Methyl 5-nitro-1H-indole-1-propanoate | 168166-55-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: Methyl 5-nitro-1H-indole-1-propanoate
• 英文别名: methyl 3-(5-nitroindol-1-yl)propanoate
• CAS: 168166-55-0
• 化学式: C₁₂H₁₂N₂O₄
• mdl: MFCD11543811
• 分子量: 248.238
• InChiKey: BHLYUMDUMYCJKN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  77
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Methyl 5-nitro-1H-indole-1-propanoate 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 生成 3-(5-氨基吲哚-1-基)丙酸甲酯
  参考文献：
  名称：

  Thromboxane modulating agents. 2. Thromboxane receptor antagonists derived from the thromboxane synthase inhibitor dazmegrel.

  摘要：

  The design of dual thromboxane synthase inhibitor/thromboxane receptor antagonists (e.g, 15) based on the structure of the thromboxane synthase inhibitor dazmegrel is described. More potent receptor antagonists (e.g, 16c) result from replacement of the pyridinyl subsituent with 4-fluorophenyl. Modelling suggests the existence of more than one site capable of interacting with the aryl sulfonamide of TxA(2) receptor antagonists. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/0960-894x(96)00299-5
• 作为产物：
  描述：

  5-硝基吲哚 、 丙烯酸甲酯（MA） 在 苄基三甲基氢氧化铵 作用下， 以 1,4-二氧六环 为溶剂， 生成 Methyl 5-nitro-1H-indole-1-propanoate
  参考文献：
  名称：

  Thromboxane modulating agents. 2. Thromboxane receptor antagonists derived from the thromboxane synthase inhibitor dazmegrel.

  摘要：

  The design of dual thromboxane synthase inhibitor/thromboxane receptor antagonists (e.g, 15) based on the structure of the thromboxane synthase inhibitor dazmegrel is described. More potent receptor antagonists (e.g, 16c) result from replacement of the pyridinyl subsituent with 4-fluorophenyl. Modelling suggests the existence of more than one site capable of interacting with the aryl sulfonamide of TxA(2) receptor antagonists. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/0960-894x(96)00299-5

文献信息

• Indole derivatives thromboxane A2 antagonists
  申请人：Pfizer Inc.

  公开号：US05744488A1

  公开（公告）日：1998-04-28

  Compounds of formula (I): ##STR1## and pharmaceutically acceptable salt and biolabile esters thereof, wherein R.sup.1 is H, C.sub.1 -C.sub.4 alkyl, phenyl optionally substituted by up to three substituents independently selected from C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, halogen and CF.sub.3, or is 1-imidazolyl, 3-pyridyl or 4-pyridyl; R.sup.2 is H or C.sub.1 -C.sub.4 alkyl, R.sup.3 is SO.sub.2 R.sup.4 or COR.sup.4 where R.sup.4 is C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.3 perfluoroalkyl(CH.sub.2).sub.p, C.sub.3 -C.sub.6 cycloalkyl(CH.sub.2).sub.p, aryl(CH.sub.2).sub.p, or heteroaryl(CH.sub.2).sub.p, p being 0, 1 or 2, or R.sup.4 may be NR.sup.5 R.sup.6 where R.sup.5 is H or C.sub.1 -C.sub.4 alkyl and R.sup.6 is C.sub.1 -C.sub.6, alkyl, C.sub.3 -C.sub.6 cycloalkyl or aryl, or R.sup.5 and R.sup.6 together with the nitrogen atom to which they are attached form a 5- to 7-membered heterocyclic ring which may optionally incorporate a carbon-carbon double bond or a further heteroatom linkage selected from O, S, NH, N(C.sub.1 -C.sub.4 alkyl) and N(C.sub.1 -C.sub.5 alkanoyl); X is CH.sub.2 or a direct link, with the proviso that when R.sup.1 is 1-imidazolyl then X is CH.sub.2 ; m is 2, or 3; n is 0, 1 or 2, and wherein the group (CH.sub.2).sub.n NHR.sup.3 is attached at the 5-position when n is 0 or 1, or at the 5- or 4-position when n is 2. These compounds are selective TXA.sub.2 and PGH.sub.2 antagonists. Some also inhibit thromboxane synthetase.

