公开(公告)号：US07279493B2

公开(公告)日：2007-10-09

申请号：US10607563

申请日：2003-06-27

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: C07D277/04 ,  A61K43/80

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: 式中的化合物：其中A，Ar，R 3，R 6和m在本文中公开，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，治疗或预防疼痛，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， 包括给予一个或多个癫痫发作，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 公开了有效量的氰酰亚胺哌嗪化合物的需要动物。

公开(公告)号：US09109007B2

公开(公告)日：2015-08-18

申请号：US13817261

申请日：2011-08-18

Applicant: Donald J. Kyle ,  Daniel A. Soltis ,  Lynda G. Tussey

Inventor： Donald J. Kyle ,  Daniel A. Soltis ,  Lynda G. Tussey

IPC: A61K38/08 ,  C07K4/00 ,  C07K7/06 ,  C07K14/47 ,  C12N9/02 ,  C12N9/12 ,  G01N33/50 ,  G01N33/68 ,  A61K39/00

CPC classification number: A61K39/0005 ,  A61K39/00 ,  C07K7/06 ,  C07K14/4747 ,  C07K14/4748 ,  C12N9/0077 ,  C12N9/1241 ,  G01N33/505 ,  G01N33/6878 ,  G01N2333/70539 ,  G01N2500/04 ,  G01N2500/10

Abstract: The invention provides for the synthesis of more effective generators of a T-cell immune response by providing peptide derivatives that are MHC class I-restricted antigens. The peptide derivatives of the present invention are prepared or derived from a parent peptide of 8 to 11 amino acid residues in length, wherein the peptide derivative contains a non-natural amino acid substituted in place of a naturally-occurring amino acid residue at one or more primary anchor positions in the parent peptide or at position 6, position 7, or the C-terminus. The exemplary polypeptides are derived from the survivin, hTERT, CYP1B1 and MART-1 antigens.

Abstract translation: 本发明通过提供作为MHC I类限制性抗原的肽衍生物来提供更有效的T细胞免疫应答发生器的合成。 本发明的肽衍生物是长度为8至11个氨基酸残基的母体肽制备或衍生的，其中肽衍生物含有非天然氨基酸代替天然存在的氨基酸残基 在母体肽中或位置6，位置7或C-末端具有更多的主要锚定位置。 示例性多肽衍生自存活蛋白，hTERT，CYP1B1和MART-1抗原。

公开(公告)号：US20140057931A1

公开(公告)日：2014-02-27

申请号：US13825241

申请日：2011-09-20

Applicant: Donald J. Kyle ,  Laykea Tafesse

Inventor： Donald J. Kyle ,  Laykea Tafesse

IPC: C07D489/12

CPC classification number: C07D489/12

Abstract: The present invention is directed to Buprenorphine Analog compounds of the Formula (I), Formula (IA) or Formula (IB) shown below, wherein R1, R2, R8, R3a, R 3b, G, X, Z and Y are as defined herein. Compounds of the Invention are useful for treating pain, constipation, and other conditions modulated by activity of opioid and ORL-1 receptors.

Abstract translation: 本发明涉及如下所示的式（I），式（IA）或式（IB）的丁丙诺啡类似物化合物，其中R 1，R 2，R 8，R 3a，R 3b，G，X，Z和Y如所定义 这里。 本发明的化合物可用于治疗由阿片样物质和ORL-1受体的活性调节的疼痛，便秘和其它状况。

公开(公告)号：US08546388B2

公开(公告)日：2013-10-01

申请号：US12603733

申请日：2009-10-22

Applicant: Donald J. Kyle ,  Laykea Tafesse

Inventor： Donald J. Kyle ,  Laykea Tafesse

IPC: A61K31/535

CPC classification number: C07D401/04 ,  A61K31/4436 ,  A61K31/502 ,  A61K31/5025 ,  A61K31/517 ,  A61K31/519 ,  A61K31/5377 ,  C07D401/14 ,  C07D409/04 ,  C07D409/14 ,  C07D417/14 ,  C07D471/04 ,  C07D487/04 ,  C07F9/65583

