公开(公告)号：US07799786B2

公开(公告)日：2010-09-21

申请号：US11899379

申请日：2007-09-04

Applicant: Donald J. Kyle ,  Qun Sun ,  Laykea Tafesse ,  Chongwu Zhang ,  Xiaoming Zhou

Inventor： Donald J. Kyle ,  Qun Sun ,  Laykea Tafesse ,  Chongwu Zhang ,  Xiaoming Zhou

IPC: C07D237/00 ,  C07D241/00 ,  A61K31/50 ,  A61K31/497

CPC classification number: C07D213/74 ,  C07D213/85 ,  C07D237/20 ,  C07D239/42 ,  C07D241/20 ,  C07D285/06 ,  C07D333/16

Abstract: A compound of formula: wherein A, Ar, R3, R6, and m are disclosed herein, or a pharmaceutically acceptable salt thereof (a “Cyanoiminopiperazine Compound”), compositions comprising an effective amount of a Cyanoiminopiperazine Compound, and methods for treating or preventing pain, urinary incontinence, an ulcer, inflammatory-bowel disease, irritable-bowel syndrome, an addictive disorder, Parkinson's disease, parkinsonism, anxiety, epilepsy, stroke, a seizure, a pruritic condition, psychosis, a cognitive disorder, a memory deficit, restricted brain function, Huntington's chorea, amyotrophic lateral sclerosis, dementia, retinopathy, a muscle spasm, a migraine, vomiting, dyskinesia or depression in an animal comprising administering to an animal in need thereof an effective amount of a Cyanoiminopiperazine Compound are disclosed.

Abstract translation: 本文公开的其中A，Ar，R 3，R 6和m的化合物或其药学上可接受的盐（“氰基亚氨基哌嗪化合物”），包含有效量的氰基亚氨基哌嗪化合物的组合物，以及治疗或预防的方法 疼痛，尿失禁，溃疡，炎性肠病，肠易激综合征，成瘾性疾病，帕金森病，帕金森综合征，焦虑症，癫痫，中风，癫痫发作，瘙痒症状，精神病，认知障碍，记忆缺陷， 限制性脑功能，亨廷顿氏舞蹈病，肌萎缩性侧索硬化，痴呆，视网膜病变，肌肉痉挛，偏头痛，呕吐，运动障碍或抑郁症，包括向有需要的动物施用有效量的氰基亚氨基哌嗪化合物。

公开(公告)号：US07767699B2

公开(公告)日：2010-08-03

申请号：US11317832

申请日：2005-12-22

Applicant: Donald J. Kyle ,  Qun Sun ,  Xiaoming Zhou

Inventor： Donald J. Kyle ,  Qun Sun ,  Xiaoming Zhou

IPC: A61K31/4439 ,  C07D401/04 ,  C07D401/12

CPC classification number: C07D401/04 ,  C07D401/12

Abstract: The invention provides a compound of formula (I): (where R1, Q, A and R2 are disclosed herein) or a pharmaceutically acceptable salt thereof (a “Pyridine-alkynyl Compound”); pharmaceutical compositions comprising an effective amount of a Pyridine-alkynyl Compound; and methods for treating or preventing a condition such as pain, urinary incontinence, an addictive disorder, Parkinson's disease, parkinsonism, anxiety, epilepsy, a seizure, stroke, a pruritic condition, psychosis, a cognitive disorder, a memory deficit, restricted brain function, Huntington's chorea, amyotrophic lateral sclerosis, dementia, retinopathy, a muscle spasm, a migraine, vomiting, dyskinesia or depression in an animal comprising administering to an animal in need thereof an effective amount of a Pyridine-alkynyl Compound.

Abstract translation: 本发明提供式（I）化合物：其中R 1，Q，A和R 2在本文中公开）或其药学上可接受的盐（“吡啶 - 炔基化合物”）; 包含有效量的吡啶 - 炔基化合物的药物组合物; 以及用于治疗或预防诸如疼痛，尿失禁，成瘾性障碍，帕金森病，帕金森综合征，焦虑，癫痫，癫痫发作，中风，瘙痒症状，精神病，认知障碍，记忆缺陷，限制性脑功能 亨廷顿舞蹈病，肌萎缩性侧索硬化症，痴呆症，视网膜病变，肌肉痉挛，偏头痛，呕吐，运动障碍或抑郁症，包括向有需要的动物施用有效量的吡啶 - 炔基化合物。

