3,5-二甲基-2-氯甲基吡啶盐酸盐 | 73590-93-9

• 物质功能分类: 分析化学 - 对照品
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 3,5-二甲基-2-氯甲基吡啶盐酸盐
• 中文别名: 2-氯甲基-3.5-二甲基-吡啶盐酸盐
• 英文名称: 2-chloromethyl-3,5-dimethylpyridine hydrochloride
• 英文别名: 2-(Chloromethyl)-3,5-dimethylpyridine hydrochloride；2-(chloromethyl)-3,5-dimethylpyridine;hydrochloride
• CAS: 73590-93-9
• 化学式: C₈H₁₀ClN*ClH
• 分子量: 192.088
• InChiKey: KTCKCIHKYBTWLK-UHFFFAOYSA-N

物化性质

• 熔点：
  >145oC (dec.)
• 溶解度：
  氯仿（微溶）、甲醇（微溶）、水（微溶）

计算性质

• 辛醇/水分配系数(LogP)：
  2.86
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  12.9
• 氢给体数：
  1
• 氢受体数：
  1

安全信息

• 海关编码：
  2933399090
• 包装等级：
  II
• 危险类别：
  8
• 危险性防范说明：
  P260,P264,P270,P280,P301+P330+P331,P303+P361+P353,P304+P340,P305+P351+P338,P310,P363,P405,P501
• 危险品运输编号：
  3261
• 危险性描述：
  H302,H314
• 储存条件：
  存储条件为2-8°C，并需保存在惰性气体环境中。

反应信息

• 作为反应物：
  描述：

  3,5-二甲基-2-氯甲基吡啶盐酸盐 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 potassium acetate 、 四丁基碘化铵 、 caesium carbonate 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 28.0h， 生成
  参考文献：
  名称：

  5-Lipoxygenase-Activating Protein (FLAP) Inhibitors. Part 4: Development of 3-[3-tert-Butylsulfanyl-1-[4-(6-ethoxypyridin-3-yl)benzyl]-5-(5-methylpyridin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethylpropionic Acid (AM803), a Potent, Oral, Once Daily FLAP Inhibitor

  摘要：

  The potent 5-lipoxygenase-activating protein (FLAP) inhibitor 3-[3-tert-butylsulfanyl-1-[4-(6-ethoxypyridin-3-yl)benzyl]-5-(5-methylpyridin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethylpropionic acid 11cc is described (AM803, now GSK2190915). Building upon AM103 (1) (Hutchinson et al. J. Med Chem. 2009, 52, 5803-5815; Stock et al. Bioorg. Med. Chem. Lett. 2010, 20, 213-217; Stock et al. Bioorg. Med. Chem. Lett. 2010, 20, 4598-4601), SAR studies centering around the pyridine moiety led to the discovery of compounds that exhibit significantly increased potency in a human whole blood assay measuring LTB4 inhibition with longer drug preincubation times (15 min vs S h). Further studies identified 11cc with a potency of 2.9 nM in FLAP binding, an IC50 of 76 nM for inhibition of LTB4 in human blood (5 h incubation) and excellent preclinical toxicology and pharmacoldnetics in rat and dog. 11cc also demonstrated an extended pharmacodynamic effect in a rodent bronchoalveolar lavage (BAL) model. This compound has successfully completed phase 1 clinical studies in healthy volunteers and is currently undergoing phase 2 trials in asthmatic patients.

  DOI：

  10.1021/jm2008369
• 作为产物：
  描述：

  2,3,5-三甲基吡啶 1-氧化物 在 sodium hydroxide 、 氯化亚砜 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 3,5-二甲基-2-氯甲基吡啶盐酸盐
  参考文献：
  名称：

  2-[[（（2-吡啶基）甲基]硫代] -1H-苯并咪唑类化合物作为体外抗幽门螺杆菌药物的结构活性关系及其体内疗效评估。

  摘要：

  描述了21个2-[[[（2-吡啶基）甲基]硫基] -1H-苯并咪唑类化合物（6）的结构与其以最小杀菌浓度（MBC）值表示的抗幽门螺杆菌活性之间的关系。观察到的MBC范围为256至1微克/毫升。结构-活性关系（SAR）表明，更大和更多的亲脂性化合物，特别是在吡啶基部分的4-位具有这种取代基的化合物，通常具有较低的MBC值。合成并测试了通过建立的SAR模型预测可能有效的四种新化合物。测试了一种这样的化合物，即2-[[（（[4-[（环丙基甲基）氧基] -3-甲基-2-吡啶基）甲基]硫代] -1H-苯并咪唑（18）在小鼠体内的功效。幽门螺杆菌模型（125 micromol / kg口服，持续4天，n = 4）。很遗憾，该模型不能清楚地证明其抗菌活性。相反，观察到有效的酸分泌抑制作用。该发现归因于甲硫基化合物在体内被氧化成相应的甲基亚磺酰基衍生物，即质子泵抑制剂。尽管该抗菌活性具有体内降低粪便链球菌