Abstract: The invention relates to compounds of formulae I(a)-I(d): and pharmaceutically acceptable derivatives thereof, compositions comprising an effective amount of a compound of formulae I(a)-I(d) or a pharmaceutically acceptable derivative thereof, and methods for treating or preventing a condition such as pain, UI, an ulcer, IBD and IBS, comprising administering to an animal in need thereof an effective amount of a compound of formulae I(a)-I(d) or a pharmaceutically acceptable derivative thereof.

Abstract translation: 本发明涉及式I（a）-I（d）的化合物及其药学上可接受的衍生物：包含有效量的式I（a）-I（d）化合物或其药学上可接受的衍生物的组合物，以及 用于治疗或预防诸如疼痛，UI，溃疡，IBD和IBS的病症的方法，包括向有需要的动物施用有效量的式I（a）-I（d）化合物或其药学上可接受的衍生物 其中。

公开(公告)号：US08530494B2

公开(公告)日：2013-09-10

申请号：US13055873

申请日：2009-07-30

Applicant: Donald J. Kyle ,  R. Richard Goehring ,  Marian E. Fundytus

Inventor： Donald J. Kyle ,  R. Richard Goehring ,  Marian E. Fundytus

IPC: A61K31/485 ,  C07D489/12

CPC classification number: C07D489/12 ,  C07D489/02

Abstract: The present invention is directed to Buprenorphine Analog compounds of the Formula I, Formula II or Formula III shown below, wherein R1, R2, R8, R3, R3a, R3b, X, Z and Y are as defined herein. Compounds of the Invention are useful for treating pain and other conditions modulated by activity of opioid and ORL1 receptors.

Abstract translation: 本发明涉及如下所示的式I，式II或式III的丁丙诺啡类似物，其中R1，R2，R8，R3，R3a，R3b，X，Z和Y如本文所定义。 本发明的化合物可用于治疗由阿片样物质和ORL1受体的活性调节的疼痛和其它状况。

公开(公告)号：US20130012541A1

公开(公告)日：2013-01-10

申请号：US13525950

申请日：2012-06-18

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

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

IPC: A61K31/444 ,  A61P25/00 ,  A61K31/4545 ,  C07D401/04 ,  C07D401/14

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：US08058292B2

公开(公告)日：2011-11-15

申请号：US12786043

申请日：2010-05-24

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

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

IPC: A61K31/4427 ,  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：US20100256111A1

公开(公告)日：2010-10-07

申请号：US12786043

申请日：2010-05-24

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

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

IPC: A61K31/4427 ,  C07D211/98 ,  C07D211/94 ,  A61K31/4545 ,  C07D401/12 ,  A61P13/00 ,  A61P21/00 ,  A61P25/00 ,  A61P29/00

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：US20080153835A1

公开(公告)日：2008-06-26

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: A61K31/501 ,  C07D401/04 ,  A61K31/497 ,  A61P25/04

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: 式中的化合物：其中A，Ar，R 3，R 6和m在本文中公开，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，治疗或预防疼痛，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， 包括给予一个或多个癫痫发作，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 公开了有效量的氰酰亚胺哌嗪化合物的需要动物。

公开(公告)号：US07022714B2

公开(公告)日：2006-04-04

申请号：US10630896

申请日：2003-07-31

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

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

IPC: A61K31/454 ,  C07D401/06 ,  C07D401/14

CPC classification number: C07D403/06 ,  C07D235/08 ,  C07D235/12

Abstract: This invention relates aryl substituted benzimidazoles of Formula I: or a pharmaceutically acceptable salt, prodrug or solvate thereof, wherein R1, R2, R10 and n 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: 本发明涉及式I的芳基取代的苯并咪唑或其药学上可接受的盐，前药或溶剂合物，其中R 1，R 2，R 10， >和n在本说明书中定义。 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。