公开(公告)号：US06372783B1

公开(公告)日：2002-04-16

申请号：US09680873

申请日：2000-10-06

Applicant: Pascal Druzgala ,  Peter G. Milner

Inventor： Pascal Druzgala ,  Peter G. Milner

IPC: A61K3134

CPC classification number: C07D307/54 ,  Y10S514/821

Abstract: The subject invention pertains to novel enantiomerically pure compounds, and compositions comprising the compounds, for the treatment of cardiac arrhythmias. The subject invention further concerns a method of making and purifying the compounds. The isolated enantiomerically purified compounds, and compositions of these compounds, exhibit unexpectedly distinct and advantageous characteristics, such as a markedly superior ability to reduce or inhibit ventricular premature beats, as compared to racemic mixtures of the compounds.

Abstract translation: 本发明涉及新颖的对映异构体纯的化合物和包含该化合物的组合物，用于治疗心律失常。 本发明还涉及制备和纯化化合物的方法。 与化合物的外消旋混合物相比，分离的对映异构体纯化的化合物和这些化合物的组合物显示出意想不到的和有利的特征，例如显着优异的减少或抑制心室过早搏动的能力。

公开(公告)号：US5736528A

公开(公告)日：1998-04-07

申请号：US581655

申请日：1995-12-29

Applicant: Luiz Belardinelli ,  Ray Olsson ,  Stephen Baker ,  Peter J. Scammells ,  Peter G. Milner ,  Jurg R. Pfister

Inventor： Luiz Belardinelli ,  Ray Olsson ,  Stephen Baker ,  Peter J. Scammells ,  Peter G. Milner ,  Jurg R. Pfister

IPC: C07H19/167 ,  A61K31/00 ,  A61K31/70 ,  A61K31/7042 ,  A61K31/7052 ,  A61K31/706 ,  A61K31/7064 ,  A61K31/7076 ,  A61P9/00 ,  A61P9/06 ,  C07D473/06 ,  C07D519/00 ,  C07H19/16

CPC classification number: C07H19/16 ,  C07D473/06 ,  Y10S514/821

Abstract: N.sup.6 -(epoxynorborn-2-yl)adenosines are Al adenosine receptor agonists that are useful for controlling atrial fibrillation, ventricular rate in atrial flutter, supraventricular tachyarrhythmia, inhibiting A--V- nodal transmission in supraventricular tachycardia, and for normalizing ventricular rhythm and hemodynamics.

Abstract translation: N6-（环氧降解-2-基）腺苷是可用于控制心房颤动，心房扑动的心室率，室上性快速性心律失常，抑制室上性心动过速中的A-V淋巴结传递以及用于使心室节律和血液动力学正常化的Al腺苷受体激动剂。

公开(公告)号：US07906482B2

公开(公告)日：2011-03-15

申请号：US11923222

申请日：2007-10-24

Applicant: Dominique P. Bridon ,  Roger Leger ,  Xicai Huang ,  Karen Thibaudeau ,  Martin Robitaille ,  Peter G. Milner

Inventor： Dominique P. Bridon ,  Roger Leger ,  Xicai Huang ,  Karen Thibaudeau ,  Martin Robitaille ,  Peter G. Milner

IPC: C07K14/00 ,  A61K38/00

CPC classification number: C07K14/57545 ,  A61K38/00 ,  C07K19/00 ,  C07K2319/01

Abstract: The present invention relates to a compound comprising a PYY peptide or a functional derivative thereof, which is coupled to a reactive group. Such a reactive group is capable of reacting on a blood component so as to form a stable covalent bond therewith. The present invention also relates to a conjugate comprising such a compound which is covalently bonded to a blood component. Moreover, the invention also relates to a method of enhancing, in a patient, the anti-obesity activity of a PYY peptide or functional derivative thereof.

Abstract translation: 本发明涉及包含与反应性基团偶联的PYY肽或其功能性衍生物的化合物。 这样的反应性基团能够对血液成分进行反应，与其形成稳定的共价键。 本发明还涉及包含共价键合到血液成分上的化合物的缀合物。 此外，本发明还涉及在患者中增强PYY肽或其功能性衍生物的抗肥胖活性的方法。

公开(公告)号：US07601691B2

公开(公告)日：2009-10-13

申请号：US11067556

申请日：2005-02-25

Applicant: Dominique P. Bridon ,  Roger Leger ,  Xicai Huang ,  Karen Thibaudeau ,  Martin Robitaille ,  Peter G. Milner

Inventor： Dominique P. Bridon ,  Roger Leger ,  Xicai Huang ,  Karen Thibaudeau ,  Martin Robitaille ,  Peter G. Milner

IPC: C07K14/00 ,  A61K38/00

CPC classification number: C07K14/57545 ,  A61K38/00 ,  C07K19/00 ,  C07K2319/01

Abstract: The present invention relates to a compound comprising a PYY peptide or a functional derivative thereof, which is coupled to a reactive group. Such a reactive group is capable of reacting on a blood component so as to form a stable covalent bond therewith. The present invention also relates to a conjugate comprising such a compound which is covalently bonded to a blood component. Moreover, the invention also relates to a method of enhancing, in a patient, the anti-obesity activity of a PYY peptide or functional derivative thereof.

