N-{[(2-甲基-2-丙基)氧基]羰基}-4-硝基-L-苯丙氨酸叔丁酯 | 116366-27-9

• 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
• 中文名称: N-{[(2-甲基-2-丙基)氧基]羰基}-4-硝基-L-苯丙氨酸叔丁酯
• 英文名称: (S)-N-[(tert-butyloxy)carbonyl]-[4-nitrophenyl]alanine tert-butyl ester
• 英文别名: tert-butyl N-(tert-butoxycarbonyl) 4-nitro-L-phenylalaninate；N-Boc-4-nitro-L-phenylalanine-T-butyl ester；tert-butyl (2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-(4-nitrophenyl)propanoate
• CAS: 116366-27-9
• 化学式: C₁₈H₂₆N₂O₆
• 分子量: 366.414
• InChiKey: CIIPFNPETNNJDS-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  26
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  110
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-{[(2-甲基-2-丙基)氧基]羰基}-4-硝基-L-苯丙氨酸叔丁酯 在 palladium 10% on activated carbon 、 氢气 、 potassium carbonate 、 sodium hydroxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 21.0h， 生成 左旋苯丙氨酸氮芥盐酸盐
  参考文献：
  名称：

  一种美法仑的合成方法

  摘要：

  本发明公开了一种美法仑的合成方法，包括以下步骤：(a)还原反应：以具有如式I所示结构的化合物为原料，与催化剂、氢气进行还原反应制得还原产物，式I中，X代表氧或氮中的一种；R1代表氢，饱和烷基或不饱和烷基中的一种；R2和R3各自代表氢，烷羰基，氨基羰基或烷氧羰基中的一种；以烷基化试剂，与所得还原产物在缚酸剂存在下进行烷基化反应制得烷基化产物，将所得烷基化产物在酸或碱中进行水解反应，浓缩后，调pH，萃取洗涤，在干燥的盐酸的醇类或酯类溶剂中成盐，再用乙腈精制得美发仑盐酸盐。本发明各步收率高、操作简单、反应条件温和、无高毒高腐蚀试剂、得到产物纯度高及适合工业化生产的优点。

  公开号：

  CN107935875B
• 作为产物：
  描述：

  4-硝基-L-苯丙氨酸 、 alkaline earth salt of/the/ methylsulfuric acid 以 1,4-二氧六环 、 水 、 甲苯 为溶剂， 反应 24.67h， 生成 N-{[(2-甲基-2-丙基)氧基]羰基}-4-硝基-L-苯丙氨酸叔丁酯
  参考文献：
  名称：

  Asymmetric Synthesis of Conformationally Restricted l-Arginine Analogues as Active Site Probes of Nitric Oxide Synthase

  摘要：

  Using the catalytic asymmetric Sharpless carbamate aminohydroxylation, conformationally restricted L-arginine and L-homoarginine derivatives (5-8) were prepared in good enantiomeric excess to investigate the binding requirements of L-arginine-based compounds with nitric oxide synthase. The L-arginine derivatives (5 and 6) inhibited both the inducible and neuronal isoforms of nitric oxide synthase with little isoform selectivity (5, IC50 = 42 and 144 mu M, 6, 8 and 12 mu M, respectively). The guanidine-containing compound (5) did not act as a nitric oxide producing substrate for nitric oxide synthase. The ability of these compounds to interact with the enzyme supports the idea that L-arginine-based inhibitors bind to the enzyme in a folded conformation. The L-homoarginine derivatives (7 and 8) did not interact with the enzyme as either substrates or inhibitors. The two-carbon L-arginine homologue (9), prepared from L-phenylalanine, demonstrated the greatest isoform selective inhibition of the compounds examined (IC50(iNOS) = 19 and IC50- (nNOS) = 147 mu M, IC50(nNOS)/IC(50)i(NOS) = 7.7). These results suggest isoform selective inhibition may be related to the folded conformations required for binding of these higher L-arginine homologues.

  DOI：

  10.1021/jo982161f

文献信息

• Aminoacid derivatives as no synthase inhibitors
  申请人：Glaxo Wellcome Inc.