公开(公告)号：US07683063B2

公开(公告)日：2010-03-23

申请号：US10867546

申请日：2004-06-14

Applicant: Donald J. Kyle ,  Qun Sun ,  Laykea Tafesse

Inventor： Donald J. Kyle ,  Qun Sun ,  Laykea Tafesse

IPC: C07D417/02 ,  A61K31/495

CPC classification number: C07D211/78 ,  C07D213/02 ,  C07D401/02 ,  C07D401/04 ,  C07D401/14 ,  C07D405/12 ,  C07D405/14 ,  C07D413/14 ,  C07D417/04 ,  C07D417/14

Abstract: A compound of formula: wherein Ar1, Ar2, V, X, R3, R4, and m are as disclosed herein or a pharmaceutically acceptable salt thereof (a “Cyclo(hetero)alkenyl Compound”); compositions comprising an effective amount of a Cyclo(hetero)alkenyl Compound; and methods for treating or preventing, e.g., pain, UI, an ulcer, IBD, or IBS in an animal, comprising administering to an animal in need thereof an effective amount of a Cyclo(hetero)alkenyl Compound are disclosed herein.

Abstract translation: 下式的化合物：其中Ar1，Ar2，V，X，R3，R4和m如本文所公开或其药学上可接受的盐（“环（杂）烯基化合物”）; 包含有效量的环（杂）烯基化合物的组合物; 以及用于在动物中治疗或预防例如疼痛，UI，溃疡，IBD或IBS的方法，包括向有需要的动物施用有效量的环（杂）烯基化合物。

公开(公告)号：US20090298878A1

公开(公告)日：2009-12-03

申请号：US12373328

申请日：2007-07-12

Applicant: Akira Matsumura ,  Hidenori Mikamiyama ,  Naoki Tsuno ,  Donald J. Kyle ,  Bin Shao ,  Jiangchao Yao

Inventor： Akira Matsumura ,  Hidenori Mikamiyama ,  Naoki Tsuno ,  Donald J. Kyle ,  Bin Shao ,  Jiangchao Yao

IPC: A61K31/445 ,  C07D211/98 ,  G01N23/00 ,  C07D401/12

CPC classification number: C07D211/72 ,  C07D211/96 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D409/12 ,  C07D413/12 ,  C07D471/04

Abstract: The invention relates to oxime compounds of Formula (I) and pharmaceutically acceptable salts, prodrugs, or solvates thereof, wherein X is hydrogen, optionally substituted aryl, optionally substituted heteroaryl or the like; Y is CO, SO2, CR3R4 or the like; Z is optionally substituted lower alkyl, optionally substituted aryl or the like; W is optionally substituted lower alkylene or optionally substituted lower alkenylene, R3 and R4 are each independently hydrogen, lower alkyl or the like; p is 0, 1, or 2 and q is 0, 1 or 2. The invention is also directed to the use compounds of Formula I to treat, prevent or ameliorate a disorder responsive to the blockade of calcium channels, and particularly N-type calcium channels. Compounds of the present invention are especially useful for treating pain.

Abstract translation: 本发明涉及式（I）的肟化合物及其药学上可接受的盐，前药或溶剂化物，其中X是氢，任选取代的芳基，任选取代的杂芳基等; Y是CO，SO2，CR3R4等; Z是任选取代的低级烷基，任选取代的芳基等; W是任选取代的低级亚烷基或任选取代的低级亚烯基，R 3和R 4各自独立地是氢，低级烷基等; p是0,1或2，q是0,1或2.本发明还涉及使用式I化合物来治疗，预防或改善对阻断钙通道有响应的病症，特别是N型 钙通道。 本发明的化合物特别适用于治疗疼痛。

公开(公告)号：US07229993B2

公开(公告)日：2007-06-12

申请号：US10386483

申请日：2003-03-13

Applicant: R. Richard Goehring ,  Sam F. Victory ,  Donald J. Kyle

Inventor： R. Richard Goehring ,  Sam F. Victory ,  Donald J. Kyle

IPC: C07D237/02 ,  C07D239/02 ,  A01N43/58 ,  A61K31/50

CPC classification number: C07D239/42 ,  C07D239/47

Abstract: This invention relates to a method of treating disorders responsive to the blockade of sodium ion channels using novel aryl-substituted pyrimidine compounds of Formula I: or a pharmaceutically acceptable salt, or solvate thereof, wherein A, R1, R2, R3 and R4 are defined in the specification. The invention is also directed to the use of compounds of Formula I for the treatment of neuronal damage following global and focal ischemia, for the treatment or prevention of neurodegenerative conditions such as amyotrophic lateral sclerosis (ALS), and for the treatment, prevention or amelioration of both acute or chronic pain, as antitinnitus agents, as anticonvulsants, and as antimanic depressants, as local anesthetics, as antiarrhythmics and for the treatment or prevention of diabetic neuropathy.

