7-(溴甲基)萘-2-甲腈 | 135942-98-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 中文名称: 7-(溴甲基)萘-2-甲腈
• 中文别名: 7-(溴甲基)-2-萘甲腈
• 英文名称: 7-(bromomethyl)naphthalene-2-carbonitrile
• 英文别名: 7-cyano-2-bromomethylnaphthalene；7-(bromomethyl)-2-naphthalenecarbonitrile；7-(Bromomethyl)-2-naphthonitrile
• CAS: 135942-98-2
• 化学式: C₁₂H₈BrN
• 分子量: 246.106
• InChiKey: VMWIZZARXXSROL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  23.8
• 氢给体数：
  0
• 氢受体数：
  1

安全信息

• 海关编码：
  2926909090

反应信息

• 作为反应物：
  描述：

  7-(溴甲基)萘-2-甲腈 在 十二/十四烷基二甲基氧化胺 、 三乙酰氧基硼氢化钠 、 溶剂黄146 作用下， 以 二氯甲烷 、 氯仿 为溶剂， 生成 7-({4-[(1-tert-butoxycarbonyl-4-piperidyl)oxy]anilino}methyl)naphthalene-2-carbonitrile
  参考文献：
  名称：

  Design, synthesis and structure–Activity relationships of benzoxazinone-Based factor Xa inhibitors

  摘要：

  A series of benzoxazinone derivatives was designed and synthesized as factor Xa inhibitors. We demonstrated that the naphthyl moiety in the aniline-based compounds I and 2 can be replaced with benzene-fused heterobicycles and biaryls to give factor Xa inhibitors with improved trypsin selectivity. The P4 modifications lead to monoamidines which are moderately active. The benzoxazinones 41-45 are potent against factor Xa, retain the improved trypsin selectivity of the corresponding aniline-based compounds, and show strong antithrombotic effect dose responsively. (C) 2002 Published by Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(02)00927-7
• 作为产物：
  描述：

  7-羟基-2-萘甲腈 在 吡啶 、 bis-triphenylphosphine-palladium(II) chloride 、 N-溴代丁二酰亚胺(NBS) 、 lithium chloride 、 过氧化苯甲酰 作用下， 以 四氯化碳 、 N,N-二甲基甲酰胺 为溶剂， 生成 7-(溴甲基)萘-2-甲腈
  参考文献：
  名称：

  Design, synthesis and structure–Activity relationships of benzoxazinone-Based factor Xa inhibitors

  摘要：

  A series of benzoxazinone derivatives was designed and synthesized as factor Xa inhibitors. We demonstrated that the naphthyl moiety in the aniline-based compounds I and 2 can be replaced with benzene-fused heterobicycles and biaryls to give factor Xa inhibitors with improved trypsin selectivity. The P4 modifications lead to monoamidines which are moderately active. The benzoxazinones 41-45 are potent against factor Xa, retain the improved trypsin selectivity of the corresponding aniline-based compounds, and show strong antithrombotic effect dose responsively. (C) 2002 Published by Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(02)00927-7

文献信息

• Aromatic amidine derivatives and salts thereof
  申请人：Daiichi Pharmaceutical Co., Ltd.

  公开号：US05576343A1

  公开（公告）日：1996-11-19

  An anticoagulant agent which comprises, as an active ingredient, an aromatic amidine derivative represented by the following general formula (1) or a salt thereof: ##STR1## wherein the group represented by ##STR2## is a group selected from indolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzoxazolyl, benzothiazolyl, naphthyl, tetrahydronaphthyl and indanyl; X is a single bond, an oxygen atom, a sulfur atom or a carbonyl group; and Y is a saturated or unsaturated 5- or 6-membered heterocyclic moiety or cyclic hydrocarbon moiety optionally having a substituent group, an amino group optionally having a substituent group or an aminoalkyl group optionally having a substituent group. The inventive compound has a high anticoagulant capacity based on its excellent FXa inhibition activity.

