N-[芴甲氧羰基]-2-甲基-L-缬氨酸 | 169566-81-8

• 物质功能分类: 化学试剂 - 有机试剂 - 多环化合物
• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 中文名称: N-[芴甲氧羰基]-2-甲基-L-缬氨酸
• 中文别名: 芴甲氧羰基-α-甲基-缬氨酸
• 英文名称: (S)-N²-<(9H-fluoren-9-yl)methoxycarbonyl>-2-methylvaline
• 英文别名: N-[(9H-fluoren-9-ylmethoxy)carbonyl]-3-methyl-L-isovaline；Fmoc-L-(αMe)Val-OH；(S)-N-Fmoc-α-methylvaline；(S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)-2,3-dimethylbutanoic acid；(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-2,3-dimethylbutanoic acid
• CAS: 169566-81-8
• 化学式: C₂₁H₂₃NO₄
• 分子量: 353.418
• InChiKey: AWEZXIRZNQCCNN-NRFANRHFSA-N

物化性质

• 沸点：
  554.1±33.0 °C(Predicted)
• 密度：
  1.209±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• TSCA：
  No
• 海关编码：
  2924299090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335

反应信息

• 作为反应物：
  描述：

  N-[芴甲氧羰基]-2-甲基-L-缬氨酸 在 吡啶 、 三聚氟氰 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 Fmoc-(αMe)Val-F
  参考文献：
  名称：

  Design, conformational studies and analysis of structure–function relationships of PTH (1–11) analogues: the essential role of Val in position 2

  摘要：

  The N-terminal 1-34 segment of parathyroid hormone (PTH) is fully active in vitro and in vivo and it elicits all the biological responses characteristic of the native intact PTH. Recent studies reported potent helical analogues of the PTH (1-11) with helicity-enhancing substitutions. This work describes the synthesis, biological activity, and conformational studies of analogues obtained from the most active non-natural PTH (1-11) peptide H-Aib-Val-Aib-Glu-Ile-Gln-Leu-Nle-His-Gln-Har-NH2; specifically, the replacement of Val in position 2 with d-Val, l-(alpha Me)-Val and N-isopropyl-Gly was studied. The synthesized analogues were characterized functionally by in-cell assays and their structures were determined by CD and NMR spectroscopy. To clarify the relationship between the structure and activity, the structural data were used to generate a pharmacophoric model, obtained overlapping all the analogues. This model underlines the fundamental functional role of the side chain of Val(2) and, at the same time, reveals that the introduction of conformationally constrained C-alpha-tetrasubstituted alpha-amino acids in the peptides increases their helical content, but does not necessarily ensure significant biological activity.

  DOI：

  10.1007/s00726-011-1065-1
• 作为产物：
  描述：

  (E)-(S)-2-Isopropyl-4-((1S,2S,5R)-2-isopropyl-5-methyl-cyclohexyl)-2-methyl-but-3-en-1-ol 在 sodium chlorite 、 sodium dihydrogenphosphate 、 jones reagent 、 2-甲基-2-丁烯 、 二苯基膦叠氮化物 、 臭氧 、 三乙胺 作用下， 以 二氯甲烷 、 丙酮 、 甲苯 、 叔丁醇 为溶剂， 反应 13.0h， 生成 N-[芴甲氧羰基]-2-甲基-L-缬氨酸
  参考文献：
  名称：

  A Stereodivergent Approach to Chiral Nonracemic N-Protected α,α-Dialkylated Amino Acids

  摘要：

  Menthyl carboxaldehyde is used as a chiral auxiliary to make quaternary amino acids of either configuration via a stereodivergent approach that includes an SN2' displacement by a cuprate reagent and a Curtius rearrangement as key steps.

  DOI：

  10.1021/ja037078a

文献信息

• CYTOTOXIC PEPTIDES AND ANTIBODY DRUG CONJUGATES THEREOF
  申请人：PFIZER INC.

  公开号：US20130129753A1

  公开（公告）日：2013-05-23

  The present invention is directed to cytotoxic pentapeptides, to antibody drug conjugates thereof, and to methods for using the same to treat cancer.

