N-Fmoc-N-Me-Asp(OBn)-OH | 131451-30-4

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-Fmoc-N-Me-Asp(OBn)-OH
• 英文别名: Fmoc-N-Me-Asp(OBn)-OH；Fmoc-N-Me-Asp(OBzl)-OH；(2S)-2-[9H-fluoren-9-ylmethoxycarbonyl(methyl)amino]-4-oxo-4-phenylmethoxybutanoic acid
• CAS: 131451-30-4
• 化学式: C₂₇H₂₅NO₆
• 分子量: 459.499
• InChiKey: VBXORJMTNSIPAW-DEOSSOPVSA-N

物化性质

• 沸点：
  662.5±55.0 °C(Predicted)
• 密度：
  1.294±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  34
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  93.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-Fmoc-N-Me-Asp(OBn)-OH 在 palladium on activated charcoal N-甲基吗啉 、 盐酸 、 (benzotriazol-1-yloxyl)tris(dimethylamino)phosphonium hexafluorophosphate 、 1-羟基苯并三唑 、 溶剂黄146 、 1,3-环己二烯 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 1-羟基苯并三唑一水物 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 二乙胺 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 23.67h， 生成 Boc-(N-Me)Trp-Lys(CONH-Ph-o-Me)-(N-Me)Asp-Phe-NH2
  参考文献：
  名称：

  Holladay; Kopecka; Miller, Journal of Medicinal Chemistry, 1994, vol. 37, # 5, p. 630 - 635

  摘要：

  DOI：
• 作为产物：
  描述：

  芴甲氧羰基-天冬氨酸-β苄脂 在 三乙基硅烷 、 对甲苯磺酸 、 三氟乙酸 作用下， 以 氯仿 、 甲苯 为溶剂， 反应 40.5h， 生成 N-Fmoc-N-Me-Asp(OBn)-OH
  参考文献：
  名称：

  Design of a Potent Combined Pseudopeptide Endothelin-A/Endothelin-B Receptor Antagonist, Ac-dBhg¹⁶-Leu-Asp-Ile-[NMe]Ile-Trp²¹ (PD 156252):  Examination of Its Pharmacokinetic and Spectral Properties

  摘要：

  The endothelins (ETs) are a family of bicyclic 21-amino acid peptides that are potent and prolonged vasoconstrictors. It has been shown that highly potent combined ETA/ETB receptor antagonists can be developed from the C-terminal hexapeptide of ET (His(16)-Leu(17)-Asp(18)-Ile(19)-Ile(20)-Trp(21)), such as Ac-DDip(16)-Leu-Asp-Ile-Ile-Trp(21) (PD 142893) and Ac-DBhg(16)-Leu-Asp-Ile-Ile-Trp(21) (PD 145065). However, these compounds are relatively unstable to enzymatic proteolysis as determined in an in vitro rat intestinal perfusate assay. This instability is thought to be due to carboxypeptidase activity. In fact, incubation of PD 145065 with carboxypeptidase inhibitors greatly increased its half-life in rat intestinal perfusate. By performing a reduced amide bond and N-methyl amino acid scan, it was discovered that N-methylation of Ile(20) resulted in a compound (Ac-DBhg(16)-Leu-Asp-Ile-[NMe]Ile-Trp(21), PD 156252) that retained full receptor affinity at both endothelin receptor subtypes along with enhanced proteolytic stability and cellular permeability. Interestingly, N-methylation of this bond allows the cis configuration to be readily accessible which greatly alters the preferred structure of the entire molecule and may be responsible for the observed enhanced metabolic stability.

  DOI：

  10.1021/jm970161m

文献信息

• [EN] TREATMENT OF INFECTIONS<br/>[FR] TRAITEMENT D'INFECTIONS
  申请人：ASCENDIS PHARMA AS

  公开号：WO2020064844A1

  公开（公告）日：2020-04-02

  The present invention relates among other aspects to a conjugate or a pharmaceutically acceptable salt thereof or a pharmaceutical composition comprising said conjugate or its pharmaceutically acceptable salt for use in a method of preventing or treating an infection, wherein said conjugate is water-insoluble and comprises a polymeric moiety -Z to which a plurality of moieties -L2-X0D-L1-D are covalently conjugated, wherein each -D is independently an antibiotic moiety; each -L1- is independently a linker moiety to which -D is covalently and reversibly conjugated; each -X0D- is independently absent or a linkage and each -L2- is independently either a chemical bond or a spacer moiety.

