公开(公告)号：US20090023791A1

公开(公告)日：2009-01-22

申请号：US12151633

申请日：2008-05-08

申请人： Stephen F. Traynelis ,  Dennis C. Liotta ,  James P. Snyder ,  Yesim Altas ,  David D. Mott ,  James J. Doherty, JR. ,  Raymond J. Dingledine

发明人： Stephen F. Traynelis ,  Dennis C. Liotta ,  James P. Snyder ,  Yesim Altas ,  David D. Mott ,  James J. Doherty, JR. ,  Raymond J. Dingledine

IPC分类号： A61K31/421 ,  C07C311/01 ,  A61K31/18 ,  A61K31/13 ,  A61P25/00 ,  C07C211/01 ,  C07C311/15 ,  C07D263/30

CPC分类号： C07C217/34 ,  C07C311/08 ,  C07C311/21 ,  C07D263/24

摘要： NMDA receptor blockers, including pH-sensitive NMDA receptor blockers, are provided as neurprotective drugs that are useful in stroke, traumatic brain injury, epilepsy, and other neurologic events that involve acidification of brain or spinal cord tissue. Compositions and methods of this invention are used for treating neurodegeneration resulting from NMDA receptor activation. The compounds described herein have enhanced activity in brain tissue having lower than normal pH due to pathological conditions such as hypoxia resulting from stroke, traumatic brain injury, global ischemia that may occur during cardiac surgery, hypoxia that may occur following cessation of breathing, pre-eclampsia, spinal cord trauma, epilepsy, chrounic pain, vascular dementia and glioma rumors. Compounds described herein are also useful in preventing neurodegeneration in patients with Parkinson's Alzheimer's, Huntington's chorea, ALS, and other neurodegenerative conditions known to the art to be responsive to treatment using NMDA receptor blockers. Prefebably the compounds provided herein are allosteric NMDA inhibitors.

摘要翻译： NMDA受体阻滞剂，包括pH敏感的NMDA受体阻断剂，作为神经保护药物提供，其可用于中风，创伤性脑损伤，癫痫以及涉及脑或脊髓组织酸化的其他神经系统事件。 本发明的组合物和方法用于治疗由NMDA受体活化引起的神经变性。 本文所述的化合物由于病理状况如卒中引起的缺氧，创伤性脑损伤，心脏手术期间可能发生的全身缺血，呼吸停止后可能发生的缺氧等病理状况，具有低于正常pH值的脑组织中的活性增强， 子痫，脊髓创伤，癫痫，腮腺炎，血管性痴呆和神经胶质瘤。 本文所述的化合物也可用于预防帕金森氏老年痴呆症，亨廷顿氏舞蹈病，ALS患者和本领域已知的对NMDA受体阻断剂治疗有反应的其它神经变性病症患者的神经变性。 本文提供的化合物可能是变构NMDA抑制剂。

公开(公告)号：US07375136B2

公开(公告)日：2008-05-20

申请号：US10469824

申请日：2002-03-08

申请人： Stephen F. Traynelis ,  Dennis C. Liotta ,  James P. Snyder ,  Yesim Altas ,  David D. Mott ,  James J. Doherty, Jr. ,  Raymond J. Dingledine

发明人： Stephen F. Traynelis ,  Dennis C. Liotta ,  James P. Snyder ,  Yesim Altas ,  David D. Mott ,  James J. Doherty, Jr. ,  Raymond J. Dingledine

IPC分类号： A61K31/18 ,  C07C311/18

CPC分类号： C07C217/34 ,  C07C311/08 ,  C07C311/21 ,  C07D263/24

摘要： NMDA receptor blockers, including pH-sensitive NMDA receptor blockers, are provided as neuroprotective drugs that are useful in stroke, traumatic brain injury, epilepsy, and other neurologic events that involve acidification of brain or spinal cord tissue. Compositions and methods of this invention are used for treating neurodegeneration resulting from NMDA receptor activation. The compounds described herein have enhanced activity in brain tissue having lower-than normal pH due to pathological conditions such as hypoxia resulting from stroke, traumatic brain injury, global ischemia that may occur during cardiac surgery, hypoxia that may occur following cessation of breathing, pre-eclampsia, spinal cord trauma, epilepsy, chronic pain, vascular dementia and glioma tumors. Compounds described herein are also useful in preventing neurodegeneration in patients with Parkinson's Alzheimer's, Huntington's chorea, ALS, and other neurodegenerative conditions known to the art to be responsive to treatment using NMDA receptor blockers. Preferably the compounds provided herein are allosteric NMDA inhibitors.

