(2,2-difluorobenzo[d][1,3]dioxol-5-yl)hydrazine hydrochloride | 918792-69-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: (2,2-difluorobenzo[d][1,3]dioxol-5-yl)hydrazine hydrochloride
• 英文别名: (2,2-difluoro-benzo[1,3]dioxol-5-yl)-hydrazine hydrochloride；(2,2-difluoro-1,3-benzodioxol-5-yl)hydrazine;hydrochloride
• CAS: 918792-69-5
• 化学式: C₇H₆F₂N₂O₂*ClH
• 分子量: 224.595
• InChiKey: DMQLNCXZUATJPO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.72
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  56.5
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-(4-oxocyclohexyl)isobutyramide 、 (2,2-difluorobenzo[d][1,3]dioxol-5-yl)hydrazine hydrochloride 在 盐酸 作用下， 以 水 为溶剂， 反应 12.0h， 以43%的产率得到N-(2,2-difluoro-6,7,8,9-tetrahydro-5H-1,3-dioxa-9-aza-cyclopenta[b]fluoren-6-yl)-isobutyramide
  参考文献：
  名称：

  WO2007/2181

  摘要：

  公开号：
• 作为产物：
  描述：

  5-氨基-2,2-二氟-1,3-苯并二噁唑 在 盐酸 、 tin(ll) chloride 、 sodium nitrite 作用下， 以 水 为溶剂， 反应 1.0h， 以26%的产率得到(2,2-difluorobenzo[d][1,3]dioxol-5-yl)hydrazine hydrochloride
  参考文献：
  名称：

  WO2007/2181

  摘要：

  公开号：

文献信息

• Synthesis of Aryl Hydrazines via CuI/BMPO Catalyzed Cross-Coupling of Aryl Halides with Hydrazine Hydrate in Water
  作者：Siripuram Vijay Kumar、Dawei Ma

  DOI：10.1002/cjoc.201800326

  日期：2018.11

  The N,N’‐bis(2,6‐dimethylphenyl)oxalamide was discovered as a powerful ligand for Cu‐catalyzed cross‐coupling of aryl halides with hydrazine hydrate, leading to the formation of a variety of aryl hydrazines at 80 oC in water under the assistance of K3PO4 and 4 mol% cetyltrimethylammonium bromide from aryl bromides and aryl iodides. Good to excellent yields were observed in most cases.

  的N，N-双（2,6-二甲基苯基）草酰胺，发现作为一个强大的配体对Cu催化的与水合肼芳基卤化物的交叉耦合，从而导致的各种芳基肼的形成在80 ö用C在K 3 PO 4和4 mol％的十六烷基三甲基溴化铵的帮助下，从芳基溴化物和芳基碘化物中加入水。在大多数情况下，观察到良好至极好的产量。
• SUBSTITUTED BENZAMIDE DERIVATIVES
  申请人：Galley Guido

  公开号：US20120316165A1

  公开（公告）日：2012-12-13

  The present invention relates to compounds of formula wherein R 1 , R 2 , R 3 , X, Z, Ar, and n are as described in the claims, Ar is phenyl or heteroaryl, selected from the group consisting of 1H-indazole-3yl, pyridine-2-yl, pyridine-3-yl, pyridine-4-yl, pyrimidine-5-yl, 1H-pyrazole-3-yl, 1H-pyrazole-4-yl and 1H-pyrazole-5-yl; or to a pharmaceutically suitable acid addition salt thereof, which may be used for the treatment of depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder (ADHD), stress-related disorders, psychotic disorders, schizophrenia, neurological diseases, Parkinson's disease, neurodegenerative disorders, Alzheimer's disease, epilepsy, migraine, hypertension, substance abuse, metabolic disorders, eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation, disorders and malfunction of body temperature homeostasis, disorders of sleep and circadian rhythm, and cardiovascular disorders.

  本发明涉及以下式中的化合物，其中R1、R2、R3、X、Z、Ar和n如索权所述，Ar为苯基或杂环芳基，所述杂环芳基选自以下群体：1H-吲哚基、吡啶-2-基、吡啶-3-基、吡啶-4-基、嘧啶-5-基、1H-吡唑-3-基、1H-吡唑-4-基和1H-吡唑-5-基；或其药学上适用的酸加盐，可用于治疗抑郁症、焦虑障碍、躁郁症、注意力缺陷多动障碍（ADHD）、与压力相关的障碍、精神障碍、精神分裂症、神经系统疾病、帕金森病、神经退行性疾病、阿尔茨海默病、癫痫、偏头痛、高血压、物质滥用、代谢障碍、进食障碍、糖尿病、糖尿病并发症、肥胖症、血脂异常、能量消耗和吸收障碍、体温稳态障碍、睡眠和昼夜节律障碍，以及心血管疾病。
• [EN] PYRAZOLE CARBOXAMIDE DERIVATIVES AS TAAR MODULATORS FOR USE IN THE TREATMENT OF SEVERAL DISORDERS, SUCH AS DEPRESSION, DIABETES AND PARKINSON'S DISEASE<br/>[FR] DÉRIVÉS DE PYRAZOLE-CARBOXAMIDE EN TANT QUE MODULATEURS DE TAAR POUR UTILISATION DANS LE TRAITEMENT DE PLUSIEURS TROUBLES, TELS QUE LA DÉPRESSION, LE DIABÈTE ET LA MALADIE DE PARKINSON
  申请人：HOFFMANN LA ROCHE

