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31. 发明申请

US20080125587A1 Synthesis of triazole compounds that modulate HSP90 activity 审中-公开
标题翻译：合成调节HSP90活性的三唑化合物
公开(公告)号：US20080125587A1
公开(公告)日：2008-05-29
申请号：US11807333
申请日：2007-05-25
申请人： Dinesh U. Chimmanamada , Chi-Wan Lee , David James , Shijie Zhang , Weiwen Ying , Junghyun Chae , Teresa Przewloka
发明人： Dinesh U. Chimmanamada , Chi-Wan Lee , David James , Shijie Zhang , Weiwen Ying , Junghyun Chae , Teresa Przewloka
IPC分类号： C07D249/12 , C07D407/02 , C07D403/02 , C07D401/02 , C07D401/04 , C07D403/10 , C07D417/02 , C07D487/04 , C07D413/12 , C07D413/02
CPC分类号： C07D403/04 , C07D249/12 , C07D249/14 , C07D401/04 , C07D401/10 , C07D403/10 , C07D413/04 , C07D417/04
摘要： The present invention provides novel methods of preparing triazole compounds which inhibit the activity of Hsp90. One embodiment of the invention is directed to methods for preparing a triazole compound represented by the following Structural Formula: or a tautomer, a pharmaceutically acceptable salt, solvate, or clathrate, or a prodrug thereof, comprising the steps of: a) reacting an amide represented by the following Structural Formula: with a thionation reagent to form a thioamide; b) reacting the thioamide of step a) with hydrazine to form a hydrazonamide; c) reacting the hydrazonamide of step b) with a carbonylation or a thiocarbonylation reagent.In one embodiment, the present invention is a method of synthesis of a compound of formula (IA) or a tautomer, a pharmaceutically acceptable salt, solvate, or clathrate, or a prodrug thereof, comprising reacting a compound of formula (IIA) with an oxidizing agent, thereby producing a compound of formula (IA).The present invention is also directed to a method of preparing a compound or a tautomer thereof represented by the following Structural Formula: or a tautomer, a pharmaceutically acceptable salt, solvate, or clathrate, or a prodrug thereof. The method comprises the step of reacting a first starting compound represented by the following Structural Formula: in the presence of a mercuric salt, with a second starting compound represented by the following Structural Formula:
摘要翻译：本发明提供抑制Hsp90活性的三唑化合物的新方法。本发明的一个实施方案涉及制备由以下结构式表示的三唑化合物或互变异构体，药学上可接受的盐，溶剂化物或包合物或其前药的方法，其包括以下步骤：a）使酰胺由以下结构式表示：用硫化试剂形成硫代酰胺; b）使步骤a）的硫代酰胺与肼反应形成腙酰胺; c）使步骤b）的腙与羰基化或硫代羰基化试剂反应。在一个实施方案中，本发明是合成式（IA）化合物或互变异构体，其药学上可接受的盐，溶剂化物或包合物或其前药的方法，包括使式（IIA）化合物与氧化剂，从而制备式（IA）化合物。本发明还涉及制备由以下结构式表示的化合物或其互变异构体的方法：或其互变异构体，药学上可接受的盐，溶剂化物或包合物或其前药。该方法包括使由以下结构式表示的第一起始化合物在汞盐存在下与由以下结构式表示的第二起始化合物反应的步骤：

