公开(公告)号：US20150191517A1

公开(公告)日：2015-07-09

申请号：US14417394

申请日：2013-07-26

Applicant: Donald James Kyle ,  Jae Hyun Park

Inventor： Donald James Kyle ,  Jae Hyun Park

IPC: C07K14/435

CPC classification number: C07K14/43518 ,  A61K38/00

Abstract: The present invention relates to C-terminal modified Protoxin II peptides that selectively inhibit the Nav1.7 sodium channel; the present invention also relates to pharmaceutical compositions useful for prophylactic or therapeutic treatment of 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.

Abstract translation: 本发明涉及选择性抑制Nav1.7钠通道的C末端修饰的Protoxin II肽; 本发明还涉及可用于预防或治疗治疗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在患有所述通道的过量活性的哺乳动物中治疗对钠通道阻塞尤其是Nav1.7钠通道有反应的病症的方法。

公开(公告)号：US06288036B1

公开(公告)日：2001-09-11

申请号：US08167051

申请日：1993-12-16

Applicant: Donald James Kyle ,  Roger Neal Hiner

Inventor： Donald James Kyle ,  Roger Neal Hiner

IPC: A61K3808

CPC classification number: C07D207/12 ,  A61K38/00 ,  C07K7/18 ,  Y10S514/803 ,  Y10S530/807 ,  Y10S530/816

Abstract: The substitution of the L-Pro at the 7-position with D-Phe or D-Tic and substitution of the L-Phe at the 8-position with hydroxyproline ethers and thioethers of the peptide hormone bradykinin and other additional substituted analogs of bradykinin converts bradykinin agonists into bradykinin antagonists. The invention further includes additional modifications at other positions within the novel 7- and 8-position modified bradykinin antagonists, which increase enzyme resistance, antagonist potency, and/or specificity of the new bradykinin antagonists. The analogs produced are useful in treating conditions and diseases of a mammal and human in which an excess of bradykinin or related kinins are produced or injected as by insect bites.

Abstract translation: 用D-Phe或D-Tic取代位于7-位的L-Pro，并用肽激素缓激肽的羟基脯氨酸醚和硫醚取代8位的L-Phe，并且其他另外的缓激肽转换的类似物 缓激肽激动剂进入缓激肽拮抗剂。 本发明进一步包括在新型7-和8-位修饰的缓激肽拮抗剂内的其它位置的其它修饰，其增加新的缓激肽拮抗剂的抗酶性，拮抗剂效力和/或特异性。 所产生的类似物可用于治疗哺乳动物和人的疾病和疾病，其中通过昆虫叮咬产生或注射过量的缓激肽或相关激肽。

公开(公告)号：US5686565A

公开(公告)日：1997-11-11

申请号：US281904

申请日：1994-07-28

Applicant: Donald James Kyle ,  Babu Joseph Mavunkel

Inventor： Donald James Kyle ,  Babu Joseph Mavunkel

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

CPC classification number: C07K7/18 ,  A61K38/00

Abstract: Pseudopeptide compounds based on a modified bradykinin sequence are potent bradykinin receptor antagonist. All or a portion of the amino acids at positions 2 through 5 of the bradykinin sequence are replaced by 2-pyrrolidinyl and/or amino-alkanoic acid or related olefinic derivatives to reduce the peptidic nature of the compounds. The analogs produced are useful in treating conditions and diseases of a mammal and human in which an excess of bradykinin or related kinins are produced or injected such as by insect bites.

