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公开(公告)号：US20090286739A1
公开(公告)日：2009-11-19
申请号：US12121526
申请日：2008-05-15
摘要： Peptides, peptidomimetics and derivatives thereof of the following general formula I: (SEQ ID NO: 1) (I)H2N-GHRPX1X2X3-β-X4X5X6X7X8X9X10-X11, in which X1-X10 denote one of the 20 genetically coded amino acids, wherein X8, X9 and X10 individually or jointly may also denote a single chemical bond X11 denotes OR1 in which R1 equals hydrogen or (C1-C10)alkyl NR2R3 with R2 and R3 are equal or different and denote hydrogen, (C1-C10)alkyl or a residue —W-PEG5-60K, in which the PEG residue is attached via a suitable spacer W to the N-atom, or a residue NH—Y-Z-PEG5-60K, in which Y denotes a single chemical bond or a genetically coded amino acids from the group S, C, K or R and in which Z denotes a spacer, via which a polyethylene glycol (PEG)-residue can be attached, as well as their physiologically acceptable salts, and in which additionally β denotes an amino acid, whether genetically coded or not, or a peptidomimetic element, which have the additional property of inducing a bend or turn in the peptide backbone. Such amino acids include without limitation L-proline, D-proline, L-hydroxyproline, D-hydroxyproline, L-(O-benzyl)-hydroxyproline, D-(O-benzyl)-hydroxyproline, L-(O-tert. butyl)-hydroxyproline, 4-(O-2-naphtyl)-hydroxyproline, 4-(O-2-naphtyl-methyl)-hydroxyproline, 4-(O-phenyl)-hydroxyproline, 4-(4-phenyl-benzyl)-proline, cis-3-phenyl-proline, cis-4-phenyl-proline, trans-4-phenyl-proline, cis-5-phenyl-proline, trans-5-phenyl-proline, 4-benzyl-proline, 4-bromobenzyl-proline, 4-cyclohexyl-proline, 4-fluor-proline, L-tetrahydroisoquinoline-2-carboxylic acid (L-Tic), all diastereomers of octahydro-indole-2-carboxylic acid (Oic), and all diastereomers of 1-aza-bicyclo[3,3,0]octane-2-carboxylic acid or a residue selected from a group of peptidomimetic residues.
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2.发明申请公开(公告)号：US20080039388A1
公开(公告)日：2008-02-14
申请号：US11678535
申请日：2007-02-23
CPC分类号： C07K14/75 , A61K38/00 , Y02A50/385
摘要： Peptides and peptide derivatives of the following general Formula I: H2H-GHRPX1X2X3X4X5X6X7X8X9X10-(I) X11PX12PPPX13X14X15X16GYR-X17, wherein: X1-X16 denote one of the 20 genetically encoded amino acids, X17 denotes OR1, with R1=hydrogen or (C1-C10-alkyl), or NR2R3, R2 and R3 being identical or different and denoting hydrogen, (C1-C10)-alkyl, or a residue -PEG5-60K, wherein the PEG-residue is linked to the N atom via a spacer, or a residue NH—Y-Z-PEG5-60K, wherein Y denotes a chemical bond or a genetically coded amino acid from among the group of S, C, K or R, and Z denotes a spacer by way of which a polyethylene glycol (PEG)-residue may be linked, as well as the physiologically acceptable salts thereof, or wherein: X15 or X16 denotes an amino acid from the group of C or K, which is linked to a residue Z-PEG5-60K via the heteroatom in the side chain, and wherein X17 denotes OR1, with R1=hydrogen or (C1-C10-alkyl), or NR2R3, R2 and R3 being identical or different and denoting hydrogen or (C1-C10)-alkyl, as well as the physiologically acceptable salts thereof.
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公开(公告)号：US09012403B2
公开(公告)日：2015-04-21
申请号：US13702490
申请日：2011-06-17
IPC分类号： A61K38/00 , C07K7/06 , C07K7/08 , C07K14/705
CPC分类号： C07K7/06 , A61K38/00 , C07K7/08 , C07K14/705
摘要： The present invention relates to compounds, in particular peptides which are capable of stabilizing barrier functions of epithelium and endothelium. The peptides and other compounds of the present invention are useful in the treatment and prevention of diseases or disorders associated with a localized or systemic breakdown of epithelial and endothelial barrier functions. Particular diseases and disorders to be treated and/or prevented with the peptides or other compounds, methods and uses provided herein are burns, acute lung injury (ALI), acute respiratory distress syndrome (ARDS), ventilator induced lung injury (VILI), systemic inflammatory response syndrome (SIRS), acute kidney injury (AKI), sepsis, multiorgan dysfunction syndrome (MODS), or edema.
