4-氯-n,2-二甲氧基-n-甲基苯甲酰胺 | 205320-02-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-氯-n,2-二甲氧基-n-甲基苯甲酰胺
• 英文名称: 4-chloro-N,2-dimethoxy-N-methylbenzamide
• CAS: 205320-02-1
• 化学式: C₁₀H₁₂ClNO₃
• 分子量: 229.663
• InChiKey: FBQWJRHUICABKO-UHFFFAOYSA-N

物化性质

• 沸点：
  388.0±32.0 °C(Predicted)
• 密度：
  1.227±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-氯-n,2-二甲氧基-n-甲基苯甲酰胺 在 三溴化硼 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 为溶剂， 反应 17.5h， 生成 1-(4-氯-2-羟基苯基)-1-丙酮
  参考文献：
  名称：

  Optimization of Chromone-2-carboxamide Melanin Concentrating Hormone Receptor 1 Antagonists:  Assessment of Potency, Efficacy, and Cardiovascular Safety

  摘要：

  Evaluation of multiple structurally distinct series of melanin concentrating hormone receptor 1 antagonists in an anesthetized rat cardiovascualar assay led to the identification of a chromone-2-carboxamide series as having excellent safety against the chosen cardiovascular endpoints at high drug concentrations in the plasma and brain. Optimization of this series led to considerable improvements in affinity, functional potency, and pharmacokinetic profile. This led to the identification of a 7-fluorochromone-2-carboxamide (22) that was orally efficacious in a diet-induced obese mouse model, retained a favorable cardiovascular profile in rat, and demonstrated dramatic improvement in effects on mean arterial pressure in our dog cardiovascular model compared to other series reported by our group. However, this analogue also led to prolongation of the QT interval in the dog that was linked to affinity for hERG channel and unexpectedly potent functional blockade of this ion channel.

  DOI：

  10.1021/jm060683e
• 作为产物：
  描述：

  2-甲氧基-4-氯苯甲酰氯 、 二甲羟胺盐酸盐 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 72.0h， 生成 4-氯-n,2-二甲氧基-n-甲基苯甲酰胺
  参考文献：
  名称：

  Antagonists of melanin concentrating hormone effects on the melanin concentrating hormone receptor

  摘要：

  本发明涉及式(I)的化合物，通过对抗黑素浓集激素（MCH）的作用，通过对抗黑素浓集激素受体，有助于预防或治疗进食障碍、体重增加、肥胖、生殖和性行为异常、甲状腺激素分泌、利尿和水/电解质稳态、感觉处理、记忆、睡眠、觉醒、焦虑、抑郁、癫痫、神经退行性疾病和精神障碍。

  公开号：

  US20050209274A1

文献信息

• US5739336A
  申请人：——

  公开号：US5739336A

  公开（公告）日：1998-04-14
• [EN] 1,3,8-TRIAZA- AND 3,8-DIAZA-1-OXASPIRO(4,5)DECANE DERIVATIVES<br/>[FR] DERIVES DE 1,3,8-TRIAZA ET 3,8-DIAZA-1-OXASPIRO(4,5)-DECANE
  申请人：F.HOFFMANN-LA ROCHE AG

  公开号：WO1997000872A1

  公开（公告）日：1997-01-09

  (EN) Heterocyclic compounds of Formula (I) in which n is 2, 3, 4, 5 or 6; t is 1, 2, 3 or 4; u is 0 or 1 (provided that t is not 1 when u is 0); X is O or N(R4), in which R4 is hydro, (C1-4)alkyl, or aryl; Y and Z are independently C(O), C(S) or CH2 (provided that Y and Z are not both CH2); R1, R2, and R3 are as defined in the specification; and their pharmaceutically acceptable salts and $i(N)-oxides, formulations containing them, their uses as therapeutic agents, and their synthesis. The compounds of this invention are selective 5-HT2C receptor antagonists.(FR) La présente invention se rapporte à des composés hétérocycliques de formule générale (I), dans laquelle n vaut 2, 3, 4, 5 ou 6; t vaut 1, 2 ,3 ou 4; u vaut 0 ou 1 (à condition que t ne soit pas égal à 1 lorsque u vaut 0); X représente O ou N(R4) dans lequel R4 représente hydro, alkyle (C1-4) ou aryle; Y et Z représentent indépendamment C(O), C(S) ou CH2 (à condition que Y et Z ne représentent pas tous les deux CH2); R1, R2 et R3 sont tels que définis dans la description; ainsi qu'à leurs sels et $i(N)-oxides pharmaceutiquement acceptables, les formulations les contenant, leur utilisation en tant qu'agents thérapeutiques et leur synthèse. Les composés de cette invention sont des antagonistes sélectifs du récepteur 5-HT2C.
• [EN] HYDROXYBENZOPHENONE DERIVATIVES AS HERBICIDES<br/>[FR] DERIVES D'HYDROXYBENZOPHENONES EN TANT QU'HERBICIDES
  申请人：——

