公开(公告)号：US5521158A

公开(公告)日：1996-05-28

申请号：US957879

申请日：1992-10-08

Applicant: Donald J. Kyle ,  Babu J. Mavunkel

Inventor： Donald J. Kyle ,  Babu J. Mavunkel

IPC: A61K38/00 ,  C07K7/18 ,  A61K38/08

CPC classification number: C07K7/18 ,  A61K38/00

Abstract: The invention relates to peptides of up to 10 amino acids that are synthesized by substituting at least one of the bradykinin amino acids found in positions 2, 3, 4 and 5 of the bradykinin peptide with a fatty acid amine. The modified bradykinin peptides produced confer increased resistance to enzymatic degradation and/or tissue specificity. The invention also relates to pharmaceutical preparations and processes of treatments using the modified bradykinin peptides.

Abstract translation: 本发明涉及通过用脂肪酸胺代替缓激肽肽​​的2,3,4和5位中的至少一种缓激肽氨基酸来合成多达10个氨基酸的肽。 产生的修饰的缓激肽多肽对酶降解和/或组织特异性的抗性增加。 本发明还涉及使用改良的缓激肽肽的药物制剂和治疗方法。

公开(公告)号：US5049555A

公开(公告)日：1991-09-17

申请号：US286153

申请日：1988-12-19

Applicant: Waclaw J. Rzeszotarski ,  Maria E. Guzewska ,  Suzanne R. Ellenberger ,  Lisa H. Conti ,  John W. Ferkany ,  Donald J. Kyle

Inventor： Waclaw J. Rzeszotarski ,  Maria E. Guzewska ,  Suzanne R. Ellenberger ,  Lisa H. Conti ,  John W. Ferkany ,  Donald J. Kyle

IPC: A61K31/66

CPC classification number: A61K31/66

Abstract: The invention pertains to a method and pharmaceutical compositions for treating, preventing or reducing neurodegeneration associated with chronic central nervous system or hypoxic, ischemic and hypoglycemic injury to the central nervous system and for the treatment of anxiety through the use of 2-amino-.omega.-phosphonoalkanoic acids having a cycloalkyl group bridging adjacent carbons on the alkyl chain, their pharmaceutically acceptable salts and derivatives as neuroprotectants and anxiolytics.

Abstract translation: 本发明涉及用于治疗，预防或减少与中枢神经系统的慢性中枢神经系统或缺氧，缺血和低血糖损伤有关的神经退行性疾病和通过使用2-氨基-ω- 在烷基链上具有邻接碳原子的环烷基的膦酰基链烷酸，其药学上可接受的盐和衍生物作为神经保护剂和抗焦虑剂。

公开(公告)号：US4761405A

公开(公告)日：1988-08-02

申请号：US21703

申请日：1987-03-04

Applicant: Waclaw J. Rzeszotarski ,  Donald J. Kyle

Inventor： Waclaw J. Rzeszotarski ,  Donald J. Kyle

IPC: C07F9/38 ,  C07F9/40 ,  A61K31/045 ,  A61K31/13 ,  A61K31/195

CPC classification number: C07F9/383 ,  C07F9/4018

Abstract: The invention pertains to novel, potent anticonvulsants, analgesics, cognition enhancers and neuroprotectants achieving their action through the antagonism of specific excitatory amino acid neurotransmitter receptors. In particular, the invention is directed to .omega.-[2-(phosphonoalkylenyl)-cycloalkyl]-2-aminoalkanoic acids having general formula: ##STR1## wherein R.sub.1 and R.sub.2 are the same or different and are selected from the group consisting of hydrogen, lower alkyl (C.sub.1 to C.sub.6), alkyl (C.sub.7 to C.sub.12), fatty acid chain (C.sub.13 to C.sub.24), aryl, aralkyl, hydroxyl; the stereoisomers being in their resolved or racemic form; n and m=0,1,2 or 3; z=0,1 or 2; the cycloalkyl ring being replaced with the cycloalkenyl ring; and the pharmaceutically acceptable salts and derivatives thereof.