Abstract translation: 本发明涉及使用新的式I的芳基取代嘧啶化合物或其药学上可接受的盐或溶剂化物来治疗对钠离子通道阻断有反应的病症的方法，其中A，R 1， 在说明书中定义了R 2，R 3和R 4。 本发明还涉及式I化合物用于治疗全身和局部缺血后的神经元损伤，用于治疗或预防神经变性疾病如肌萎缩性侧索硬化（ALS）以及治疗，预防或改善的用途 作为抗惊厥剂，作为抗惊厥剂，作为抗躁狂抑制剂，作为局部麻醉剂，作为抗心律失常药物和用于治疗或预防糖尿病性神经病变。

公开(公告)号：US07071335B2

公开(公告)日：2006-07-04

申请号：US10355186

申请日：2003-01-31

Applicant: Donald J. Kyle ,  Sun Qun

Inventor： Donald J. Kyle ,  Sun Qun

IPC: C07D401/04 ,  A61K31/496

CPC classification number: C07D405/12 ,  C07D213/74 ,  C07D417/12

Abstract: A Compound of formula (wherein X is O or S and R1–R5 are disclosed herein) or a pharmaceutically acceptable salt thereof (each being a “Piperazine Compound”), pharmaceutical compositions comprising a Piperazine Compound and methods for treating or preventing pain, UI, an ulcer, IBD, IBS, an addictive disorder, Parkinson's disease, parkinsonism, anxiety, epilepsy, stroke, a seizure, a pruritic condition, psychosis, a cognitive disorder, a memory deficit, restricted brain function, Huntington's chorea, amyotrophic lateral sclerosis, dementia, retinopathy, a muscle spasm, a migraine, vomiting, dyskinesia, or depression in an animal comprising administering to an animal in need thereof an effective amount of a Piperazine Compound are disclosed.

Abstract translation: 式（其中X为O或S和R 1 -R 5）的化合物或其药学上可接受的盐（各自为“哌嗪化合物”）， ，包含哌嗪化合物的药物组合物和治疗或预防疼痛，UI，溃疡，IBD，IBS，成瘾性障碍，帕金森病，帕金森综合征，焦虑症，癫痫，中风，癫痫发作，瘙痒症状，精神病，认知 障碍，记忆缺陷，限制性脑功能，亨廷顿氏舞蹈病，肌萎缩性侧索硬化，痴呆，视网膜病，肌肉痉挛，偏头痛，呕吐，运动障碍或抑郁症，包括向有需要的动物施用有效量的 哌嗪化合物被公开。

公开(公告)号：US06974818B2

公开(公告)日：2005-12-13

申请号：US10374863

申请日：2003-02-27

Applicant: Donald J. Kyle ,  Qun Sun

Inventor： Donald J. Kyle ,  Qun Sun

IPC: A61K31/496 ,  A61K45/00 ,  A61P1/04 ,  A61P1/08 ,  A61P9/00 ,  A61P25/04 ,  A61P25/06 ,  A61P25/14 ,  A61P25/16 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P27/02 ,  A61P29/00 ,  A61P43/00 ,  C07D285/10 ,  C07D417/04

CPC classification number: C07D285/10

Abstract: A compound of formula: (wherein X is O or S and R1, R3, R4, and R5 are disclosed herein) or a pharmaceutically acceptable salt thereof (a “Thiadiazolylpiperazine Compound”), pharmaceutical compositions comprising a Thiadiazolylpiperazine Compound, and methods for treating or preventing pain in a patient comprising administering to a patient in need thereof an effective amount of a Thiadiazolylpiperazine Compound are disclosed.

