2,3,5-三甲基吡啶 1-氧化物 | 74409-42-0

• 物质功能分类: 医药中间体 - 杂环化合物 - 吡啶类化合物
• 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: 2,3,5-三甲基吡啶 1-氧化物
• 中文别名: 2,3,5-三甲基吡啶-1-氧化物；2,3,4,6-四苄基-D-吡喃葡萄糖；2,3,5-三甲基吡啶氮氧化物；2,3,5-三甲基吡啶1-氧化物；2,3,5-三甲基吡啶氧化物
• 英文名称: 2,3,5-trimethylpyridine 1-oxide
• 英文别名: 2,3,5-trimethylpyridine-N-oxide；2,3,5-trimethyl-1-oxidopyridin-1-ium
• CAS: 74409-42-0
• 化学式: C₈H₁₁NO
• mdl: MFCD00126841
• 分子量: 137.181
• InChiKey: YSBDSWBSEXCSSE-UHFFFAOYSA-N

物化性质

• 熔点：
  40-41 °C
• 沸点：
  95-98 °C(Press: 0.00998 Torr)
• 密度：
  0.99±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.375
• 拓扑面积：
  25.5
• 氢给体数：
  0
• 氢受体数：
  1

安全信息

• 海关编码：
  2933399090
• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H320,H335
• 储存条件：
  室温

制备方法与用途

2,3,5-三甲基吡啶氧化物用于制备奥美拉唑的代谢物作为中间体。

反应信息

• 作为反应物：
  描述：

  2,3,5-三甲基吡啶 1-氧化物 在 四(三苯基膦)钯 溴 、 potassium carbonate 作用下， 以 四氢呋喃 、 四氯化碳 、 甲苯 为溶剂， 反应 6.0h， 生成 2,3,4,5-tetramethylpyridine N-oxide
  参考文献：
  名称：

  Rationally Designed High-Affinity 2-Amino-6-halopurine Heat Shock Protein 90 Inhibitors That Exhibit Potent Antitumor Activity

  摘要：

  Heat shock protein 90 (Hsp90) is a molecular chaperone protein implicated in stabilizing the conformation and maintaining the function of many cell-signaling proteins. Many oncogenic proteins are more dependent on Hsp90 in maintaining their conformation, stability, and maturation than their normal counterparts. Furthermore, recent data show that Hsp90 exists in an activated form in malignant cells but in a latent inactive form in normal tissues, suggesting that inhibitors selective for the activated form could provide a high therapeutic index. Hence, Hsp90 is emerging as an exciting new target for the treatment of cancer. We now report on a novel series of 2-amino-6-halopurine Hsp90 inhibitors exemplified by 2-amino-6-chloro-9-(4-iodo-3,5-dimethylpyridin-2-ylmethyl)purine (30). These highly potent inhibitors (IC50 of 30 = 0.009 mu M in a HER-2 degradation assay) also display excellent antiproliferative activity against various tumor cell lines (IC50 of 30 = 0.03 mu M in MCF7 cells). Moreover, this class of inhibitors shows higher affinity for the activated form of Hsp90 compared to our earlier 8-sulfanylpurine Hsp90 inhibitor series. When administered orally to mice, these compounds exhibited potent tumor growth inhibition (> 80%) in an N87 xenograft model, similar to that observed with 17-allylamino-17-desmethoxygeldanamycin (17-AAG), which is a compound currently in phase I/II clinical trials.

