D-valine methyl ester isocyanate | 30293-85-7

• 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: D-valine methyl ester isocyanate
• 英文别名: N-carbonyl-D-valine methyl ester；methyl (S)-2-isocyanato-2-isopropyl acetate；N^α-isocyano-L-valine methyl ester；methyl (2R)-2-isocyanato-3-methylbutanoate
• CAS: 30293-85-7
• 化学式: C₇H₁₁NO₃
• 分子量: 157.169
• InChiKey: JCVZXXSBCISMLJ-ZCFIWIBFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  11
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  55.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  D-valine methyl ester isocyanate 在 lithium hydroxide 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 (R)-methyl 2-((R)-2-(3-benzyl-3-((2R,3R)-3-(tert-butoxycarbonyl)-2-hydroxy-4-phenylbutyl)ureido)-3-methylbutanamido)-3-methylbutanoate
  参考文献：
  名称：

  Stereochemical Analysis of (Hydroxyethyl)urea Peptidomimetic Inhibitors of γ-Secretase

  摘要：

  (Hydroxyethyl)urea peptidomimetics systematically altered at positions P2-P3' with hydrophobic D-amino acids were synthesized. An all D-amino acid containing analogue was identified that effectively blocked gamma-secretase activity in a cell-free system (IC50 = 30 nM). Systematic alteration of the stereocenters of a potent compound revealed interdependence between the various positions. Although typically less potent than their L-peptidomimetic counterparts. selected all D-amino acid containing analogues were equipotent. to their counterparts in a cell-based assay when incubated for extended times.

  DOI：

  10.1021/jm049566e
• 作为产物：
  描述：

  三光气 、 D-缬氨酸甲酯盐酸盐 以 甲苯 为溶剂， 反应 3.0h， 以80%的产率得到D-valine methyl ester isocyanate
  参考文献：
  名称：

  Enantiomeric recognition of carboxylic anions by a library of neutral receptors derived from α-amino acids and o-phenylenediamine

  摘要：

  A library of eight neutral anion receptors consisting of a-amino acid esters attached to o-phenylenediamine by urea groups was synthesized and analysed in terms of capacity for chiral recognition of carboxylates. The NMR titrations revealed that the association constants of complexes consisting of a chiral guest and a chiral host are two orders of magnitude lower than those of achiral partners. Diverse substituents in the receptor structure modify both the affinities and enantioselectivities. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2014.06.004

文献信息

• Sulfonamide inhibitors of aspartyl protease
  申请人：Vertex Pharmaceuticals, Incorporated

  公开号：US06372778B1

  公开（公告）日：2002-04-16

  The present invention relates to a novel class of sulfonamides which are aspartyl protease inhibitors. In one embodiment, this invention relates to a novel class of HIV aspartyl protease inhibitors characterized by specific structural and physicochemical features. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting HIV-1 and HIV-2 protease activity and consequently, may be advantageously used as anti-viral agents against the HIV-1 and HIV-2 viruses. This invention also relates to methods for inhibiting the activity of HIV aspartyl protease using the compounds of this invention and methods for screening compounds for anti-HIV activity.

  本发明涉及一种新型磺胺类化合物，其为天冬氨酸蛋白酶抑制剂。在一个实施例中，本发明涉及一种新型HIV天冬氨酸蛋白酶抑制剂，其具有特定的结构和理化特征。本发明还涉及包含这些化合物的药物组合物。本发明的化合物和药物组合物特别适用于抑制HIV-1和HIV-2蛋白酶活性，因此，可以有利地用作抗HIV-1和HIV-2病毒的抗病毒剂。本发明还涉及使用本发明的化合物抑制HIV天冬氨酸蛋白酶活性的方法，以及筛选具有抗HIV活性的化合物的方法。
• Amino acid derived latent isocyanates: irreversible inactivation of porcine pancreatic elastase and human leukocyte elastase
  作者：William C. Groutas、William R. Abrams、Michael C. Theodorakis、Annette M. Kasper、Steven A. Rude、Robert C. Badger、Timothy D. Ocain、Kevin E. Miller、Min K. Moi

  DOI：10.1021/jm00380a010

  日期：1985.2

  were found to inhibit irreversibly both enzymes. Compound 10 was found to be a specific and selective inhibitor of human leukocyte elastase. In contrast to these, inhibitors derived from glycine methyl ester 1, D-valine methyl ester 4, and D-norvaline methyl ester 6 were found to be inactive. The results of the present study show that latent isocyanates derived from appropriate amino acids can serve as

