公开(公告)号：US06426357B1

公开(公告)日：2002-07-30

申请号：US09629180

申请日：2000-07-31

申请人： Randall A. Scheuerman ,  Stephen D. Yanofsky ,  Christopher P. Holmes ,  Derek MacLean ,  Beatrice Ruhland ,  Ronald W. Barrett ,  Jay E. Wrobel ,  Ariamala Gopalsamy

发明人： Randall A. Scheuerman ,  Stephen D. Yanofsky ,  Christopher P. Holmes ,  Derek MacLean ,  Beatrice Ruhland ,  Ronald W. Barrett ,  Jay E. Wrobel ,  Ariamala Gopalsamy

IPC分类号： A61K31427

CPC分类号： C07D417/04 ,  C07D417/14

摘要： The present invention provides a compound of the formula: and methods for using the same, wherein R1, R2, R3, R4 and X are those defined herein.

摘要翻译： 本发明提供下式的化合物及其使用方法：其中R1，R2，R3，R4和X为本文定义的化合物。

公开(公告)号：US5880096A

公开(公告)日：1999-03-09

申请号：US463076

申请日：1995-06-05

申请人： Ronald W. Barrett ,  Stephen D. Yanofsky

发明人： Ronald W. Barrett ,  Stephen D. Yanofsky

IPC分类号： A61K38/00 ,  C07K14/545 ,  A61K38/04

CPC分类号： C07K14/545 ,  A61K38/00

摘要： Peptides that bind to the interleukin-1 type I receptor (IL-1RtI) can be used to assay the amount of IL-1R, or an IL-1R agonist or antagonist, in a sample and comprise a sequence of amino acids selected from the group consisting of (1) WXXXGZ.sub.1 W where Z.sub.1 is L, I, A, or Q (SEQ ID NO:2); (2) XXQZ.sub.5 YZ.sub.6 XX where Z.sub.5 is P or Aze where Aze is azetidine; and Z.sub.6 is S, A, V, or L (SEQ ID NO:1); and (3) Z.sub.23 NZ.sub.24 SZ.sub.25 Z.sub.26 Z.sub.27 Z.sub.28 Z.sub.29 Z.sub.30 L where Z.sub.23 is D or Y; Z.sub.24 is D or S; Z.sub.25 is S or W; Z.sub.26 is S or Y; Z.sub.27 is D or V; Z.sub.28 is S or W; Z.sub.29 is F or L; and Z.sub.30 is D or L (SEQ ID NO:27); and where each amino acid is indicated by standard one letter abbreviation; and each X can be selected from any one of the 20 genetically coded L-amino acids or the stereoisomeric D-amino acids. Also provided are peptides which bind to the IL-1RtI, which are 11 to 40 amino acids in length, which comprise the core sequence of amino acids:Z.sub.31 XWZ.sub.32 Z.sub.33 Z.sub.34 Z.sub.35 Z.sub.36 QZ.sub.37 Z.sub.38where each letter represents the standard one letter abbreviation for an amino acid or an analog thereof; X is selected from the group of natural or unnatural amino acids; Z.sub.37 is a natural or unnatural cyclic amino acid; Z.sub.31 is selected from phenylalanine and acetylated phenylalanine; Z.sub.32 is a natural or unnatural amino acid; Z.sub.33 is selected from proline and pipecolic acid; Z.sub.34 is selected from glycine, d-alanine, d-valine, sarcosine and aminoisobutyric acid; Z.sub.35 is a natural or unnatural amino acid and Z.sub.36 is selected from tyrosine, phosphotyrosine, phenylalanine and tryptophan; and Z.sub.38 is selected from tyrosinamide and substituted tyrosinamide (SEQ ID NO:392).

摘要翻译： 结合白细胞介素-1 I型受体（IL-1RtI）的肽可用于测定样品中IL-1R或IL-1R激动剂或拮抗剂的量，并且包含选自以下的氨基酸序列： 由（1）WXXXGZ1W组成的组，其中Z1是L，I，A或Q（SEQ ID NO：2）; （2）XXQZ5YZ6XX其中Z5为P或Aze，其中Aze为氮杂环丁烷; Z6是S，A，V或L（SEQ ID NO：1）; 和（3）Z23NZ24SZ25Z26Z27Z28Z29Z30L其中Z23为D或Y; Z24是D或S; Z25为S或W; Z26为S或Y; Z27为D或V; Z28为S或W; Z29为F或L; Z30为D或L（SEQ ID NO：27）; 并且其中每个氨基酸由标准单字母缩写指示; 并且每个X可以选自20个遗传编码的L-氨基酸或立体异构体D-氨基酸中的任一个。 还提供了与IL-1RtI结合的肽，其长度为11至40个氨基酸，其包含氨基酸核心序列：Z31XWZ32Z33Z34Z35Z36QZ37Z38，其中每个字母表示氨基酸或其类似物的标准单字母缩写; X选自天然或非天然氨基酸组; Z37是天然或非天然环状氨基酸; Z31选自苯丙氨酸和乙酰化苯丙氨酸; Z32是天然或非天然氨基酸; Z33选自脯氨酸和哌啶酸; Z34选自甘氨酸，d-丙氨酸，d-缬氨酸，肌氨酸和氨基异丁酸; Z35是天然或非天然氨基酸，Z36选自酪氨酸，磷酸酪氨酸，苯丙氨酸和色氨酸; Z38选自酪氨酰胺和取代的酪氨酰胺（SEQ ID NO：392）。