  公开号：US05874472A1

  公开（公告）日：1999-02-23

  Compounds of formula (I) and salts, esters and amides thereof, wherein R.sup.1 is a C.sub.1-6 straight or branched chain alkyl group, a C.sub.3-6 cycloalkyl group, a thiol group optionally substituted by a C.sub.1-6 alkyl group, or an amino group optionally substituted by one or two alkyl or alkenyl groups; R.sup.2 is H, C.sub.1-7 straight or branched chain alkyl, C.sub.3-6 cycloalkyl, C.sub.2-7 alkenyl or benzyl; A is a 5 or 6 membered aromatic carbocyclic or heterocyclic ring which may optionally be substituted by one or more suitable substituents such as C.sub.1-6 alkyl, C.sub.1-6 alkoxy, hydroxy, halo, nitro, cyano, trifluoro C.sub.1-6 alkyl, amino, C.sub.1-6 alkylamino or di C.sub.1-6 alkylamino; r is 0, 1 or 2; their use in medicine and in particular for conditions requiring inhibition of the NO Synthase enzyme, pharmaceutical formulations and processes for the preparation thereof are disclosed. ##STR1##

  化合物的化学式（I）及其盐、酯和酰胺，其中R.sup.1是C.sub.1-6直链或支链烷基，C.sub.3-6环烷基，可能由C.sub.1-6烷基取代的硫醇基团，或者可能由一到两个烷基或烯基基团取代的氨基团；R.sup.2是H，C.sub.1-7直链或支链烷基，C.sub.3-6环烷基，C.sub.2-7烯基或苄基；A是一个5或6成员芳香碳环或杂环，可以选择性地由一个或多个适当的基团取代，如C.sub.1-6烷基，C.sub.1-6烷氧基，羟基，卤素，硝基，氰基，三氟甲基烷基，氨基，C.sub.1-6烷基氨基或二C.sub.1-6烷基氨基；r为0、1或2；其在医学上的应用，特别是用于需要抑制NO合酶酶的条件，以及用于制备药物配方和制备过程的方法已被披露。
• PTERIDINE DERIVATIVES AS POLO-LIKE KINASE INHIBITORS USEFUL IN THE TREATMENT OF CANCER
  申请人：Moffat David Festus Charles

  公开号：US20100216802A1

  公开（公告）日：2010-08-26

  Compound of formula (I) are inhibitors of Polo-like kinases (PLKs), and are useful in treatment of cell proliferative diseases: wherein R 1 and R 2 are hydrogen, or an optionally substituted (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl or (C 3 -C 6 )cycloalkyl group; R 3 and R 3 ′ are independently selected from hydrogen, —CN, hydroxyl, halogen, optionally substituted (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl or (C 3 -C 6 )cycloalkyl, —NR 5 R 6 or C 1 -C 4 alkoxy, wherein R 5 and R 6 are independently hydrogen or optionally substituted (C 1 -C 6 )alkyl; ring A is an optionally substituted mono- or bi-cyclic carbocyclic or heterocyclic ring or a ring system having up to 12 ring atoms; T is a radical of formula R-L 1 -Y 1 — wherein R is an alpha amino acid or alpha amino acid ester motif, linked to ring A by linker R-L 1 -Y 1 — as defined in the claims.

  式(I)的化合物是Polo样激酶（PLKs）的抑制剂，可用于治疗细胞增殖性疾病：其中R1和R2是氢，或者是可选取代的（C1-C6）烷基，（C2-C6）烯基，（C2-C6）炔基或（C3-C6）环烷基；R3和R3'分别选自氢，—CN，羟基，卤素，可选取代的（C1-C6）烷基，（C2-C6）烯基，（C2-C6）炔基或（C3-C6）环烷基，—NR5R6或C1-C4烷氧基，其中R5和R6分别独立地是氢或可选取代的（C1-C6）烷基；环A是可选取代的单环或双环碳环或杂环，或具有多达12个环原子的环系；T是公式R-L1-Y1—的基团，其中R是α-氨基酸或α-氨基酸酯基序列，通过定义中的连接基R-L1-Y1—与环A相连。
• Pozdnev, V. F., Journal of general chemistry of the USSR, 1988, vol. 58, # 3, p. 592 - 597
  作者：Pozdnev, V. F.

  DOI：——

  日期：——
• WO2008/50096
  申请人：——

  公开号：——

  公开（公告）日：——
• POZDNEV, V. F., ZH. OBSHCH. XIMII, 58,(1988) N 3, 670-675
  作者：POZDNEV, V. F.

  DOI：——

  日期：——