摘要翻译： 提供NMDA受体阻滞剂，包括pH敏感的NMDA受体阻断剂，作为神经保护药物，其可用于中风，创伤性脑损伤，癫痫和涉及脑或脊髓组织酸化的其它神经系统事件。 本发明的组合物和方法用于治疗由NMDA受体活化引起的神经变性。 本文所述的化合物由于病理状况如中风，外伤性脑损伤，心脏手术期间可能发生的全身缺血，呼吸停止后可能发生的缺氧等病理状况，具有低于正常pH值的脑组织中的活性增强， 癫痫，脊髓创伤，癫痫，慢性疼痛，血管性痴呆和神经胶质瘤。 本文所述的化合物还可用于预防帕金森氏老年痴呆症，亨廷顿舞蹈症，ALS患者和本领域已知的对NMDA受体阻断剂治疗有反应的其它神经变性病症患者的神经变性。 优选地，本文提供的化合物是变构NMDA抑制剂。

公开(公告)号：US20140031363A1

公开(公告)日：2014-01-30

申请号：US13862647

申请日：2013-04-15

申请人： Dennis C. Liotta ,  James P. Snyder ,  Stephen F. Traynelis ,  Lawrence Wilson ,  Cara Mosley ,  Raymond J. Dingledine ,  Scott Myers ,  Yesim Altas Tahirovic

发明人： Dennis C. Liotta ,  James P. Snyder ,  Stephen F. Traynelis ,  Lawrence Wilson ,  Cara Mosley ,  Raymond J. Dingledine ,  Scott Myers ,  Yesim Altas Tahirovic

IPC分类号： C07D295/088 ,  C07D213/74 ,  C07D209/34 ,  C07D211/52 ,  C07D215/227 ,  C07D233/32 ,  C07C311/08 ,  C07D263/58

CPC分类号： C07D209/34 ,  C07C217/20 ,  C07C235/20 ,  C07C311/08 ,  C07D211/52 ,  C07D213/74 ,  C07D215/227 ,  C07D233/32 ,  C07D233/34 ,  C07D235/26 ,  C07D263/58 ,  C07D295/088

摘要： Provided are compounds, pharmaceutical compositions and methods of treatment or prophylaxis of disorders associated with NMDA receptor activity, including neuropathic pain, stroke, traumatic brain injury, epilepsy, and related neurologic events or neurodegeneration. Compounds are of the general Formula I, or a pharmaceutically acceptable salt, ester, prodrug or derivative thereof are provided: wherein: each (L)k-Ar1 is a substituted or unsubstituted, mono or bicyclic aryl or heteroaryl; W is a bond, alkyl, or alkenyl; X is a bond, NR1 or O and each R1 and R2 is independently H, alkyl, alkenyl or aralkyl or R1 and R2 taken together form a 5-8 membered ring; R3-R6 are selected from certain specific substituents or a carbonyl; Y is a bond, O, S, SO, SO2, CH2, NH, N(alkyl), or NHC(═O); and Z is OH, NR6R7, NR8SO2(alkyl), NR8C(O)NR6R7, NR8C(O)O(alkyl), NR8-dihydrothiazole, or NR8-dihydroimidazole or wherein Z can fuse with Ar2 to form selected heterocycles.

