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1. 发明申请

WO1996000581A1 PROCESS TO INHIBIT BINDING OF THE INTEGRIN ALPHA 4 BETA 1 TO VCAM-1 OR FIBRONECTIN 审中-公开
标题翻译：抑制INTEGRIN ALPHA 4 BETA 1与VCAM-1或FIBRONECTIN的结合过程
公开(公告)号：WO1996000581A1
公开(公告)日：1996-01-11
申请号：PCT/US1995008353
申请日：1995-06-27
申请人： TEXAS BIOTECHNOLOGY CORPORATION , KOGAN, Timothy, P. , REN, Kaijun , VANDERSLICE, Peter , BECK, Pamela, J.
发明人： TEXAS BIOTECHNOLOGY CORPORATION
IPC分类号： A61K38/12
CPC分类号： C07K14/78 , A61K38/00
摘要： The present invention is directed to an isolated and purified cyclic peptide of from 5 to about 13 residues modeled after a portion of the CS1 peptide. A peptide of this invention preferably has the amino acid residue sequence of SEQ ID NO:2-14 or 16-42. The present invention is further directed to a process of selectively inhibiting the binding of alpha 4 beta 1 integrin to a protein such as VCAM-1, fibronectin or invasin comprising exposing a cell that expresses alpha 4 beta 1 integrin to that protein in the presence of an effective inhibiting amount of such a peptide. The present invention is still further directed to a pharmaceutical composition comprising a physilogically acceptable carrier and a cyclic peptide of the invention.
摘要翻译：本发明涉及在一部分CS1肽之后建模的分离和纯化的5至约13个残基的环肽。本发明的肽优选具有SEQ ID NO：2-14或16-42的氨基酸残基序列。本发明进一步涉及选择性抑制α4β1整联蛋白与蛋白质如VCAM-1，纤连蛋白或侵袭素的结合的方法，包括在存在下暴露表达α4β1整联蛋白的细胞与该蛋白质这种肽的有效抑制量。本发明还涉及包含本发明的物理学上可接受的载体和环肽的药物组合物。

2. 发明申请

WO1996035418A1 METHOD FOR INHIBITING THE BINDING OF SELECTINS TO SIALYL-LEWISES 审中-公开
标题翻译：阻止选择与SIALYL-LEWISES结合的方法
公开(公告)号：WO1996035418A1
公开(公告)日：1996-11-14
申请号：PCT/US1996006453
申请日：1996-05-06
申请人： TEXAS BIOTECHNOLOGY CORPORATION , KOGAN, Timothy, P. , SCOTT, Ian, L. , KELLER, Karin, M. , DUPRE, Brian , BJERCKE, Robert, J. , MARKET, Robert, V. , SHERWOOD, Sidney, J. , YEH, Edward, T. , TILTON, Ronald, G. , KINT, Phi, Nga, Thi , BUI, Huong, M. , BECK, Pamela, J.
发明人： TEXAS BIOTECHNOLOGY CORPORATION
IPC分类号： A61K31/19
CPC分类号： A61K31/4164 , A61K31/192 , A61K31/194 , A61K31/198
摘要： This invention relates to a method of inhibiting the binding of E-selectin, P-selectin and/or L-selectin to sialyl-Lewis , sialyl-Lewis , Lewis and/or Lewis presented on a cell surface comprising the step of administering to a patient in need of such treatment a pharmaceutically effective amount of at least one compound having the formula XCOCH2CH2COOR3 wherein X is (a); (b); (c); (d); or (e); R1 is an alkyl group, an alkoxy group or a halogen atom; R2 is a halogen atom or a hydrogen atom; and R3 is an alkyl group or a hydrogen atom; (I) where R1 is as defined above and AA is an alpha -amino acid; (II); (III) and where R3 is NO2; (f); and the pharmaceutically acceptable salts, esters, amides and prodrugs thereof.
摘要翻译：本发明涉及一种抑制E-选择蛋白，P-选择蛋白和/或L-选择蛋白与唾液酸 - 路易斯，唾液酸 - 路易斯，路易斯x和/或Lewis 呈现在细胞表面上，包括向需要这种治疗的患者施用药学有效量的至少一种具有式XCOCH 2 CH 2 COOR 3的化合物，其中X为（a）; （B）; （C）; （D）; 或（e）; R1是烷基，烷氧基或卤素原子; R2是卤素原子或氢原子; 并且R 3是烷基或氢原子; （I）其中R1如上所定义，AA是α-氨基酸; （II）; （III），其中R3为NO2; （F）; 及其药学上可接受的盐，酯，酰胺和前药。

