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1. 发明授权

US5229366A Peptide-containing polyethylene glycol derivatives and application thereof 失效
标题翻译：含肽聚乙二醇衍生物及其应用
公开(公告)号：US5229366A
公开(公告)日：1993-07-20
申请号：US780081
申请日：1991-10-21
申请人： Yoshihisa Tsukada , Atsushi Orikasa
发明人： Yoshihisa Tsukada , Atsushi Orikasa
IPC分类号： A61K38/04 , A61K47/48
CPC分类号： A61K47/48215 , A61K38/04
摘要： A peptide-containing polyethylene glycol derivative represented by the following general formula [I] or [II]: ##STR1## wherein each R.sup.1 independently represents a peptide residue represented by the following general formula [IIIa] or [IIIa]:-([X]-Arg-Gly-Asp-[Y]).sub.m -Z [IIIa]([X]-Glu-Ile-Leu-Asp-val-Pro-Ser-Thr-[Y]).sub.m (IIIb)wherein Arg, Gly, Asp, Glu, Ile, Leu, val, Pro, Ser and Thr represent arginine, glycine, aspartic acid, glutamic acid, isoleucine, leucine, valine, proline, serine and threonine residue respectively; [X] and [Y] each represents an amino acid or peptide residue which may be present or absent; n is an integer ranging from 1 to 150; m is an integer ranging from 1 to 5 and Z represents --OH or --NH.sub.2, provided that the peptide residue [IIIb] and the triazine ring is bonded at the position of [X] (if [X] is absent, at the position of Glu) or [Y] (or if [Y] is absent, at the position of Thr) or a salt thereof. The compound is useful as an effective ingredient of a composition for inhibiting adhesion of animal cells comprising or for inhibiting coagulation/cohesion of blood platelets.
摘要翻译：由以下通式[I]或[II]表示的含肽聚乙二醇衍生物：其中各R1独立地表示由以下通式[IIIa]表示的肽残基，或[IIIa]： - （[X] -Arg-Gly-Asp- [Y]）mZ [IIIa]（[X] -Glu-Ile-Leu-Asp-val-Pro-Ser-Thr- [Y]） m（IIIb）其中Arg，Gly，Asp，Glu，Ile，Leu，Val，Pro，Ser和Thr分别表示精氨酸，甘氨酸，天冬氨酸，谷氨酸，异亮氨酸，亮氨酸，缬氨酸，脯氨酸，丝氨酸和苏氨酸残基; [X]和[Y]各自表示可以存在或不存在的氨基酸或肽残基; n为1〜150的整数; m为1〜5的整数，Z为-OH或-NH 2，条件是肽残基[IIIb]和三嗪环在[X]的位置（如果[X]不存在）的Glu）或[Y]（或如果[Y]不存在，则在Thr的位置）或其盐。该化合物可用作抑制血小板凝集/凝聚的动物细胞粘附的组合物的有效成分。

