4-二甲基氨基四氢-2H-吡喃-4-甲腈 | 176445-77-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氧烷类
• 中文名称: 4-二甲基氨基四氢-2H-吡喃-4-甲腈
• 英文名称: 4-(dimethylamino)tetrahydro-2H-pyran-4-carbonitrile
• 英文别名: 4-cyano-4-dimethylamino-tetrahydro-4H-pyrane；4-(dimethylamino)oxane-4-carbonitrile
• CAS: 176445-77-5
• 化学式: C₈H₁₄N₂O
• 分子量: 154.212
• InChiKey: FDGOISRHLNMQRE-UHFFFAOYSA-N

物化性质

• 熔点：
  51 °C
• 沸点：
  263.3±40.0 °C(Predicted)
• 密度：
  1.03±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  36.3
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2932999099

反应信息

• 作为反应物：
  描述：

  4-二甲基氨基四氢-2H-吡喃-4-甲腈 在 lithium aluminium tetrahydride 、 硫酸 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 生成 4-amino-5-chloro-N-(4-dimethylamino-4-tetrahydro-4H-pyranyl)methyl-2-methoxybenzamide
  参考文献：
  名称：

  Serotoninergic properties of new conformationally restricted benzamides

  摘要：

  A new series of benzamides derived from metoclopramide have been synthesized, in which the vicinal carbon of the basic nitrogen atom of the ethyl chain is situated on the C-3, C-4, C-5 and C-6 rings. The diamino derivatives were prepared through Strecker's reaction from the corresponding ketones except for the cyclopropyl derivatives where 1-ethoxy-1-trimethylsiloxy cyclopropane was used as the starting material. The benzamides were prepared using the mixed anhydride method. They were tested in binding assays for D-2, 5-HT3 and 5-HT4 receptors. The results show a marked increase in the selectivity and potency of these derivatives for 5-HT3 receptors with regard to metoclopramide (compound 1d: 5-HT3 K-i = 9.03 nM; 5-HT4 K-i > 5000; D-2 K-i > 5000). The influences of steric hindrance and hydrophobic properties on the affinity of benzamide derivatives for 5-HT3 receptors were also emphasized by these data. The X-ray crystal structure of compound 1d was compared with that of the minimal energy conformer of BRL 24682, a reference 5-HT3 receptor antagonist benzamide, determined using the Random Search program. Superimposition of the two structures showed a suitable fit between the pharmacophore groups previously determined to be important for 5-HT3 receptor antagonists. On the other hand, the hydrophobic parts of the basic moieties had different spatial occupancies.

  DOI：

  10.1016/0223-5234(96)89139-2
• 作为产物：
  描述：

  4-氰基四氢吡喃-4-羧酸 在 盐酸 、 DPPA 、 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 4.44h， 生成 4-二甲基氨基四氢-2H-吡喃-4-甲腈
  参考文献：
  名称：

  杂环化合物及其盐的制备方法

  摘要：

  本发明属于有机化学领域，具体涉及式I所示杂环化合物及其盐的制备方法。与现有技术相比，本发明避免了剧毒物质氰化物的使用，反应后的产物以及反应废弃物中不存在氰根离子残余的问题，大大减轻了环保负担。而且，本发明反应原料的价格低，制备方法简单，产率高，适于工业化的大规模生产。另外，发明人意外地发现，采用方案4的方法，例如使用还原剂和在酸性条件下进行，可以使化合物VIII一步反应同时实现脱保护基、烷基化和氰基还原，得到目标产物。极大地改善了现有技术需要进行多步反应的缺陷。

  公开号：

  CN109836400B

文献信息

• NOVEL BENZAMIDE DERIVATIVE AND USE THEREOF
  申请人：VIVOZON, INC.

  公开号：US20140336378A1

  公开（公告）日：2014-11-13

  Disclosed are a novel benzamide derivative and pharmaceutical use thereof, and more particularly, a novel benzamide derivative having a structure of Formula 1 or pharmaceutically acceptable salts thereof, and a composition for prevention or treatment of pain or itching including the above material. The novel benzamide derivative and pharmaceutically acceptable salt thereof according to the present invention exhibit excellent pain-suppressive effect and, in particular, pain-suppressive effect in not only a neuropathic animal model but also other models such as a formalin model, and therefore, may be used in suppression of different pains such as nociceptive pain, chronic pain, etc. Further, since it was demonstrated that the present invention displays anti-pruritic efficacy even in an itching model, to which a mechanism and treatment concept established with respect to pain is applied, the present invention may also be effectively used in radical treatment of atopic dermatitis by applying the inventive product to an anti-pruritic composition in order to suppress an initial itching stage and treat symptoms thereof, thus preventing skin damage or inflammation after the scratching stage.