摘要翻译： 本发明涉及能够稳定上皮和内皮的屏障功能的化合物，特别是肽。 本发明的肽和其它化合物可用于治疗和预防与上皮和内皮屏障功能的局部或全身分解相关的疾病或病症。 用肽或其他化合物治疗和/或预防的特殊疾病和病症，本文提供的方法和用途是烧伤，急性肺损伤（ALI），急性呼吸窘迫综合征（ARDS），呼吸机诱导的肺损伤（VILI），系统性 炎性反应综合征（SIRS），急性肾损伤（AKI），败血症，多器官功能障碍综合征（MODS）或水肿。
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4.发明授权公开(公告)号：US08088890B2
公开(公告)日：2012-01-03
申请号：US12239579
申请日：2008-09-26
摘要： Peptides, peptidomimetics and derivatives thereof of the general formula I: H2N-GHRPX1-β-X4X5X6X7X8X9X10-X11 (I), in which X1-X10 denote one of the 20 genetically coded amino acids, wherein X8, X9 and X10 may also denote a single chemical bond; X11 denotes OR1 in which R1 equals hydrogen or (C1-C10) alkyl NR2R3 with R2 and R3 are equal or different and denote hydrogen, (C1-C10) alkyl, or a residue —W-PEG5-60K, in which the PEG residue is attached via a suitable spacer W to the N-atom, or a residue NH—Y—Z-PEG5-60K, in which Y denotes a chemical bond or a genetically coded amino acids from the group S, C, K or R and Z denotes a spacer, via which a polyethylene glycol (PEG)-residue can be attached, and their physiologically acceptable salts, and β denotes an amino acid, or a peptidomimetic element, which induces a bend or turn in the peptide backbone.
摘要翻译： 通式I：H2N-GHRPX1-＆bgr; -X4X5X6X7X8X9X10-X11（I）的肽，肽模拟物及其衍生物，其中X 1 -X 10表示20个遗传编码氨基酸之一，其中X8，X9和X10也可以表示 单一化学键; X11表示其中R1等于氢的OR1或其中R2和R3相同或不同的（C1-C10）烷基NR2R3，表示氢，（C1-C10）烷基或残基-W-PEG5-60K，其中PEG残基 或者残基NH-Y-Z-PEG5-60K，其中Y表示化学键或来自S，C，K或R族的遗传编码氨基酸，和 Z表示可以连接聚乙二醇（PEG）残留物的间隔物及其生理学上可接受的盐， 表示在肽主链中诱导弯曲或转向的氨基酸或拟肽元件。
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5.发明授权Compounds and methods for prevention and/or treatment of inflammation using the same 失效使用其预防和/或治疗炎症的化合物和方法公开(公告)号：US07884074B2
公开(公告)日：2011-02-08
申请号：US12121526
申请日：2008-05-15
摘要： The invention is directed to compounds and methods for prevention and/or treatment of inflammation using the same.
摘要翻译： 本发明涉及使用其的预防和/或治疗炎症的化合物和方法。
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6.发明申请公开(公告)号：US20100081787A1
公开(公告)日：2010-04-01
申请号：US12239579
申请日：2008-09-26
IPC分类号： C07K14/00
摘要： Peptides, peptidomimetics and derivatives thereof of the general formula I: H2N-GHRPX1-β-X4X5X6X7X8X9X10-X11 (I), in which X1-X10 denote one of the 20 genetically coded amino acids, wherein X8, X9 and X10 may also denote a single chemical bond; X11 denotes OR1 in which R1 equals hydrogen or (C1-C10) alkyl NR2R3 with R2 and R3 are equal or different and denote hydrogen, (C1-C10) alkyl, or a residue —W-PEG5-60K, in which the PEG residue is attached via a suitable spacer W to the N-atom, or a residue NH—Y-Z-PEG5-60K, in which Y denotes a chemical bond or a genetically coded amino acids from the group S, C, K or R and Z denotes a spacer, via which a polyethylene glycol (PEG)-residue can be attached, and their physiologically acceptable salts, and β denotes an amino acid, or a peptidomimetic element, which induces a bend or turn in the peptide backbone.