  一种抗凝剂，其包括作为活性成分的芳香胺基衍生物，其由以下一般式（1）或其盐所表示：##STR1## 其中由##STR2##表示的基团是从吲哚基，苯并呋喃基，苯并噻吩基，苯并咪唑基，苯并噁唑基，苯并噻唑基，萘基，四氢萘基和吲哚基中选择的基团；X是单键，氧原子，硫原子或羰基；Y是饱和或不饱和的5-或6-成员杂环基团或环烃基团，可选地具有取代基团，可选地具有取代基团的氨基团或可选地具有取代基团的氨基烷基团。这种创新化合物具有基于其出色的FXa抑制活性的高抗凝能力。
• Naphthyl-substituted benzimidazole derivatives as anti-coagulants
  申请人：Berlex Laboratories, Inc.

  公开号：US05849759A1

  公开（公告）日：1998-12-15

  Compounds of formula (I): ##STR1## wherein: n, A, R.sup.1, R.sup.2, R.sup.3, and R.sup.4 have meanings as defined herein, or a pharmaceutically acceptable salt thereof, are useful as anti-coagulants.

  公式(I)的化合物：##STR1## 其中：n、A、R.sup.1、R.sup.2、R.sup.3和R.sup.4的含义如本文所述，或其药用可接受盐，可用作抗凝剂。
• N,N-di(aryl) cyclic urea derivatives as anti-coagulants
  申请人：Berlex Laboratories, Inc.

  公开号：US05612363A1

  公开（公告）日：1997-03-18

  N,N-di(aryl) cyclic urea derivatives, such as the compounds of the following formula: ##STR1## wherein R.sup.1 is --C(NH)NH.sub.2, --C(NH)N(H)OR.sup.11, --C(NH)N(H)C(O)R.sup.9, or --C(NH)N(H)C(O)OR.sup.11 ; R.sup.2 and R.sup.3 are independently hydrogen, halo, lower alkyl, lower haloalkyl, aryl, --OR.sup.11, --C(O)OR.sup.11, --C(O)N(R.sup.11)R.sup.12, --N(R.sup.11)R.sup.12, --N(H)C(O)R.sup.11, or --N(H)S(O).sub.2 R.sup.11 ; R.sup.4 is halo, lower haloalkyl, imidazolyl, --C(NH)NH.sub.2, --C(NH)NHOR.sup.11, --C(NH)N(H)C(O)R.sup.9, --C(NH)N(H)C(O)OR.sup.11, --OR.sup.11, --C(O)R.sup.13, --(CH.sub.2).sub.n C(O)OR.sup.11 (where n is 0 to 6), --C(O)N(R.sup.11)R.sup.12, or --N(R.sup.11)R.sup.12 ; R.sup.7 and R.sup.8 are independently hydrogen, lower alkyl, lower haloalkyl, 4-pyridinyl, --C(O)OR.sup.11, --C(O)N(R.sup.11)R.sup.12, or aryl (optionally substituted by one or more substituents selected from the group consisting of halo, hydroxy, lower alkyl, lower haloalkyl, lower alkoxy and --N(R.sup.11 R.sup.12); R.sup.11 and R.sup.12 are independently hydrogen, lower alkyl, aryl or lower aralkyl; or R.sup.13 is pyrrolidinyl, 4-morpholinyl, piperazinyl, N-methylpiperazinyl, or piperidinyl; or a pharmaceutically acceptable salt thereof, are disclosed herein as being inhibitors of factor Xa and thereby being useful as anticoagulants.