32. 发明授权

US07067514B2 Pyrimidine compounds 有权
公开(公告)号：US07067514B2
公开(公告)日：2006-06-27
申请号：US10656671
申请日：2003-09-05
申请人： Mitsunori Ono , Shijie Zhang , Teresa Przewloka , Keizo Koya , Elena Kostik , Yuniko Wada , Lijun Sun , Weiwen Ying
发明人： Mitsunori Ono , Shijie Zhang , Teresa Przewloka , Keizo Koya , Elena Kostik , Yuniko Wada , Lijun Sun , Weiwen Ying
IPC分类号： A61K31/506 , A61P3/10 , A61P17/06 , A61P19/02 , A61P25/28
CPC分类号： C07D239/48 , A61K31/506 , A61K31/53 , A61K31/5377 , A61K31/541 , C07D401/12 , C07D401/14 , C07D403/12
摘要： This invention features pyrimidine compounds of formula (I): R1 is aryl, or heteroaryl; each of R2 and R4, independently, is Rc, halogen, nitro, cyano, isothionitro, SRc, or ORc; or R2 and R4, taken together, is carbonyl; R3 is Rc, alkenyl, alkynyl, ORc, OC(O)Rc, SO2Rc, S(O)Rc, S(O2)NRcRd, SRc, NRcRd, NRcCORd, NRcC(O)ORd, NRcC(O)NRcRd, NRcSO2Rd, CORc, C(O)ORc, or C(O)NRcRd; R5 is H or alkyl; n is 0, 1, 2, 3, 4, 5, or 6; X is O, S, S(O), S(O2), or NRc; Y is a covalent bond, CH2, C(O), C═N—Rc, C═N—ORc, C═N—SRc, O, S, S(O), S(O2), or NRc; Z is N or CH; one of U and V is N, and the other is CRc; and W is O, S, S(O), S(O2), NRc, or NC(O)Rc; in which each of Ra and Rb, independently, is H, alkyl, aryl, heteroaryl; and each of Rc and Rd, independently, is H, alkyl, aryl, heteroaryl, cyclyl, heterocyclyl, or alkylcarbonyl.

33. 发明申请

US20060025409A1 Pyrimidine compounds 失效
公开(公告)号：US20060025409A1
公开(公告)日：2006-02-02
申请号：US11193001
申请日：2005-07-29
申请人： Mitsunori Ono , Shijie Zhang , Teresa Przewloka , Keizo Koya , Elena Kostik , Yuniko Wada , Lijun Sun , Weiwen Ying
发明人： Mitsunori Ono , Shijie Zhang , Teresa Przewloka , Keizo Koya , Elena Kostik , Yuniko Wada , Lijun Sun , Weiwen Ying
IPC分类号： A61K31/541 , A61K31/5377 , A61K31/53 , A61K31/506
CPC分类号： C07D239/48 , A61K31/506 , A61K31/53 , A61K31/5377 , A61K31/541 , C07D401/12 , C07D401/14 , C07D403/12
摘要： This invention features pyrimidine compounds of formula (I): R1 is aryl, or heteroaryl; each of R2 and R4, independently, is Rc, halogen, nitro, cyano, isothionitro, SRc, or ORc; or R2 and R4, taken together, is carbonyl; R3 is Rc, alkenyl, alkynyl, ORc, OC(O)Rc, SO2Rc, S(O)Rc, S(O2)NRcRd, SRc, NRcRd, NRcCORd, NRcC(O)ORd, NRcC(O)NRcRd; NRcSO2Rd, CORc, C(O)ORc, or C(O)NRcRd, R5 is H or alkyl; n is 0, 1, 2, 3, 4, 5, or 6; X is O, S, S(O), S(O2), or NRc; Y is a covalent bond, CH2, C(O), C═N—Rc, C═N—ORc, C═N—SRc, O, S, S(O), S(O2), or NRc; Z is N or CH; one of U and V is N, and the other is CRc; and W is O, S, S(O), S(O2), NRc, or NC(O)Rc; in which each of Ra and Rb, independently, is H, alkyl, aryl, heteroaryl; and each of Rc and Rd, independently, is H, alkyl, aryl, heteroaryl, cyclyl, heterocyclyl, or alkylcarbonyl.

