(2R,3R)-3-[(t-丁氧羰基)氨基]-4-苯基-1,2-环氧丁烷 | 156474-21-4

• 物质功能分类: 有机原料 - 氨基化合物
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: (2R,3R)-3-[(t-丁氧羰基)氨基]-4-苯基-1,2-环氧丁烷
• 英文名称: tert-butyl [(2R,3R)]-(-)-(1-oxiranyl-2-phenylethyl)carbamate
• 英文别名: tert-butyl (R)-1-((R)-oxiran-2-yl)-2-phenylethylcarbamate；(R,R)-1-oxiranyl-2-phenylethylcarbamic acid tert-butyl ester；tert-butyl [(R,R)]-(-)-(1-oxiranyl-2-phenylethyl)carbamate；erythro-N-Boc-D-phenylalanine epoxide；tert-butyl N-[(1R)-1-[(2R)-oxiran-2-yl]-2-phenylethyl]carbamate
• CAS: 156474-21-4
• 化学式: C₁₅H₂₁NO₃
• 分子量: 263.337
• InChiKey: NVPOUMXZERMIJK-OLZOCXBDSA-N

物化性质

• 沸点：
  398.8±25.0 °C(Predicted)
• 密度：
  1.118±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  50.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2R,3R)-3-[(t-丁氧羰基)氨基]-4-苯基-1,2-环氧丁烷 以 二氯甲烷 、 异丙醇 为溶剂， 反应 18.0h， 生成 (R)-2-[3-Benzyl-3-((2S,3R)-3-tert-butoxycarbonylamino-2-hydroxy-4-phenyl-butyl)-ureido]-4-methyl-pentanoic acid methyl ester
  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：

  D-苯丙氨酸甲酯 在 甲基氯化镁 、 aluminum isopropoxide 、 碳酸氢钠 、 异丙醇 、 sodium hydroxide 作用下， 以 四氢呋喃 、 丙酮 为溶剂， 反应 23.75h， 生成 (2R,3R)-3-[(t-丁氧羰基)氨基]-4-苯基-1,2-环氧丁烷
  参考文献：
  名称：

  Babu, Kilaru Ravendra; Rao, Valasani Koteswara; Sudhakar, Yellapu, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2012, vol. 51, # 6, p. 849 - 854

  摘要：

  DOI：

文献信息

• HUMAN IMMUNODEFICIENCY VIRUS PROTEASE INHIBITORS
  申请人：Ganguly A.K.

  公开号：US20110112068A1

  公开（公告）日：2011-05-12

  The described invention relates to novel human immunodeficiency virus protease inhibitors, pharmaceutical compositions containing at least one such inhibitor, methods of preparing such inhibitors, and methods of utilizing such inhibitors to treat HIV and HIV-related disorders.

  所描述的发明涉及新型人类免疫缺陷病毒蛋白酶抑制剂，包含至少一种此类抑制剂的药物组合物，制备此类抑制剂的方法，以及利用此类抑制剂治疗艾滋病毒及艾滋病毒相关疾病的方法。
• Diastereoselective epoxidation of allylically substituted alkenes using metalloporphyrin catalysts
  申请人：Che Chi-Ming

  公开号：US20050209470A1

  公开（公告）日：2005-09-22

  Diastereoselective epoxidation of allylically substituted alkenes using metalloporphyrins as catalyst provides high trans-selectivities (i.e., trans-:cis-epoxide ratio). A diversity of cycloalkenes bearing different allylic substituents are shown to be efficiently epoxidized to afford the corresponding trans-epoxides with excellent trans-selectivities (up to >98%) and good yields (up to 99%). Acyclic allylic alkenes bearing different allylic substituents are efficiently epoxidized to afford the corresponding erythro-epoxides with good erythro-selectivities. The metalloporphyrin-catalyzed reactions exhibit up to 20 times higher trans-selectivities than the conventional method using m-chloroperoxybenzoic acid as oxidant.