  N,N-二(芳基)环脲衍生物，例如以下式的化合物：##STR1## 其中R.sup.1为--C(NH)NH.sub.2，--C(NH)N(H)OR.sup.11，--C(NH)N(H)C(O)R.sup.9，或--C(NH)N(H)C(O)OR.sup.11；R.sup.2和R.sup.3独立地为氢，卤素，低烷基，低卤代烷基，芳基，--OR.sup.11，--C(O)OR.sup.11，--C(O)N(R.sup.11)R.sup.12，--N(R.sup.11)R.sup.12，--N(H)C(O)R.sup.11，或--N(H)S(O).sub.2R.sup.11；R.sup.4为卤素，低卤代烷基，咪唑基，--C(NH)NH.sub.2，--C(NH)NHOR.sup.11，--C(NH)N(H)C(O)R.sup.9，--C(NH)N(H)C(O)OR.sup.11，--OR.sup.11，--C(O)R.sup.13，--(CH.sub.2).sub.nC(O)OR.sup.11（其中n为0至6），--C(O)N(R.sup.11)R.sup.12，或--N(R.sup.11)R.sup.12；R.sup.7和R.sup.8独立地为氢，低烷基，低卤代烷基，4-吡啶基，--C(O)OR.sup.11，--C(O)N(R.sup.11)R.sup.12，或芳基（可选地由来自卤素，羟基，低烷基，低卤代烷基，低烷氧基和--N(R.sup.11R.sup.12)的一个或多个取代基取代）；R.sup.11和R.sup.12独立地为氢，低烷基，芳基或低芳基烷基；或R.sup.13为吡咯啉基，4-吗啉基，哌嗪基，N-甲基哌嗪基，或哌啶基；或其药学上可接受的盐，本文披露为Xa因子的抑制剂，因此可用作抗凝剂。
• Prodrug-based design, synthesis, and biological evaluation of N-benzenesulfonylpiperidine derivatives as novel, orally active factor Xa inhibitors
  作者：Tsukasa Ishihara、Norio Seki、Fukushi Hirayama、Masaya Orita、Hiroyuki Koshio、Yuta Taniuchi、Yumiko Sakai-Moritani、Yoshiyuki Iwatsuki、Seiji Kaku、Tomihisa Kawasaki、Yuzo Matsumoto、Shin-ichi Tsukamoto

  DOI：10.1016/j.bmc.2007.03.066

  日期：2007.6

  of a new series of orally active fXa inhibitors based on a prodrug strategy. Solid-phase parallel synthesis identified a unique series of fXa inhibitors with a substituted benzenesulfonyl group as a novel S4 binding element. This series resulted in compound 39, which exhibited potent inhibitory activity against fXa (IC50 = 13 nM) and excellent selectivity over thrombin (>7000-fold). The masking of its

  我们在这里描述了我们根据前药策略对一系列口服活性fXa抑制剂进行的研究。固相平行合成鉴定出一系列独特的fXa抑制剂，它们具有取代的苯磺酰基作为新型S4结合元素。该系列化合物39化合物显示出对fXa的有效抑制活性（IC50 = 13 nM），并且对凝血酶的选择性极佳（> 7000倍）。其高亲水性基团的掩蔽导致产生相关的前药28，其在口服给药后表现出抗凝作用。
• Process for preparing 2-phenyl-3-naphthylpropionic acid derivatives
  申请人：Daiichi Pharmaceutical Co., Ltd.

  公开号：US06252088B1

  公开（公告）日：2001-06-26

  A process for preparing a compound represented by general formulae (5) and (6) in the following reaction scheme or salts thereof, wherein R1 represents a protective group for a nitrogen atom; R2 represents a methanesulfonyl group or p-toluenesulfonyl group; R3 represents a hydrogen atom, an aralkyl group, or an alkyl group having 1 to 6 carbon atoms; and X represents a halogen atom. The above process is useful as an industrial process for preparing intermediates of anticoagulant aromatic amidine derivatives described in Japanese Patent Application Laid-Open (kokai) No. 208946/1993.

  一种制备以下反应方案中的通用化合物（5）和（6）或其盐的方法，其中R1代表氮原子的保护基团；R2代表甲磺酰基团或对甲苯磺酰基团；R3代表氢原子、芳基烷基或具有1至6个碳原子的烷基；X代表卤素原子。上述方法可用作制备日本专利申请公开（公开号208946/1993）中描述的抗凝血芳香胺衍生物中间体的工业过程。