公开(公告)号：US08754038B2

公开(公告)日：2014-06-17

申请号：US13510864

申请日：2010-11-18

申请人： Françoise Jung ,  Frank Otto Gombert ,  Daniel Obrecht ,  Christian Bisang ,  Sophie Barthélémy ,  Alexander Lederer ,  Eric Chevalier

发明人： Françoise Jung ,  Frank Otto Gombert ,  Daniel Obrecht ,  Christian Bisang ,  Sophie Barthélémy ,  Alexander Lederer ,  Eric Chevalier

IPC分类号： A61K38/00 ,  A61P11/06 ,  C07K7/06 ,  C07K7/08

CPC分类号： A61K38/00 ,  C07K7/06 ,  C07K7/08 ,  C07K7/64

摘要： Novel template-fixed β-hairpin peptidomimetics of the general formula (I) wherein the single elements T or P are α-amino acid residues connected in either direction which, depending on their positions in the chain, are as defined in the description and the claims, and salts thereof, have the property to antagonize the receptor CCR10. They can be used as medicaments to treat or prevent diseases or conditions in the area of dermatological and cutaneous disorders, inflammation, allergic disorders, respiratory diseases, diseases of the gastro-intestinal tract, ophthalmic diseases, haematology and cancer. These β-hairpin peptidomimetics can be manufactured by a process which is based on a mixed solid- and solution phase synthetic strategy.

摘要翻译： 通式（I）的新型模板固定型和平滑型肽模拟物，其中单元素T或P是沿任一方向连接的α-氨基酸残基，其取决于其在链中的位置如说明书中所定义， 权利要求书及其盐具有拮抗受体CCR10的性质。 它们可以用作治疗或预防皮肤病和皮肤疾病，炎症，过敏性疾病，呼吸系统疾病，胃肠道疾病，眼科疾病，血液学和癌症领域的疾病或病症的药物。 这些可以通过基于混合固相和溶液相合成策略的方法制造。

公开(公告)号：US20110319291A1

公开(公告)日：2011-12-29

申请号：US13196712

申请日：2011-08-02

申请人： Jan Wim Vrijbloed ,  Daniel Obrecht ,  Sergio Locurio ,  Frank Otto Gombert ,  Christian Ludin ,  Françoise Jung

发明人： Jan Wim Vrijbloed ,  Daniel Obrecht ,  Sergio Locurio ,  Frank Otto Gombert ,  Christian Ludin ,  Françoise Jung

IPC分类号： C40B30/04

CPC分类号： C07K1/047 ,  C12N15/1037 ,  C40B40/02

摘要： Template-fixed β-hairpin mimetics and libraries including a plurality of these mimetics are provided. The template-fixed β-hairpin mimetics are of the following general formula: R1-Cys-Z-Cys-R2  I wherein the two cysteine residues are bridged by a disulfide bond, thereby forming a cyclic peptide; R1 and R2 are di- or tripeptide moieties of certain types, as defined herein; and Z is a chain of n amino acid residues with n being an integer from 4 to 20 and with each of these n amino acid residues being, independently, derived from any naturally occurring L-α-amino acid.

公开(公告)号：US08642560B2

公开(公告)日：2014-02-04

申请号：US13196658

申请日：2011-08-02

申请人： Jan Wim Vrijbloed ,  Daniel Obrecht ,  Sergio Locurio ,  Frank Otto Gombert ,  Christian Ludin ,  Françoise Jung

发明人： Jan Wim Vrijbloed ,  Daniel Obrecht ,  Sergio Locurio ,  Frank Otto Gombert ,  Christian Ludin ,  Françoise Jung

IPC分类号： A61K38/10 ,  A61K38/08

CPC分类号： C07K1/047 ,  C12N15/1037 ,  C40B40/02

摘要： Template-fixed β-hairpin mimetics and libraries including a plurality of these mimetics are provided. The template-fixed β-hairpin mimetics are of the following general formula: R1-Cys-Z-Cys-R2  I wherein the two cysteine residues are bridged by a disulfide bond, thereby forming a cyclic peptide; R1 and R2 are di- or tripeptide moieties of certain types, as defined herein; and Z is a chain of n amino acid residues with n being an integer from 4 to 20 and with each of these n amino acid residues being, independently, derived from any naturally occurring L-α-amino acid.