公开(公告)号：US5786331A

公开(公告)日：1998-07-28

申请号：US465391

申请日：1995-06-05

申请人： Ronald W. Barrett ,  Stephen D. Yanofsky ,  David Baldwin ,  Jeff W. Jacobs ,  Phillipe R. Bovy ,  Ellen M. Leahy ,  Richard S. Pottorf

发明人： Ronald W. Barrett ,  Stephen D. Yanofsky ,  David Baldwin ,  Jeff W. Jacobs ,  Phillipe R. Bovy ,  Ellen M. Leahy ,  Richard S. Pottorf

IPC分类号： A61K38/00 ,  C07K14/545 ,  A61K38/08 ,  C07K7/04

CPC分类号： C07K14/545 ,  A61K38/00

摘要： Peptides that bind to the interleukin-1 type I receptor (IL-1RtI) can be used to assay the amount of IL-1R, or an IL-1R agonist or antagonist, in a sample and comprise a sequence of amino acids selected from the group consisting of (1) WXXXGZ.sub.1 W where Z.sub.1 is L, I, A, or Q; (2) XXQZ.sub.5 YZ.sub.6 XX where Z.sub.5 is P or Aze where Aze is azetidine; and Z.sub.6 is S, A, V, or L; and (3) Z.sub.23 NZ.sub.24 SZ.sub.25 Z.sub.26 Z.sub.27 Z.sub.28 Z.sub.29 Z.sub.30 L where Z.sub.23 is D or Y; Z.sub.24 is D or S; Z.sub.25 is S or W; Z.sub.26 is S or Y; Z.sub.27 is D or V; Z.sub.28 is S or W; Z.sub.29 is F or L; and Z.sub.30 is D or L; and where each amino acid is indicated by standard one letter abbreviation; and each X can be selected from any one of the 20 genetically coded L-amino acids or the stereoisomeric D-amino acids. Also provided are peptides which bind to the IL-1RtI, which are 11 to 40 amino acids in length, which comprise the core sequence of amino acids: Z.sub.31 XWZ.sub.32 Z.sub.33 Z.sub.34 Z.sub.35 Z.sub.36 QZ.sub.37 Z.sub.38 where each letter represents the standard one letter abbreviation for an amino acid or an analog thereof; X is selected from the group of natural or unnatural amino acids; Z.sub.37 is a natural or unnatural cyclic amino acid; Z.sub.31 is selected from phenylalanine and acetylated phenylalanine; Z.sub.32 is a natural or unnatural amino acid; Z.sub.33 is selected from proline and pipecolic acid; Z.sub.34 is selected from glycine, d-alanine, d-valine, sarcosine and aminoisobutyric acid; Z.sub.35 is a natural or unnatural amino acid and Z.sub.36 is selected from tyrosine, phosphotyrosine, phenylalanine and tryptophan; and Z.sub.38 is selected from tyrosinamide and substituted tyrosinamide.

公开(公告)号：US5861476A

公开(公告)日：1999-01-19

申请号：US464538

申请日：1995-06-05

申请人： Ronald W. Barrett ,  Stephen D. Yanofsky ,  David Baldwin ,  Jeff W. Jacobs ,  Phillipe R. Bovy ,  Ellen M. Leahy ,  Richard S. Pottorf

发明人： Ronald W. Barrett ,  Stephen D. Yanofsky ,  David Baldwin ,  Jeff W. Jacobs ,  Phillipe R. Bovy ,  Ellen M. Leahy ,  Richard S. Pottorf