  本发明涉及细胞毒性五肽，其抗体药物偶联物，以及使用它们治疗癌症的方法。
• <scp>L</scp>-Phenylalanine Cyclohexylamide: A simple and convenient auxiliary for the synthesis of optically pure α,α-disubstituted (<i>R</i>)- and (<i>S</i>)-amino acids
  作者：Daniel Obrecht、Udo Bohdal、Clemens Broger、Daniel Bur、Christian Lehmann、Ruth Ruffieux、Peter Schönholzer、Clive Spiegler、Klaus Müller

  DOI：10.1002/hlca.19950780305

  日期：1995.5.10

  synthesis of a series of optically pure α,α-disubstituted (R)- and (S)-amino acids of type 1, such as (R)- and (S)-2-methyl-phenylalanine (1a), (R)- and (S)-2-methyl-2-phenylglycine (1b), and (R)- and (S)-2-methylvaline (1c; Scheme 3). These amino acids were efficiently transformed into the suitably protected and activated amino acid building blocks (R)- and (S)-12b and (R)- and (S)-12c (Scheme 4) which are

  这项工作描述了L-苯丙氨酸环己基酰胺（5C），其为简单的，价格便宜，且功能强大的手性助剂为一系列光学纯α，α-二取代的（的合成- [R ）-和（小号）型的α-氨基酸1，这样如（R）-和（S）-2-甲基-苯丙氨酸（1a），（R）-和（S）-2-甲基-2-苯甘氨酸（1b）以及（R）-和（S）-2 -甲基缬氨酸（1c；方案3）。这些氨基酸被有效地转化为适当保护和活化的氨基酸构件（R）和（S）-12b以及（R）-和（S）-12c（方案4），它们已经准备好通过溶液或固相技术掺入肽中。基于属于非对映异构体肽系列6和7的6b，6c和7a的晶体结构，确定该系列的每个成员的绝对构型。对于6b和7a分别观察到II'和I型的β-转角几何形状，而6c以扩展构象结晶。讨论了侧链变化对这些三酰胺的构象和晶体堆积的影响。
• COMPOUNDS AND RELATED METHODS OF USE
  申请人：Jacobsen Eric N.

  公开号：US20130066109A1

  公开（公告）日：2013-03-14

  Described herein are compounds of formula (I), related compositions, and their use, for example in the formation of α-amino acids or a precursor thereof such as an α-aminonitrile.

  本文描述了式（I）的化合物、相关组合物及其用途，例如在形成α-氨基酸或其前体（如α-氨基腈）中的应用。
• Cytotoxic peptides and antibody drug conjugates thereof
  申请人：Pfizer Inc.

  公开号：US08828401B2

  公开（公告）日：2014-09-09

  The present invention is directed to cytotoxic pentapeptides, to antibody drug conjugates thereof, and to methods for using the same to treat cancer.

  本发明涉及细胞毒性五肽、其抗体药物联合物，以及使用它们治疗癌症的方法。
• Aryl-cyanoguanidine compounds
  申请人：Bayer Pharma Aktiengesellschaft

  公开号：US10023539B2

  公开（公告）日：2018-07-17

  The present invention relates to protein-lysine N-methyltransferase SMYD2 (SET and MYND domain-containing protein 2) inhibitors, in particular SMYD2-inhibitory substituted cyanoguanidine-pyrazolines of general formula (I) wherein R1, R2, R3, R4, R5, X and r have the meaning as described and defined herein, as well as to pharmaceutical compositions comprising compounds according to the invention and to their prophylactic and therapeutic use for hyper-proliferative disorders, in particular for cancer, respectively tumor disorders. The present invention furthermore relates to the use of SMYD2 inhibitors for benign hyperplasias, atherosclerotic disorders, sepsis, autoimmune disorders, vascular disorders, viral infections, neurodegenerative disorders, inflammatory disorders, atherosclerotic disorders and the control of male fertility.

  本发明涉及蛋白-赖氨酸N-甲基转移酶SMYD2（含SET和MYND结构域的蛋白2）抑制剂，特别是通式（I）的SMYD2-抑制性取代氰胍-吡唑啉类，其中R1、R2、R3、R4、R5、X和r具有本文所述和定义的含义；本发明还涉及包含根据本发明的化合物的药物组合物，以及它们对过度增殖性疾病，特别是癌症、肿瘤疾病的预防和治疗用途。本发明还涉及 SMYD2 抑制剂在良性增生性疾病、动脉粥样硬化性疾病、败血症、自身免疫性疾病、血管疾病、病毒感染、神经退行性疾病、炎症性疾病、动脉粥样硬化性疾病和控制男性生育能力方面的用途。