  公开号：WO1998013341A1

  公开（公告）日：1998-04-02

  [EN] The invention relates to hydroxybenzophenone derivatives of formula (I), wherein R<1>, R<2>, R<3>, R<4>, R<5>, R<6>, R<7> and R<8> are as defined in the description, and to their use as herbicides.
  [FR] L'invention concerne des dérivés d'hydroxybenzophénones selon la formule (I). Dans cette dernière, R<1>, R<2>, R<3>, R<4>, R<5>, R<6>, R<7> et R<8> sont tels que définis dans le descriptif. L'invention traite également de l'utilisation de ces composés comme herbicides.
• Antagonists of melanin concentrating hormone effects on the melanin concentrating hormone receptor
  申请人：Lynch K. John

  公开号：US20050209274A1

  公开（公告）日：2005-09-22

  The present invention is directed to compounds of formula (I), which antagonize of the effects of melanin-concentrating hormone (MCH) through the melanin concentrating hormone receptor which is useful for the prevention or treatment of eating disorders, weight gain, obesity, abnormalities in reproduction and sexual behavior, thyroid hormone secretion, diuresis and water/electrolyte homeostasis, sensory processing, memory, sleeping, arousal, anxiety, depression, seizures, neurodegeneration and psychiatric disorders.

  本发明涉及式(I)的化合物，通过对抗黑素浓集激素（MCH）的作用，通过对抗黑素浓集激素受体，有助于预防或治疗进食障碍、体重增加、肥胖、生殖和性行为异常、甲状腺激素分泌、利尿和水/电解质稳态、感觉处理、记忆、睡眠、觉醒、焦虑、抑郁、癫痫、神经退行性疾病和精神障碍。
• Optimization of Chromone-2-carboxamide Melanin Concentrating Hormone Receptor 1 Antagonists:  Assessment of Potency, Efficacy, and Cardiovascular Safety
  作者：John K. Lynch、Jennifer C. Freeman、Andrew S. Judd、Rajesh Iyengar、Mathew Mulhern、Gang Zhao、James J. Napier、Dariusz Wodka、Sevan Brodjian、Brian D. Dayton、Doug Falls、Christopher Ogiela、Regina M. Reilly、Thomas J. Campbell、James S. Polakowski、Lisa Hernandez、Kennan C. Marsh、Robin Shapiro、Victoria Knourek-Segel、Brian Droz、Eugene Bush、Michael Brune、Lee C. Preusser、Ryan M. Fryer、Glenn A. Reinhart、Kathryn Houseman、Gilbert Diaz、Ann Mikhail、James T. Limberis、Hing L. Sham、Christine A. Collins、Philip R. Kym

  DOI：10.1021/jm060683e

  日期：2006.11.1

  Evaluation of multiple structurally distinct series of melanin concentrating hormone receptor 1 antagonists in an anesthetized rat cardiovascualar assay led to the identification of a chromone-2-carboxamide series as having excellent safety against the chosen cardiovascular endpoints at high drug concentrations in the plasma and brain. Optimization of this series led to considerable improvements in affinity, functional potency, and pharmacokinetic profile. This led to the identification of a 7-fluorochromone-2-carboxamide (22) that was orally efficacious in a diet-induced obese mouse model, retained a favorable cardiovascular profile in rat, and demonstrated dramatic improvement in effects on mean arterial pressure in our dog cardiovascular model compared to other series reported by our group. However, this analogue also led to prolongation of the QT interval in the dog that was linked to affinity for hERG channel and unexpectedly potent functional blockade of this ion channel.