Abstract translation: 本发明涉及通过特异性兴奋性氨基酸神经递质受体的拮抗作用来实现其作用的新型有效的抗惊厥药，镇痛药，认知增强剂和神经保护剂。 特别地，本发明涉及具有以下通式的ω-[2-（膦酰基亚烷基） - 环烷基] -2-氨基链烷酸：其中R 1和R 2相同或不同，并且选自氢， 低级烷基（C1至C6），烷基（C7至C12），脂肪酸链（C13至C24），芳基，芳烷基，羟基; 立体异构体处于其解离或外消旋形式; n和m = 0,1,2或3; z = 0,1或2; 环烯基环被环烯基环取代; 及其药学上可接受的盐和衍生物。

公开(公告)号：US09279003B2

公开(公告)日：2016-03-08

申请号：US13808504

申请日：2011-07-07

Applicant: Jae Hyun Park ,  Donald J. Kyle

Inventor： Jae Hyun Park ,  Donald J. Kyle

IPC: C07K14/435 ,  A61K38/00

CPC classification number: C07K14/43518 ,  A61K38/00

Abstract: The present invention relates to a peptide and its analogs that selectively inhibit the Nav1.7 sodium channel. The present invention also relates to pharmaceutical compositions useful for treating or preventing a disorder responsive to the blockade of sodium ion channels, especially Nav1.7 sodium ion channels. The present invention further provides methods of treating a disorder responsive to the blockade of sodium channels, and particularly Nav1.7 sodium channels, in a mammal suffering from excess activity of the channels, compositions and methods for providing analgesia by administering a peptide of the invention.

Abstract translation: 本发明涉及选择性抑制Nav1.7钠通道的肽及其类似物。 本发明还涉及用于治疗或预防对阻断钠离子通道尤其是Nav1.7钠离子通道有响应的病症的药物组合物。 本发明进一步提供了治疗患有过量活性通道的哺乳动物钠通道阻断，尤其是Nav1.7钠通道的病症的治疗方法，通过施用本发明的肽来提供止痛的组合物和方法 。

公开(公告)号：US09221831B2

公开(公告)日：2015-12-29

申请号：US13825241

申请日：2011-09-20

Applicant: Donald J. Kyle ,  Laykea Tafesse

Inventor： Donald J. Kyle ,  Laykea Tafesse

IPC: A61K31/485 ,  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：US20130296247A1

公开(公告)日：2013-11-07

申请号：US13808504

申请日：2011-07-07

Applicant: Jae Hyun Park ,  Donald J. Kyle

Inventor： Jae Hyun Park ,  Donald J. Kyle

IPC: C07K14/435

CPC classification number: C07K14/43518 ,  A61K38/00

Abstract: The present invention relates to a peptide and analogs thereof that selectively inhibit the Nav1.7 sodium channel. The present invention also relates to pharmaceutical compositions useful for treating or preventing a disorder responsive to the blockade of sodium ion channels, especially Nav1.7 sodium ion channels. The present invention further provides methods of treating a disorder responsive to the blockade of sodium channels, and particularly Nav1.7 sodium channels, in a mammal suffering from excess activity of said channels, compositions and methods for providing analgesia by administering a peptide of the invention.

Abstract translation: 本发明涉及选择性抑制Nav1.7钠通道的肽及其类似物。 本发明还涉及用于治疗或预防对阻断钠离子通道尤其是Nav1.7钠离子通道有响应的病症的药物组合物。 本发明进一步提供了治疗对所述通道过度活性的哺乳动物患钠通道阻断反应性障碍的方法，尤其是Nav1.7钠通道，通过施用本发明的肽来提供止痛的组合物和方法 。

公开(公告)号：US08421484B2

公开(公告)日：2013-04-16

申请号：US12671309

申请日：2008-07-30

Applicant: Camelia Prodan ,  Victor I. Ilyin ,  Donald J. Kyle ,  Kevin Carlin ,  Gang Wu

Inventor： Camelia Prodan ,  Victor I. Ilyin ,  Donald J. Kyle ,  Kevin Carlin ,  Gang Wu

IPC: G01R27/08

CPC classification number: G01N33/6872 ,  G01N33/5008

Abstract: A method for measuring membrane potential using dielectric spectroscopy is described. A new theoretical model allows for the determination of membrane potential from low-frequency impedance measurements to provide a non-evasive method which is both rapid and inexpensive.