摘要翻译： 提供了治疗或预防与NMDA受体活性相关的病症的化合物，药物组合物和方法，包括神经性疼痛，中风，创伤性脑损伤，癫痫以及相关的神经系统事件或神经变性。 化合物为通式I，或其药学上可接受的盐，酯，前药或衍生物：其中：（L）k-Ar1为取代或未取代的单或双环芳基或杂芳基; W是键，烷基或烯基; X是键，NR 1或O，并且每个R 1和R 2独立地是H，烷基，烯基或芳烷基，或者R 1和R 2一起形成5-8元环; R 3 -R 6选自某些具体取代基或羰基; Y是键，O，S，SO，SO 2，CH 2，NH，N（烷基）或NHC（= O）; 并且Z是OH，NR 6 R 7，NR 8 SO 2（烷基），NR 8 C（O）NR 6 R 7，NR 8 C（O）O（烷基），NR 8 - 二氢噻唑或NR 8 - 二氢咪唑，或其中Z可与Ar 2融合形成选定的杂环。

公开(公告)号：US09079852B2

公开(公告)日：2015-07-14

申请号：US13862647

申请日：2013-04-15

申请人： Dennis C. Liotta ,  James P. Snyder ,  Stephen F. Traynelis ,  Lawrence Wilson ,  Cara Mosley ,  Raymond J. Dingledine ,  Scott Myers ,  Yesim Altas Tahirovic

发明人： Dennis C. Liotta ,  James P. Snyder ,  Stephen F. Traynelis ,  Lawrence Wilson ,  Cara Mosley ,  Raymond J. Dingledine ,  Scott Myers ,  Yesim Altas Tahirovic

IPC分类号： A61K31/421 ,  A61K31/4166 ,  A61K31/495 ,  C07D241/04 ,  C07D263/18 ,  C07D233/08 ,  C07D209/34 ,  C07C217/20 ,  C07C235/20 ,  C07C311/08 ,  C07D215/227 ,  C07D233/34 ,  C07D235/26 ,  C07D263/58 ,  C07D295/088 ,  C07D211/52 ,  C07D213/74 ,  C07D233/32

CPC分类号： C07D209/34 ,  C07C217/20 ,  C07C235/20 ,  C07C311/08 ,  C07D211/52 ,  C07D213/74 ,  C07D215/227 ,  C07D233/32 ,  C07D233/34 ,  C07D235/26 ,  C07D263/58 ,  C07D295/088

摘要： Provided are compounds, pharmaceutical compositions and methods of treatment or prophylaxis of disorders associated with NMDA receptor activity, including neuropathic pain, stroke, traumatic brain injury, epilepsy, and related neurologic events or neurodegeneration. Compounds are of the general Formula I, or a pharmaceutically acceptable salt, ester, prodrug or derivative thereof are provided: wherein: each (L)k-Ar1 is a substituted or unsubstituted, mono or bicyclic aryl or heteroaryl; W is a bond, alkyl, or alkenyl; X is a bond, NR1 or O and each R1 and R2 is independently H, alkyl, alkenyl or aralkyl or R1 and R2 taken together form a 5-8 membered ring; R3−-R6 are selected from certain specific substituents or a carbonyl; Y is a bond, O, S, SO, SO2, CH2, NH, N(alkyl), or NHC(═O); and Z is OH, NR6R7, NR8SO2(alkyl), NR8C(O)NR6R7, NR8C(O)O(alkyl), NR8-dihydrothiazole, or NR8-dihydroimidazole or wherein Z can fuse with Ar2 to form selected heterocycles.

摘要翻译： 提供了治疗或预防与NMDA受体活性相关的病症的化合物，药物组合物和方法，包括神经性疼痛，中风，创伤性脑损伤，癫痫以及相关的神经系统事件或神经变性。 化合物为通式I，或其药学上可接受的盐，酯，前药或衍生物：其中：（L）k-Ar1为取代或未取代的单或双环芳基或杂芳基; W是键，烷基或烯基; X是键，NR 1或O，并且每个R 1和R 2独立地是H，烷基，烯基或芳烷基，或者R 1和R 2一起形成5-8元环; R 3 -R 6选自某些具体取代基或羰基; Y是键，O，S，SO，SO 2，CH 2，NH，N（烷基）或NHC（= O）; 并且Z是OH，NR 6 R 7，NR 8 SO 2（烷基），NR 8 C（O）NR 6 R 7，NR 8 C（O）O（烷基），NR 8 - 二氢噻唑或NR 8 - 二氢咪唑，或其中Z可与Ar 2融合形成选定的杂环。