  DOI：

  10.1021/jm970165r

文献信息

• 5-LIPOXYGENASE-ACTIVATING PROTEIN (FLAP) INHIBITORS
  申请人：Hutchinson H. John

  公开号：US20070105866A1

  公开（公告）日：2007-05-10

  Described herein are compounds and pharmaceutical compositions containing such compounds, which modulate the activity of 5-lipoxygenase-activating protein (FLAP). Also described herein are methods of using such FLAP modulators, alone and in combination with other compounds, for treating respiratory, cardiovascular, and other leukotriene-dependent or leukotriene mediated conditions or diseases.

  本发明描述了调节5-脂氧合酶激活蛋白(FLAP)活性的化合物和含有该化合物的药物组合物。本发明还描述了单独使用和与其他化合物联合使用FLAP调节剂，用于治疗呼吸系统、心血管系统和其他白三烯依赖性或白三烯介导的状况或疾病。
• (Bezimidazol-2-yl)-pyridinium compounds
  申请人：Hoffman-La Roche Inc.

  公开号：US04766133A1

  公开（公告）日：1988-08-23

  (Benzimidazol-2-yl)-pyridinium compounds of the formula ##STR1## wherein A is --SR.sup.9, --SO.sub.3.sup.- or --S--SO.sub.3.sup.- ; R.sup.1 and R.sup.3 each is hydrogen or (C.sub.1 -C.sub.7)-alkyl; R.sup.2 is hydrogen, (C.sub.1 -C.sub.7)-alkyl, (C.sub.1 -C.sub.7)-alkoxy or a negatively charged oxygen atom; R.sup.4 is hydrogen or a negative charge; R.sup.5, R.sup.6, R.sup.7 and R.sup.8 each is hydrogen, (C.sub.1 -C.sub.7)-alkyl, aryl, halogen, cyano, nitro, formyl, (C.sub.2 -C.sub.7)-alkanoyl, arylcarbonyl, carboxy, carboxy-(C.sub.1 -C.sub.7)-alkyl, (C.sub.1 -C.sub.7)-alkoxycarbonyl, aryloxycarbonyl, aryl-(C.sub.1 -C.sub.7)-alkoxycarbonyl, (C.sub.1 -C.sub.7)-alkoxycarbonyl-(C.sub.1 -C.sub.7)-alkyl, carbamoyl, mono- or di-(C.sub.1 -C.sub.7)-alkylcarbamoyl, pyrrolidinocarbonyl, piperidinocarbonyl, carbamoyl-(C.sub.1 -C.sub.7)-alkyl, mono- or di-(C.sub.1 -C.sub.7)-alkylcarbamoyl-(C.sub.1 -C.sub.7)-alkyl, pyrrolidinocarbonyl-(C.sub.1 -C.sub.7)-alkyl, piperdinocarbonyl-(C.sub.1 -C.sub.7)-alkyl, hydroxy, (C.sub.1 -C.sub.7)-alkoxy, (C.sub.2 -C.sub.7)-alkanoloxy, aryloxy, arylcarbonyloxy, (C.sub.1 -C.sub.7)-alkoxycarbonyloxy, aryl-(C.sub.1 -C.sub.7)-alkoxycarbonyloxy, aryloxycarbonyloxy, carbamoyloxy, mono- or di-(C.sub.1 -C.sub.7)-alkylcarbamoyloxy, pyrrolidinocarbonyloxy, piperidinocarbonyloxy, hydroxy-(C.sub.1 -C.sub.7)-alkyl, trifluoromethyl, di-(C.sub.1 -C.sub.7)-alkoxymethyl or (C.sub.2 -C.sub.3)-alkylenedioxymethyl or two of these substituents which are adjacent jointly and together with the carbon atoms to which they are attached are a 5-, 6- or 7-membered ring; and R.sup.9 is (C.sub.1 -C.sub.20)-alkyl, (C.sub.3 -C.sub.7)-cycloalkyl, (C.sub.3 -C.sub.7)-alkenylalkyl, (C.sub.3 -C.sub.7)-alkynylalkyl, substituted (C.sub.3 -C.sub.7)- alkenyl-alkyl, aryl, aryl-(C.sub.1 -C.sub.7)-alkyl, hydroxy- (C.sub.2 -C.sub.7)-alkyl, (C.sub.1 -C.sub.7)-alkoxy- (C.sub.2 -C.sub.7)-alkyl, (C.sub.1 -C.sub.7)-alkoxycarbonyl- (C.sub.1 -C.sub.7)-alkyl, carboxy-(C.sub.1 -C.sub.7)-alkyl, di-(C.sub.1 -C.sub.7)-alkoxycarbonyl-(C.sub.2 -C.sub.7)-alkyl, dicarboxy-(C.sub.2 -C.sub.7)-alkyl, carboxy-(C.sub.1 -C.sub.7)-alkylcarbamoyl-(C.sub.1 -C.sub.7)-alkyl, optionally N-substituted amino-(C.sub.2 -C.sub.7)-alkyl, optionally N-substituted amino-carboxy-(C.sub.2 -C.sub.7)-alkyl, optionally N-substituted amino-(C.sub.1 -C.sub.7)-alkoxycarbonyl-(C.sub.2 -C.sub.7)-alkyl, heteroaryl, heteroaryl-(C.sub.1 -C.sub.7)-alkyl or a residue derived from a cysteine-containing oligopeptide by elimination of the SH group; provided that when there is a net single positive charge there is an external anion, or a pharmaceutically acceptable acid addition salt thereof.