34. 发明授权

US06693097B2 Pyrimidine compounds 有权
标题翻译：嘧啶化合物
公开(公告)号：US06693097B2
公开(公告)日：2004-02-17
申请号：US10000742
申请日：2001-11-30
申请人： Mitsunori Ono , Shijie Zhang , Teresa Przewloka , K. Koya , Elena Kostik , Yuniko Wada , Lijun Sun , Weiwen Ying
发明人： Mitsunori Ono , Shijie Zhang , Teresa Przewloka , K. Koya , Elena Kostik , Yuniko Wada , Lijun Sun , Weiwen Ying
IPC分类号： C07D41704
CPC分类号： C07D239/48 , A61K31/506 , A61K31/53 , A61K31/5377 , A61K31/541 , C07D401/12 , C07D401/14 , C07D403/12
摘要： This invention features pyrimidine compounds of formula (I): aryl, or heteroaryl; each of R2 and R4, independently, is Rc, halogen, nitro, cyano, isothionitro, SRc, or ORc; or R2 and R4, taken together, is carbonyl; R3 is Rc, alkenyl, alkynyl, ORc, OC(O)Rc, SO2Rc, S(O)Rc, S(O2)NRcRd, SRc, NRcRd, NRcCORd, NRcC(O)ORd, NRcC(O)NRcRd, NRcSO2Rd, CORc, C(O)ORc, or C(O)NRcRd; R5 is H or alkyl; n is 0, 1, 2, 3, 4, 5, or 6; X is O, S, S(O), S(O2), or NRc; Y is a covalent bond, CH2, C(O), C═N—Rc, C═N—ORc, C═N—SRc, O, S, S(O), S(O2), or NRc; Z is N or CH; one of U and V is N, and the other is CRc; and W is O, S, S(O), S(O2), NRc, or NC(O)Rc; in which each of Ra and Rb, independently, is H, alkyl, aryl, heteroaryl; and each of Rc and Rd, independently, is H, alkyl, aryl, heteroaryl, cyclyl, heterocyclyl, or alkylcarbonyl.
摘要翻译：本发明的特征在于式（I）的嘧啶化合物：芳基或杂芳基; R 2和R 4各自独立地是R c，卤素，硝基，氰基，异硫代，SR c或OR c; 或R 2和R 4一起是羰基; R 3是R c，链烯基，炔基，OR c，OC（O）R c，SO 2 R c，S（O）R c，S（O 2）NR c NR c C（O）OR d，NR c C（O）NR c， R d，NR c，SO 2 R d，COR c，C（O）OR c或C（O）NR c R d; R5是H或烷基; n是0，1，2，3，4，5或6; X是O，S，S（O），S（O 2）或NR c; Y是共价键，CH 2，C（O），C = NR c，C = N-OR c，C = N-SR c，O，S，S（O））或NR ; Z是N或CH; U和V之一是N，另一个是CR ; 并且W是O，S，S（O），S（O 2），NR c或NC（O）R c; 其中R 1和R 2各自独立地是H，烷基，芳基，杂芳基; R c和R d各自独立地是H，烷基，芳基，杂芳基，环基，杂环基或烷基羰基。