  DOI：

  10.1021/jm050752+
• 作为产物：
  描述：

  2,3,5-三甲基吡啶 在 双氧水 、 溶剂黄146 作用下， 以 水 为溶剂， 反应 6.0h， 以57%的产率得到2,3,5-三甲基吡啶 1-氧化物
  参考文献：
  名称：

  一种化学伴侣为基础的药物候选人在肌萎缩性侧索硬化症（ALS）的小鼠模型中有效。

  摘要：

  肌萎缩性侧索硬化症（ALS）是一种致命的神经退行性疾病，其特征在于运动神经元的选择性死亡和骨骼肌萎缩。大多数ALS病例是自发获得的，遗传性疾病仅占所有病例的10％。最近的研究提供了令人信服的证据，即错误折叠的蛋白质聚集体是这两种ALS的基础。小分子（例如人工伴侣）可以预防甚至逆转与各种人类疾病相关的蛋白质的聚集。然而，它们非常高的活性浓度（微摩尔范围）严重限制了其作为药物的用途。我们合成了化学伴侣的几种酯和酰胺衍生物。铅化合物14，3 -（（5-（（4,6-二甲基吡啶-2--2-基）甲氧基）-5-氧戊烷酰基）氧基）N，在微摩尔浓度范围内，N-二甲基丙烷-1-胺氧化物在体外对神经元和星形胶质细胞都有保护作用。每日剂量为10 mg kg -1 14可以改善ALS小鼠的神经功能并延迟体重减轻。这种新的化学分子伴侣衍生物类的成员是开发用于ALS患者的新药的强有力的候选者。

  DOI：

  10.1002/cmdc.201500045

文献信息

• Benzimidazole compound
  申请人：Miyazawa Shuhei

  公开号：US20070010542A1

  公开（公告）日：2007-01-11

  An object of the present invention is to provide a novel chemical compound useful as a therapeutic or prophylactic agent for acid-related diseases, having an excellent inhibitory effect against gastric acid secretion, an excellent effect of maintaining the inhibitory effect against gastric acid secretion, thereby maintaining intragastric pH high for a long time, and having more safety and appropriate physicochemical stability. Provided is a compound represented by where R 1 and R 3 may be the same or different and each represent a hydrogen atom or a C1-C6 alkyl group; R 2 represents (5,5-dimethyl-1,3-dioxan-2-yl)methoxy group, 5,7-dioxaspiro[2.5]oct-6-ylmethoxy group, 1,5,9-trioxaspiro[5.5]undec-3-ylmethoxy group, or (2,2-dimethyl-1,3-dioxan-5-yl)methoxy group; R 4 , R 5 , R 6 and R 7 represent a hydrogen atom, halogen atom, C1-C6 alkyl group, C1-C6 haloalkyl group, C1-C6 alkoxy group or C1-C6 haloalkoxy group; and W 1 represents a single bond, methylene or ethylene group, a salt thereof or a solvate of these.

  本发明的目的是提供一种新型化合物，可用作治疗或预防酸相关疾病的药物，具有出色的抑制胃酸分泌作用，保持抑制胃酸分泌作用的出色效果，从而长时间保持胃内pH值高，并具有更高的安全性和适当的理化稳定性。 提供的化合物表示为 其中R 1 和R 3 可以相同也可以不同，每个代表氢原子或C1-C6烷基；R 2 表示(5,5-二甲基-1,3-二氧杂环戊烷-2-基)甲氧基基团，5,7-二氧杂螺[2.5]辛-6-基甲氧基基团，1,5,9-三氧杂螺[5.5]十一烷-3-基甲氧基基团，或(2,2-二甲基-1,3-二氧杂环戊烷-5-基)甲氧基基团； R 4 ，R 5 ，R 6 和R 7 代表氢原子，卤原子，C1-C6烷基，C1-C6卤代烷基，C1-C6烷氧基或C1-C6卤代烷氧基；W 1 表示单键，亚甲基或乙烯基，其盐或这些的溶剂化合物。
• Metal- and base-free regioselective thiolation of the methyl C(sp³)–H bond in 2-picoline <i>N</i>-oxides
  作者：Dong Wang、Zhenlin Liu、Zhentao Wang、Xinyue Ma、Peng Yu

  DOI：10.1039/c8gc03072c

  日期：——

  A one-pot, two-step synthesis of pyridine-2-ylmethyl thioethers is developed through a TFAA-mediated [3,3]-sigmatropic rearrangement of pyridine N-oxides and TBAB-catalyzed direct conversion of trifluoroacetates into thioethers under metal- and base-free conditions. This methodology enables thiolation of the unactivated methyl C(sp3)–H bond in 2-picolines with thiols. Remarkable features of the method