摘要翻译： 通式I：H2N-GHRPX1-＆bgr; -X4X5X6X7X8X9X10-X11（I）的肽，肽模拟物及其衍生物，其中X 1 -X 10表示20个遗传编码氨基酸之一，其中X8，X9和X10也可以表示 单一化学键; X11表示其中R1等于氢的OR1或其中R2和R3相同或不同的（C1-C10）烷基NR2R3，表示氢，（C1-C10）烷基或残基-W-PEG5-60K，其中PEG残基 或者残基NH-YZ-PEG5-60K，其中Y表示化学键或来自S，C，K或R和Z的基因编码氨基酸，Z表示 可以连接聚乙二醇（PEG）残基的间隔物及其生理上可接受的盐， 表示在肽主链中诱导弯曲或转向的氨基酸或拟肽元件。
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7.发明申请PEPTIDES AND PEPTIDE DERIVATIVES AS WELL AS PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME 审中-公开肽和肽衍生物作为含有其的药物组合物公开(公告)号：US20110098442A1
公开(公告)日：2011-04-28
申请号：US12280543
申请日：2007-02-23
IPC分类号： C07K14/00
CPC分类号： C07K14/75 , A61K38/00 , Y02A50/385
摘要： Peptides and peptide derivatives of the following general Formula (I): H2N-GHRPX1X2X3X4X5X6X7X8X9X10X11PX12PPPX13X14X15X16GYR—X17 (I), wherein: X1-X16 denote one of the 20 genetically encoded amino acids, X17 denotes OR1, with R1=hydrogen or (C1-C10-alkyl), or NR2R3, R2 and R3 being identical or different and denoting hydrogen, (C1-C10)-alkyl, or a residue -PEG5-60K, wherein the PEG-residue is linked to the N atom via a spacer, or a residue NH—Y-Z-PEG5-60K, wherein Y denotes a chemical bond or a genetically coded amino acid from among the group of S, C, K or R, and Z denotes a spacer by way of which a polyethylene glycol (PEG)-residue may be linked, as well as the physiologically acceptable salts thereof, or wherein: X15 or X16 denotes an amino acid from the group of C or K, which is linked to a residue Z-PEG5-60K via the heteroatom in the side chain, and wherein X17 denotes OR1, with R1=hydrogen or (C1-C10-alkyl), or NR2R3, R2 and R3 being identical or different and denoting hydrogen or (C1-C10)-alkyl, as well as the physiologically acceptable salts thereof.
摘要翻译： 下列通式（I）的肽和肽衍生物：H2N-GHRPX1X2X3X4X5X6X7X8X9X10X11PX12PPPX13X14X15X16GYR-X17（I），其中：X1-X16表示20个遗传编码氨基酸之一，X17表示OR1，其中R1 =氢或（C1-C10 - 烷基）或NR 2 R 3，R 2和R 3相同或不同，表示氢，（C 1 -C 10） - 烷基或残基-PEG 5-60K，其中PEG残基通过间隔基与N原子相连，或 残基NH-YZ-PEG5-60K，其中Y表示S，C，K或R组中的化学键或遗传编码的氨基酸，Z表示间隔基，通过其可以使用聚乙二醇（PEG） 可以连接残基，以及其生理上可接受的盐，或其中：X15或X16表示C或K基团的氨基酸，其通过侧面的杂原子与残基Z-PEG5-60K连接 链，其中X17表示OR1，其中R1 =氢或（C1-C10-烷基）或NR2R3，R2和R3相同或不同，表示氢 基或（C 1 -C 10） - 烷基，以及其生理上可接受的盐。
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8.发明授权公开(公告)号：US07799758B2
公开(公告)日：2010-09-21
申请号：US11678535
申请日：2007-02-23
CPC分类号： C07K14/75 , A61K38/00 , Y02A50/385
摘要： Therapeutic compositions can include modified peptides which are derived from the chain of the Bbeta(15-42)-fibrin fragment and wherein one or several of the amino acids of the sequence have been substituted by genetically encoded or not genetically encoded amino acids or peptidomimetics. They may exist as free peptides or as C-terminal derivative and/or being linked to a polyethylene glycol (PEG)-polymer, and have anti-inflammatory and/or endothelium stabilizing effects. Esters or amides may for instance be taken into consideration as C-terminal derivatives. Processes for production of the peptides and derivatives thereof are also described.