  本发明涉及一种共轭物或其药用可接受的盐，或包含所述共轭物或其药用可接受的盐的药物组合物，用于预防或治疗感染的方法，其中所述共轭物不溶于水，包括一个聚合物基团-Z，其中多个基团-L2-X0D-L1-D以共价结合方式共轭，其中每个-D独立地是抗生素基团；每个-L1-独立地是连接基团，与-D以共价和可逆方式结合；每个-X0D-独立地不存在或是一个连接，每个-L2-独立地是化学键或间隔基团。
• Long acting insulin composition
  申请人：Sprogoe Kennett

  公开号：US09265723B2

  公开（公告）日：2016-02-23

  The present invention relates to a pharmaceutical composition comprising an insulin compound in a concentration that is sufficient to maintain a therapeutically effective level of the insulin compound in blood plasma for at least 3 days characterized by having a pharmacokinetic profile in vivo with substantially no burst of the insulin compound. The present invention further relates to the use of an insulin compound for preparing said pharmaceutical composition as well as a kit of parts comprising said pharmaceutical composition.

  本发明涉及一种药物组合物，其包括一种胰岛素化合物，其浓度足以在血浆中维持胰岛素化合物的治疗有效水平至少3天，其特征在于在体内具有基本没有胰岛素化合物突发的药代动力学特征。本发明还涉及利用胰岛素化合物制备所述药物组合物以及包括所述药物组合物的配件套件的用途。
• PRODRUGS COMPRISING AN INSULIN LINKER CONJUGATE
  申请人：SANOFI-AVENTIS DEUTSCHLAND GMBH

  公开号：US20150258207A1

  公开（公告）日：2015-09-17

  The present invention relates to a prodrug or a pharmaceutically acceptable salt thereof comprising an insulin linker conjugate D-L, wherein D represents the insulin moiety; and -L is a non-biologically active linker moiety -L 1 represented by formula (I), wherein the dashed line indicates the attachment to one of the amino groups of the insulin by forming an amide bond. The invention further relates to pharmaceutical compositions comprising said prodrugs as well as their use as a medicament for treating or preventing diseases or disorders which can be treated by insulin.

  本发明涉及一种前药或其药用可接受的盐，包括胰岛素连接物D-L，其中D代表胰岛素部分；-L是一种非生物活性的连接物-L1，其由式(I)表示，虚线表示通过形成酰胺键与胰岛素的氨基团之一结合。该发明还涉及包括所述前药的药物组合物，以及它们作为治疗或预防可以通过胰岛素治疗的疾病或紊乱的药物的用途。
• [EN] CONJUGATION METHOD FOR CARRIER-LINKED PRODRUGS<br/>[FR] PROCÉDÉ DE CONJUGAISON POUR PROMÉDICAMENTS LIÉS À UN SUPPORT
  申请人：ASCENDIS PHARMA AS

  公开号：WO2018011266A1

  公开（公告）日：2018-01-18

  The present invention relates to reagents comprising a substituted acyl borate or a substituted hydroxyl amine, to a method of synthesizing a carrier-linked prodrug using said reagents and to carrier-linked prodrugs obtainable by said method.

  本发明涉及包含取代酰硼酸酯或取代羟胺的试剂，以及使用这些试剂合成载体连接的前药的方法，以及通过该方法获得的载体连接的前药。
• [EN] CNP PRODRUGS WITH CARRIER ATTACHMENT AT THE RING MOIETY<br/>[FR] PROMÉDICAMENTS DE CNP AVEC FIXATION D'UN SUPPORT SUR LA PARTIE CYCLIQUE
  申请人：ASCENDIS PHARMA GROWTH DISORDERS AS

  公开号：WO2017118698A1

  公开（公告）日：2017-07-13

  The present invention relates to CNP prodrugs in which the carrier is covalently and reversibly attached to the ring moiety of a CNP moiety, to pharmaceutical compositions comprising such CNP prodrugs, to their uses and to methods of treating diseases that can be treated with the CNP prodrugs of the present invention.

  本发明涉及一种CNP前药，其中载体以共价和可逆地连接到CNP基团的环基团上，涉及包含这种CNP前药的药物组合物，涉及它们的用途以及用于治疗可以用本发明的CNP前药治疗的疾病的方法。