3. 发明申请

WO1995029681A1 COMPOSITIONS AND METHODS FOR INHIBITING THE BINDING OF E-SELECTIN OR P-SELECTIN TO SIALYL-LEWISx OR SIALYL-LEWISa 审中-公开
标题翻译：用于抑制E-选择素或P-选择素与SIALYL-LEWIS结合的组合物和方法 SIALYL-LEWIS

公开(公告)号：WO1995029681A1

公开(公告)日：1995-11-09

申请号：PCT/US1995005359

申请日：1995-05-01

申请人： TEXAS BIOTECHNOLOGY CORPORATION , KOGAN, Timothy, P. , DUPRE', Brian , DAO, Huong , BECK, Pamela, J.
发明人： TEXAS BIOTECHNOLOGY CORPORATION
IPC分类号： A61K31/70
CPC分类号： A61K31/7034 , C07H15/20 , C07H15/203
摘要： This invention relates to compounds that inhibit the binding of E-selectin or P-selectin to sialyl-Lewis or sialyl-Lewis presented on a cell surface having the general structure (II), wherein X is selected from the group consisting of -CO2R, -(CH2)nO(CH2)mCO2R, -(CH2)nCO2R, -O(CH2)nCO2R, -CONH(CHR2)nCO2R, -(CH2)nSO3H, -(CH2)nPO3D1D2, and -OH; A1 and A2 are independently selected from the group consisting of hydrogen, halogen, lower alkyl, -OR, -(CH2)nNR(CH2)mCO2R, -NRR, -CN, -N3, and -NO2; and A3 is hydrogen, halogen, lower alkyl, -(CH2)pNH2, -(CH2)pNR(CH2)qCO2R, or -(CH2)pNH(CH2)qCH3; where n and m are independently 1 to 6, p and q are independently 0 to 12, R is lower alkyl or hydrogen, R2 is any functional group that can be derived from an available alpha or beta amino acid, and D1 and D2 are independently hydrogen or methyl, and the pharmaceutically acceptable salts, esters, amides and prodrugs thereof. This invention also relates to methods of inhibiting the binding of E-selectin or P-selectin to sialyl-Lewis or sialyl-Lewis presented on a cell surface using said compounds and to pharmaceutically active compositions comprising compounds that inhibit the binding of E-selectin to sialyl-Lewis and to methods of treatment of septic shock, ARDS, Crohn's disease, chronic inflammatory diseases, such as psoriasis and rheumatoid arthritis, and reperfusion injuries that occur following heart attacks, strokes and organ transplants and to the treatment of cancer.
摘要翻译：本发明涉及抑制E-选择蛋白或P-选择蛋白与呈现在具有通式结构（II）的细胞表面上的唾液酸 - 路易斯或唾液酸 - 路易斯结合的化合物，其中X选自（CH 2）n CO 2 R， - （CH 2）n CO 2 R，-CONH（CHR 2）n CO 2 R， - （CH 2）n SO 3 H - ，（CH 2）n PO 3 D 1 D 2，哦; A1和A2独立地选自氢，卤素，低级烷基，-OR， - （CH2）nNR（CH2）mCO2R，-NRR，-CN，-N3和-NO2; 和（A3）是氢，卤素，低级烷基， - （CH2）pNH2， - （CH2）pNR（CH2）qCO2R或 - （CH2）pNH（CH2）qCH3; 其中n和m独立地为1至6，p和q独立地为0至12，R为低级烷基或氢，R 2为可衍生自可用的α或β氨基酸的任何官能团，且D1和D2独立地为氢或甲基，以及其药学上可接受的盐，酯，酰胺和前药。本发明还涉及使用所述化合物抑制E-选择蛋白或P-选择蛋白与呈现在细胞表面上的唾液酸基-LXX或唾液酸 - 路易斯结合的方法，以及包含抑制 E-选择蛋白与唾液酸 - 路易斯结合，以及治疗败血性休克，ARDS，克罗恩病，慢性炎性疾病如牛皮癣和类风湿性关节炎的治疗方法以及心脏病发作，中风和器官移植后发生的再灌注损伤和治疗癌症。