Abstract translation: 基于修饰的缓激肽序列的伪肽化合物是有效的缓激肽受体拮抗剂。 缓激肽序列的2至5位氨基酸的全部或部分被2-吡咯烷基和/或氨基 - 链烷酸或相关烯属衍生物所取代，以降低化合物的肽性质。 所产生的类似物可用于治疗其中产生或注射过量的缓激肽或相关激肽的哺乳动物和人的病症和疾病，例如通过昆虫叮咬。

公开(公告)号：US06770741B1

公开(公告)日：2004-08-03

申请号：US08359642

申请日：1994-12-20

Applicant: Donald James Kyle ,  Roger Neal Hiner

Inventor： Donald James Kyle ,  Roger Neal Hiner

IPC: A61K3800

CPC classification number: C07K7/18 ,  A61K38/00 ,  C07D207/12

Abstract: The substitution of the L-Pro at the 7-position of the peptide hormone bradykinin or other substituted analogs of bradykinin with a D-configuration hydroxyproline ether or thioether converts bradykinin agonists into bradykinin antagonists. The invention further includes the intermediate compounds and additional modifications at other positions within the novel 7-position modified bradykinin antagonists which increase enzyme resistance, antagonist potency, and/or specificity of the new bradykinin antagonists. The analogs produced are useful in treating conditions and diseases of a mammal and human in which an excess of bradykinin or related kinins are produced or injected such as by insect bites.

Abstract translation: 肽类激素缓激肽或缓激肽的其他取代类似物的L-位置被D-构型羟脯氨酸醚或硫醚取代，将缓激肽激动剂转化为缓激肽拮抗剂。 本发明还包括中间体化合物和在新的7-位修饰的缓激肽拮抗剂中的其它位置的其他改变，其增加新的缓激肽拮抗剂的抗酶性，拮抗剂效力和/或特异性。 所产生的类似物可用于治疗其中产生或注射过量的缓激肽或相关激肽的哺乳动物和人的病症和疾病，例如通过昆虫叮咬。

公开(公告)号：US06458923B1

公开(公告)日：2002-10-01

申请号：US08302988

申请日：1994-09-12

Applicant: Donald James Kyle

Inventor： Donald James Kyle

IPC: A61K3800

CPC classification number: C07K7/18 ,  A61K38/00 ,  Y10S530/807 ,  Y10S530/816

Abstract: The substitution of the L-Pro at the 7-position of the peptide hormone bradykinin or other substituted analogs of bradykinin with an isoquinoline derivative which converts bradykinin agonists into bradykinin antagonists. The invention further includes the novel 7-position modified bradykinin antagonists which increase enzyme resistance, antagonist potency, and/or specificity of the new bradykinin antagonists. The analogs produced are useful in treating conditions and diseases of a mammal and human in which an excess of bradykinin or related kinins are produced or injected as by insect bites.

Abstract translation: 肽激素缓激肽或缓激肽的其他取代类似物的7位上的L-Pro被替换为缓激肽激动剂变为缓激肽拮抗剂的异喹啉衍生物。 本发明还包括增加新的缓激肽拮抗剂的酶抗性，拮抗剂效力和/或特异性的新型7-位修饰缓激肽拮抗剂。 所产生的类似物可用于治疗哺乳动物和人的疾病和疾病，其中通过昆虫叮咬产生或注射过量的缓激肽或相关激肽。

公开(公告)号：US5817756A

公开(公告)日：1998-10-06

申请号：US401595

申请日：1995-03-09

Applicant: Donald James Kyle ,  Babu Joseph Mavunkel ,  Sarjavit Chakravarty ,  Zhijian Lu

Inventor： Donald James Kyle ,  Babu Joseph Mavunkel ,  Sarjavit Chakravarty ,  Zhijian Lu

IPC: A61K38/00 ,  C07K7/18 ,  A61K38/06

CPC classification number: C07K7/18 ,  A61K38/00

Abstract: The invention provides bradykinin antagonist compounds wherein many (or all) of the peptide bonds of bradykinin are eliminated to yield compounds which specifically compete with bradykinin for binding to the bradykinin receptor. More particularly, the invention relates to compounds having, in appropriate spatial arrangement, two positively charged moieties flanking a hydrophobic organic moiety and a moiety which mimics a beta turn conformation.

Abstract translation: 本发明提供缓激肽拮抗剂化合物，其中消除缓激肽的许多（或全部）肽键，以产生与缓激肽特异性竞争结合缓激肽受体的化合物。 更具体地说，本发明涉及在适当的空间排列中具有侧翼于疏水性有机部分的两个带正电荷的部分和模拟β转角构象的部分的化合物。