(3R,5R,1'S)-5-<1-<<(tert-butyloxy)carbonyl>amino>-2-phenylethyl>-3-methyldihydrofuran-2(3H)-one | 104293-43-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (3R,5R,1'S)-5-<1-<<(tert-butyloxy)carbonyl>amino>-2-phenylethyl>-3-methyldihydrofuran-2(3H)-one
• 英文别名: (3R,5R)-3-methyl-5-{(1S)-1-[(tert-butoxycarbonyl)amino]-2-phenylethyl}tetrahydrofuran-2-one；tert-butyl N-[(1S)-1-[(2R,4R)-4-methyl-5-oxooxolan-2-yl]-2-phenylethyl]carbamate
• CAS: 104293-43-8
• 化学式: C₁₈H₂₅NO₄
• 分子量: 319.401
• InChiKey: GVDHVKDRRJNWDW-VHDGCEQUSA-N

物化性质

• 沸点：
  493.4±28.0 °C(Predicted)
• 密度：
  1.111±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (3R,5R,1'S)-5-<1-<<(tert-butyloxy)carbonyl>amino>-2-phenylethyl>-3-methyldihydrofuran-2(3H)-one 在 lithium aluminium tetrahydride 、 sodium hydrogen sulfate 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 水 为溶剂， 反应 0.5h， 以76%的产率得到(2S,3R,5R)-2-tert-butoxycarbonylamino-1-phenyl-5-methylhexan-3,6-diol
  参考文献：
  名称：

  Aspartyl protease inhibitors

  摘要：

  本发明提供具有以下公式的化合物：1其中R1、R′、R2、R3、R3′、R4、X1、X2和X3如本文所定义，以及其药物组合物。本发明还提供抑制蛋白酶的方法，更具体地是抑制天冬氨酸蛋白酶。在某些实施方式中，这些化合物抑制BACE（β-APP剪切酶），因此在治疗或预防大脑中存在β-淀粉样沉积的疾病（包括但不限于阿尔茨海默病）方面是有用的。本发明还提供制备本发明化合物的方法。

  公开号：

  US20040147454A1
• 作为产物：
  描述：

  N-Boc-L-苯丙氨醛 在 palladium on activated charcoal 三异丙氧基氯化钛 、 氢气 作用下， 以 乙酸乙酯 、 xylene 为溶剂， 反应 34.0h， 生成 (3R,5R,1'S)-5-<1-<<(tert-butyloxy)carbonyl>amino>-2-phenylethyl>-3-methyldihydrofuran-2(3H)-one
  参考文献：
  名称：

  Dipeptide analogs. Versatile synthesis of the hydroxyethylene isostere

  摘要：

  DOI：

  10.1021/jo00371a001

文献信息

• [EN] ASPARTYL PROTEASE INHIBITORS<br/>[FR] INHIBITEURS DE L'ASPARTYL-PROTEASE
  申请人：SUNESIS PHARMACEUTICALS INC

  公开号：WO2003106405A1

  公开（公告）日：2003-12-24

  The present invention provides compounds having formula (I): wherein R’, R0, R1, X1, R2, R3, R3’, X2, X3, and R4 are as defined herein, and pharmaceuticals compositions thereof. The present invention also provides methods of inhibiting proteases, more specially aspartyl proteases. In certain embodiments, compounds inhibit BACE (β-site APP-cleaving enzyme), and thus are useful in the treatment or prevention of a disease characterized by β-amyloid deposits in the brain (including, but not limited to, Alzheimer’s Disease). The present invention also provides methods for preparing compounds of the invention.

  本发明提供具有以下结构的化合物（I）：其中R'、R0、R1、X1、R2、R3、R3'、X2、X3和R4如本文所定义，并且其药物组合物。本发明还提供抑制蛋白酶的方法，更具体地是天冬氨酸蛋白酶。在某些实施例中，这些化合物抑制BACE（β-APP裂解酶），因此可用于治疗或预防大脑中存在β-淀粉样沉积的疾病（包括但不限于阿尔茨海默病）。本发明还提供了制备本发明化合物的方法。
• Studies of HIV-1 Protease Inhibitors. II. Incorporation of Four Types of Hydroxyethylene Dipeptide Isosteres at the Scissile Site of Substrate Sequences.
  作者：Mitsuya SAKURAI、Susumu HIGASHIDA、Machiko SUGANO、Takahide NISHI、Fujio SAITO、Yasuo OHATA、Hiroshi HANDA、Tomoaki KOMAI、Ryuichi YAGI、Takashi NISHIGAKI、Yuichiro YABE