4. 发明申请

WO1995029682A1 BINDING OF E-SELECTIN, P-SELECTIN OR L-SELECTIN TO SIALYL-LEWISx OR SIALYL-LEWISa 审中-公开
标题翻译： E-SELECTIN，P-选择素或L-选择素与SIALYL-LEWIS结合或SIALYL-LEWIS

公开(公告)号：WO1995029682A1

公开(公告)日：1995-11-09

申请号：PCT/US1995005463

申请日：1995-04-28

申请人： TEXAS BIOTECHNOLOGY CORPORATION , KOGAN, Timothy, P. , DUPRE', Brian , SCOTT, Ian, L. , KELLER, Karin , DAO, Huong , BECK, Pamela, J.
发明人： TEXAS BIOTECHNOLOGY CORPORATION
IPC分类号： A61K31/70
CPC分类号： C07H15/18 , C07H15/203
摘要： This invention relates to compounds having general structure (II) that inhibit the binding of E-selectin and/or P-selectin to sialyl-Lewis or sialyl-Lewis presented on a cell surface. This invention also relates to methods of inhibiting the binding of E-selectin and/or P-selectin to sialyl-Lewis or sialyl-Lewis presented on a cell surface using said compounds, and to pharmaceutically active compositions comprising compounds that inhibit the binding of E-selectin to sialyl-Lewis . This invention also concerns methods of using said compounds for treatment of septic shock, ARDS, Crohn's disease, chronic inflammatory disease such as psoriasis and rheumatoid arthritis, and reperfusion injuries that occur following heart attacks, strokes and organ transplants.
摘要翻译：本发明涉及具有抑制E-选择蛋白和/或P-选择蛋白与呈现在细胞表面上的唾液酸 - 路易斯x或唾液酸 - 路易斯结合的通式结构（II）的化合物。本发明还涉及使用所述化合物抑制E-选择蛋白和/或P-选择蛋白与呈现在细胞表面上的唾液酸 - 路易斯x或唾液酸 - 路易斯结合的方法，以及包含化合物的药物活性组合物其抑制E-选择蛋白与唾液酸 - 路易斯的结合。本发明还涉及使用所述化合物治疗败血性休克，ARDS，克罗恩病，慢性炎症性疾病如牛皮癣和类风湿性关节炎的方法，以及在心脏病发作，中风和器官移植后发生的再灌注损伤。

5. 发明申请

WO1997010839A1 COMPOSITIONS AND METHODS FOR INHIBITING THE BINDING OF PECAM 审中-公开
标题翻译：用于抑制PECAM结合的组合物和方法
公开(公告)号：WO1997010839A1
公开(公告)日：1997-03-27
申请号：PCT/US1996014940
申请日：1996-09-18
申请人： TEXAS BIOTECHNOLOGY CORPORATION , BECK, Pamela , KINT, Phi, Nga , REVELLE, B., Mitch , SHERWOOD, Sid , BJERCKE, Robert, J. , REN, Kaijun
发明人： TEXAS BIOTECHNOLOGY CORPORATION
IPC分类号： A61K38/12
CPC分类号： C07K14/70503 , A61K38/00 , C07K2319/00 , C12N2799/026
摘要： The present invention is directed to an isolated and purified linear peptide of from 4 to about 13 residues modeled after a C2-type, IG domain of the PECAM-1 peptide. A peptide of this invention can be linear or cyclic and has the amino acid residue sequence of any SEQ ID NOs: 2-105. The present invention is further directed to a process of selectively inhibiting the binding of PECAM-1 to itself comprising exposing a first cell that expresses PECAM-1 to a second cell that expresses PECAM-1 in the presence of an effective inhibiting amount of such a peptide. The present invention is still further directed to a pharmaceutical composition comprising a physiologically acceptable carrier and a peptide of the invention.
摘要翻译：本发明涉及在PECAM-1肽的C2型，IG结构域之后建模的分离和纯化的4至约13个残基的线性肽。本发明的肽可以是直链或环状的并且具有任何SEQ ID NO：2-105的氨基酸残基序列。本发明进一步涉及选择性抑制PECAM-1与其自身的结合的方法，其包括将有表达PECAM-1的第一细胞暴露于表达PECAM-1的第二细胞中，所述第二细胞在有效抑制量的这种肽。本发明还涉及包含本发明的生理学上可接受的载体和肽的药物组合物。

