7-formylnaphthalene-2-carbonitrile | 179756-49-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 7-formylnaphthalene-2-carbonitrile
• 英文别名: 7-formyl-2-naphthonitrile；7-formyl-2-naphthalene-carbonitrile
• CAS: 179756-49-1
• 化学式: C₁₂H₇NO
• 分子量: 181.194
• InChiKey: RVJFZDZSVLMRGT-UHFFFAOYSA-N

物化性质

• 沸点：
  382.5±15.0 °C(Predicted)
• 密度：
  1.22±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  40.9
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  7-formylnaphthalene-2-carbonitrile 以 硫酸 、 水 、 丙酮 为溶剂， 生成 7-cyanonaphthalene-2-carboxylic acid
  参考文献：
  名称：

  Amidinonaphthyl derivative or salt thereof

  摘要：

  以下是由下列通式（I）表示的酰胺基萘衍生物，具有凝血因子X抑制作用，可用作抗血栓剂等，其盐，中间体以及包括该酰胺基萘衍生物的药物组成物。由下列通式（I）或其药学上可接受的盐表示的酰胺基萘衍生物。 ##STR1## （式中符号的含义如下：R1：氢原子或由公式--A--W--R4表示的基团，A：由公式表示的基团##STR2##由公式表示的基团##STR3##或由公式--SO.sub.2--表示的基团，X：氧原子或硫原子，W：单键或由公式--NR5--表示的基团，R4：羟基，低级烷氧基等，R5：氢原子，氨基甲酰基，低级烷氧羰基基团等，R2：低级烷基，R3：氢原子，卤原子，羧基，B：低级烷基撑或羰基基团，n：0或1）。

  公开号：

  US05869501A1
• 作为产物：
  描述：

  2,7-萘二羧酸 在 氯化亚砜 、 氨 、 二异丁基氢化铝 作用下， 以 正己烷 、 二氯甲烷 为溶剂， 反应 21.25h， 生成 7-formylnaphthalene-2-carbonitrile
  参考文献：
  名称：

  Folding of dihelicenetriamines in water

  摘要：

  Diastereomeric triamines containing two helicene moieties, 1,12-dimethylbenzo[c]phenanthrene, were synthesized and found to form folded structures in the water. Such folding was not observed for an achiral compound possessing a naphthalene moiety. The (M,M)-dihelicenetriamine with matching configuration at the helicene moieties formed a more stable folded structure than the (P,M)-isomer containing two enantiomeric helicene groups. The most stable folded conformation was predicted by the Monte Carlo method with Amber force field of the dihelicenetriamine. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(02)00249-5
• 作为试剂：
  描述：

  7-formylnaphthalene-2-carbonitrile 、 4-(4-氨基苯氧基)-1-哌啶甲酸叔丁酯 在 7-formylnaphthalene-2-carbonitrile 作用下， 以79的产率得到7-({4-[(1-tert-butoxycarbonyl-4-piperidyl)oxy]anilino}methyl)naphthalene-2-carbonitrile
  参考文献：
  名称：

  Bioorg. Med. Chem. 2002, 10, 1509-1523

  摘要：

  DOI：

文献信息

• Indoline Derivatives I: Synthesis and Factor Xa (FXa) Inhibitory Activities
  作者：Tetsuji Noguchi、Naoki Tanaka、Toyoki Nishimata、Riki Goto、Miho Hayakawa、Atsuhiro Sugidachi、Taketoshi Ogawa、Fumitoshi Asai、Yumi Matsui、Koichi Fujimoto

  DOI：10.1248/cpb.54.163

  日期：——

  A series of bisamidine derivatives each having a ring structure in the center of the molecule was synthesized and their Factor Xa (FXa) inhibitory activities were evaluated. Among them, some indoline derivatives showed potent inhibitory activities in vitro. In particular, (R)-18a having an (R)-configuration at the 2-position of the indoline ring exhibited the most potent FXa inhibitory activity in vitro, more potent than DX-9065a. Furthermore, (R)-18a exhibited more potent anticoagulant activity than DX-9065a. We also succeeded in obtaining an X-ray crystal structure of FXa bound with (R)-18a.

