1-(4-nitrophenoxy)carbonyloxy-4-vinylbutane | 923278-25-5

• 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: 1-(4-nitrophenoxy)carbonyloxy-4-vinylbutane
• 英文别名: O-(hex-5-enyl)-O-(4-nitrophenyl) carbonate；hex-5-en-1-yl 4-nitrophenyl carbonate；Hex-5-enyl (4-nitrophenyl) carbonate
• CAS: 923278-25-5
• 化学式: C₁₃H₁₅NO₅
• 分子量: 265.266
• InChiKey: FJNLCRQTWWJLDJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  19
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  81.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-{[4-(7-methoxy-2-phenyl-quinolin-4-yloxy)-pyrrolidine-2-carbonyl]-amino}-2-vinyl-cyclopropanecarboxylic acid ethyl ester 、 1-(4-nitrophenoxy)carbonyloxy-4-vinylbutane 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 生成 hex-5-enyl (2S,4R)-2-[[(1R,2S)-2-ethenyl-1-ethoxycarbonylcyclopropyl]carbamoyl]-4-(7-methoxy-2-phenylquinolin-4-yl)oxypyrrolidine-1-carboxylate
  参考文献：
  名称：

  Discovery of novel, potent and bioavailable proline-urea based macrocyclic HCV NS3/4A protease inhibitors

  摘要：

  A novel series of P3-truncated macrocyclic HCV NS3/4A protease inhibitors containing a P2 proline-urea or carbamate scaffold was synthesized. Very potent inhibitors were obtained through the optimization of the macrocycle size, urea and proline substitution, and bioisosteric replacement of the P1 carboxylic acid moiety. Variation of the lipophilicity by introduction of small lipophilic substituents resulted in improved PK profiles, ultimately leading to compound 13Bh, an extremely potent (K-i = 0.1 nM, EC50 = 4.5 nM) and selective (CC50 (Huh-7 cells) > 50 mu M) inhibitor, displaying an excellent PK pro. le in rats characterized by an oral bioavailability of 54% and a high liver exposure after oral administration. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.10.004
• 作为产物：
  描述：

  hex-5-en-1-yl succinimidyl carbonate 、 对硝基苯基氯甲酸酯 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 以73%的产率得到1-(4-nitrophenoxy)carbonyloxy-4-vinylbutane
  参考文献：
  名称：

  WO2007/14920

  摘要：

  公开号：

文献信息

• Acid-Labile Lipophilic Prodrugs of Cancer Chemotherapeutic Agents
  申请人：McChesney James D.

  公开号：US20120309819A1

  公开（公告）日：2012-12-06

  The present application discloses an acid labile lipophilic molecular conjugate of cancer chemotherapeutic agents and methods for reducing or substantially eliminating the side effects of chemotherapy associated with the administration of a cancer chemotherapeutic agent to a patient in need thereof.

  本申请公开了一种酸敏感的亲脂性分子结合物，其与癌症化疗药物结合，并且揭示了减少或基本消除与向需要的患者施用癌症化疗药物相关的化疗副作用的方法。
• PROCESS FOR THE SYNTHESIS OF OLIGONUCLEOTIDES
  申请人：Leuck Michael

  公开号：US20080064867A1

  公开（公告）日：2008-03-13

  The present invention discloses novel methods for the synthesis of oligonucleotides with nucleoside phosphoramidites on solid supports. The methods comprise the stepwise chain assembly of oligonucleotides on supports with 5′-acyl phosphoramidites. The synthesis cycles consist of a front end deprotection step which is conducted with a solution of a primary amine or a phenolate, a phosphoramidite coupling step with a 5′-acyl nucleoside phosphoramidite in the presence of an activator, a phosphite oxidation step and an optional capping step. The novel methods improve the quality of synthetic oligonucleotides due to the irreversibility of the front end deprotection step, which prevents the formation of deletion sequences, and due to the avoidance of acidic reagents in the synthesis cycles, which prevent the formation of depurination side products. The invention further discloses novel nucleoside phosphoramidite compositions wherein the phosphoramidites carry acyl front end protective groups which are cleavable with primary amines or phenolates. The invention is applicable to the synthesis of oligodeoxyribonucleotides, oligoribonucleotides and oligonucleotides with modifications in their sugar or phosphate groups.