6. 发明申请

WO1998003181A1 POLYSULFOLITHOCOLIC ACIDS AS GROWTH FACTOR RECEPTOR INHIBITORS 审中-公开
标题翻译：多聚脂肪酸作为生长因子受体抑制剂
公开(公告)号：WO1998003181A1
公开(公告)日：1998-01-29
申请号：PCT/US1997013103
申请日：1997-07-22
申请人： TEXAS BIOTECHNOLOGY CORPORATION , KOGAN, Timothy, P. , BIEDIGER, Ronald, J. , STEPHAN, Clifford, C. , TILTON, Ronald, G. , SCOTT, Ian, L. , BROCK, Tommy, A.
发明人： TEXAS BIOTECHNOLOGY CORPORATION
IPC分类号： A61K31/575
CPC分类号： C07J41/0061
摘要： A compound of the formula [RLys(R)]2X or R2X where R = (1) and X is any diamine. This invention is also directed to pharmaceutical compositions and methods of inhibiting cellular proliferation using these compounds.
摘要翻译：式[RLys（R）] 2 X或R 2 X的化合物，其中R =（1），X为任何二胺。本发明还涉及使用这些化合物抑制细胞增殖的药物组合物和方法。

7. 发明申请

WO1997044344A1 HIGH YIELD STEREOSPECIFIC MANNOSYLATION 审中-公开
标题翻译：高效立体声曼尼托化学
公开(公告)号：WO1997044344A1
公开(公告)日：1997-11-27
申请号：PCT/US1997008726
申请日：1997-05-20
申请人： TEXAS BIOTECHNOLOGY CORPORATION , SCOTT, Ian, L. , KOGAN, Timothy, P. , MECKLER, Harold
发明人： TEXAS BIOTECHNOLOGY CORPORATION
IPC分类号： C07H13/02
CPC分类号： C07H13/04
摘要： A process of preparing mannosylated alcohols or phenols in high chemical yield and purity using tetra- O -pivaloylmannosylfluoride and a Lewis acid catalyst.
摘要翻译：使用四-O-新戊酰基甘露糖基氟化物和路易斯酸催化剂制备具有高化学产率和纯度的甘露糖基化醇或酚的方法。

8. 发明申请

WO1997001335A1 DI- AND TRIVALENT SMALL MOLECULE SELECTIN INHIBITORS 审中-公开
标题翻译：双向和多态小分子选择素抑制剂
公开(公告)号：WO1997001335A1
公开(公告)日：1997-01-16
申请号：PCT/US1996011032
申请日：1996-06-26
申请人： TEXAS BIOTECHNOLOGY CORPORATION , KOGAN, Timothy, P. , DUPRE, Brian , SCOTT, Ian, L. , BUI, Huong , WHEELER, Kathy, L. , KELLER, Karin, M. , KASSIR, Jamal, M.
发明人： TEXAS BIOTECHNOLOGY CORPORATION
IPC分类号： A61K31/35
CPC分类号： C07H15/203
摘要： The present invention provides compounds having structure (II), and the pharmaceutically acceptable salts, esters, amides and prodrugs thereof.
摘要翻译：本发明提供具有结构（II）的化合物及其药学上可接受的盐，酯，酰胺和前药。