  使用金属卟啉作为催化剂的烯丙基取代烯烃的非对映选择性环氧化反应提供高选择性（即反式：顺式环氧化物比）。显示出带有不同烯丙基取代基的多样环烯烃能够有效地环氧化，产生相应的反式环氧化物，具有优异的反式选择性（高达>98%）和良好的产率（高达99%）。带有不同烯丙基取代基的无环烯丙基烯烃能够有效地环氧化，产生相应的顺式环氧化物，具有良好的顺式选择性。金属卟啉催化的反应显示出比使用m-氯过氧苯甲酸作为氧化剂的传统方法高达20倍的反式选择性。
• Hydroxyethylamine Based Phthalimides as New Class of Plasmepsin Hits: Design, Synthesis and Antimalarial Evaluation
  作者：Anil K. Singh、Sumit Rathore、Yan Tang、Nathan E. Goldfarb、Ben M. Dunn、Vinoth Rajendran、Prahlad C. Ghosh、Neelu Singh、N. Latha、Brajendra K. Singh、Manmeet Rawat、Brijesh Rathi

  DOI：10.1371/journal.pone.0139347

  日期：——

  A novel class of phthalimides functionalized with privileged scaffolds was designed, synthesized and evaluated as potential inhibitors of plasmepsin 2 (Ki: 0.99 ± 0.1 μM for 6u) and plasmepsin 4 (Ki: 3.3 ± 0.3 μM for 6t), enzymes found in the digestive vacuole of the plasmodium parasite and considered as crucial drug targets. Three compounds were identified as potential candidates for further development. The listed compounds were also assayed for their antimalarial efficacy against chloroquine (CQ) sensitive strain (3D7) of Plasmodium falciparum. Assay of twenty seven hydroxyethylamine derivatives revealed four (5e, 6j, 6o and 6s) as strongly active, which were further evaluated against CQ resistant strain (7GB) of P. falciparum. Compound 5e possessing the piperidinopiperidine moiety exhibited promising antimalarial activity with an IC50 of 1.16 ± 0.04 μM. Further, compounds 5e, 6j, 6o and 6s exhibited low cytotoxic effect on MCF-7 cell line. Compound 6s possessing C2 symmetry was identified as the least cytotoxic with significant antimalarial activity (IC50: 1.30 ± 0.03 μM). The combined presence of hydroxyethylamine and cyclic amines (piperazines and piperidines) was observed as crucial for the activity. The current studies suggest that hydroxyethylamine based molecules act as potent antimalarial agent and may be helpful in drug development.

  我们设计、合成并评估了一类新型邻苯二甲酰亚胺，并将其作为疟原虫消化液泡中的疟原蛋白酶 2（6u 的 Ki 值为 0.99 ± 0.1 μM）和疟原蛋白酶 4（6t 的 Ki 值为 3.3 ± 0.3 μM）的潜在抑制剂。三个化合物被确定为进一步开发的潜在候选化合物。还对所列化合物进行了抗恶性疟原虫氯喹（CQ）敏感株（3D7）的抗疟药效测定。在对 27 种羟乙基胺衍生物进行检测后发现，其中 4 种（5e、6j、6o 和 6s）具有很强的活性。具有哌啶基的化合物 5e 表现出良好的抗疟活性，其 IC50 为 1.16 ± 0.04 μM。此外，化合物 5e、6j、6o 和 6s 对 MCF-7 细胞系的细胞毒性较低。具有 C2 对称性的化合物 6s 被确定为细胞毒性最小的化合物，具有显著的抗疟活性（IC50：1.30 ± 0.03 μM）。据观察，羟乙基胺和环胺（哌嗪和哌啶）的共同存在对活性至关重要。目前的研究表明，基于羟乙基胺的分子是有效的抗疟药物，可能有助于药物开发。
• 1-Amino Linked Compounds
  申请人：Blaszczak Larry Chris