  已经合成了几种氨基酸衍生的偶氮内酯（I），并研究了它们对人白细胞弹性蛋白酶和猪胰弹性蛋白酶的抑制活性。发现抑制活性取决于前体氨基酸酯的性质。因此，发现衍生自L-缬氨酸甲酯3，L-正缬氨酸甲酯5，DL-正亮氨酸甲酯9和L-甲硫氨酸甲酯10的化合物不可逆地抑制两种酶。发现化合物10是人白细胞弹性蛋白酶的特异性和选择性抑制剂。与这些相反，发现衍生自甘氨酸甲酯1，D-缬氨酸甲酯4和D-去甲缬氨酸甲酯6的抑制剂是无活性的。
• Transfer of Chiral Information through Molecular Assembly
  作者：Ronald K. Castellano、Colin Nuckolls、Julius Rebek

  DOI：10.1021/ja993165k

  日期：1999.12.1

  Calix[4]arenes substituted with ureas on their upper, wider rims form dimers in solution held together by a seam of 16 hydrogen bonds. The resulting molecular capsules have interiors capable of accommodating small-molecule guests. By virtue of the assembly process, a head-to-tail arrangement of ureas is formed that can assume either a clockwise or counterclockwise orientation around the equator of

  杯[4]芳烃在其上部较宽的边缘被脲取代，在溶液中形成二聚体，通过 16 个氢键的接缝连接在一起。由此产生的分子胶囊具有能够容纳小分子客人的内部结构。凭借组装过程，形成了尿素头尾相连的排列，它可以围绕胶囊的赤道呈顺时针或逆时针方向。尿素功能上的氨基酸对杯芳烃的二聚化行为具有显着影响。首先，手性衍生物倾向于与芳基脲取代的杯芳烃结合，而不是与它们自身结合。异亮氨酸和缬氨酸等具有 β 支链侧链的氨基酸对异源二聚化具有这种选择性。第二，氨基酸的点手性在组装时被转移，从而形成一个手性胶囊，其尿素的头尾排列只有一个方向。圆二向色光谱用于分配...
• Dutta, Anand S.; Giles, Michael, B.; Gormley, James J., Journal of the Chemical Society. Perkin transactions I, 1987, p. 111 - 120
  作者：Dutta, Anand S.、Giles, Michael, B.、Gormley, James J.、Williams, Joseph C.、Kusner, Edward J.

  DOI：——

  日期：——
• The Isocyanate Route to Cyclopentadienyl-Carboxamide- and Cyclopentadienyl-Amino Ester-Substituted Metallocene Complexes
  作者：Markus Oberhoff、Lothar Duda、Jörn Karl、Roland Mohr、Gerhard Erker、Roland Fröhlich、Matthias Grehl

  DOI：10.1021/om960234k

  日期：1996.9.17

  Lithium cyclopentadienide adds to a variety of isocyanates [R-N=C=O, R = tert-butyl (a), n-butyl (b), cyclohexyl (c), phenyl (d), 3-pyridyl (e), 2-tetrahydropyranyl (f), adamantyl (g)] to yield the monocarbamoyl-substituted cyclopentadienides C(5)H(4)CONHR(-) 3 admired with varying amounts of the respective 1,2-dicarbamoyl-substituted C5H3(CONHR)(2)(-) systems 4 and a corresponding quantity of the C5H5- Starting material. Subsequent treatment of these reaction mixtures with anhydrous FeCl2 gave the 1,1'-dicarbamoylferrocenes 6 and the corresponding monocarbamoylferrocenes 5, which were easily separated by chromatography. The carbamoylferrocenes 5b, 5c, and 6d were characterized by X-ray crystal structure analyses. The (N-phenyl- and (N-adamantylcarbamoyl)cyclopentadienides were treated with CpTiCl(3) to give the carboxamide-substituted titanocene dichloride complexes [CP(C(5)H(4)CONHR)TiCl2] 8a (R = Ph) and Sh (R = adamantyl), respectively. Complex 8b was also characterized by X-ray diffraction. The valine ester-derived isocyanate reacts with lithium cyclopentadienide to give the N-valinyl-substituted carbamoylcyclopentadienide 3h. Subsequent treatment with FeCl2 or FeCl2/CpLi, respectively, produces the 1,1'-difunctionalized ferrocene 6h or the monofunctionalized ferrocene 5h. Both complexes were characterized by X-ray crystal structure analyses.