2. 发明授权

US5436221A Tumor metastasis inhibiting compounds and methods 失效
标题翻译：肿瘤转移抑制化合物及方法
公开(公告)号：US5436221A
公开(公告)日：1995-07-25
申请号：US834848
申请日：1992-02-13
申请人： Hiroshi Kitaguchi , Hiroyuki Komazawa , Masayoshi Kojima , Hideto Mori , Naoyuki Nishikawa , Hideaki Satoh , Atsushi Orikasa , Mitsunori Ono , Ichiro Azuma , Ikuo Saiki
发明人： Hiroshi Kitaguchi , Hiroyuki Komazawa , Masayoshi Kojima , Hideto Mori , Naoyuki Nishikawa , Hideaki Satoh , Atsushi Orikasa , Mitsunori Ono , Ichiro Azuma , Ikuo Saiki
IPC分类号： A61K38/00 , A61K38/06 , A61K38/07 , A61K38/08 , A61K47/48 , A61P35/00 , C07K5/08 , C07K5/09 , C07K5/10 , C07K5/11 , C07K7/06 , C07K7/08 , C07K9/00 , C07K14/00 , C07K14/78 , C07K17/08 , C07K17/10 , C08F289/00 , C08G69/10 , C07K5/00 , C07K7/00
CPC分类号： A61K38/06 , A61K38/07 , A61K38/08 , A61K47/48238 , C07K14/001 , C07K14/78 , C07K5/0817 , C07K5/1019 , C07K9/001 , C08F289/00 , C08G69/10
摘要： A peptide derivative containing 1 to 20 units of peptide unit represented by the following general formula [I] or a pharmaceutically acceptable salt thereof;[Z]--Arg--X--Asp--[Y] [I]wherein Arg represents L- or D-arginine residue, Asp represents L-aspartic acid residue, X represents L- or D-leucine, D-isoleucine, L- or D-norleucine, L- or D-phenylalanine, D-phenylglycine or D-alanine residue, and [Z] and [Y] each represents an amino acid or a peptide residue, which may be present or absent, selected from glycine, L-serine, L-threonine, L- and D-aspartic acid, L-alanine, L- and D-glutamic acid, L-proline residues and a peptide residue constituted by the foregoing amino acid residues, and a pharmaceutical composition comprising the peptide derivative. The composition of the present invention is useful as an agent for inhibiting tumor metastasis.
摘要翻译：含有1〜20个单元的由下列通式[I]表示的肽单元的肽衍生物或其药学上可接受的盐; [Z] -Arg-X-Asp- [Y] [I]其中Arg表示L-或D-精氨酸残基，Asp表示L-天冬氨酸残基，X表示L-或D-亮氨酸，D-异亮氨酸，或D-正亮氨酸，L-或D-苯丙氨酸，D-苯基甘氨酸或D-丙氨酸残基，[Z]和[Y]各自表示可以存在或不存在的氨基酸或肽残基，其选自甘氨酸， L-丝氨酸，L-苏氨酸，L-和D-天冬氨酸，L-丙氨酸，L-和D-谷氨酸，L-脯氨酸残基和由上述氨基酸残基构成的肽残基，以及药物组合物，肽衍生物。本发明的组合物可用作抑制肿瘤转移的药剂。

3. 发明授权

US5763408A Amino acid derivatives and application thereof 失效
标题翻译：氨基酸衍生物及其应用
公开(公告)号：US5763408A
公开(公告)日：1998-06-09
申请号：US392258
申请日：1995-02-22
申请人： Naoyuki Nishikawa , Atsushi Orikasa , Hiroyuki Komazawa , Masayoshi Kojima , Ikuo Saiki , Ichiro Azuma
发明人： Naoyuki Nishikawa , Atsushi Orikasa , Hiroyuki Komazawa , Masayoshi Kojima , Ikuo Saiki , Ichiro Azuma
IPC分类号： A61K38/00 , C07C233/47 , C07C279/14 , C07D251/52 , C07K5/02 , C07K5/072 , A61K38/03
CPC分类号： C07K5/0202 , C07C233/47 , C07C279/14 , C07D251/52 , C07K5/0205 , C07K5/0215 , C07K5/06095 , C07K5/06113 , A61K38/00
摘要： There are disclosed amino acid derivatives represented by the following general formula (I): ##STR1## wherein L.sup.1 and L.sup.2 represent an amino acid residue etc., A.sup.1 and A.sup.3 represent C.dbd.O, A.sup.2 represents an alkylene group etc., m and n represent an integer of 1 to 5, V represents --NHC(.dbd.NH)NH.sub.2 etc., W represents --COOH etc., R.sup.1 and R.sup.2 represent hydrogen atom, alkyl group etc., R.sup.3 and R.sup.4 represent hydrogen etc. and X and Y represent --NH-- or --O-- and pharmaceutically acceptable salts thereof and agents for inhibiting tumor matastasis containing the compounds, and the amino acid derivatives exhibit high activity for inhibiting tumor metastasis and weak platelet aggregation inhibition activity and weak anticoagulation activity.
摘要翻译：公开了由以下通式（I）表示的氨基酸衍生物：通式（I）其中L1和L2表示氨基酸残基等，A1和A3表示C = O，A2表示亚烷基等，m和n表示1〜5的整数，V表示-NHC（= NH）NH 2等，W表示-COOH等，R 1和R 2表示氢原子，烷基等，R 3和R 4表示氢等 X和Y表示-NH-或-O-及其药学上可接受的盐，以及用于抑制含有该化合物的肿瘤转移的药剂，氨基酸衍生物表现出高的抑制肿瘤转移和血小板聚集抑制活性弱，抗凝活性低的活性。