公开(公告)号：US08420680B2

公开(公告)日：2013-04-16

申请号：US12165308

申请日：2008-06-30

申请人： Dennis C. Liotta ,  James P. Snyder ,  Stephen F. Traynelis ,  Lawrence Wilson ,  Cara Mosley ,  Raymond J. Dingledine ,  Yesim Altas Tahirovic ,  Scott J. Myers

发明人： Dennis C. Liotta ,  James P. Snyder ,  Stephen F. Traynelis ,  Lawrence Wilson ,  Cara Mosley ,  Raymond J. Dingledine ,  Yesim Altas Tahirovic ,  Scott J. Myers

IPC分类号： A61K31/4166 ,  A61K31/421 ,  A61K31/495 ,  C07D241/04 ,  C07D263/18 ,  C07D233/08

CPC分类号： C07D209/34 ,  C07C217/20 ,  C07C235/20 ,  C07C311/08 ,  C07D211/52 ,  C07D213/74 ,  C07D215/227 ,  C07D233/32 ,  C07D233/34 ,  C07D235/26 ,  C07D263/58 ,  C07D295/088

摘要： Provided are compounds, pharmaceutical compositions and methods of treatment or prophylaxis of disorders associated with NMDA receptor activity, including neuropathic pain, stroke, traumatic brain injury, epilepsy, and related neurologic events or neurodegeneration. Compounds are of the general Formula I, or a pharmaceutically acceptable salt, ester, prodrug or derivative thereof are provided: wherein: each (L)k-Ar1 is a substituted or unsubstituted, mono or bicyclic aryl or heteroaryl; W is a bond, alkyl, or alkenyl; X is a bond, NR1 or O and each R1 and R2 is independently H, alkyl, alkenyl or aralkyl or R1 and R2 taken together form a 5-8 membered ring; R3−R6 are selected from certain specific substituents or a carbonyl; Y is a bond, O, S, SO, SO2, CH2, NH, N(alkyl), or NHC(═O); and Z is OH, NR6R7, NR8SO2(alkyl), NR8C(O)NR6R7, NR8C(O)O(alkyl), NR8-dihydrothiazole, or NR8-dihydroimidazole or wherein Z can fuse with Ar2 to form selected heterocycles.

摘要翻译： 提供了治疗或预防与NMDA受体活性相关的病症的化合物，药物组合物和方法，包括神经性疼痛，中风，创伤性脑损伤，癫痫以及相关的神经系统事件或神经变性。 化合物为通式I，或其药学上可接受的盐，酯，前药或衍生物：其中：（L）k-Ar1为取代或未取代的单或双环芳基或杂芳基; W是键，烷基或烯基; X是键，NR 1或O，并且每个R 1和R 2独立地是H，烷基，烯基或芳烷基，或者R 1和R 2一起形成5-8元环; R 3 -R 6选自某些具体取代基或羰基; Y是键，O，S，SO，SO 2，CH 2，NH，N（烷基）或NHC（= O）; 并且Z是OH，NR 6 R 7，NR 8 SO 2（烷基），NR 8 C（O）NR 6 R 7，NR 8 C（O）O（烷基），NR 8 - 二氢噻唑或NR 8 - 二氢咪唑，或其中Z可与Ar 2融合形成选定的杂环。

公开(公告)号：US20090253710A1

公开(公告)日：2009-10-08

申请号：US12165308

申请日：2008-06-30

申请人： Dennis C. Liotta ,  James P. Snyder ,  Stephen F. Traynelis ,  Lawrence Wilson ,  Cara Mosley ,  Raymond J. Dingledine ,  Scott Myers ,  Yesim Altas Tahirovic

发明人： Dennis C. Liotta ,  James P. Snyder ,  Stephen F. Traynelis ,  Lawrence Wilson ,  Cara Mosley ,  Raymond J. Dingledine ,  Scott Myers ,  Yesim Altas Tahirovic

IPC分类号： A61K31/496 ,  C07D241/04 ,  C07D401/04 ,  A61P25/00 ,  A61K31/495

CPC分类号： C07D209/34 ,  C07C217/20 ,  C07C235/20 ,  C07C311/08 ,  C07D211/52 ,  C07D213/74 ,  C07D215/227 ,  C07D233/32 ,  C07D233/34 ,  C07D235/26 ,  C07D263/58 ,  C07D295/088