Abstract translation: 本发明涉及包含与反应性基团偶联的PYY肽或其功能性衍生物的化合物。 这样的反应性基团能够对血液成分进行反应，与其形成稳定的共价键。 本发明还涉及包含共价键合到血液成分上的化合物的缀合物。 此外，本发明还涉及在患者中增强PYY肽或其功能性衍生物的抗肥胖活性的方法。

公开(公告)号：US20090175821A1

公开(公告)日：2009-07-09

申请号：US11982033

申请日：2007-10-31

Applicant: Dominique P. Bridon ,  Alan M. Ezrin ,  Peter G. Milner ,  Darren L. Holmes ,  Karen Thibaudeau

Inventor： Dominique P. Bridon ,  Alan M. Ezrin ,  Peter G. Milner ,  Darren L. Holmes ,  Karen Thibaudeau

IPC: A61K38/38 ,  C07K19/00 ,  A61K38/21 ,  A61K38/28 ,  A61K38/22 ,  A61K38/18

CPC classification number: C07K14/57563 ,  A61K38/38 ,  A61K47/62 ,  A61K47/643

Abstract: A method for protecting a peptide from peptidase activity in vivo, the peptide being composed of between 2 and 50 amino acids and having a C-terminus and an N-terminus and a C-terminus amino acid and an N-terminus amino acid is described. In the first step of the method, the peptide is modified by attaching a reactive group to the C-terminus amino acid, to the N-terminus amino acid, or to an amino acid located between the N-terminus and the C-terminus, such that the modified peptide is capable of forming a covalent bond in vivo with a reactive functionality on a blood component. In the next step, a covalent bond is formed between the reactive group and a reactive functionality on a blood component to form a peptide-blood component conjugate, thereby protecting said peptide from peptidase activity. The final step of the method involves the analyzing of the stability of the peptide-blood component conjugate to assess the protection of the peptide from peptidase activity.

Abstract translation: 描述了一种在体内保护肽免受肽酶活性的方法，所述肽由2-50个氨基酸组成且具有C末端和N末端以及C末端氨基酸和N-末端氨基酸 。 在该方法的第一步中，通过将反应性基团连接到C末端氨基酸，N末端氨基酸或位于N末端和C末端之间的氨基酸来修饰肽， 使得修饰的肽能够在体内与血液成分上的反应性官能团形成共价键。 在下一步骤中，在反应性基团和血液成分上的反应性官能团之间形成共价键以形成肽 - 血液成分缀合物，从而保护所述肽免受肽酶活性。 该方法的最后步骤包括分析肽 - 血液成分缀合物的稳定性，以评估肽对肽酶活性的保护。

公开(公告)号：US20080199483A1

公开(公告)日：2008-08-21

申请号：US11877221

申请日：2007-10-23

Applicant: Dominique P. Bridon ,  Robert S. Dufresne ,  Nissab Boudjellab ,  Martin Robitaille ,  Peter G. Milner

Inventor： Dominique P. Bridon ,  Robert S. Dufresne ,  Nissab Boudjellab ,  Martin Robitaille ,  Peter G. Milner

IPC: A61K39/00 ,  C07K14/00 ,  C07K16/00

CPC classification number: C07K14/005 ,  A61K38/00 ,  C12N2740/16122

Abstract: Peptides exhibiting anti-viral and anti-fusogenic activity are modified to provide greater stability and improved half-life in vivo. The selected peptides include fusion inhibitors DP178 and DP107 and related peptides and analogs thereof. The modified peptides are capable of forming covalent bonds with one or more blood components, preferably a mobile blood component.

公开(公告)号：US06849714B1

公开(公告)日：2005-02-01

申请号：US09623548

申请日：2000-05-17

Applicant: Dominique P. Bridon ,  Alan M. Ezrin ,  Peter G. Milner ,  Darren L. Holmes ,  Karen Thibaudeau

Inventor： Dominique P. Bridon ,  Alan M. Ezrin ,  Peter G. Milner ,  Darren L. Holmes ,  Karen Thibaudeau

IPC: A61K38/00 ,  C07K1/107 ,  C07K17/00

CPC classification number: C07K1/1077 ,  A61K38/00 ,  Y02P20/55

Abstract: A method of synthesizing a modified therapeutic peptide capable of forming a peptidase-stabilized therapeutic peptide conjugate, the peptide having between 3 and 50 amino acids, is k. In a first step of the method, a therapeutic peptide having a carboxy terminal amino acid and amino terminal amino acid is synthesized. In a second step, pairs of cysteine residues present in the therapeutic peptide are sequentially and selectively oxidized to form disulfide bridges in the therapeutic peptide. In a third step, a protecting group is attached to remaining cysteine residues that do not form disulfide bridges in the therapeutic peptide. Finally, the peptide is coupled to a reactive group capable of reacting with amino groups, hydroxyl groups or thiol groups on a blood component to form a covalent bond therewith.