  公开号：US20080207735A1

  公开（公告）日：2008-08-28

  The present invention is directed to compounds of formula (I): or a pharmaceutically acceptable salt thereof; wherein A is (II); X is selected from CH, CF and N, R8 is selected from H, C 1 -C 6 alkyl, aryl, heteroaryl, C 1 -C 6 alkylaryl, C 1 -C 6 alkylheteroaryl, C 2 -C 6 alkyl-O—C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, hydroxy C 2 -C 6 alkyl, —C(O)R9 and —SO 2 R9, or R7 and R8 combine to form (III), (IV); W is selected from CR1O and CR15, R1O is selected from H, halo, —C(O)NR13R14, C 1 -C 6 alkyl, aryl, heteroaryl, C 1 -C 6 alkylaryl, C 1 -C 6 alkylheteroaryl, C 1 -C 6 alkyl-O—C 1 -C 6 alkyl and hydroxy C 1 -C 6 alkyl; Het is a N-linked 5-membered heteroaryl ring optionally substituted with 1-3 substituents selected from methoxy, Cl, F, CH 3 , CF 3 , aryl, heteroaryl, C 1 -C 4 alkylaryl or C 1 -C 4 alkylheteroaryl, for use as inhibitors of the DPP-IV enzyme in the treatment or prevention of conditions including Type II diabetes.

  本发明涉及以下式(I)的化合物或其药学上可接受的盐;其中A为(II);X选自CH、CF和N，R8选自H、C1-C6烷基、芳基、杂环芳基、C1-C6烷基芳基、C1-C6烷基杂环芳基、C2-C6烷基-O-C1-C6烷基、C1-C6卤代烷基、羟基C2-C6烷基、-C（O）R9和-SO2R9，或R7和R8结合形成(III)、(IV);W选自CR1O和CR15，R1O选自H、卤、-C（O）NR13R14、C1-C6烷基、芳基、杂环芳基、C1-C6烷基芳基、C1-C6烷基杂环芳基、C1-C6烷基-O-C1-C6烷基和羟基C1-C6烷基;Het是一种N-连接的5-成员杂环芳基环，可选地被1-3个取代基所取代，所述取代基选自甲氧基、Cl、F、CH3、CF3、芳基、杂环芳基、C1-C4烷基芳基或C1-C4烷基杂环芳基，用作DPP-IV酶的抑制剂，治疗或预防包括II型糖尿病在内的疾病。
• 1-amino linked compounds
  申请人：Eli Lilly and Company

  公开号：US08106090B2

  公开（公告）日：2012-01-31

  The present invention is directed to compounds of formula (I): or a pharmaceutically acceptable salt thereof; wherein A is (II); X is selected from CH, CF and N, R8 is selected from H, C1-C6 alkyl, aryl, heteroaryl, C1-C6 alkylaryl, C1-C6 alkylheteroaryl, C2-C6 alkyl-O—C1-C6 alkyl, C1-C6 haloalkyl, hydroxy C2-C6 alkyl, —C(O)R9 and —SO2R9, or R7 and R8 combine to form (III), (IV); W is selected from CR1O and CR15, R1O is selected from H, halo, —C(O)NR13R14, C1-C6 alkyl, aryl, heteroaryl, C1-C6 alkylaryl, C1-C6 alkylheteroaryl, C1-C6 alkyl-O—C1-C6 alkyl and hydroxy C1-C6 alkyl; Het is a N-linked 5-membered heteroaryl ring optionally substituted with 1-3 substituents selected from methoxy, Cl, F, CH3, CF3, aryl, heteroaryl, C1-C4 alkylaryl or C1-C4 alkylheteroaryl, for use as inhibitors of the DPP-IV enzyme in the treatment or prevention of conditions including Type II diabetes.

  本发明涉及式(I)的化合物或其药学上可接受的盐；其中A为(II)；X选自CH、CF和N，R8选自H、C1-C6烷基、芳基、杂环芳基、C1-C6烷基芳基、C1-C6烷基杂环芳基、C2-C6烷基-O-C1-C6烷基、C1-C6卤代烷基、羟基C2-C6烷基、-C(O)R9和-SO2R9，或R7和R8结合形成(III)、(IV)；W选自CR1O和CR15，R1O选自H、卤素、-C(O)NR13R14、C1-C6烷基、芳基、杂环芳基、C1-C6烷基芳基、C1-C6烷基杂环芳基、C1-C6烷基-O-C1-C6烷基和羟基C1-C6烷基；Het是一种N-连接的5-成员杂环芳基环，可选地被1-3个取代基所取代，所述取代基选自甲氧基、Cl、F、CH3、CF3、芳基、杂环芳基、C1-C4烷基芳基或C1-C4烷基杂环芳基，用作DPP-IV酶抑制剂，用于治疗或预防包括II型糖尿病在内的疾病。