摘要翻译： 治疗组合物可以包括衍生自Bβ（15-42） - 纤维蛋白片段的链的修饰肽，并且其中序列的一个或几个氨基酸已被遗传编码的或未经遗传编码的氨基酸或肽模拟物取代。 它们可以作为游离肽或C末端衍生物存在和/或与聚乙二醇（PEG） - 聚合物连接，并具有抗炎和/或内皮稳定作用。 酯或酰胺可以例如被考虑为C末端衍生物。 还描述了肽及其衍生物的制备方法。
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9.发明申请PEPTIDES AND DERIVATIVES THEREOF, THE MANUFACTURING THEREOF AS WELL AS THEIR USE FOR PREPARING A THERAPEUTICALLY AND/OR PREVENTIVELY ACTIVE PHARMACEUTICAL COMPOSITION 审中-公开其制备方法及其衍生物，其制备方法及其用于制备治疗性和/或预防性活性药物组合物的用途公开(公告)号：US20090286725A1
公开(公告)日：2009-11-19
申请号：US12121544
申请日：2008-05-15
摘要： Peptides and peptide derivatives of the following general Formula I: (SEQ ID NO: 15) (I) H2N-GHRPX1X2X3X4X5X6X7X8PX9X10X11PX12PPPX13X14X15 X16GYR-X17, wherein: X1-X16 denote one of the 20 genetically encoded amino acids, X17 denotes OR1, with R1=hydrogen or (C1-C10-alkyl), or NR2R3, R2 and R3 being identical or different and denoting hydrogen, (C1-C10)-alkyl, or a residue -PEG5-60K, wherein the PEG-residue is linked to the N atom via a spacer, or a residue NH—Y-Z-PEG5-60K, wherein Y denotes a chemical bond or a genetically coded amino acid from among the group of S, C, K or R, and Z denotes a spacer by way of which a polyethylene glycol (PEG)-residue may be linked, as well as the physiologically acceptable salts thereof, or wherein: X15 or X16 denotes an amino acid from the group of C or K, which is linked to a residue Z-PEG5-60K via the heteroatom in the side chain, and wherein X17 denotes OR1, with R1=hydrogen or (C1-C10-alkyl), or NR2R3, R2 and R3 being identical or different and denoting hydrogen or (C1-C10)-alkyl, as well as the physiologically acceptable salts thereof.
摘要翻译： 以下通式I的肽和肽衍生物：（SEQ ID NO：15）（I）H 2 N-GHRPX1X2X3X4X5X6X7X8PX9X10X11PX12PPPX13X14X15 X16GYR-X17，其中：X1-X16表示20个遗传编码氨基酸之一，X17表示OR1，R1 = 氢或（C 1 -C 10 - 烷基）或NR 2 R 3，R 2和R 3相同或不同并且表示氢，（C 1 -C 10） - 烷基或残基-PEG 5 - 60K，其中所述PEG-残基连接到N 或者残基NH-YZ-PEG5-60K，其中Y表示S，C，K或R组中的化学键或遗传编码氨基酸，Z表示间隔基，通过其间隔， 可以连接聚乙二醇（PEG）残基以及其生理上可接受的盐，或其中：X 15或X 16表示与C或K基团相连的氨基酸，其与残基Z-PEG5-60K连接 并且其中X17表示OR1，其中R1 =氢或（C1-C10-烷基）或NR2R3，R2和R3相同或不同，并且de 注意氢或（C1-C10） - 烷基，以及其生理学上可接受的盐。
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10.发明申请公开(公告)号：US20090018310A1
公开(公告)日：2009-01-15
申请号：US12280544
申请日：2007-02-23
IPC分类号： C07K14/00
CPC分类号： C07K14/75
摘要： The invention relates to peptides and peptide derivatives of the following general Formulas (Ia) and (Ib) as well as in particular anti-inflammatory drugs containing these peptides.
摘要翻译： 本发明涉及以下通式（Ia）和（Ib）的肽和肽衍生物，特别是含有这些肽的抗炎药。
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