摘要： Provided are compounds, pharmaceutical compositions and methods of treatment or prophylaxis of disorders associated with NMDA receptor activity, including neuropathic pain, stroke, traumatic brain injury, epilepsy, and related neurologic events or neurodegeneration. Compounds are of the general Formula I, or a pharmaceutically acceptable salt, ester, prodrug or derivative thereof are provided: wherein: each (L)k-Ar1 is a substituted or unsubstituted, mono or bicyclic aryl or heteroaryl; W is a bond, alkyl, or alkenyl; X is a bond, NR1 or O and each R1 and R2 is independently H, alkyl, alkenyl or aralkyl or R1 and R2 taken together form a 5-8 membered ring; R3−R6 are selected from certain specific substituents or a carbonyl; Y is a bond, O, S, SO, SO2, CH2, NH, N(alkyl), or NHC(═O); and Z is OH, NR6R7, NR8SO2(alkyl), NR8C(O)NR6R7, NR8C(O)O(alkyl), NR8-dihydrothiazole, or NR8-dihydroimidazole or wherein Z can fuse with Ar2 to form selected heterocycles.

摘要翻译： 提供了治疗或预防与NMDA受体活性相关的病症的化合物，药物组合物和方法，包括神经性疼痛，中风，创伤性脑损伤，癫痫以及相关的神经系统事件或神经变性。 化合物为通式I，或其药学上可接受的盐，酯，前药或衍生物：其中：（L）k-Ar1为取代或未取代的单或双环芳基或杂芳基; W是键，烷基或烯基; X是键，NR 1或O，并且每个R 1和R 2独立地是H，烷基，烯基或芳烷基，或者R 1和R 2一起形成5-8元环; R 3 -R 6选自某些具体取代基或羰基; Y是键，O，S，SO，SO 2，CH 2，NH，N（烷基）或NHC（-O）; 并且Z是OH，NR 6 R 7，NR 8 SO 2（烷基），NR 8 C（O）NR 6 R 7，NR 8 C（O）O（烷基），NR 8 - 二氢噻唑或NR 8 - 二氢咪唑，或其中Z可与Ar 2融合形成选定的杂环。

公开(公告)号：US08507673B2

公开(公告)日：2013-08-13

申请号：US13156969

申请日：2011-06-09

申请人： Dennis C. Liotta ,  James P. Snyder ,  Ashutosh S. Jogalekar ,  Anthony G. M. Barrett ,  Matthew John Fuchter ,  Matthew J. Cook ,  Sebastian H. B. Kroll

发明人： Dennis C. Liotta ,  James P. Snyder ,  Ashutosh S. Jogalekar ,  Anthony G. M. Barrett ,  Matthew John Fuchter ,  Matthew J. Cook ,  Sebastian H. B. Kroll

IPC分类号： C07D487/04

CPC分类号： C07D487/04

摘要： Processes for the preparation of certain 5,7-diaminopyrazolo[1,5-α]pyrimidine compounds comprising the reaction of a primary or secondary amine and a protected 5-halo-7-aminopyrazolo[1,5-α]pyrimidine compound in solvent system comprising water and one or more organic solvents, optionally in the presence of an exogenous base.

摘要翻译： 制备某些5,7-二氨基吡唑并[1,5-a]嘧啶化合物的方法，其包括伯胺或仲胺与受保护的5-卤代-7-氨基吡唑并[1,5-a]嘧啶化合物在溶剂中的反应 系统，其包含水和一种或多种有机溶剂，任选地在外源性碱的存在下。

公开(公告)号：US20080234320A1

公开(公告)日：2008-09-25

申请号：US12055068

申请日：2008-03-25

申请人： James P. Snyder ,  Matthew C. Davis ,  Brian Adams ,  Mamoru Shoji ,  Dennis C. Liotta ,  Eva M. Ferstl ,  Ustun B. Sunay

