N-Boc-3-(p-nitrophenyl)allylamine | 139200-38-7

• 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: N-Boc-3-(p-nitrophenyl)allylamine
• 英文别名: tert-butyl N-[(2E)-3-(4-nitrophenyl)prop-2-en-1-yl]carbamate；tert-butyl N-[(E)-3-(4-nitrophenyl)prop-2-enyl]carbamate
• CAS: 139200-38-7
• 化学式: C₁₄H₁₈N₂O₄
• 分子量: 278.308
• InChiKey: WASJMWVTTNYAHW-SNAWJCMRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  84.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-Boc-3-(p-nitrophenyl)allylamine 、 三氟乙酸 以62%的产率得到1-(p-nitrophenyl)-3-aminopropenyl trifluoroacetate
  参考文献：
  名称：

  Structure-activity relationships for inhibition of papain by peptide Michael acceptors

  摘要：

  Two series of peptidyl Michael acceptors, N-Ac-L-Phe-NHCH2CH = CH-E with different electron withdrawing groups (E = CO2CH3, 1a; SO2CH3, 1b; CO2H, 1c; CN, 1d; CONH2, 1e; and C6H4-p-NO2, 1f) and R-NHCH2CH = CHCOOCH3 with different recognition and binding groups (R = N-Ac-D-Phe, 2a; N-Ac-L-Leu, 3a; N-Ac-L-Met, 4a; PhCH2CH2CO, 5a; PhCO, 6a), were synthesized and evaluated as inactivators against papain. It was found that the inhibition of papain by peptidyl Michael acceptors is a general phenomenon and that the intrinsic chemical reactivity of the E group in the Michael acceptors has a direct effect on the kinetics of the inactivation process as reflected in k2/K(i). At pH 6.2, the reactivity of papain toward the Michael acceptors is about 283 000-fold higher than the reactivity of the model thiol 3-mercaptopropionate. This large increase in reactivity is attributable to at least 2 factors; one is the low apparent pK(a) of Cys-25 of papain, and the other is the recruitment of catalytic power by specific enzyme-substrate interactions. The unexpectedly high reactivity of 1c (E = COOH) was rationalized by proposing a direct interaction of the acid group with His-159 in the active site of papain. The unexpected inactivity of 1f (E = C6H4-p-NO2) as a Michael acceptor and its very powerful competitive inhibition of papain were rationalized by molecular graphics which showed the nitrophenyl moiety rotated out of conjugation with the olefin and interacting instead with the hydrophobic S1' region of papain. A plot of log (k2/K(i)) for 1a-6a vs log (k(cat)/K(m)) for analogous R-Gly-p-NA substrates was linear (r = 0.98) with slope of 0.83, suggesting that binding energy from specific enzyme-ligand interactions can be used to drive the self-inactivation reaction to almost the same extent as it is used to drive catalysis.

  DOI：

  10.1021/jm00084a012
• 作为产物：
  描述：

  叔丁氧基 N-氨基甲酸丙烯 在 二甲基硫 、 乙醇 、 sodium 、 臭氧 作用下， 反应 9.0h， 生成 N-Boc-3-(p-nitrophenyl)allylamine
  参考文献：
  名称：

  Structure-activity relationships for inhibition of papain by peptide Michael acceptors

  摘要：

  Two series of peptidyl Michael acceptors, N-Ac-L-Phe-NHCH2CH = CH-E with different electron withdrawing groups (E = CO2CH3, 1a; SO2CH3, 1b; CO2H, 1c; CN, 1d; CONH2, 1e; and C6H4-p-NO2, 1f) and R-NHCH2CH = CHCOOCH3 with different recognition and binding groups (R = N-Ac-D-Phe, 2a; N-Ac-L-Leu, 3a; N-Ac-L-Met, 4a; PhCH2CH2CO, 5a; PhCO, 6a), were synthesized and evaluated as inactivators against papain. It was found that the inhibition of papain by peptidyl Michael acceptors is a general phenomenon and that the intrinsic chemical reactivity of the E group in the Michael acceptors has a direct effect on the kinetics of the inactivation process as reflected in k2/K(i). At pH 6.2, the reactivity of papain toward the Michael acceptors is about 283 000-fold higher than the reactivity of the model thiol 3-mercaptopropionate. This large increase in reactivity is attributable to at least 2 factors; one is the low apparent pK(a) of Cys-25 of papain, and the other is the recruitment of catalytic power by specific enzyme-substrate interactions. The unexpectedly high reactivity of 1c (E = COOH) was rationalized by proposing a direct interaction of the acid group with His-159 in the active site of papain. The unexpected inactivity of 1f (E = C6H4-p-NO2) as a Michael acceptor and its very powerful competitive inhibition of papain were rationalized by molecular graphics which showed the nitrophenyl moiety rotated out of conjugation with the olefin and interacting instead with the hydrophobic S1' region of papain. A plot of log (k2/K(i)) for 1a-6a vs log (k(cat)/K(m)) for analogous R-Gly-p-NA substrates was linear (r = 0.98) with slope of 0.83, suggesting that binding energy from specific enzyme-ligand interactions can be used to drive the self-inactivation reaction to almost the same extent as it is used to drive catalysis.