  揭示了一种新的苯甲酰胺衍生物及其药用，更具体地说，一种具有化学式1结构或其药用盐的新苯甲酰胺衍生物，以及包括上述材料的用于预防或治疗疼痛或瘙痒的组合物。根据本发明，所述新的苯甲酰胺衍生物及其药用盐表现出优异的镇痛效果，特别是在不仅神经病理动物模型中而且其他模型如福尔马林模型中表现出的镇痛效果，因此，可用于抑制不同类型的疼痛，如伤害性疼痛、慢性疼痛等。此外，由于证明了本发明在瘙痒模型中显示出抗瘙痒功效，应用于疼痛方面建立的机制和治疗概念，因此，本发明还可通过将创新产品应用于抗瘙痒组合物中，以抑制初始瘙痒阶段并治疗其症状，从而预防刮痒阶段后的皮肤损伤或炎症。
• 苯甲酰胺衍生物的制备方法及其应用
  申请人：江苏海洋大学

  公开号：CN112679457B

  公开（公告）日：2022-11-04

  本发明提供了一种4‑丁氧基‑N‑((4‑(二甲氨基)四氢‑2H‑吡喃‑4‑基)甲基)‑3,5‑二甲氧基苯甲酰胺的制备方法及其应用。4‑丁氧基‑N‑((4‑(二甲氨基)四氢‑2H‑吡喃‑4‑基)甲基)‑3,5‑二甲氧基苯甲酰胺具有式I的结构。本发明提供的制备方法，通过Strecker、还原、缩合、取代四步反应即可得到4‑丁氧基‑N‑(((4‑(二甲氨基)四氢‑2H‑吡喃‑4‑基)甲基)‑3,5‑二甲氧基苯甲酰胺。该制备方法生产操作简单，原料易得，劳动防护要求低，收率较高，副产物少，更适用于工业化大生产。
• [EN] CYCLIC PYRIMIDIN-4-CARBOXAMIDES AS CCR2 RECEPTOR ANTAGONISTS FOR TREATMENT OF INFLAMMATION, ASTHMA AND COPD<br/>[FR] PYRIMIDINE-4 CARBOXAMIDES CYCLIQUES EN TANT QU'ANTAGONISTES DU RÉCEPTEUR CCR2 POUR LE TRAITEMENT D'INFLAMMATIONS, DE L'ASTHME ET DES BRONCHO-PNEUMOPATHIES CHRONIQUES OBSTRUCTIVES
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2010070032A1

  公开（公告）日：2010-06-24

  The present invention relates to novel antagonists for CCR2 (CC chemokine receptor 2) and their use for providing medicaments for treating conditions and diseases, especially pulmonary diseases like asthma and COPD. Formula (I), wherein A is selected from among a single bond, =CH-, -CH2-, -O-, -S-, and -NH-; wherein n is 1, 2 or 3; wherein Z is C or N, the other variables are as defined in the claims, as well as in form of their acid addition salts with pharmacologically acceptable acids.

  本发明涉及用于治疗疾病和疾病的新型CCR2（CC趋化因子受体2）拮抗剂及其用途，特别是用于治疗肺部疾病如哮喘和慢性阻塞性肺病的药物。公式（I），其中A从单键，=CH-，-CH2-，-O-，-S-和-NH-中选择；其中n为1、2或3；其中Z为C或N，其他变量如声明中所定义，以及以药理学上可接受的酸的酸盐形式存在。
• [EN] KRAS G12D INHIBITORS<br/>[FR] INHIBITEURS DE KRAS G12D
  申请人：MIRATI THERAPEUTICS INC

  公开号：WO2022031678A1

  公开（公告）日：2022-02-10

  The present invention relates to compounds that inhibit KRas G12D. In particular, the present invention relates to compounds that inhibit the activity of KRas G12D, pharmaceutical compositions comprising the compounds and methods of use therefor.

  本发明涉及抑制KRas G12D的化合物。具体而言，本发明涉及抑制KRas G12D活性的化合物，包括含有这些化合物的药物组合物以及使用方法。
• NEW CCR2 RECEPTOR ANTAGONISTS AND USES THEREOF
  申请人：EBEL Heiner

  公开号：US20140235661A1

  公开（公告）日：2014-08-21

  The present invention relates to novel antagonists for CCR2 (CC chemokine receptor 2) and their use for providing medicaments for treating conditions and diseases, especially pulmonary diseases like asthma and COPD.