9. 发明申请

WO1997035864A1 PHOSPHORAMIDATES AND PHOSPHINIC AMIDES, THEIR USE TO MODULATE THE ACTIVITY OF ENDOTHELIN 审中-公开
标题翻译：磷酸酰胺和磷酰胺，它们用于调节内皮素的活性
公开(公告)号：WO1997035864A1
公开(公告)日：1997-10-02
申请号：PCT/US1997004364
申请日：1997-03-18
申请人： TEXAS BIOTECHNOLOGY CORPORATION
发明人： TEXAS BIOTECHNOLOGY CORPORATION , CHAN, Ming, F. , VERNER, Erik, J.
IPC分类号： C07F09/24
CPC分类号： C07F9/247 , C07F9/650905 , C07F9/6512 , C07F9/653
摘要： Phosphoramidates and phosphinic amides and related compounds are provided. Also provided are methods that use the compounds for modulating the activity of the endothelin family of peptides are provided. In particular, compounds having formula (IIa) or (II), in which A, B, R and R are as described are provided. Also provided are methods for treating endothelin-mediated disorders by administering effective amounts of one or more of these compounds or prodrugs thereof. Methods for elucidating the physiological and pathophysiological roles of endothelin, as well as isolating endothelin receptors are also provided.
摘要翻译：提供了磷酰胺化物和次膦酰胺和相关化合物。还提供了使用化合物调节肽的内皮素家族的活性的方法。特别地，提供了具有式（IIa）或（II）的化合物，其中A，B，R 1和R 2如上所述。还提供了通过施用有效量的一种或多种这些化合物或其前药来治疗内皮素介导的病症的方法。还提供了阐明内皮素的生理和病理生理学作用以及分离内皮素受体的方法。

10. 发明申请

WO1994015943A1 ANTISENSE MOLECULES DIRECTED AGAINST A PLATELET DERIVED GROWTH FACTOR RECEPTOR RELATED GENE 审中-公开
标题翻译：抗体生成因子受体相关基因的抗原分子
公开(公告)号：WO1994015943A1
公开(公告)日：1994-07-21
申请号：PCT/US1993012602
申请日：1993-12-28
申请人： TEXAS BIOTECHNOLOGY CORPORATION
发明人： TEXAS BIOTECHNOLOGY CORPORATION , DENNER, Larry, A. , REGE, Ajay, A. , DIXON, Richard, A., F.
IPC分类号： C07H17/00
CPC分类号： C12N15/1138 , C07H21/00 , C12N2310/315
摘要： The present invention is directed to a polynucleotide of about 10 to about 50 nucleic acid bases in length, which polynucleotide hybridizes to the platelet derived growth factor receptor related gene. The present invention is also directed to a pharmaceutical composition comprising the above polynucleotide dissolved or dispersed in a physiologically tolerable diluent. The present invention is further directed to a process for inhibiting vascular smooth muscle cell proliferation and to a process for treating vascular smooth muscle cell proliferation that comprises contacting the vascular smooth muscle cells with, or administering to a host mammal in need of such treatment an effective amount of a polynucleotide of about 10 to about 50 nucleic acid bases in length, said polynucleotide hybridizing to the platelet derived growth factor receptor related gene.
摘要翻译：本发明涉及长度为约10至约50个核酸碱基的多核苷酸，该多核苷酸与血小板衍生的生长因子受体相关基因杂交。本发明还涉及包含溶解或分散在生理上可耐受的稀释剂中的上述多核苷酸的药物组合物。本发明进一步涉及一种抑制血管平滑肌细胞增殖的方法和治疗血管平滑肌细胞增殖的方法，该方法包括使血管平滑肌细胞与需要这种治疗的宿主哺乳动物接触有效量的长度为约10至约50个核酸碱基的多核苷酸，所述多核苷酸与血小板衍生生长因子受体相关基因杂交。

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