Abstract translation: 描述了使用介电光谱测量膜电位的方法。 新的理论模型允许从低频阻抗测量中确定膜电位，以提供快速和便宜的非回避方法。

公开(公告)号：US08399486B2

公开(公告)日：2013-03-19

申请号：US12595066

申请日：2008-04-08

Applicant: Donald J. Kyle ,  Jiangchao Yao

Inventor： Donald J. Kyle ,  Jiangchao Yao

IPC: A61K31/445 ,  C07D211/56 ,  C07D211/58 ,  C07D211/98

CPC classification number: C07D211/96 ,  C07D207/48

Abstract: The invention relates to pyrrolidinyl, piperidinyl, and hexahydroazepinyl compounds of Formula I: and pharmaceutically acceptable salts, prodrugs, or solvates thereof, wherein R1, R2, Z and m are defined as set forth in the specification. The invention is also directed to the use compounds of Formula I to treat 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的吡咯烷基，哌啶基和六氢氮杂卟啉化合物及其药学上可接受的盐，前药或溶剂化物，其中R1，R2，Z和m如本说明书所述定义。 本发明还涉及使用式I化合物来治疗对阻断钙通道，特别是N型钙通道有响应的病症。 本发明的化合物特别适用于治疗疼痛。

公开(公告)号：US08030310B2

公开(公告)日：2011-10-04

申请号：US12715825

申请日：2010-03-02

Applicant: Donald J. Kyle ,  Qun Sun

Inventor： Donald J. Kyle ,  Qun Sun

IPC: C07D213/75 ,  A61K31/496 ,  A61K31/44

CPC classification number: C07D401/04 ,  C07D213/74 ,  C07D213/85

Abstract: Compounds of formulae: where X is S or O and Ar2, R1, R2, R3, R8, n, m, t, and v are disclosed herein, or a pharmaceutically acceptable salt thereof (a “3-substituted Pyridyl Compound”), compositions comprising an effective amount of a 3-substituted Pyridyl 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 3-substituted Pyridyl Compound are disclosed herein.

Abstract translation: 其中X为S或O且Ar 2，R 1，R 2，R 3，R 8，n，m，t和v为本文公开的化合物或其药学上可接受的盐（“3-取代的吡啶基化合物”）， 包含有效量的3-取代的吡啶基化合物的组合物，以及治疗或预防疼痛，尿失禁，溃疡，炎性肠病，肠易激综合征，上瘾性疾病，帕金森病，帕金森综合征，焦虑症，癫痫症， 卒中，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， 向有需要的动物施用有效量的3-取代的吡啶基化合物。

公开(公告)号：US20110098281A9

公开(公告)日：2011-04-28

申请号：US12595066

申请日：2008-04-08

Applicant: Donald J. Kyle ,  Jiangchao Yao

Inventor： Donald J. Kyle ,  Jiangchao Yao

IPC: A61K31/4468 ,  C07D211/56 ,  C07D207/48 ,  C07D223/04 ,  A61K31/40 ,  A61K31/55 ,  A61P25/00 ,  A61P9/12 ,  A61P25/24 ,  A61P25/22 ,  G01N33/53

CPC classification number: C07D211/96 ,  C07D207/48

Abstract: The invention relates to pyrrolidinyl, piperidinyl, and hexahydroazepinyl compounds of Formula I: and pharmaceutically acceptable salts, prodrugs, or solvates thereof, wherein R1, R2, Z and m are defined as set forth in the specification. The invention is also directed to the use compounds of Formula I to treat 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的吡咯烷基，哌啶基和六氢氮杂卟啉化合物及其药学上可接受的盐，前药或溶剂化物，其中R1，R2，Z和m如本说明书所述定义。 本发明还涉及使用式I化合物来治疗对阻断钙通道，特别是N型钙通道有响应的病症。 本发明的化合物特别适用于治疗疼痛。