  DOI：10.1248/cpb.41.1378

  日期：——

  hydroxyethylene dipeptide isosteres. For the synthesis of the latter two isosteres, a newly developed synthetic method for gamma-lactone was applied. The inhibitory activities of these peptides were evaluated by cleavage assay of partially purified gag proteins or purified synthetic peptide. Of the inhibitors examined, compounds 2c (Z-Asn-(2S,3R,4S,5S)-Phe-psi[H.E.]-Pro-NHB(un); Bu(n) = n-butyl, Ki

  设计并合成了包含四种类型的羟乙烯二肽等排体的人免疫缺陷病毒1型（HIV-1）蛋白酶抑制剂。这些抑制剂由八种苯丙氨酰基脯氨酸的立体异构体（Phe-psi [HE] -Pro），四种苯丙氨酰基丙氨酸[Phe-psi [HE] -Ala]立体异构体和一种苯丙酰基甘氨酸（Phe-psi [HE] -Gly）立体异构体组成。和环己基丙氨酰丙氨酸（Cha-psi [HE] -Ala）羟乙烯二肽等排体。对于后两个等排物的合成，使用了新开发的γ-内酯合成方法。这些肽的抑制活性通过部分纯化的gag蛋白或纯化的合成肽的裂解测定来评估。在所检测的抑制剂中，化合物2c（Z-Asn-（2S，3R，4S，5S）-Phe-psi [HE] -Pro-NHB（un）; Bu（n）=正丁基，Ki = 0.50 microM） ，21a（Z-Asn-（2R，4S，5S）-Phe-psi [HE] -Ala-NHBu（n），Ki
• Aminoethylenes:  A Tetrahedral Intermediate Isostere Yielding Potent Inhibitors of the Aspartyl Protease BACE-1
  作者：Wenjin Yang、Wanli Lu、Yafan Lu、Min Zhong、Jian Sun、Anila E. Thomas、Jennifer M. Wilkinson、Raymond V. Fucini、Melissa Lam、Mike Randal、Xiao-Ping Shi、Jeffrey W. Jacobs、Robert S. McDowell、Eric M. Gordon、Marcus D. Ballinger

  DOI：10.1021/jm0509142

  日期：2006.2.1

  A series of novel beta-site amyloid precursor protein cleaving enzyme (BACE-1) inhibitors containing an aminoethylene (AE) tetrahedral intermediate isostere were synthesized and evaluated in comparison to corresponding hydroxyethylene (HE) compounds. Enzymatic inhibitory values were similar for both isosteres, as were structure-activity relationships with respect to stereochemical preference and substituent variation (P2/P3, P1, and P2'); however, the AE compounds were markedly more potent in a cell-based assay for reduction of beta-secretase activity. The incorporation of preferred P2/ P3, P1, and P2' substituents into the AE pharmacophore yielded compound 7, which possessed enzymatic and cell assay IC(50)s of 26 nM and 180 nM, respectively. A three-dimensional crystal structure of 7 in complex with BACE-1 revealed that the amino group of the inhibitor core engages the catalytic aspartates in a manner analogous to hydroxyl groups in HE inhibitors. The AE isostere class represents a promising advance in the development of BACE-1 inhibitors.
• A new synthetic route for the γ-lactone precursors of hydroxyethylene dipeptide isosteres
  作者：Mitsuya Sakurai、Tadashi Hata、Yuichiro Yabe

  DOI：10.1016/s0040-4039(00)73819-6

  日期：1993.9

  Delta-Phthalimido-gamma-ketoesters were obtained by the Pd catalyzed coupling reaction between acid chlorides and organozinc reagents derived from beta-iodoesters, and were converted into the gamma-lactone precursors of Phe-psi[H.E.]-Ala and Phe-psi[H.E.]-Pro (15a,b-18a,b).
• US7132568B2
  申请人：——

  公开号：US7132568B2

  公开（公告）日：2006-11-07