  苯并咪唑-2-基吡啶化合物的化学式为##STR1##其中A为--SR.sup.9，--SO.sub.3.sup.-或--S--SO.sub.3.sup.-；R.sup.1和R.sup.3分别为氢或(C.sub.1 -C.sub.7)-烷基；R.sup.2为氢，(C.sub.1 -C.sub.7)-烷基，(C.sub.1 -C.sub.7)-烷氧基或带负电荷的氧原子；R.sup.4为氢或带负电荷；R.sup.5，R.sup.6，R.sup.7和R.sup.8分别为氢，(C.sub.1 -C.sub.7)-烷基，芳基，卤素，氰基，硝基，甲酰基，(C.sub.2 -C.sub.7)-烷酰基，芳基羰基，羧基，羧基-(C.sub.1 -C.sub.7)-烷基，(C.sub.1 -C.sub.7)-烷氧羰基，芳氧羰基，芳基-(C.sub.1 -C.sub.7)-烷氧羰基，(C.sub.1 -C.sub.7)-烷氧羰基-(C.sub.1 -C.sub.7)-烷基，氨基甲酰基，单或双-(C.sub.1 -C.sub.7)-烷基氨基甲酰基，吡咯烷甲酰基，哌啶甲酰基，氨基甲酰基-(C.sub.1 -C.sub.7)-烷基，单或双-(C.sub.1 -C.sub.7)-烷基氨基甲酰基-(C.sub.1 -C.sub.7)-烷基，吡咯烷甲酰基-(C.sub.1 -C.sub.7)-烷基，哌啶甲酰基-(C.sub.1 -C.sub.7)-烷基，羟基，(C.sub.1 -C.sub.7)-烷氧基，(C.sub.2 -C.sub.7)-烷氧基，芳氧基，芳基羰氧基，(C.sub.1 -C.sub.7)-烷氧羰氧基，芳基-(C.sub.1 -C.sub.7)-烷氧羰氧基，芳氧羰氧基，氨基氧基，单或双-(C.sub.1 -C.sub.7)-烷基氨基氧基，吡咯烷甲酰氧基，哌啶甲酰氧基，羟基-(C.sub.1 -C.sub.7)-烷基，三氟甲基，双-(C.sub.1 -C.sub.7)-烷氧甲基或(C.sub.2 -C.sub.3)-烷二氧甲基或其中两个相邻的这些取代基与它们连接的碳原子一起形成5、6或7元环；R.sup.9为(C.sub.1 -C.sub.20)-烷基，(C.sub.3 -C.sub.7)-环烷基，(C.sub.3 -C.sub.7)-烯基烷基，(C.sub.3 -C.sub.7)-炔基烷基，取代的(C.sub.3 -C.sub.7)-烯基-烷基，芳基，芳基-(C.sub.1 -C.sub.7)-烷基，羟基-(C.sub.2 -C.sub.7)-烷基，(C.sub.1 -C.sub.7)-烷氧基-(C.sub.2 -C.sub.7)-烷基，(C.sub.1 -C.sub.7)-烷氧羰基-(C.sub.1 -C.sub.7)-烷基，羧基-(C.sub.1 -C.sub.7)-烷基，双-(C.sub.1 -C.sub.7)-烷氧羰基-(C.sub.2 -C.sub.7)-烷基，二羧基-(C.sub.2 -C.sub.7)-烷基，羧基-(C.sub.1 -C.sub.7)-烷基氨基甲酰基-(C.sub.1 -C.sub.7)-烷基，可选地N-取代氨基-(C.sub.2 -C.sub.7)-烷基，可选地N-取代氨基-羧基-(C.sub.2 -C.sub.7)-烷基，可选地N-取代氨基-(C.sub.1 -C.sub.7)-烷氧羰基-(C.sub.2 -C.sub.7)-烷基，杂环芳基，杂环芳基-(C.sub.1 -C.sub.7)-烷基或通过消除-SH基而得到的半胱氨酸寡肽的残基；但当存在净正电荷时，存在外部阴离子，或其药用可接受酸盐。
• 邻硝基芳酰化衍生物类化合物、制备方法及其应用
  申请人：兰州大学