Abstract translation: 下式的化合物：其中X是O或S和R 1，R 3，R 4和R 5， / SUP>在本文中公开）或其药学上可接受的盐（“噻二唑基哌嗪化合物”），包含噻二唑基哌嗪化合物的药物组合物，以及用于治疗或预防患者疼痛的方法，包括向有需要的患者施用有效量的 公开了噻二唑基哌嗪化合物。

公开(公告)号：US06956038B2

公开(公告)日：2005-10-18

申请号：US10195530

申请日：2002-07-16

Applicant: Qun Sun ,  Donald J. Kyle

Inventor： Qun Sun ,  Donald J. Kyle

Abstract: This invention relates aryl substituted thiazolidinones of Formula I: or a pharmaceutically acceptable salt, or solvate thereof, wherein R1 and R2, are defined in the specification. The invention is also directed to the use of compounds of Formula I for the treatment of neuronal damage following global and focal ischemia, for the treatment or prevention of neurodegenerative conditions such as amyotrophic lateral sclerosis (ALS), and for the treatment, prevention or amelioration of both acute or chronic pain, as antitinnitus agents, as anticonvulsants, and as antimanic depressants, as local anesthetics, as antiarrhythmics and for the treatment or prevention of diabetic neuropathy.

公开(公告)号：US06864261B2

公开(公告)日：2005-03-08

申请号：US10429078

申请日：2003-05-02

Applicant: Parviz Gharagozloo ,  Khondaker Islam ,  Donald J. Kyle ,  Qun Sun ,  Laykea Tafesse ,  John William Frank Whitehead ,  Ji Yang ,  Xiaoming Zhou

Inventor： Parviz Gharagozloo ,  Khondaker Islam ,  Donald J. Kyle ,  Qun Sun ,  Laykea Tafesse ,  John William Frank Whitehead ,  Ji Yang ,  Xiaoming Zhou

IPC: A61P25/00 ,  A61P29/00 ,  C07D213/74 ,  C07D213/80 ,  C07D213/85 ,  C07D401/04 ,  C07D401/14 ,  C07D405/12 ,  A61K31/496

CPC classification number: C07D213/74 ,  C07D213/80 ,  C07D213/85 ,  C07D401/04 ,  C07D401/14 ,  C07D405/12

Abstract: A compound of formula (wherein A, R1, R2, R6, m and n are disclosed herein) or a pharmaceutically acceptable salt thereof (a “Piperazine Compound”); pharmaceutical compositions comprising a Piperazine Compound; and methods for treating pain, urinary incontinence (UI), an addictive disorder, Parkinson's disease, parkinsonism, anxiety, epilepsy, stroke, a seizure, a pruritic condition, psychosis, a cognitive disorder, a memory deficit, restricted brain function, Huntington's chorea, amyotrophic lateral sclerosis (ALS), dementia, retinopathy, a muscle spasm, a migraine, vomiting, dyskinesia and depression in an animal comprising administering to an animal in need thereof an effective amount of a Piperazine Compound are disclosed.

Abstract translation: 式（其中A，R 1，R 2，R 6，m和n在本文中公开）的化合物或其药学上可接受的盐（“哌嗪化合物”）; 包含哌嗪化合物的药物组合物; 和治疗疼痛，尿失禁（UI），成瘾性障碍，帕金森病，帕金森综合征，焦虑症，癫痫，中风，癫痫发作，瘙痒症状，精神病，认知障碍，记忆缺陷，限制性脑功能，亨廷顿氏舞蹈症 ，肌萎缩性侧索硬化（ALS），痴呆，视网膜病变，肌肉痉挛，偏头痛，呕吐，运动障碍和抑郁症，包括向有需要的动物施用有效量的哌嗪化合物。

公开(公告)号：US06825205B2

公开(公告)日：2004-11-30

申请号：US10668326

申请日：2003-09-24

Applicant: Donald J. Kyle

Inventor： Donald J. Kyle

IPC: A61K31485

CPC classification number: C07D489/04 ,  C07D489/02

Abstract: This invention relates to N-substituted hydromorphones of Formula I: or a pharmaceutically acceptable salt thereof, wherein R is C1-6 alkyl. These compounds act as &mgr; opioid receptor agonists. The invention is also directed to the use of compounds of Formula I for the treatment, prevention or amelioration of both acute and chronic pain.

Abstract translation: 本发明涉及式I的N-取代的氢原子或其药学上可接受的盐，其中R是C 1-6烷基。 这些化合物作为μ阿片受体激动剂。 本发明还涉及式I化合物用于治疗，预防或改善急性和慢性疼痛的用途。