摘要翻译： 提供了模板固定的β-发夹模拟物和包括多个这些模拟物的文库。 模板固定的β-发夹模拟物具有以下通式：R1-Cys-Z-Cys-R2I，其中两个半胱氨酸残基通过二硫键桥连，由此形成环肽; R1和R2是如本文所定义的某些类型的二肽或三肽部分; 并且Z是n个氨基酸残基的链，n是4至20的整数，并且这些n个氨基酸残基中的每一个独立地衍生自任何天然存在的L-α-氨基酸。

公开(公告)号：US20110294702A1

公开(公告)日：2011-12-01

申请号：US13196658

申请日：2011-08-02

申请人： Jan Wim Vrijbloed ,  Daniel Obrecht ,  Sergio Locurio ,  Frank Otto Gombert ,  Christian Ludin ,  Françoise Jung

发明人： Jan Wim Vrijbloed ,  Daniel Obrecht ,  Sergio Locurio ,  Frank Otto Gombert ,  Christian Ludin ,  Françoise Jung

IPC分类号： C40B40/10

CPC分类号： C07K1/047 ,  C12N15/1037 ,  C40B40/02

摘要： Template-fixed β-hairpin mimetics and libraries including a plurality of these mimetics are provided. The template-fixed β-hairpin mimetics are of the following general formula: R1-Cys-Z-Cys-R2  I wherein the two cysteine residues are bridged by a disulfide bond, thereby forming a cyclic peptide; R1 and R2 are di- or tripeptide moieties of certain types, as defined herein; and Z is a chain of n amino acid residues with n being an integer from 4 to 20 and with each of these n amino acid residues being, independently, derived from any naturally occurring L-α-amino acid.

摘要翻译： 提供了模板固定模板和包含多个这些模拟物的文库。 模板固定和双螺旋模拟物具有以下通式：R1-Cys-Z-Cys-R2I，其中两个半胱氨酸残基通过二硫键桥接，从而形成环肽; R1和R2是如本文所定义的某些类型的二肽或三肽部分; 并且Z是n个氨基酸残基的链，n是4至20的整数，并且这些n个氨基酸残基中的每一个独立地衍生自任何天然存在的L-α-氨基酸。

公开(公告)号：US07994118B2

公开(公告)日：2011-08-09

申请号：US10579104

申请日：2003-11-15

申请人： Jan Wim Vrijbloed ,  Daniel Obrecht ,  Sergio Locurio ,  Frank Otto Gombert ,  Christian Ludin ,  Françoise Jung

发明人： Jan Wim Vrijbloed ,  Daniel Obrecht ,  Sergio Locurio ,  Frank Otto Gombert ,  Christian Ludin ,  Françoise Jung

IPC分类号： A61K38/04 ,  A61K38/12

CPC分类号： C07K1/047 ,  C12N15/1037 ,  C40B40/02

摘要： Template-fixed β-hairpin mimetics and libraries including a plurality of these mimetics are provided. The template-fixed β-hairpin mimetics are of the following general formula: R1-Cys-Z-Cys-R2  (I) wherein the two cysteine residues are bridged by a disulfide bond, thereby forming a cyclic peptide; R1 and R2 are di- or tripeptide moieties of certain types, as defined herein; and Z is a chain of n amino acid residues with n being an integer from 4 to 20 and with each of these n amino acid residues being, independently, derived from any naturally occurring L-α-amino acid.