IPC分类号： A61K38/00 ,  C07K14/545 ,  C07K7/04 ,  A61K38/04

CPC分类号： C07K14/545 ,  A61K38/00 ,  Y10S930/141

摘要： Peptides that bind to the interleukin-1 type I receptor (IL-1RtI) can be used to assay the amount of IL-1R, or an IL-1R agonist or antagonist, in a sample and comprise a sequence of amino acids selected from the group consisting of (1) WXXXGZ.sub.1 W where Z.sub.1 is L, I, A, or Q; (2) XXQZ.sub.5 YZ.sub.6 XX where Z.sub.5 is P or Aze where Aze is azetidine; and Z.sub.6 is S, A, V, or L; and (3) Z.sub.23 NZ.sub.24 SZ.sub.25 Z.sub.26 Z.sub.27 Z.sub.28 Z.sub.29 Z.sub.30 L where Z.sub.23 is D or Y; Z.sub.24 is D or S; Z.sub.25 is S or W; Z.sub.26 is S or Y; Z.sub.27 is D or V; Z.sub.28 is S or W; Z.sub.29 is F or L; and Z.sub.30 is D or L; and where each amino acid is indicated by standard one letter abbreviation; and each X can be selected from any one of the 20 genetically coded L-amino acids or the stereoisomeric D-amino acids. Also provided are peptides which bind to the IL-1RtI, which are 11 to 40 amino acids in length, which comprise the core sequence of amino acids:Z.sub.31 XWZ.sub.32 Z.sub.33 Z.sub.34 Z.sub.35 Z.sub.36 QZ.sub.37 Z.sub.38where each letter represents the standard one letter abbreviation for an amino acid or an analog thereof; X is selected from the group of natural or unnatural amino acids; Z.sub.37 is a natural or unnatural cyclic amino acid; Z.sub.31 is selected from phenylalanine and acetylated phenylalanine; Z.sub.32 is a natural or unnatural amino acid; Z.sub.33 is selected from proline and pipecolic acid; Z.sub.34 is selected from glycine, d-alanine, d-valine, sarcosine and aminoisobutyric acid; Z.sub.35 is a natural or unnatural amino acid and Z.sub.36 is selected from tyrosine, phosphotyrosine, phenylalanine and tryptophan; and Z.sub.38 is selected from tyrosinamide and substituted tyrosinamide.

摘要翻译： 结合白细胞介素-1 I型受体（IL-1RtI）的肽可用于测定样品中IL-1R或IL-1R激动剂或拮抗剂的量，并且包含选自以下的氨基酸序列： 由（1）WXXXGZ1W组成的组，其中Z1是L，I，A或Q; （2）XXQZ5YZ6XX其中Z5为P或Aze，其中Aze为氮杂环丁烷; Z6为S，A，V或L; 和（3）Z23NZ24SZ25Z26Z27Z28Z29Z30L其中Z23为D或Y; Z24是D或S; Z25为S或W; Z26为S或Y; Z27为D或V; Z28为S或W; Z29为F或L; Z30为D或L; 并且其中每个氨基酸由标准单字母缩写指示; 并且每个X可以选自20个遗传编码的L-氨基酸或立体异构体D-氨基酸中的任一个。 还提供了与IL-1RtI结合的肽，其长度为11至40个氨基酸，其包含氨基酸的核心序列：Z31XWZ32Z33Z34Z35Z36QZ37Z38，其中每个字母表示氨基酸或其类似物的标准单字母缩写; X选自天然或非天然氨基酸组; Z37是天然或非天然环状氨基酸; Z31选自苯丙氨酸和乙酰化苯丙氨酸; Z32是天然或非天然氨基酸; Z33选自脯氨酸和哌啶酸; Z34选自甘氨酸，d-丙氨酸，d-缬氨酸，肌氨酸和氨基异丁酸; Z35是天然或非天然氨基酸，Z36选自酪氨酸，磷酸酪氨酸，苯丙氨酸和色氨酸; Z38选自酪氨酰胺和取代的酪氨酰胺。