  合成了一系列每个分子中心具有环结构的双氨基衍生物，并评估了它们对Xa因子（FXa）的抑制活性。其中，一些吲哚啉衍生物在体外显示出明显的抑制活性。特别是，具有(R)-构型的(R)-18a在吲哚啉环的2位表现出最强的FXa抑制活性，优于DX-9065a。此外，(R)-18a的抗凝活性也超过了DX-9065a。我们还成功获得了与(R)-18a结合的FXa的X射线晶体结构。
• Indoline Derivatives II: Synthesis and Factor Xa (FXa) Inhibitory Activities
  作者：Tetsuji Noguchi、Naoki Tanaka、Toyoki Nishimata、Riki Goto、Miho Hayakawa、Atsuhiro Sugidachi、Taketoshi Ogawa、Fumitoshi Asai、Tomoko Ozeki、Koichi Fujimoto

  DOI：10.1248/cpb.55.393

  日期：——

  Factor Xa (FXa) is well known to play a pivotal role in blood coagulation, so FXa inhibitor is a promising drug candidate for prophylaxis and treatment of thromboembolic diseases. In the course of our research, we have found that (R)-5-[1-(acetimidoyl)piperidin-4-yloxy]-2-(7-amidinonaphthalen-2-yl)-1-(ethanesulfonyl)indoline ((R)-1) showed potent FXa inhibitory activity in vitro. However, single oral administation (RS)-1 showed high toxicity in mice. Among newly synthesized compounds, ((RS)-5-[1-(acetimidoyl)piperidin-4-yloxy]-2-(7-amidinonaphthalen-2-yl)indolin-1-yl}sulfonyl)acetic acid ((RS)-11d) showed more potent FXa inhibitory activity and higher safety than (RS)-1. The R-isoform of compound 11d ((R)-11d) exhibited potent in vitro anticoagulant activity in human and hamster plasma. Orally administered (R)-11d also showed dose-dependent potent anticoagulant activity in hamsters, marmosets and cynomolgus monkeys. Compound (R)-11d with potent anticoagulant activity and high safety is therefore favorable as a novel oral FXa inhibitor.

  因子Xa（FXa）在血液凝固中发挥着重要作用，因此FXa抑制剂是预防和治疗血栓栓塞性疾病的有前景的药物候选者。在我们的研究中，我们发现(R)-5-[1-(乙酰亚胺基)piperidin-4-yloxy]-2-(7-氨基萘-2-基)-1-(乙烷磺酰基)吲哚((R)-1)在体外展示了强效的FXa抑制活性。然而，单次口服给药的(RS)-1在小鼠中显示出高毒性。在新合成的化合物中，((RS)-5-[1-(乙酰亚胺基)piperidin-4-yloxy]-2-(7-氨基萘-2-基)吲哚-1-基}磺酰基)乙酸((RS)-11d)显示出比(RS)-1更强的FXa抑制活性和更高的安全性。化合物11d的R-异构体((R)-11d)在人的和仓鼠的血浆中表现出强效的体外抗凝活性。口服给药的(R)-11d在仓鼠、狨猴和恒河猴中也显示出剂量依赖的强效抗凝活性。因此，具有强抗凝活性和高安全性的化合物(R)-11d是作为一种新型口服FXa抑制剂的有利选择。
• Hexahydro-1,4-diazepine derivatives or salts thereof
  申请人：Yamanouchi Pharmaceutical Co.

  公开号：US06333320B1

  公开（公告）日：2001-12-25

  Hexahydro-1,4-diazepine derivatives represented by general formula (I); pharmaceutically acceptable salts thereof; and drugs containing the same as the active ingredient, such as activated blood coagulation factor X inhibitor, wherein A: phenylene, pyridylene, or the like; B: a 5- or 6-membered aryl or heteroaryl ring; X: —CO—, —CONH—, —CSNH—, —SO2—, —SO2NH—, or the like; Y: a bond or alkylene; R1: hydrogen, alkyl, —Y—(hetero) aryl, or the like; R2: hydrogen, alkoxy, —COOH, or the like; R3: amidino or a group capable of being converted into amidino; and R4, R5: each independently hydrogen or lower alkyl.