  DOI：

  10.1021/jm00084a012

文献信息

• Bimodal ligands with macrocyclic and acyclic binding moieties, complexes and compositions thereof, and methods of using
  申请人：Chong Hyun-soon

  公开号：US20100322855A1

  公开（公告）日：2010-12-23

  Substituted 1,4,7-triazacyclononane-N,N′,N″-triacetic acid and 1,4,7,10-tetraazacyclcododecane-N,N′,N″,N′″-tetraacetic acid compounds with a pendant amino or hydroxyl group, metal complexes thereof, compositions thereof, and methods of making and use in diagnostic imaging and treatment of cellular disorders.

  用带有氨基或羟基的1,4,7-三氮杂环庚烷-N,N′,N″-三乙酸和1,4,7,10-四氮杂环十二烷-N,N′,N″,N′″-四乙酸化合物替代，以及它们的金属配合物、组合物、制备方法，以及在细胞疾病的诊断成像和治疗中的应用。
• Synthesis and evaluation of a bifunctional chelate for development of Bi(III)-labeled radioimmunoconjugates
  作者：Mamta Dadwal、Chi Soo Kang、Hyun A. Song、Xiang Sun、Anzhi Dai、Kwamena E. Baidoo、Martin W. Brechbiel、Hyun-Soon Chong

  DOI：10.1016/j.bmcl.2011.06.107

  日期：2011.12

  A new bifunctional ligand C-DEPA was designed and synthesized as a component for antibody-targeted radiation therapy (radioimmunotherapy, RIT) of cancer. C-DEPA was conjugated to a tumor targeting antibody, trastuzumab, and the corresponding C-DEPA-trastuzumab conjugate was evaluated for radiolabeling kinetics with (205/6)Bi. C-DEPA-trastuzumab conjugate rapidly bound (205/6)Bi, and (205/6)Bi-C-DEPA-trastuzumab conjugate was stable in human serum for 72 h. The in vitro radiolabeling kinetics and serum stability data suggest that C-DEPA is a potential chelate for preclinical RIT applications using (212)Bi and (213)Bi. (C) 2011 Published by Elsevier Ltd.
• US9115094B2
  申请人：——

  公开号：US9115094B2

  公开（公告）日：2015-08-25
• Structure-activity relationships for inhibition of papain by peptide Michael acceptors
  作者：Siming Liu、Robert P. Hanzlik

  DOI：10.1021/jm00084a012

  日期：1992.3

  Two series of peptidyl Michael acceptors, N-Ac-L-Phe-NHCH2CH = CH-E with different electron withdrawing groups (E = CO2CH3, 1a; SO2CH3, 1b; CO2H, 1c; CN, 1d; CONH2, 1e; and C6H4-p-NO2, 1f) and R-NHCH2CH = CHCOOCH3 with different recognition and binding groups (R = N-Ac-D-Phe, 2a; N-Ac-L-Leu, 3a; N-Ac-L-Met, 4a; PhCH2CH2CO, 5a; PhCO, 6a), were synthesized and evaluated as inactivators against papain. It was found that the inhibition of papain by peptidyl Michael acceptors is a general phenomenon and that the intrinsic chemical reactivity of the E group in the Michael acceptors has a direct effect on the kinetics of the inactivation process as reflected in k2/K(i). At pH 6.2, the reactivity of papain toward the Michael acceptors is about 283 000-fold higher than the reactivity of the model thiol 3-mercaptopropionate. This large increase in reactivity is attributable to at least 2 factors; one is the low apparent pK(a) of Cys-25 of papain, and the other is the recruitment of catalytic power by specific enzyme-substrate interactions. The unexpectedly high reactivity of 1c (E = COOH) was rationalized by proposing a direct interaction of the acid group with His-159 in the active site of papain. The unexpected inactivity of 1f (E = C6H4-p-NO2) as a Michael acceptor and its very powerful competitive inhibition of papain were rationalized by molecular graphics which showed the nitrophenyl moiety rotated out of conjugation with the olefin and interacting instead with the hydrophobic S1' region of papain. A plot of log (k2/K(i)) for 1a-6a vs log (k(cat)/K(m)) for analogous R-Gly-p-NA substrates was linear (r = 0.98) with slope of 0.83, suggesting that binding energy from specific enzyme-ligand interactions can be used to drive the self-inactivation reaction to almost the same extent as it is used to drive catalysis.