35. 发明授权

US07465725B2 Pyrimidine compounds 失效
标题翻译：嘧啶化合物
公开(公告)号：US07465725B2
公开(公告)日：2008-12-16
申请号：US11193001
申请日：2005-07-29
申请人： Mitsunori Ono , Lijun Sun , Teresa Przewloka , Shijie Zhang , Elena Kostik , Weiwen Ying , Yumiko Wada , Keizo Koya
发明人： Mitsunori Ono , Lijun Sun , Teresa Przewloka , Shijie Zhang , Elena Kostik , Weiwen Ying , Yumiko Wada , Keizo Koya
IPC分类号： A61K31/506 , A61P17/06 , A61P19/02 , A61P25/28 , C07D401/04 , C07D405/04 , C07D413/04 , C07D417/04 , C07D239/24
CPC分类号： C07D239/48 , A61K31/506 , A61K31/53 , A61K31/5377 , A61K31/541 , C07D401/12 , C07D401/14 , C07D403/12
摘要： This invention features pyrimidine compounds of formula (I): R1 is aryl, or heteroaryl; each of R2 and R4, independently, is Rc, halogen, nitro, cyano, isothionitro, SRc, or ORc; or R2 and R4, taken together, is carbonyl; R3 is Rc, alkenyl, alkynyl, ORc, OC(O)Rc, SO2Rc, S(O)Rc, S(O2)NRcRd, SRc, NRcRd, NRcCORd, NRcC(O)ORd, NRcC(O)NRcRd, NRcSO2Rd, CORc, C(O)ORc, or C(O)NRcRd; R5 is H or alkyl; n is 0, 1, 2, 3, 4, 5, or 6; X is O, S, S(O), S(O2), or NRc; Y is a covalent bond, CH2, C(O), C═N—Rc, C═N—ORc, C═N—SRc, O, S, S(O), S(O2), or NRc; Z is N or CH; one of U and V is N, and the other is CRc; and W is O, S, S(O), S(O2), NRc, or NC(O)Rc; in which each of Ra and Rb, independently, is H, alkyl, aryl, heteroaryl; and each of Rc and Rd, independently, is H, alkyl, aryl, heteroaryl, cyclyl, heterocyclyl, or alkylcarbonyl.
摘要翻译：本发明具有式（I）的嘧啶化合物：R1是芳基或杂芳基; R 2和R 4各自独立地是Rc，卤素，硝基，氰基，异硫脲，SRc或ORc; 或R 2和R 4一起是羰基; R3是Rc，烯基，炔基，ORc，OC（O）Rc，SO2Rc，S（O）Rc，S（O2）NRcRd，SRc，NRcRd，NRcCORd，NRcC（O）ORd，NRcC（O）NRcRd，NRcSO2Rd， CORc，C（O）ORc或C（O）NRcRd; R5是H或烷基; n是0，1，2，3，4，5或6; X是O，S，S（O），S（O 2）或NR c; Y是共价键，CH2，C（O），C-N-Rc，C-N-ORc，C-N-SRc，O，S，S（O），S（O 2）或NRc; Z是N或CH; U和V之一是N，另一个是CRc; 并且W是O，S，S（O），S（O 2），NR c或NC（O）R c; 其中R a和R b各自独立地为H，烷基，芳基，杂芳基; R c和R d各自独立地为H，烷基，芳基，杂芳基，环基，杂环基或烷基羰基。

36. 发明申请

US20060122156A1 Heteroaryl compounds 有权
标题翻译：杂芳基化合物
公开(公告)号：US20060122156A1
公开(公告)日：2006-06-08
申请号：US11271704
申请日：2005-11-10
申请人： Lijun Sun , Shijie Zhang , Keizo Koya , Dinesh Chimmanamada , Hao Li , David James , Elena Kostik
发明人： Lijun Sun , Shijie Zhang , Keizo Koya , Dinesh Chimmanamada , Hao Li , David James , Elena Kostik
IPC分类号： A61K31/541 , A61K31/5377 , A61K31/655
CPC分类号： C07D213/75 , C07D213/77 , C07D239/47 , C07D239/48 , C07D239/50 , C07D239/56 , C07D251/42 , C07D251/52 , C07D401/04 , C07D401/12 , C07D401/14 , C07D403/04 , C07D403/12 , C07D405/14 , C07D409/04 , C07D409/14 , C07D413/12 , C07D413/14 , C07D417/04 , C07D417/14 , C07D491/10
摘要： This invention relates to compounds of formula (I): their compositions and methods of use thereof. The compounds (and compositions) are useful in modulating IL-12 production and processes mediated by IL-12.
摘要翻译：本发明涉及式（I）化合物：它们的组成及其使用方法。化合物（和组合物）可用于调节由IL-12介导的IL-12产生和过程。