  公开号：CN107915736A

  公开（公告）日：2018-04-17

  本发明公开一种如式所示的邻硝基芳酰化衍生物类化合物，以及这种化合物的制备方法及用途。本发明的邻硝基芳酰化衍生物类化合物可用于制备HSP90抑制剂药物，特别是用于制备抗肿瘤药物，并具有对肿瘤细胞的选择性较高，对机体的毒性较小的优点。
• Synthesis and characterization of one impurity in esomeprazole, an antiulcerative drug
  作者：Zhen-Tao Liu、Xia Meng、Shi-Min Fang、Li-Zhen Wang、Zhen-Zheng Wang、Geng Yang、Hong-Dong Duan、Ai-You Hao

  DOI：10.1007/s11696-019-00918-3

  日期：2020.3

  During drug synthesis, control of impurities is very important to get high-qualified drugs. A number of studies have devoted to synthesize the impurities and study the structures to support the method of purification. In this paper, we first synthesize one impurity in esomeprazole, rel-2-[[(3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-6-methoxy-1H-benzimidazole, with readily available raw materials, simple

  在药物合成过程中，控制杂质对获得高质量药物非常重要。大量研究致力于合成杂质并研究结构以支持纯化方法。在本文中，我们首先合成了埃索美拉唑中的一种杂质，rel-2-[[[（（3,5-二甲基-2-吡啶基）甲基]亚磺酰基] -6-甲氧基-1 H-苯并咪唑，原料容易获得，简单易行。操作程序和反应比较温和。此外，我们通过MS，IR，1 H-NMR和HPLC分析表征了其结构。目标化合物的纯度高达99.58％，可作为埃索美拉唑杂质的参考物质。
• Imidazo[4,5-b] pyridine compounds, process for preparing same and pharmaceutical compositions containing same
  申请人：TOKYO TANABE COMPANY LIMITED

  公开号：EP0254588A1

  公开（公告）日：1988-01-27

  Imidazo[4,5-b]pyridine compounds of the general formula [I] are provided: where R¹ is straight-chain or branched C1-8 alkoxy (which may be substituted with cycloalkyl) or C2-4 fluoro­alkyloxy, R² is H, methyl or methoxy, and R³ and R⁴ are each H or methyl and may be the same or different. All these compounds exhibit good inhibition of potassium ion-dependent adenosine triphosphatase and excellent storage stability, so that they are usable for the treatment of gastric and/or duodenal ulcers.

  提供了通式[I]的咪唑并[4,5-b]吡啶化合物：其中R¹是直链或支链C1-8烷氧基（可以用环烷基取代）或C2-4氟烷氧基，R²是H、甲基或甲氧基，而R³和R⁴分别是H或甲基，可以相同也可以不同。所有这些化合物均表现出良好的钾离子依赖性腺苷酸三磷酸酶抑制作用和卓越的储存稳定性，因此它们可用于治疗胃和/或十二指肠溃疡。