  一般式（I）所代表的六氢-1,4-二氮杂环衍生物；其药学上可接受的盐；以及包含其作为活性成分的药物，例如激活的血凝血因子X抑制剂，其中A：苯撑基，吡啶撑基或类似物；B：5-或6-成员芳基或杂芳基环；X：-CO-，-CONH-，-CSNH-，-SO2-，-SO2NH-或类似物；Y：键或烷基；R1：氢，烷基，-Y-（杂）芳基或类似物；R2：氢，烷氧基，-COOH或类似物；R3：酰胺基或可转化为酰胺基的基团；以及R4，R5：各自独立地为氢或低级烷基。
• Amidinonaphthyl derivative or salt thereof
  申请人：Yamanouchi Pharmaceutical Co. Ltd

  公开号：US05869501A1

  公开（公告）日：1999-02-09

  An amidinonaphthyl derivative represented by the following general formula (I) which has coagulation factor X inhibiting action and is useful as an anti-thrombus agent and the like, a salt thereof, an intermediate thereof and a pharmaceutical composition which comprises the amidinonaphthyl derivative. An amidinonaphthyl derivative represented by the following general formula (I) or a pharmaceutically acceptable salt thereof. ##STR1## (symbols in the formula have the following meanings; R.sup.1 : a hydrogen atom or a group represented by the formula --A--W--R.sup.4, A: a group represented by the formula ##STR2## a group represented by the formula ##STR3## or a group represented by the formula --SO.sub.2 --, X: an oxygen atom or a sulfur atom, W: a single bond or a group represented by the formula --NR.sup.5 --, R.sup.4 : a hydroxyl group, a lower alkoxy group, etc., R.sup.5 : a hydrogen atom, a carbamoyl group, a lower alkoxycarbonyl group, etc., R.sup.2 : a lower alkyl group, R.sup.3 : a hydrogen atom, a halogen atom, a carboxyl group, B: a lower alkylene group or a carbonyl group, and n: 0 or 1).

  以下是由下列通式（I）表示的酰胺基萘衍生物，具有凝血因子X抑制作用，可用作抗血栓剂等，其盐，中间体以及包括该酰胺基萘衍生物的药物组成物。由下列通式（I）或其药学上可接受的盐表示的酰胺基萘衍生物。 ##STR1## （式中符号的含义如下：R1：氢原子或由公式--A--W--R4表示的基团，A：由公式表示的基团##STR2##由公式表示的基团##STR3##或由公式--SO.sub.2--表示的基团，X：氧原子或硫原子，W：单键或由公式--NR5--表示的基团，R4：羟基，低级烷氧基等，R5：氢原子，氨基甲酰基，低级烷氧羰基基团等，R2：低级烷基，R3：氢原子，卤原子，羧基，B：低级烷基撑或羰基基团，n：0或1）。
• NOVEL AMIDINONAPHTHYL DERIVATIVE OR SALT THEREOF
  申请人：YAMANOUCHI PHARMACEUTICAL CO. LTD.

  公开号：EP0798295A1

  公开（公告）日：1997-10-01

  An amidinonaphthyl derivative represented by the following general formula (I) which has a platelet aggregation inhibiting action based on the activated blood coagulation factor X inhibiting action and is useful as an anti-thrombus agent and the like, a salt thereof, an intermediate thereof and a pharmaceutical composition which comprises the amidinonaphthyl derivative. An amidinonaphthyl derivative represented by the following general formula (I) or a pharmaceutically acceptable salt thereof. (symbols in the formula have the following meanings; R1: a hydrogen atom or a group represented by the formula -A-W-R4, A: a group represented by the formula a group represented by the formula or a group represented by the formula -SO2-, X: an oxygen atom or a sulfur atom, W: a single bond or a group represented by the formula -NR5-, R4: a hydroxyl group, a lower alkoxy group, etc., not a hydroxyl group or a lower alkoxy group, R5: a hydrogen atom, a carbamoyl group, a lower alkoxycarbonyl group, etc., R2: a lower alkyl group, R3: a hydrogen atom, a halogen atom, a carboxyl group, B: a lower alkylene group or a carbonyl group, and n: 0 or 1).

  一种由下式通式（I）表示的脒基萘衍生物、其盐、中间体和包含该脒基萘衍生物的药物组合物，该脒基萘衍生物具有基于活化血液凝固因子 X 抑制作用的血小板聚集抑制作用，可用作抗血栓剂等。 由以下通式（I）代表的脒基萘衍生物或其药学上可接受的盐。 (式中符号含义如下； R1：氢原子或由式-A-W-R4 所代表的基团、 A：由式 式所代表的基团 或由式 -SO2- 代表的基团、 X：氧原子或硫原子，W：单键或由式-NR5-代表的基团，R4：羟基、低级烷氧基等，不是羟基或低级烷氧基，R5：氢原子、氨基甲酰基、低级烷氧基羰基等，R2：低级烷基，R3：氢原子、卤素原子、羧基，B：低级亚烷基或羰基，n：0 或 1）。