37. 发明申请

US20060069090A1 Triazine compounds 审中-公开
标题翻译：三嗪化合物
公开(公告)号：US20060069090A1
公开(公告)日：2006-03-30
申请号：US11264981
申请日：2005-11-01
申请人： M. Ono , Lijun Sun , Shijie Zhang , Teresa Przewloka , David James , Wenli Ding , Yumiko Wada
发明人： M. Ono , Lijun Sun , Shijie Zhang , Teresa Przewloka , David James , Wenli Ding , Yumiko Wada
IPC分类号： A61K31/541 , A61K31/5377 , A61K31/53
CPC分类号： C07D231/12 , A61K31/53 , A61K31/5377 , A61K31/541 , C07D233/56 , C07D249/08 , C07D401/14 , C07D403/12 , C07D403/14 , C07D405/12 , C07D405/14 , C07D409/12 , C07D409/14 , C07D417/12
摘要： This invention relates to triazine compounds of formula (I): R1 is aryl, or heteroaryl; each of R2, R4, and R5, independently, is Rc, halogen, nitro, nitroso, cyano, azide, isothionitro, SRc, or ORc; R3 is Rc, alkenyl, alkynyl, aryl, heteroaryl, cyclyl, heterocyclyl, ORc, OC(O)Rc, SO2Rc, S(O)Rc, S(O2)NRcRd, SRc, NRcRd, NRcCORd, NRcC(O)ORd, NRcC(O)NRcRd, NRcSO2, CORc, C(O)ORc, or C(O)NRcRd; n is 0, 1, 2, 3, 4, 5, 6, or 7; X is O, S, S(O), S(O2), or NRc; Y is a covalent bond, CH2, C(O), C═N—Rc, C═N—ORc, C═N—SRc, O, S, S(O), or S(O2); Z is N; and W is O, S, S(O), S(O2), NRc, or NC(O)Rc; in which each of Ra and Rb, independently, is H, alkyl, aryl, heteroaryl; and each of Rc and Rd, independently, is H, alkyl, or alkylcarbonyl.
摘要翻译：本发明涉及式（I）的三嗪化合物：

38. 发明授权

US06680315B2 Triazine compounds 有权
标题翻译：三嗪化合物
公开(公告)号：US06680315B2
公开(公告)日：2004-01-20
申请号：US10006624
申请日：2001-11-30
申请人： Mitsunori Ono , Lijun Sun , Shijie Zhang , Teresa Przewloka , David A. James , Wenli Ding , Yumiko Wada
发明人： Mitsunori Ono , Lijun Sun , Shijie Zhang , Teresa Przewloka , David A. James , Wenli Ding , Yumiko Wada
IPC分类号： C07D40304
CPC分类号： C07D231/12 , A61K31/53 , A61K31/5377 , A61K31/541 , C07D233/56 , C07D249/08 , C07D401/14 , C07D403/12 , C07D403/14 , C07D405/12 , C07D405/14 , C07D409/12 , C07D409/14 , C07D417/12
摘要： This invention relates to triazine compounds of formula (I): R1 is, aryl, or heteroaryl; each of R2, R4, and R5, independently, is Rc, halogen, nitro, nitroso, cyano, azide, isothionitro, SRc, or ORc; R3 is Rc, alkenyl, alkynyl, aryl, heteroaryl, cyclyl, heterocyclyl, ORc, OC(O)Rc, SO2Rc, S(O)Rc, S(O2)NRcRd, SRc, NRcRd, NRcCORd, NRcC(O)ORd, NRcC(O)NRcRd, NRcSO2Rd, CORc, C(O)ORc, or C(O)NRcRd; n is 0, 1, 2, 3, 4, 5, 6, or 7; X is O, S, S(O), S(O2), or NRc; Y is a covalent bond, CH2, C(O), C═N—Rc, C═N—ORc, C═N—SRc, O, S, S(O), or S(O2); Z is N; and W is O, S, S(O), S(O2), NRc, or NC(O)Rc; in which each of Ra and Rb, independently, is H, alkyl, aryl, heteroaryl; and each of Rc and Rd, independently, is H, alkyl, or alkylcarbonyl.
摘要翻译：本发明涉及式（I）的三嗪化合物：R1是芳基或杂芳基; R 2，R 4和R 5各自独立地是R c，卤素，硝基，亚硝基，氰基，叠氮化物，异硫脲，SR c或OR c; R 3是R c，烯基，炔基，芳基，杂芳基，环基，杂环基，OR c，OC（O）R c，SO 2 R c，S（O）R c， NR c，R c，NR c，R d，NR c R d，NR c C（O）OR d，NR c， C（O）NR c R d，NR c SO 2 R d，COR c，C（O）OR c或C（O）NR c R d; n为0，1，2，3，4，5，6或7; X是O，S，S（O），S（O 2）或NR c; Y是共价键，CH 2，C（O），C = NR c，C = N-OR c，C = N-SR c，O，S，S（O） O2）; Z是N; 并且W是O，S，S（O），S（O 2），NR c或NC（O）R c; 其中R 1和R 2各自独立地是H，烷基，芳基，杂芳基; R c和R d各自独立地是H，烷基或烷基羰基。