4. 发明授权

US6046289A Propenamide derivatives containing Arg-Gly-Asp polymers obtained therefrom 失效
标题翻译：含有由其获得的Arg-Gly-Asp聚合物的丙烯酰胺衍生物
公开(公告)号：US6046289A
公开(公告)日：2000-04-04
申请号：US278251
申请日：1994-07-20
申请人： Hiroyuki Komazawa , Masayoshi Kojima , Atsushi Orikasa
发明人： Hiroyuki Komazawa , Masayoshi Kojima , Atsushi Orikasa
IPC分类号： A61K38/00 , A61K47/48 , C07K5/09 , C07K14/75 , C07K14/78 , C12N5/00 , A61K38/02 , C07K5/00 , C08H1/00
CPC分类号： C07K5/0817 , A61K47/48238 , C07K14/75 , C07K14/78 , C12N5/0068 , A61K38/00 , C12N2533/30
摘要： A propenamide derivative of the formula (I) having, as an essential structural unit, an adhesive peptide represented by the formula (II) in the side chain or salts thereof:Formula (I): R.sup.1 R.sup.2 C.dbd.CR.sup.3 --CO--[NH]--Formula (II): --[R.sup.4 ]--[CO]--([X]-Arg-Gly-Asp-[Y]).sub.n -[Z]--[R.sup.5 ]--wherein R.sup.1 and R.sup.2 each represents a hydrogen atom or a carboxyl group and R.sup.3 represents a hydrogen or halogen atom, methyl, ethyl or carboxymethyl group; X and Y each represents an amino acid residue selected from the group consisting of Ser, Gly, Val, Asn and Pro or a peptide residue consisting of two or more of the amino acids; z represents --O-- or --NH--; one of R.sup.4 and R.sup.5 represents a hydrogen atom, and the other represents a linear or branched alkylene group having 1 to 11 carbon atoms or an arylene group having 6 to 11 carbon atoms wherein the alkylene and arylene groups may be substituted with one or more halogen atom, carbonyl, carboxyl, amino, hydroxyl, sulfo, aryl, nitro or cyano group, or unsaturated double or triple bond; n is an integer of from 1 to 5; and [ ] means that each corresponding group or residue therebetween may be present or absent. A copolymer and crosslinked copolymer of the derivative with an anionic or cationic monomer or additional polyfunctional polymer. The use of the compounds for inhibiting adhesion of animal cells, or coagulation.cndot.adhesion of blood platelets, or for cultivating animal cells.
摘要翻译：作为必要结构单元的式（I）的丙烯酰胺衍生物，其侧链中的式（II）表示的粘合剂肽或其盐：式（I）：R1R2C = CR3-CO- [NH] - 式（II）：[R 4] - [CO] - （[X] -Arg-Gly-Asp- [Y]）n - [Z] - [R 5] - 其中R 1和R 2各自表示氢原子或羧基，R 3表示氢或卤素原子，甲基，乙基或羧甲基; X和Y各自表示选自Ser，Gly，Val，Asn和Pro的氨基酸残基或由两个或更多个氨基酸组成的肽残基; z表示-O-或-NH-; R4和R5之一表示氢原子，另一个表示碳原子数1〜11的直链或支链亚烷基或碳原子数6〜11的亚芳基，其中亚烷基和亚芳基可被一个或多个卤素原子，羰基，羧基，氨基，羟基，磺基，芳基，硝基或氰基，或不饱和双键或三键; n为1〜5的整数，和[]表示它们之间的每个相应组或残基可以存在或不存在。衍生物与阴离子或阳离子单体或另外的多官能聚合物的共聚物和交联共聚物。化合物用于抑制动物细胞粘附，凝血，血小板粘附或培养动物细胞的用途。

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