开(公告)号：US5106541A

公开(公告)日：1992-04-21

申请号：US462665

申请日：1990-01-09

申请人： William E. Fristad ,  Alan G. Olivero ,  Steven Young ,  Christopher S. Sykes ,  Brock M. Siegel

发明人： William E. Fristad ,  Alan G. Olivero ,  Steven Young ,  Christopher S. Sykes ,  Brock M. Siegel

IPC分类号： C07C51/353 ,  C07C67/465 ,  C11C3/00

CPC分类号： C07C67/465 ,  C07C51/353 ,  C11C3/00

摘要： Oligomers and addition products obtained from the reaction of a saturated or olefinically unsaturated carboxylic acid, alcohol, ether, or ester with a substituted or unsubstituted acetic anhydride in the presence of a Mn compound, and processes for their preparation.

摘要翻译： 由Mn化合物存在下，饱和或烯属不饱和羧酸，醇，醚或酯与取代或未取代的乙酸酐的反应获得的低聚物和加成产物及其制备方法。

公开(公告)号：US08883799B2

公开(公告)日：2014-11-11

申请号：US13326524

申请日：2011-12-15

申请人： Jennafer Dotson ,  Robert Andrew Heald ,  Timothy Heffron ,  Graham Elgin Jones ,  Sussie Lerche Krintel ,  Neville James McLean ,  Chudi Ndubaku ,  Alan G. Olivero ,  Laurent Salphati ,  Lan Wang ,  BinQing Wei

发明人： Jennafer Dotson ,  Robert Andrew Heald ,  Timothy Heffron ,  Graham Elgin Jones ,  Sussie Lerche Krintel ,  Neville James McLean ,  Chudi Ndubaku ,  Alan G. Olivero ,  Laurent Salphati ,  Lan Wang ,  BinQing Wei

IPC分类号： C07D471/04 ,  C07D471/22 ,  C07D487/04 ,  C07D413/00 ,  C07D265/00 ,  C07D498/00 ,  A61K31/535 ,  C07D498/14 ,  C07D491/14 ,  C07D495/14 ,  C07D487/14

CPC分类号： C07D498/22 ,  A61K31/5377 ,  A61K31/5383 ,  A61K31/5386 ,  A61K39/3955 ,  A61K2039/505 ,  C07D471/14 ,  C07D471/22 ,  C07D487/14 ,  C07D491/14 ,  C07D491/147 ,  C07D495/14 ,  C07D498/14 ,  C07D498/20 ,  C07K16/22 ,  C07K2317/24

摘要： Tricyclic PI3k inhibitor compounds of Formula I with anti-cancer activity, anti-inflammatory activity, or immunoregulatory properties, and more specifically with PI3 kinase modulating or inhibitory activity are described. Methods are described for using the tricyclic PI3K inhibitor compounds of Formula I for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, organisms, or associated pathological conditions. Formula I compounds include stereoisomers, geometric isomers, tautomers, and pharmaceutically acceptable salts thereof. The dashed lines indicate an optional double bond, and at least one dashed line is a double bond. The substituents are as described.

摘要翻译： 描述了具有抗癌活性，抗炎活性或免疫调节特性，更具体地与PI3激酶调节或抑制活性的式I的三环PI3k抑制剂化合物。 描述了使用式I的三环PI3K抑制剂化合物用于体外，原位和体内诊断或治疗哺乳动物细胞，生物体或相关病理条件的方法。 式I化合物包括立体异构体，几何异构体，互变异构体及其药学上可接受的盐。 虚线表示可选的双键，至少一条虚线是双键。 取代基如所述。

公开(公告)号：US08242104B2

公开(公告)日：2012-08-14

申请号：US12890812

申请日：2010-09-27

申请人： Nicole Blaquiere ,  Steven Do ,  Danette Dudley ,  Adrian Folkes ,  Robert Heald ,  Timothy Heffron ,  Mark Jones ,  Aleksandr Kolesnikov ,  Chudi Ndubaku ,  Alan G. Olivero ,  Stephen Price ,  Steven Staben ,  Lan Wang

发明人： Nicole Blaquiere ,  Steven Do ,  Danette Dudley ,  Adrian Folkes ,  Robert Heald ,  Timothy Heffron ,  Mark Jones ,  Aleksandr Kolesnikov ,  Chudi Ndubaku ,  Alan G. Olivero ,  Stephen Price ,  Steven Staben ,  Lan Wang

IPC分类号： A61K31/553 ,  C07D498/04 ,  C07D498/14

CPC分类号： C07D498/04 ,  A61K31/553 ,  A61K45/06 ,  C07D491/044 ,  C07D498/14 ,  C07D519/00

摘要： Benzoxazepin compounds of Formula I, including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, wherein: Z1 is CR1 or N; Z2 is CR2 or N; Z3 is CR3 or N; Z4 is CR4 or N; and B is a pyrazolyl, imidazolyl, or triazolyl ring fused to the benzoxepin ring, are useful for inhibiting lipid kinases including p110 alpha and other isoforms of PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

摘要翻译： 式I的苯并氧氮杂化合物，包括立体异构体，几何异构体，互变异构体，溶剂合物，代谢物及其药学上可接受的盐，其中：Z1是CR1或N; Z2为CR2或N; Z3为CR3或N; Z4是CR4或N; B是与苯并氧杂环环稠合的吡唑基，咪唑基或三唑基环，可用于抑制脂质激酶，包括p110α和PI3K的其他同种型，并用于治疗由脂质激酶介导的癌症等疾病。 公开了使用式I化合物在体外，原位和体内诊断，预防或治疗哺乳动物细胞或相关病理状况中的这种病症的方法。