(2S,3R,4R,6E)-3-羟基-4-甲基-2-(甲基氨基)-6-辛烯酸 | 59865-23-5

• 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
• 中文名称: (2S,3R,4R,6E)-3-羟基-4-甲基-2-(甲基氨基)-6-辛烯酸
• 英文名称: (2S,3R,4R,6E)-3-hydroxy-4-methyl-2-methylamino-6-octenoic acid
• 英文别名: 4-(2E)-2-Buten-1-yl-2,4,5-trideoxy-2-(methylamino)-L-xylonic acid；(E,2S,3R,4R)-3-hydroxy-4-methyl-2-(methylamino)oct-6-enoic acid
• CAS: 59865-23-5
• 化学式: C₁₀H₁₉NO₃
• 分子量: 201.266
• InChiKey: AHQFCPOIMVMDEZ-UNISNWAASA-N

物化性质

• 熔点：
  240-241° (Wenger); mp 242-243° (Evans, Weber)
• 比旋光度：
  D20 +13.5° (c = 0.50 in water, pH 7); D +17° (c = 0.51 in 0.4N aq HCl)
• 沸点：
  366.3±42.0 °C(Predicted)
• 密度：
  1.063±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.3
• 重原子数：
  14
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  69.6
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2S,3R,4R,6E)-3-羟基-4-甲基-2-(甲基氨基)-6-辛烯酸 在 N-甲基吗啉 、 盐酸 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 (E)-(2S,3R,4R)-2-[((S)-2-{[(S)-2-(Acetyl-methyl-amino)-4-methyl-pentanoyl]-methyl-amino}-3-methyl-butyryl)-methyl-amino]-3-hydroxy-4-methyl-oct-6-enoic acid ((S)-1-dimethylcarbamoyl-propyl)-methyl-amide
  参考文献：
  名称：

  Is there a scaffolding domain within the structure of the immunosuppressive agent cyclosporin a (CsA)? Studies of the cyclophilin binding domain of CsA

  摘要：

  DOI：

  10.1016/s0040-4039(00)82401-6
• 作为产物：
  描述：

  (4S,5R)-5-((E)-(R)-1-Methyl-pent-3-enyl)-2-phenyl-4,5-dihydro-oxazole-4-carboxylic acid methyl ester 在 盐酸 、 sodium hydroxide 、 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 9.5h， 生成 (2S,3R,4R,6E)-3-羟基-4-甲基-2-(甲基氨基)-6-辛烯酸
  参考文献：
  名称：

  Synthesis of (4)-4-(()-2-butenyl)-4,-dimethyl--threonine (MeBMT), the characteristic amino acid of cyclosporine

  摘要：

  DOI：

  10.1016/s0040-4039(00)96225-7

文献信息

• [EN] STABILIZED TRIOXACARCIN ANTIBODY DRUG CONJUGATES AND USES THEREOF<br/>[FR] CONJUGUÉS MÉDICAMENT TRIOXACARCINE-ANTICORPS STABILISÉS ET UTILISATIONS DE CEUX-CI
  申请人：HARVARD COLLEGE

  公开号：WO2021252708A1

  公开（公告）日：2021-12-16

  Provided herein are antibody drug conjugates of Formula (I): G-R7(I) and pharmaceutically acceptable salts thereof, wherein G is a molecular payload; and R7 is - L-A-B, wherein L is a linking group, A is a conjugating group, and B is an antibody or antibody fragment. Also provided are methods of preparing the antibody-drug conjugates, pharmaceutically acceptable compositions thereof, and methods of their use and treatment. Further provided are precursors to the antibody drug conjugates (e.g., compounds of Formula (III), novel trioxacarcins without an antibody conjugated thereto), pharmaceutical compositions thereof, and methods of their use and treatment.

  提供的是公式(I)的抗体药物偶联物：G-R7(I)及其药用可接受的盐，其中G是分子有效载荷；R7是-L-A-B，其中L是连接基团，A是偶联基团，B是抗体或抗体片段。还提供了制备抗体-药物偶联物的方法，药用可接受的组合物，以及其使用和治疗方法。还提供了抗体药物偶联物的前体（例如，公式(III)的化合物，没有抗体偶联的新型三氧杂卡菌素），其药用组合物，以及其使用和治疗方法。
• [EN] TRIOXACARCIN-ANTIBODY CONJUGATES AND USES THEREOF<br/>[FR] CONJUGUÉS TRIOXACARCINE-ANTICORPS ET UTILISATIONS ASSOCIÉES
  申请人：HARVARD COLLEGE

  公开号：WO2019032961A1

  公开（公告）日：2019-02-14

  Provided herein are trioxacarcin-antibody drug conjugates of Formula (I): and pharmaceutically acceptable salts thereof, wherein R7 is -L-B, wherein L is a linking group, and B is an antibody or antibody fragment. Also provided are methods of preparing the antibody-drug conjugates, pharmaceutically acceptable compositions thereof, and methods of their use and treatment. Further provided are precursors to the trioxacarcin- antibody drug conjugates (e.g., compounds of Formula (II), novel trioxacarcins without an antibody conjugated thereto), pharmaceutical compositions thereof, and methods of their use and treatment.