  本发明揭示了一种新的方法，用于在固相支持上合成具有核苷酸磷酰胺酯的寡核苷酸。该方法包括使用5'-酰基磷酰胺酯在支持上逐步组装寡核苷酸链。合成周期包括前端去保护步骤，该步骤使用一种原始胺或酚酸溶液进行，磷酰胺酯偶联步骤使用5'-酰基核苷酸磷酰胺酯在活化剂存在下进行，磷酸酯氧化步骤和可选的帽子步骤。由于前端去保护步骤的不可逆性防止了缺失序列的形成，而避免使用酸性试剂在合成周期中防止了去噻嗪副产物的形成，因此，这种新方法提高了合成寡核苷酸的质量。本发明进一步揭示了新的核苷酸磷酰胺酯组合物，其中磷酰胺酯携带可用原始胺或酚酸裂解的酰基前端保护基团。该发明适用于合成具有糖或磷酸基团修饰的寡脱氧核苷酸，寡核糖核苷酸和寡核苷酸。
• MACROCYLIC INHIBITORS OF HEPATITIS C VIRUS
  申请人：Simmen Kenneth Alan

  公开号：US20100120855A1

  公开（公告）日：2010-05-13

  Inhibitors of HCV replication of formula (I), the N-oxides, salts, and stereochemically isomeric forms thereof, wherein each dashed line (represented by represents an optional double bond; X is N, CH and where X bears a double bond it is C; R 1 is aryl or a saturated, a partially unsaturated or completely unsaturated 5 or 6 membered monocyclic or 9 to 12 membered bicyclic heterocyclic ring system wherein said ring system contains one nitrogen, and optionally one to three additional heteroatoms selected from the group consisting of oxygen, sulfur and nitrogen, and wherein the remaining ring members are carbon atoms; wherein said ring system may be optionally substituted on any carbon or nitrogen ring atom with one, two, three, or four substituents; L is a direct bond, —O—, —O—C 1-4 alkanediyl-, —O—C(═O)—, —O—C(═O)—NR 4a — or —O—C(═O)—NR 4a C 1-4 alkanediyl-; R 2 is hydrogen, —OR 5 , —C(O)OR 5 , —C(═O)R 6 , —C(═O)NR 4a R 4b , —C(═O)NHR 4c , —NR 4a R 4b , —NHR 4c , —NR 4a SO p NR 4a R 4b , —NR 4a SO p R 7 , or B(OR 5 ) 2 ; R 3 is hydrogen, and where X is C or CH, R 3 may also be C 1-6 alkyl; n is 3, 4, 5, or 6; p is 1 or 2; aryl is phenyl, naphthyl, indanyl, or 1,2,3,4-tetrahydronaphthyl, each of which may be optionally substituted with one, two or three substituents; Het is a 5 or 6 membered saturated, partially unsaturated or completely unsaturated heterocyclic ring containing 1 to 4 heteroatoms each independently selected from nitrogen, oxygen and sulfur, being optionally condensed with a benzene ring, and wherein the group Het as a whole may be optionally substituted with one, two or three substituents; pharmaceutical compositions containing compounds (I) and processes for preparing compounds (I). Bioavailable combinations of the inhibitors of HCV of formula (I) with ritonavir are also provided.

  公式（I）的HCV复制抑制剂，其中N-氧化物，盐和立体化学异构体，其中每个虚线（由表示，表示可选的双键; X是N，CH，其中X带有双键，则为C; R1是芳基或饱和，部分不饱和或完全不饱和的5个或6个成员的单环或9至12个成员的双环杂环环系，其中所述环系含有一个氮，并且可选地含有一个至三个选自氧，硫和氮的群组的其他杂原子，其中剩余的环成员是碳原子;其中所述环系可以在任何碳或氮环原子上选择一个，两个，三个或四个取代基; L是直接键，-O-，-O-C1-4烷二基，-O-C（=O）-，-O-C（=O）-NR4a-或-O-C（=O）-NR4aC1-4烷二基; R2是氢，-OR5，-C（O）OR5，-C（=O）R6，-C（=O）NR4aR4b，-C（=O）NHR4c，-NR4aR4b，-NHR4c，-NR4aSOpNR4aR4b，-NR4aSOpR7或B（OR5）2; R3是氢，其中X是C或CH时，R3也可以是C1-6烷基; n为3、4、5或6; p为1或2;芳基是苯基，萘基，茚基或1,2,3,4-四氢萘基，每个都可以选择性地用一个，两个或三个取代基取代; Het是一个5个或6个成员的饱和，部分不饱和或完全不饱和的杂环环，其中每个独立选择自氮，氧和硫的1至4个杂原子，可选择地与苯环缩合，并且整个Het基团可以选择性地用一个，两个或三个取代基取代;含有化合物（I）的制药组合物和制备化合物（I）的过程也提供。还提供了公式（I）的HCV抑制剂与利托那韦的生物利用度组合。
• Macrocyclic Inhibitors of Hepatitis C Virus
  申请人：Simmen Kenneth Alan