摘要翻译： 提供了模板固定模板和包含多个这些模拟物的文库。 模板固定和模板模拟物具有以下通式：R1-Cys-Z-Cys-R2（I），其中两个半胱氨酸残基用二硫键桥连，从而形成环肽; R1和R2是如本文所定义的某些类型的二肽或三肽部分; 并且Z是n个氨基酸残基的链，n是4至20的整数，并且这些n个氨基酸残基中的每一个独立地衍生自任何天然存在的L-α-氨基酸。

公开(公告)号：US08796183B2

公开(公告)日：2014-08-05

申请号：US13196712

申请日：2011-08-02

申请人： Jan Wim Vrijbloed ,  Daniel Obrecht ,  Sergio Locurio ,  Frank Otto Gombert ,  Christian Ludin ,  Françoise Jung

发明人： Jan Wim Vrijbloed ,  Daniel Obrecht ,  Sergio Locurio ,  Frank Otto Gombert ,  Christian Ludin ,  Françoise Jung

IPC分类号： C40B30/04 ,  C07K5/00

CPC分类号： C07K1/047 ,  C12N15/1037 ,  C40B40/02

摘要： A method of screening for template-fixed β-hairpin mimetics and libraries including a plurality of these mimetics is provided. The template-fixed β-hairpin mimetics are of the following general formula: R1-Cys-Z-Cys-R2  I wherein the two cysteine residues are bridged by a disulfide bond, thereby forming a cyclic peptide; R1 and R2 are di- or tripeptide moieties of certain types, as defined herein; and Z is a chain of n amino acid residues with n being an integer from 4 to 20 and with each of these n amino acid residues being, independently, derived from any naturally occurring L-α-amino acid.

摘要翻译： 提供了一种筛选模板固定和模板模拟物的方法和包括多种这些模拟物的文库。 模板固定和双螺旋模拟物具有以下通式：R1-Cys-Z-Cys-R2I，其中两个半胱氨酸残基通过二硫键桥接，从而形成环肽; R1和R2是如本文所定义的某些类型的二肽或三肽部分; 并且Z是n个氨基酸残基的链，n是4至20的整数，并且这些n个氨基酸残基中的每一个独立地衍生自任何天然存在的L-α-氨基酸。

公开(公告)号：US08658604B2

公开(公告)日：2014-02-25

申请号：US11816589

申请日：2005-02-17

申请人： Steven J. DeMarco ,  Kerstin Moehle ,  Heiko Henze ,  Odile Sellier ,  Françoise Jung ,  Frank Gombert ,  Daniel Obrecht ,  Christian Ludin

发明人： Steven J. DeMarco ,  Kerstin Moehle ,  Heiko Henze ,  Odile Sellier ,  Françoise Jung ,  Frank Gombert ,  Daniel Obrecht ,  Christian Ludin

IPC分类号： A61K38/10 ,  A61K38/12

CPC分类号： C07K7/06 ,  A61K38/00 ,  C07K1/061 ,  C07K7/08 ,  C07K7/64

摘要： Template-fixed β-hairpin peptidomimetics of the general formulae wherein Z is a chain of 11 α-amino acid residues which, depending on their positions in the chain (counted starting from the N-terminal amino acid) are Gly, or Pro, or Pro(4NHCOPhe), or of certain types which, as the remaining symbols in the above formula, are defined in the description and the claims, and salts thereof, have the property to inhibit proteases, in particular serine proteases, especially Cathepsin G or Elastase or Tryptase. These β-hairpin peptidomimetics can be manufactured by processes which are based on a mixed solid- and solution phase synthetic strategy.

摘要翻译： 具有通式的模板固定的β-发夹肽模拟物，其中Z是11个α-氨基酸残基的链，其取决于其在链中的位置（从N-末端氨基酸开始计数）是Gly或Pro，或 Pro（4NHCOPhe）或某些类型，其作为上述式中的其余符号在说明书和权利要求书及其盐中定义，具有抑制蛋白酶，特别是丝氨酸蛋白酶，特别是组织蛋白酶G或弹性蛋白酶 或Tryptase。 这些β-发夹肽模拟物可以通过基于混合固相和溶液相合成策略的方法制备。