Abstract translation: 描述了能够形成肽酶稳定的治疗性肽缀合物的修饰的治疗肽的方法，所述肽具有3至50个氨基酸。 在该方法的第一步中，合成具有羧基末端氨基酸和氨基末端氨基酸的治疗肽。 在第二步中，存在于治疗肽中的成对的半胱氨酸残基被顺序地和选择性氧化，以在治疗肽中形成二硫键。 在第三步中，将保护基连接到在治疗肽中不形成二硫键的剩余半胱氨酸残基。 最后，肽与能够与血液成分上的氨基，羟基或硫醇基反应以形成与其共价键的反应性基团偶联。

公开(公告)号：US06784199B2

公开(公告)日：2004-08-31

申请号：US09961538

申请日：2001-09-21

Applicant: Pascal Druzgala ,  Peter G. Milner

Inventor： Pascal Druzgala ,  Peter G. Milner

IPC: A61K31423

CPC classification number: C07D277/20 ,  C07D261/12 ,  C07D277/34 ,  C07D311/70 ,  C07D413/04 ,  C07D413/12 ,  C07D417/04 ,  C07D417/12 ,  C07D417/14

Abstract: The subject invention provides pharmaceutical compounds useful in the treatment of Type II diabetes. These compounds are advantageous because they are readily metabolized by the metabolic drug detoxification systems. Particularly, isoxazolidine compounds which have been designed to include esters within the structure of the compounds are provided. This invention is also drawn to methods of treating disorders, such as diabetes, comprising the administration of therapeutically effective compositions comprising compounds which have been designed to be metabolized by serum or intracellular hydrolases and esterases. Pharmaceutical compositions of the isoxazolidine compounds are also taught.

Abstract translation: 本发明提供了可用于治疗II型糖尿病的药物化合物。 这些化合物是有利的，因为它们容易被代谢药物解毒系统代谢。 特别地，提供了已被设计为在化合物的结构内包含酯的异恶唑烷化合物。 本发明还涉及治疗疾病如糖尿病的方法，其包括施用治疗有效的组合物，其包含被设计为由血清或细胞内水解酶和酯酶代谢的化合物。 还教导了异恶唑烷化合物的药物组合物。

公开(公告)号：US06683086B2

公开(公告)日：2004-01-27

申请号：US10145601

申请日：2002-05-13

Applicant: Pascal Druzgala ,  Peter G. Milner

Inventor： Pascal Druzgala ,  Peter G. Milner

IPC: C07D23962

CPC classification number: C07D239/62 ,  C07D239/66

Abstract: The subject invention concerns novel compounds that are useful as ultrashort acting hypnotic barbiturates. Specifically exemplified are derivatives of barbituric and thiobarbituric acids. They are rapidly metabolized by blood and tissue enzymes to form polar metabolites with no hypnotic activity and which are rapidly eliminated.

Abstract translation: 本发明涉及可用作超短效催眠巴比妥酸盐的新型化合物。 具体举例说明的是巴比妥酸和硫代巴比妥酸的衍生物。 它们被血液和组织酶快速代谢，以形成无催眠活性的极性代谢物，并迅速消除。

公开(公告)号：US06610825B2

公开(公告)日：2003-08-26

申请号：US09798119

申请日：2001-03-01

Applicant: Alan M. Ezrin ,  Dominique P. Bridon ,  Darren L. Holmes ,  Peter G. Milner

Inventor： Alan M. Ezrin ,  Dominique P. Bridon ,  Darren L. Holmes ,  Peter G. Milner

IPC: C07K700

CPC classification number: C07K14/70 ,  A61K38/00 ,  A61K47/64 ,  C07K14/665 ,  C07K2319/00

Abstract: Conjugates are prepared from antinociceptive agents, particularly opioids or opioid analogs, more particularly dynorphins, endorphins, deltorphins, enkephalins or analogs thereof, by combining said antinociceptive agent with a material providing a functionally reactive group capable of reacting with a blood component (preferably a blood cell or protein). Said conjugates permit extension of the therapeutic life of the antinociceptive agent. They may be administered to patients to alleviate pain, produce analgesic effects, or assist in cases of narcotics withdrawal, and may also be used as probes for receptor activity. The administration to the patient may be made either in vivo or ex vivo and may be performed by either introducing the derivative including the reactive functional group into the patient's vascular system or preparing such a conjugate externally (or in vitro) and introducing that conjugate to the patient's vascular system.

Abstract translation: 通过将所述抗伤害感受剂与提供能够与血液成分（优选血液）反应的功能反应性基团的材料组合，由抗伤害感受剂，特别是阿片样物质或阿片样物质类似物，更具体地说是强啡肽，内啡肽，delphphins，脑啡肽或其类似物制备缀合物 细胞或蛋白质）。 所述缀合物允许延长抗伤害感受剂的治疗寿命。 可以向患者施用以缓解疼痛，产生镇痛作用或辅助麻醉药物撤出的情况，也可用作受体活性的探针。 对患者的施用可以在体内或体外制备，并且可以通过将包含反应性官能团的衍生物引入患者的血管系统或者在外部（或体外）中制备这种缀合物并将该缀合物引入到 患者血管系统。