  本发明提供了三氧杂卡林-抗体药物偶联物，其化学公式为(I)：以及药用可接受的盐，其中R7是-L-B，L是连接基团，B是抗体或抗体片段。还提供了制备抗体-药物偶联物的方法，药用可接受的组合物，以及其使用和治疗方法。进一步提供的是三氧杂卡林-抗体药物偶联物的前体（例如，化学公式为(II)的化合物，没有抗体偶联的新三氧杂卡林），其药用组合物，以及其使用和治疗方法。
• Pro-drug and use thereof as a medicament
  申请人：——

  公开号：US20040138108A1

  公开（公告）日：2004-07-15

  The invention relates to a pro-drug comprising a cyclic undecapeptide wherein the peptide chain thereof comprises at least one amino acid residue of general formula (1) wherein the carbon atom C a is one of the links in said undecapeptide cycle; —substituents Y individually represent a hydrogen atom or form a bond together; —substitutents R 1 and R 3 independently represent a hydrogen atom, an aralkyl group, an alkaryl group, a heteroalkyl group, a heterocyclic group, a heterocyclic alkyl group, an alkyl heterocyclic group or an alkyl group having 1-6 carbon atoms which is linear or branched, and which is optionally substituted by at least one of the groups chosen from among —COOH, —CONHR 8 , —NHCO═NH(NH 2 ), —NHC═NR 8 (NH 2 ), —NH 2 , —NHR 8 , —NR 8 2 , —N + R 8 3 , —OH, —OPO(OR 8 ) 2 , —OPO(OH)(OR 8 ), —OPO(OH) 2 , —OSO(OR 8 ) 2 , —OSO(OH)(OR 8 ), —OSO(OH) 2 , and the different salts produced therefrom, each of the substituents R 8 independently representing alkyl group which is linear or ramified having 1-6 carbon atoms; —substituents R 2 and R 4 independently represent a hydrogen atom, an alkaryl group or an alkyl group having 1-6 carbon atoms which is linear or branched; —the substituents R 5 and R 6 individually represent a hydrogen atom, an aralkyl group, an alkyl group having 1-6 carbon atoms which is linear or branched; and substituent R 7 represents an alkaryl group, a heteroalkyl group, a heterocylic group, a heterocylic alkyl group, an alkyl heterocyclic group or an alkyl group having 1-6 carbon atoms which is linear or branched.

  该发明涉及一种前药，包括一个环式十一肽，其中其肽链至少包括一个一般式（1）中的氨基酸残基，其中碳原子C a 是所述十一肽环中的链接之一；—取代基Y分别表示氢原子或共同形成键；—取代基R 1 和R 3 独立地表示氢原子、芳基烷基、烷基芳基、杂原子烷基、杂环基、杂环烷基、烷基杂环基或具有1-6个碳原子的线性或支链烷基，其可以被所选自—COOH、—CONHR 8 、—NHCO═NH(NH 2 )、—NHC═NR 8 (NH 2 )、—NH 2 、—NHR 8 、—NR 8 2 、—N + R 8 3 、—OH、—OPO(OR 8 ) 2 、—OPO(OH)(OR 8 )、—OPO(OH) 2 、—OSO(OR 8 ) 2 、—OSO(OH)(OR 8 )、—OSO(OH) 2 及由此产生的不同盐中的至少一个取代基取代；其中每个取代基R 8 独立地表示具有1-6个碳原子的线性或支链烷基；—取代基R 2 和R 4 独立地表示氢原子、烷基芳基或具有1-6个碳原子的线性或支链烷基；—取代基R 5 和R 6 分别表示氢原子、芳基烷基、具有1-6个碳原子的线性或支链烷基；取代基R 7 表示芳基烷基、杂原子烷基、杂环基、杂环烷基、烷基杂环基或具有1-6个碳原子的线性或支链烷基。
• Asymmetric glycine enolate aldol reactions: synthesis of cyclosporin's unusual amino acid, MeBmt
  作者：David A. Evans、Ann E. Weber

  DOI：10.1021/ja00281a049

  日期：1986.10

  Synthese de l'acide (hydroxy-3 methyl-4 methylamino-2) octene-6oique apr aldolisation entre l'enolate de la (benzyl-4 isothiocyanatoacetyl-3) oxazolidone-2 et des alcenals

  合成 de l'acide (hydroxy-3methyl-4methylamino-2) octene-6oique apr aldolisation entre l'enolate de la (benzyl-4 isothiocyanatoacetyl-3) oxazolidone-2 et des alcenals
• [EN] STAPLED AND STITCHED POLYPEPTIDES AND USES THEREOF<br/>[FR] POLYPEPTIDES À AGRAFES ET À SUTURE ET LEURS UTILISATIONS
  申请人：HARVARD COLLEGE

  公开号：WO2014159969A1

  公开（公告）日：2014-10-02

  The present invention provides stapled polypeptides of the Formulae (I) and (VI): (I) (VI) and salts thereof; wherein the groups =====; R1a, R1b, R1c, R2a, R3a, R2b, R3b, R4a, R4b, RA, RZ, L1a, L1b, L2, L3, XAA, v, w, p, m, s, n, t, and q are as defined herein. The present invention further provides methods of preparing the inventive stapled polypeptides from unstapled polypeptide precursors. The present invention further provides pharmaceutical compositions comprising a stapled polypeptide of Formula (I) or (VI), and methods of using the stapled peptides. The present invention also provides modifications of the staples post ring closing metathesis.

  本发明提供了Formulae (I)和(VI)的订书钉多肽：(I) (VI)及其盐；其中的基团=====；R1a、R1b、R1c、R2a、R3a、R2b、R3b、R4a、R4b、RA、RZ、L1a、L1b、L2、L3、XAA、v、w、p、m、s、n、t和q如本文所定义。本发明还提供了从未定书钉的多肽前体制备创新的定书钉多肽的方法。本发明还提供了包含Formula (I)或(VI)的定书钉多肽的药物组合物，以及使用这些定书钉肽的方法。本发明还提供了环闭合交换反应后订书钉的修饰。