  通过TFAA介导的吡啶N-氧化物的[3,3]-σ重排和TBAB催化的三氟乙酸盐在金属和金属催化下直接转化为三氟乙酸的反应，可以开发一锅两步的吡啶-2-基甲基硫醚合成方法无碱条件。这种方法可以使未活化的甲基C（sp 3硫醇化）–2-甲基吡啶与硫醇的氢键。该方法的显着特征包括区域选择性高，阶跃和原子经济，条件温和，操作简单，底物范围广和可扩展性。此外，该方法已成功地用于合成奥美拉唑硫化物和雷贝拉唑硫化物，而无需TBAB催化。全面的绿色化学指标分析表明，该方法比报道的雷贝拉唑硫化物更有效，更环保。
• Intermolecular C–O Bond Formation with Alkoxyl Radicals: Photoredox-Catalyzed α-Alkoxylation of Carbonyl Compounds
  作者：Camille Banoun、Flavien Bourdreux、Emmanuel Magnier、Guillaume Dagousset

  DOI：10.1021/acs.orglett.1c03444

  日期：2021.11.19

  high reactivity of alkoxyl (RO·) radicals and their propensity to easily undergo β-scission or Hydrogen Atom Transfer (HAT) reactions, intermolecular alkoxylations involving RO· radicals are barely described. We report herein for the first time the efficient intermolecular trapping of alkoxyl radicals by silyl enol ethers. This photoredox-mediated protocol enables the introduction of both structurally

  由于烷氧基 (RO·) 自由基的高反应性及其容易发生 β 断裂或氢原子转移 (HAT) 反应的倾向，几乎没有描述涉及 RO· 自由基的分子间烷氧基化。我们在此首次报道了甲硅烷基烯醇醚对烷氧基自由基的有效分子间捕获。这种光氧化还原介导的协议能够将结构简单和更复杂的烷氧基引入范围广泛的酮和酰胺中。
• [EN] PYRIDINE DERIVATIVES AND THEIR USE AS MEDICAMENTS FOR TREATING DISEASES RELATED TO MCH RECEPTOR<br/>[FR] DERIVES DE PYRIDINE ET LEUR UTILISATION EN TANT QUE MEDICAMENTS POUR LE TRAITEMENT DES MALADIES LIEES AUX RECEPTEURS MCH
  申请人：TAISHO PHARMA CO LTD

  公开号：WO2006035967A1

  公开（公告）日：2006-04-06

  The present invention encompasses novel substituted pyridine compounds of Formula (I), which act as MCH receptor antagonists. These compositions and pharmaceutical compositions thereof are useful in the prophylaxis or treatment of improving memory function, sleeping and arousal, anxiety, depression, mood disorders, seizure, obesity, diabetes, appetite and eating disorders, cardiovascular disease, hypertension, dyslipidemia, myocardial infarction, binge eating disorders including bulimia, anorexia, mental disorders including manic depression, schizophrenia, delirium, dementia, stress, cognitive disorders, attention deficit disorder, substance abuse disorders and dyskinesias including Parkinson's disease, epilepsy, and addiction.

  本发明涵盖了化学式（I）的新型取代吡啶化合物，其作为MCH受体拮抗剂。这些组合物及其药物组合物在预防或治疗改善记忆功能、睡眠和觉醒、焦虑、抑郁、情绪障碍、癫痫、肥胖、糖尿病、食欲和进食障碍、心血管疾病、高血压、血脂异常、心肌梗死、暴饮暴食障碍包括暴食症、厌食症、精神障碍包括躁郁症、精神分裂症、谵妄、痴呆、压力、认知障碍、注意力缺陷障碍、物质滥用障碍和运动障碍包括帕金森病、癫痫和成瘾症方面具有用处。
• (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。