首页> 外国专利> Nleu4-lys17-lys18-alpha1-25-acth-val25-amide

Nleu4-lys17-lys18-alpha1-25-acth-val25-amide

机译:Nleu4-lys17-lys18-alpha1-25-acth-val25-酰胺

摘要

The pentacosapeptide H - Ser - Tyr - Ser - Nle-Glu(OH) - His - Phe - Arg - Try - Gly - Lys - Pro-Val - Gly - Lys - Lys - Lys - Lys - Pro - Val-Lys -Val-Tyr-Pro-ValNH2 and its acid addition salts are prepared by condensing H-Val-Lys(R)-Val-Tyr-Pro-ValNH2 with Z-Val-Gly-Lys(R)-Lys(R)-Lys(R)-Lys(R)-Lys(R)-ProOCP, removing the Z-group from the resulting Z-Val-Gly-Lys(R)-Lys(R) - Lys(R) - Lys(R) - Pro - Val - Lys(R)-Val-Tyr-Pro-ValNH2 condensing the tridecapeptide with Tri-Glu(OtBu)-His(Tri)-Phe-Arg-Try-Gly-Lys(R)-Pro-OCP, removing the terminal Tri-group from Tri-Glu(OtBu)-His(Tri)-Phe - Arg - Try - Gly - Lys(R) - Pro - Val - Gly-Lys(R) - Lys(R) - Lys(R) - Lys(R) - Pro - Val-Lys(R)-Val-Try-Pro-Val-NH2, condensing the eicosapeptide with R1-Ser-Tyr-Ser-NleN3 and removing in one or more processes the blocking groups R, Tri and R1, where R and R1 are N-blocking groups used in peptide chemistry especially the butoxycarbonyl (BOC) and tertamyloxy carbonyl (CAT) group. Tri is triphenylmethyl, Z is carbobenzoxy, and CP is 2,4,5-trichlorophenyl. The following intermediates and starting materials are prepared: Z-Lys(BOC)OCP; H-Val - Lys(BOC) - Val - Tyr - Pro - ValNH2; Z-Tyr - Pro - ValNH2; H - Tyr - Pro - Val - NH2-HBr; Z - Val - Tyr - Pro - Val - NH2; H - Val-Tyr - Pro - ValNH2HBr; Z - Lys(BOC) - Val-Tyr - Pro - Val - NH2; H - Lys(BOC) - Val - Tyr-Pro - Val - NH2HBr; Z - Lys(BOC) - ProOMe and its free acid; H-Lys(BOC)-Pro-OH; Z-Lys-(BOC) - Lys(BOC) - ProOH; H - Lys(BOC)-Lys(BOC) - ProOH; Z - Lys(BOC) - Lys(BOC)-OMe; Z - Val - Gly - Lys(BOC) - Lys(BOC)OMe; Z - Val - Gly - Lys(BOC) - Lys(BOC) - NHNH2 and its azide; Z-Val-Gly-Lys(BOC)-Lys(BOC)-Lys(BOC)-Lys(BOC)-ProOH and its -CP ester; Z - Arg(NO2) - Try - GlyOH and its -CP ester; Z - Arg(NO2) - Try - Gly - Lys(BOC) - Pro - OH - H - Arg - Try - Gly - Lys(BOC) - Pro - OH; Z-Glu(OtBu) - His - Phe - OMe; Tri - Glu(OtBu); His(Tri) - Phe - OMe and its hydrazide and azide; Tri - Glu(OtBu) - His(Tri) - Phe - Arg-Try - Gly - Lys(BOC) - ProOH and its -CP ester, HCl sa Tri-Ser-Tyr-OMe and its hydrazide; Z - Ser - Nle-OMe; H - Ser - NleOMeHCl; Tri - Ser - Tyr - Ser - Nle - OMe and its hydrazide and azide; tert amyl-thiophenyl carbonate; tertamyl carbazate; Z-Lys(CAT)OH and its methyl and -CP esters; H - Val - Lys(CAT) - Val - Tyr-Pro-ValNH2 and its Z-derivative; H-Lys(CAT)-Val-Tyr-Pro-ValNH2 and its Z-derivative; H-Lys(CAT)-Pro-OH and its Z-derivative; H-Lys-(CAT) -Lys(CAT)-ProOH and its Z-derivative; Z - Lys(CAT) - Lys(CAT)OMe; Z - Val - Gly-Lys(CAT) - Lys(CAT)OMe and -NHNH2; Z - Val - Gly - Lys(CAT) - Lys(CAT) - Lys-(CAT) - Lys(CAT) - ProOH and its -CP ester; H - Val - Gly - Lys(CAT) - Lys(CAT) - Lys(CAT) - Lys(CAT) - Pro - Val - Lys(CAT) - Val-Tyr-Pro-ValNH2 and its Z-derivative; H-Arg-Try-Gly-Lys(CAT)-ProOH and its Z- and NO2-derivative and Tri-Glu(OtBu)-His(Tri)-Phe-Arg-Arg-Try-Gly-Lys(CAT)-ProOH and its -CP ester, HCl salt. Pharmaceutical compositions comprise the pentacosapeptide or a salt thereof and a carrier. The compositions may be in a form suitable for enteral or parenteral administration.
机译:五肽肽H-Ser-Tyr-Ser-Nle-Glu(OH)-His-Phe-Arg-Try-Gly-Lys-Pro-Val-Gly-Lys-Lys-Lys-Lys-Pro-Val-Lys -Val -Tyr-Pro-ValNH2及其酸加成盐是通过将H-Val-Lys(R)-Val-Tyr-Pro-ValNH2与Z-Val-Gly-Lys(L)-Lys-Lys( R)-Lys(R)-Lys(R)-ProOCP,从所得的Z-Val-Gly-Lys(R)-Lys(R)-Lys(R)-Lys(R)-Pro中除去Z-基团-Val-Lys(R)-Val-Tyr-Pro-ValNH2与Tri-Glu(OtBu)-His(Tri)-Phe-Arg-Try-Gly-Lys(R)-Pro-OCP缩合三肽Tri-Glu(OtBu)-His(Tri)-Phe-Arg的末端Tri-group-Try-Gly-Lys(R)-Pro-Val-Gly-Lys(R)-Lys(R)-Lys(R) -Lys(R)-Pro-Val-Lys(R)-Val-Try-Pro-Val-NH2,将二十碳肽与R1-Ser-Tyr-Ser-NleN3缩合,并在一个或多个过程中除去保护基团R, Tri和R1,其中R和R1是肽化学中使用的N封闭基团,尤其是丁氧羰基(BOC)和叔戊氧羰基(CAT)基团。 Tri是三苯基甲基,Z是碳苯并,CP是2,4,5-三氯苯基。制备以下中间体和起始原料:Z-Lys(BOC)OCP; MS-MS。 H-Val-Lys(BOC)-Val-Tyr-Pro-ValNH2; Z-Tyr-Pro-ValNH2; H-Tyr-Pro-Val-NH2-HBr; Z-Val-Tyr-Pro-Val-NH2; H-Val-Tyr-Pro-ValNH2HBr; Z-Lys(BOC)-Val-Tyr-Pro-Val-NH2; H-Lys(BOC)-Val-Tyr-Pro-Val-NH2HBr; Z-Lys(BOC)-ProOMe及其游离酸; H-赖氨酸(BOC)-Pro-OH; Z-Lys-(BOC)-Lys(BOC)-ProOH; H-Lys(BOC)-Lys(BOC)-ProOH; Z-Lys(BOC)-Lys(BOC)-OMe; Z-Val-Gly-Lys(BOC)-Lys(BOC)OMe; Z-Val-Gly-Lys(BOC)-Lys(BOC)-NHNH2及其叠氮化物; Z-Val-Gly-Lys(BOC)-Lys(BOC)-Lys(BOC)-Lys(BOC)-ProOH及其-CP酯; Z-Arg(NO2)-尝试-GlyOH及其-CP酯; Z-Arg(NO2)-尝试-Gly-Lys(BOC)-Pro-OH-H-Arg-尝试-Gly-Lys(BOC)-Pro-OH; Z-Glu(OtBu)-他的-Phe-OMe;三-Glu(OtBu); His(Tri)-Phe-OMe及其酰肼和叠氮化物; Tri-Glu(OtBu)-His(Tri)-Phe-Arg-Try-Gly-Lys(BOC)-ProOH及其-CP酯,HCl盐; Tri-Ser-Tyr-OMe及其酰肼; Z-Ser-Nle-OMe; H-Ser-NleOMeHCl; Tri-Ser-Tyr-Ser-Nle-OMe及其酰肼和叠氮化物;碳酸叔戊基苯硫基酯;氨基甲酸叔丁基酯; Z-Lys(CAT)OH及其甲基和-CP酯; H-Val-Lys(CAT)-Val-Tyr-Pro-ValNH2及其Z衍生物​​; H-Lys(CAT)-Val-Tyr-Pro-ValNH2及其Z衍生物​​; H-Lys(CAT)-Pro-OH及其Z衍生物​​; H-Lys-(CAT)-Lys(CAT)-ProOH及其Z衍生物​​; Z-Lys(CAT)-Lys(CAT)OMe; Z-Val-Gly-Lys(CAT)-Lys(CAT)OMe和-NHNH2; Z-Val-Gly-Lys(CAT)-Lys(CAT)-Lys-(CAT)-Lys(CAT)-ProOH及其-CP酯; H-Val-Gly-Lys(CAT)-Lys(CAT)-Lys(CAT)-Lys(CAT)-Pro-Val-Lys(CAT)-Val-Tyr-Pro-ValNH2及其Z衍生物​​; H-Arg-Try-Gly-Lys(CAT)-ProOH及其Z-和NO2-衍生物和Tri-Glu(OtBu)-His(Tri)-Phe-Arg-Arg-Arg-Try-Gly-Lys(CAT)- ProOH及其-CP酯,HCl盐。药物组合物包含五碳糖肽或其盐和载体。所述组合物可以为适合肠内或肠胃外施用的形式。

著录项

  • 公开/公告号US3352844A

    专利类型

  • 公开/公告日1967-11-14

    原文格式PDF

  • 申请/专利权人 SANDOZ LTD.;

    申请/专利号US19650427599

  • 申请日1965-01-25

  • 分类号A61K38;C07K5/103;C07K14/695;

  • 国家 US

  • 入库时间 2022-08-23 12:59:00

获取专利

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号