发明人： James P. Snyder ,  Matthew C. Davis ,  Brian Adams ,  Mamoru Shoji ,  Dennis C. Liotta ,  Eva M. Ferstl ,  Ustun B. Sunay

IPC分类号： A61K31/45 ,  A61K31/382 ,  A61K31/351

CPC分类号： C07D295/205 ,  C07C45/292 ,  C07C45/62 ,  C07C45/74 ,  C07C49/233 ,  C07C49/235 ,  C07C49/248 ,  C07C49/255 ,  C07C49/697 ,  C07C49/747 ,  C07C49/753 ,  C07C225/22 ,  C07C235/34 ,  C07C251/40 ,  C07C275/24 ,  C07C317/10 ,  C07C321/20 ,  C07D209/34 ,  C07D213/63 ,  C07D317/50 ,  C07D451/02

摘要： The present invention is directed to curcumin analogs exhibiting anti-tumor and anti-angiogenic properties, pharmaceutical formulations including such compounds and methods of using such compounds.

摘要翻译： 本发明涉及显示抗肿瘤和抗血管生成性质的姜黄素类似物，包括这些化合物的药物制剂和使用这些化合物的方法。

公开(公告)号：US20080227799A1

公开(公告)日：2008-09-18

申请号：US11776465

申请日：2007-07-11

申请人： Dennis C. Liotta ,  James P. Snyder ,  Weiqiang Zhan

发明人： Dennis C. Liotta ,  James P. Snyder ,  Weiqiang Zhan

IPC分类号： A61K31/505 ,  C07D239/42 ,  A61K31/506 ,  C07D401/12 ,  A61P35/00

CPC分类号： C07D239/42 ,  C07D213/64 ,  C07D213/74 ,  C07D239/48 ,  C07D241/20 ,  C07D413/12

摘要： The invention provides compounds, pharmaceutical compositions and methods of use of certain compounds that are antagonists of the chemokine CXCR4 receptor for the treatment of proliferative conditions mediated by CXCR4 receptors. The compounds provided interfere with the binding of SDF1 to the receptor. These compounds are particularly useful for treating or reducing the severity of hyperproliferative diseases by inhibiting metastasis.

摘要翻译： 本发明提供化合物，药物组合物和使用作为趋化因子CXCR4受体的拮抗剂的某些化合物用于治疗CXCR4受体介导的增殖性病症的化合物，药物组合物和方法。 所提供的化合物干扰SDF1与受体的结合。 这些化合物特别可用于通过抑制转移来治疗或降低过度增殖性疾病的严重性。

公开(公告)号：US08080659B2

公开(公告)日：2011-12-20

申请号：US11776476

申请日：2007-07-11

申请人： Dennis C. Liotta ,  James P. Snyder ,  Weiqiang Zhan

发明人： Dennis C. Liotta ,  James P. Snyder ,  Weiqiang Zhan

IPC分类号： C07D403/12 ,  C07D403/14 ,  A61K31/506 ,  A61P35/00

CPC分类号： C07D239/42 ,  C07D239/47 ,  C07D239/52 ,  C07D401/12 ,  C07D403/06 ,  C07D403/12

摘要： The invention provides compounds, pharmaceutical compositions and methods of use of certain compounds that are antagonists of the chemokine CXCR4 receptor for the treatment of proliferative conditions mediated by CXCR4 receptors or for the treatment of viral infections. The compounds provided interfere with the binding of SDF1 to the receptor. These compounds are particularly useful for treating or reducing the severity of hyperproliferative diseases by inhibiting metastasis, or for reducing entry of HIV in to a cell while not reducing the capacity of the stem cells to proliferate. The compounds may be useful for long term treatment regimes.

摘要翻译： 本发明提供化合物，药物组合物和使用作为趋化因子CXCR4受体的拮抗剂的某些化合物用于治疗由CXCR4受体介导的增殖性病症或用于治疗病毒感染的化合物，药物组合物和方法。 所提供的化合物干扰SDF1与受体的结合。 这些化合物特别可用于通过抑制转移或减少HIV进入细胞而不降低干细胞增殖的能力来治疗或降低过度增殖性疾病的严重性。 这些化合物可用于长期治疗方案。