39. 发明授权

US07919487B2 Heteroaryl compounds 有权
标题翻译：杂芳基化合物
公开(公告)号：US07919487B2
公开(公告)日：2011-04-05
申请号：US11271704
申请日：2005-11-10
申请人： Lijun Sun , Shijie Zhang , Keizo Koya , Dinesh Chimmanamada , Hao Li , David James , Elena Kostik
发明人： Lijun Sun , Shijie Zhang , Keizo Koya , Dinesh Chimmanamada , Hao Li , David James , Elena Kostik
IPC分类号： A61K31/397 , A61K31/5377 , A61K31/50 , A61K31/53 , A61K31/505 , C07D413/14 , C07D251/02 , C07D401/14
CPC分类号： C07D213/75 , C07D213/77 , C07D239/47 , C07D239/48 , C07D239/50 , C07D239/56 , C07D251/42 , C07D251/52 , C07D401/04 , C07D401/12 , C07D401/14 , C07D403/04 , C07D403/12 , C07D405/14 , C07D409/04 , C07D409/14 , C07D413/12 , C07D413/14 , C07D417/04 , C07D417/14 , C07D491/10
摘要： This invention relates to compounds of formula (I): their compositions and methods of use thereof. The compounds (and compositions) are useful in modulating IL-12 production and processes mediated by IL-12.
摘要翻译：本发明涉及式（I）化合物：它们的组成及其使用方法。化合物（和组合物）可用于调节由IL-12介导的IL-12产生和过程。

40. 发明申请

US20050148633A1 Method for modulating calcium ion-release-activated calcium ion channels 审中-公开
标题翻译：钙离子释放活化钙离子通道调节方法
公开(公告)号：US20050148633A1
公开(公告)日：2005-07-07
申请号：US10897682
申请日：2004-07-22
申请人： Yu Xie , Mats Holmqvist , Jerome Mahiou , Mitsunori Ono , Lijun Sun , Shoujun Chen , Shijie Zhang , Jun Jiang , Dinesh Chimmanamada , Andrea Fleig , Chih-Yi Yu
发明人： Yu Xie , Mats Holmqvist , Jerome Mahiou , Mitsunori Ono , Lijun Sun , Shoujun Chen , Shijie Zhang , Jun Jiang , Dinesh Chimmanamada , Andrea Fleig , Chih-Yi Yu
IPC分类号： A61K31/35 , A61K31/381 , A61K31/40 , A61K31/41 , A61K31/415 , A61K31/4196 , A61K31/42 , A61K31/4439 , A61K31/444 , A61K31/535 , A61K31/724 , A61P20060101 , A61P27/00 , C07D20060101
CPC分类号： C07C233/66 , A61K31/40 , A61K31/41 , A61K31/415 , A61K31/42 , A61K31/535 , C07C237/42 , C07D213/81 , C07D231/14 , C07D239/28 , C07D263/34 , C07D277/56 , C07D285/06 , C07D333/38 , Y02A50/422
摘要： The invention relates to a method for modulating Ca2+-release-activated Ca2+ channels (CRAC) in a cell by administering to the cell a compound of formula (I): or a pharmaceutically acceptable salt, solvate, clathrate, or prodrug thereof wherein X, Y, A, Z, L and n are defined herein.
摘要翻译：本发明涉及一种通过向细胞施用式（I（I））化合物来调节细胞中的Ca 2+ - 释放激活的Ca 2+ 2 +通道（CRAC）的方法）或其药学上可接受的盐，溶剂化物，包合物或前药，其中X，Y，A，Z，L和n如本文所定义。

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