  公开号：US20110237621A1

  公开（公告）日：2011-09-29

  Inhibitors of HCV replication of formula (I) the N-oxides, salts, and stereochemically isomeric forms thereof, wherein each dashed line (represented by ) represents an optional double bond; X is N, CH and where X bears a double bond it is C; R 1 is aryl or a saturated, a partially unsaturated or completely unsaturated 5 or 6 membered monocyclic or 9 to 12 membered bicyclic heterocyclic ring system wherein said ring system contains one nitrogen, and optionally one to three additional heteroatoms selected from the group consisting of oxygen, sulfur and nitrogen, and wherein the remaining ring members are carbon atoms; wherein said ring system may be optionally substituted on any carbon or nitrogen ring atom with one, two, three, or four substituents; L is a direct bond, —O—, —O—C 1-4 alkanediyl-, —O—C(═O)—, —O—C(═O)—NR 4a — or —O—C(═O)—NR 4a C 1-4 alkanediyl-; R 2 is hydrogen, —OR 5 , —C(═O)OR 5 , —C(═O)R 6 , —C(═O)NR 4a R 4b , —C(═O)NHR 4c , —NR 4a R 4b , —NHR 4c , —NR 4a SO p NR 4a R 4b , —NR 4a SO p R 7 , or B(OR 5 ) 2 ; R 3 is hydrogen, and where X is C or CH, R 3 may also be C 1-6 alkyl; n is 3, 4, 5, or 6; p is 1 or 2; aryl is phenyl, naphthyl, indanyl, or 1,2,3,4-tetrahydronaphthyl, each of which may be optionally substituted with one, two or three substituents; Het is a 5 or 6 membered saturated, partially unsaturated or completely unsaturated heterocyclic ring containing 1 to 4 heteroatoms each independently selected from nitrogen, oxygen and sulfur, being optionally condensed with a benzene ring, and wherein the group Het as a whole may be optionally substituted with one, two or three substituents; pharmaceutical compositions containing compounds (I) and processes for preparing compounds (I). Bioavailable combinations of the inhibitors of HCV of formula (I) with ritonavir are also provided.

  公式（I）的HCV复制抑制剂包括其N-氧化物，盐和立体化学异构体，其中每个虚线（表示）代表可选的双键；X为N，CH，其中X带有双键时为C；R1为芳基或饱和的，部分不饱和的或完全不饱和的5或6个环成员的单环或9至12个环成员的双环杂环环系，其中所述环系含有一个氮，且可选地含有选自氧，硫和氮的一至三个附加杂原子，且所述剩余环成员为碳原子；其中所述环系可以在任何碳或氮环原子上可选地用一，二，三或四个取代基取代；L为直接键，—O—，—O—C1-4烷基二基，—O—C（═O）—，—O—C（═O）—NR4a—或—O—C（═O）—NR4aC1-4烷基二基；R2为氢，—OR5，—C（═O）OR5，—C（═O）R6，—C（═O）NR4aR4b，—C（═O）NHR4c，—NR4aR4b，—NHR4c，—NR4aSOpNR4aR4b，—NR4aSOpR7或B（OR5）2；R3为氢，且当X为C或CH时，R3也可以为C1-6烷基；n为3，4，5或6；p为1或2；芳基为苯基，萘基，茚基或1,2,3,4-四氢萘基，每个芳基可以选择地用一个，两个或三个取代基取代；Het为含有1至4个异原子的5或6个成员饱和的，部分不饱和的或完全不饱和的杂环环，每个异原子可独立地选自氮，氧和硫，可选择地与苯环融合，且作为整体的Het基团可以选择地用一个，两个或三个取代基取代；还提供了含有化合物（I）的制药组合物和制备化合物（I）的过程。公式（I）的HCV抑制剂与利托那韦的生物利用度组合也提供。
• MACROCYCLIC INHIBITORS OF HEPATITIS C VIRUS
  申请人：Tibotec Pharmaceuticals Ltd.

  公开号：EP1912996A1

  公开（公告）日：2008-04-23