公开(公告)号：US5767234A

公开(公告)日：1998-06-16

申请号：US383474

申请日：1995-02-01

申请人： Stephen D. Yanofsky ,  Ronald W. Barrett ,  David Baldwin ,  Jeff W. Jacobs

发明人： Stephen D. Yanofsky ,  Ronald W. Barrett ,  David Baldwin ,  Jeff W. Jacobs

IPC分类号： A61K38/00 ,  C07K14/545 ,  C07K5/00 ,  C07K7/00

CPC分类号： C07K14/545 ,  A61K38/00

摘要： Peptides that bind to the interleukin-1 type I receptor (IL-1RtI) can be used to assay the amount of IL-1R, or an IL-1R agonist or antagonist, in a sample and comprise a sequence of amino acids selected from the group consisting of (1) WXXXGZ.sub.1 W (SEQ ID NO: 2) where Z.sub.1 is L, I, A, or Q; (2) XXQZ.sub.5 YZ.sub.6 XX where (SEQ ID NO: 1) Z.sub.5 is P or Aze where Aze is azetidine; and Z.sub.6 is S, A, V, or L; and (3) Z.sub.23 NZ.sub.24 SZ.sub.25 Z.sub.26 Z.sub.27 Z.sub.28 Z.sub.29 Z.sub.30 L (SEQ ID NO: 313) where Z.sub.23 is D or Y; Z.sub.24 is D or S; Z.sub.25 is S or W; Z.sub.26 is S or Y; Z.sub.27 is D or V; Z.sub.28 is S or W; Z.sub.29 is F or L; and Z.sub.30 is D or L; and where each amino acid is indicated by standard one letter abbreviation; and each X can be selected from any one of the 20 genetically coded L-amino acids or the stereoisomeric D-amino acids.

摘要翻译： 结合白细胞介素-1 I型受体（IL-1RtI）的肽可用于测定样品中IL-1R或IL-1R激动剂或拮抗剂的量，并且包含选自以下的氨基酸序列： 由（1）WXXXGZ1W（SEQ ID NO：2）组成的组，其中Z1是L，I，A或Q; （2）XXQZ5YZ6XX其中（SEQ ID NO：1）Z5为P或Aze，其中Aze为氮杂环丁烷; Z6为S，A，V或L; 和（3）Z23NZ24SZ25Z26Z27Z28Z29Z30L（SEQ ID NO：313），其中Z23是D或Y; Z24是D或S; Z25为S或W; Z26为S或Y; Z27为D或V; Z28为S或W; Z29为F或L; Z30为D或L; 并且其中每个氨基酸由标准单字母缩写指示; 并且每个X可以选自20个遗传编码的L-氨基酸或立体异构体D-氨基酸中的任一个。

公开(公告)号：US5608035A

公开(公告)日：1997-03-04

申请号：US190788

申请日：1994-02-02

申请人： Stephen D. Yanofsky ,  Ronald W. Barrett ,  David N. Baldwin ,  Jeff W. Jacobs

发明人： Stephen D. Yanofsky ,  Ronald W. Barrett ,  David N. Baldwin ,  Jeff W. Jacobs

IPC分类号： A61K38/00 ,  C07K14/545 ,  A61K38/02 ,  C07K5/00 ,  C07K7/00

CPC分类号： C07K14/545 ,  A61K38/00

摘要： Peptides that bind to the interleukin-1 type I receptor (IL-1RtI) can be used to assay the amount of IL-1R, or an IL-1R agonist or antagonist, in a sample and comprise a sequence of amino acids selected from the group consisting of (1) WXXXGZ.sub.1 W (SEQ ID NO: 1) where Z.sub.1 is L, I, A, or Q; (2) XXQZ.sub.5 YZ.sub.6 XX (SEQ ID NO: 6) where Z.sub.5 is P or Aze where Aze is azetidine; and Z.sub.6 is S, A, V, or L; and (3) Z.sub.23 NZ.sub.24 SZ.sub.25 Z.sub.26 Z.sub.27 Z.sub.28 Z.sub.29 Z.sub.30 L (SEQ ID NO: 17) where Z.sub.23 is D or Y; Z.sub.24 is D or S; Z.sub.25 is S or W; Z.sub.26 is S or Y; Z.sub.27 is D or V; Z.sub.28 is S or W; Z.sub.29 is F or L; and Z.sub.30 is D or L; and where each amino acid is indicated by standard one letter abbreviation; and each X can be selected from any one of the 20 genetically coded L-amino acids or the stereoisomeric D-amino acids.

摘要翻译： 结合白细胞介素-1 I型受体（IL-1RtI）的肽可用于测定样品中IL-1R或IL-1R激动剂或拮抗剂的量，并且包含选自以下的氨基酸序列： 由（1）WXXXGZ1W（SEQ ID NO：1）组成的组，其中Z1是L，I，A或Q; （2）其中Z5为P的XXQZ5YZ6XX（SEQ ID NO：6）或其中Aze为氮杂环丁烷的Aze; Z6为S，A，V或L; 和（3）Z23NZ24SZ25Z26Z27Z28Z29Z30L（SEQ ID NO：17），其中Z23是D或Y; Z24是D或S; Z25为S或W; Z26为S或Y; Z27为D或V; Z28为S或W; Z29为F或L; Z30为D或L; 并且其中每个氨基酸由标准单字母缩写指示; 并且每个X可以选自20个遗传编码的L-氨基酸或立体异构体D-氨基酸中的任一个。