  化合物的分子式为（I）： ##STR1## 包括其药学上可接受的盐和生物可降解酯，其中R.sup.1为H，C.sub.1-C.sub.4烷基，苯基可选地被最多三个取自C.sub.1-C.sub.4烷基、C.sub.1-C.sub.4烷氧基、卤素和CF.sub.3的取代基取代，或者为1-咪唑基、3-吡啶基或4-吡啶基；R.sup.2为H或C.sub.1-C.sub.4烷基，R.sup.3为SO.sub.2R.sup.4或COR.sup.4，其中R.sup.4为C.sub.1-C.sub.6烷基、C.sub.1-C.sub.3全氟烷基(CH.sub.2).sub.p、C.sub.3-C.sub.6环烷基(CH.sub.2).sub.p、芳基(CH.sub.2).sub.p或杂芳基(CH.sub.2).sub.p，p为0、1或2，或者R.sup.4可以是NR.sup.5R.sup.6，其中R.sup.5为H或C.sub.1-C.sub.4烷基，R.sup.6为C.sub.1-C.sub.6烷基、C.sub.3-C.sub.6环烷基或芳基，或者R.sup.5和R.sup.6与它们连接的氮原子一起形成一个5-至7元杂环，该杂环可以选择性地包括一个碳-碳双键或进一步的来自O、S、NH、N（C.sub.1-C.sub.4烷基）和N（C.sub.1-C.sub.5酰基）的杂原子键；X为CH.sub.2或直接连接，但当R.sup.1为1-咪唑基时，X为CH.sub.2；m为2或3；n为0、1或2，其中当n为0或1时，（CH.sub.2）.sub.nNHR.sup.3基团连接在5位，当n为2时，连接在5位或4位。这些化合物是选择性的TXA.sub.2和PGH.sub.2拮抗剂。其中一些还抑制血栓素合成酶。
• INDOLE DERIVATIVES AS THROMBOXANE A2 ANTAGONISTS
  申请人：Pfizer Limited

  公开号：EP0715627B1

  公开（公告）日：1998-09-09
• INDOLE DERIVATIVES THROMBOXANE A2 ANTAGONISTS
  申请人：Pfizer Limited

  公开号：EP0715627A1

  公开（公告）日：1996-06-12
• US5744488A
  申请人：——

  公开号：US5744488A

  公开（公告）日：1998-04-28
• [EN] INDOLE DERIVATIVES THROMBOXANE A2 ANTAGONISTS<br/>[FR] ANTAGONISTES DE LA THROMBOXANE A2 DERIVES D'UN INDOLE
  申请人：——

  公开号：WO1995006046A1

  公开（公告）日：1995-03-02

  [EN] Compounds of formula (I) and pharmaceutically acceptable salts and biolabile esters thereof, wherein R<1> is H, C1-C4 alkyl, phenyl optionally substituted by up to three substituents independently selected from C1-C4 alkyl, C1-C4 alkoxy, halogen and CF3, or is 1-imidazolyl, 3-pyridyl or 4-pyridyl, R<2> is H or C1-C4 alkyl, R<3> is SO2R<4> or COR<4> where R<4> is C1-C6 alkyl, C1-C3 perfluoroalkyl(CH2)p, C3-C6 cycloalkyl(CH2)p, aryl(CH2)p or heteroaryl(CH2)p, p being 0, 1 or 2, or R<4> may be NR<5>R<6> where R<5> is H or C1-C4 alkyl and R<6> is C1-C6 alkyl, C3-C6 cycloalkyl or aryl, or R<5> and R<6> together with the nitrogen atom to which they are attached form a 5- to 7-membered heterocyclic ring which may optionally incorporate a carbon-carbon double bond or a further heteroatom linkage selected from O, S, NH, N(C1-C4 alkyl) and N(C1-C5 alkanoyl); X is CH2 or a direct link, with the proviso that when R<1> is 1-imidazolyl then X is CH2; m is 2, or 3; n is 0, 1 or 2 and wherein the group (CH2)nNHR<3> is attached at the 5-position when n is 0 or 1, or at the 5- or 4-position when n is 2. These compounds are selective TXA2 and PGH2 antagonists. Some also inhibit thromboxane synthetase.
  [FR] Composés selon la formule (I) et sels et esters biolabiles pharmaceutiquement acceptables de ceux-ci, dans lesquels R<1> est H, un alkyle C1-C4, un phényle avec substitution éventuelle par un à trois substituants choisis indépendamment parmi un alkyle C1-C4, un alcoxy C1-C4, un halogène et CF3, ou est du 1-imidazolyle, du 3-pyridyle ou du 4-pyridyle, R<2> est H ou un alkyle C1-C4, R<3> est SO2R<4> ou COR<4>, où R<4> est un alkyle C1-C6, un perfluoroalkyle(CH2)p C1-C4, un cycloalkyle(CH2)p C3-C6, un aryle(CH2)p ou un hétéroaryle(CH2)p, p étant 0, 1 ou 2, ou R<4> peut être NR<5>R<6> où R<5> est H ou un alkyle C1-C4 et R<6> est un alkyle C1-C4, cycloalkyle C3-C6 ou un aryle, ou R<5> et R<6>, avec l'atome d'azote auquel ils sont liés, forment un cycle hétérocyclique à 5 à 7 membres qui peut éventuellement comprendre une double liaison carbone-carbone ou une autre liaison hétéroatomique choisie parmi O, S, NH, N(alkyle C1-C4) et N(alcanoyle C1-C5); X est CH2 ou une liaison directe, à la condition que lorsque R<1> est du 1-imidazolyle, X soit CH2; m est 2 ou 3, n est 0, 1 ou 2, et dans lesquels le groupe (CH2)nNHR<3> est lié dans la position 5 lorsque n est égal à 0 ou 1, ou dans la position 5 ou 4 lorsque n est égal à 2. Ces composés sont des antagonistes sélectifs de la TXA2 et de la PGH2. Certains inhibent également la thromboxane-synthétase.