  公开号：WO2014041007A1

  公开（公告）日：2014-03-20

  The present invention relates to compounds of formula (I) wherein R1 is phenyl, optionally substituted by halogen, lower alkyl, lower cycloalkyl, lower alkoxy, cyano, lower alkyl substituted by halogen, lower alkyl substituted by hydroxy, lower alkoxy substituted by halogen or lower alkoxy substituted by hydroxy; or is pyridine-2, 3 or 4-yl, optionally substituted by halogen, lower alkyl, lower cycloalkyl, cyano, lower alkyl substituted by halogen, lower alkyl substituted by hydroxy, lower alkoxy, lower alkoxy substituted by halogen or lower alkoxy substituted by hydroxyl; or is pyrimidin-2, 4 or 5-yl, optionally substituted by halogen, lower alkyl, lower cycloalkyl, lower alkyl substituted by hydroxy or lower alkyl substituted by halogen; or is pyrazin-2-yl, optionally substituted by halogen, lower alkyl, lower cycloalkyl, lower alkyl substituted by halogen, lower alkyl substituted by hydroxy or cyano; or is 2,2-difluorobenzo[d][l,3]dioxol-5-yl, or is thiazolyl, optionally substituted by lower alkyl substituted by halogen; R2 is hydrogen or lower alkyl; R3 is hydrogen, amino or lower alkyl; Z is a bond, -CH2- or -O-; or to a pharmaceutically suitable acid addition salt thereof. It has now been found that the compounds of formulas I have a good affinity to the trace amine associated receptors (TAARs), especially for TAAR1. The compounds may be used for the treatment of depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder (ADHD), stress-related disorders, psychotic disorders such as schizophrenia, neurological diseases such as Parkinson's disease, neurodegenerative disorders such as Alzheimer's disease, epilepsy, migraine, hypertension, substance abuse and metabolic disorders such as eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation, disorders and malfunction of body temperature homeostasis, disorders of sleep and circadian rhythm, and cardiovascular disorders.

  本发明涉及以下式（I）的化合物，其中R1是苯基，可以被卤素、较低烷基、较低环烷基、较低烷氧基、氰基、被卤素取代的较低烷基、被羟基取代的较低烷基、被卤素取代的较低烷氧基或被羟基取代的较低烷氧基；或是吡啶-2、3或4-基，可以被卤素、较低烷基、较低环烷基、氰基、被卤素取代的较低烷基、被羟基取代的较低烷基、较低烷氧基、被卤素取代的较低烷氧基或被羟基取代的较低烷氧基取代；或是嘧啶-2、4或5-基，可以被卤素、较低烷基、较低环烷基、被羟基取代的较低烷基或被卤素取代的较低烷基取代；或是吡嗪-2-基，可以被卤素、较低烷基、较低环烷基、被卤素取代的较低烷基、被羟基取代的较低烷基或氰基取代；或是2,2-二氟苯并[d][1,3]二氧杂环-5-基，或是噻唑基，可以被被卤素取代的较低烷基取代；R2是氢或较低烷基；R3是氢、氨基或较低烷基；Z是键，-CH2-或-O-；或其药学上适用的酸盐。现已发现，式I的化合物对追踪胺相关受体（TAARs）有很好的亲和力，尤其是对TAAR1。这些化合物可用于治疗抑郁症、焦虑症、双相情感障碍、注意力缺陷多动障碍（ADHD）、与压力相关的障碍、精神分裂症等精神障碍、帕金森病等神经系统疾病、阿尔茨海默病等神经退行性疾病、癫痫、偏头痛、高血压、物质滥用以及代谢障碍，如进食障碍、糖尿病、糖尿病并发症、肥胖症、血脂异常、能量消耗和吸收障碍、体温稳态障碍、睡眠和昼夜节律障碍，以及心血管疾病。
• TETRAHYDROCARBAZOLE DERIVATIVES USEFUL AS ANDROGEN RECEPTOR MODULATORS
  申请人：Fales Kevin Robert

  公开号：US20100022550A1

  公开（公告）日：2010-01-28

  The present invention provides a compound of the formula: Formula (I) or a pharmaceutically acceptable salt thereof; pharmaceutical compositions comprising an effective amount of a compound of Formula (I) in combination with a suitable carrier, diluent, or excipient; and methods for treating physiological disorders, particularly frailty, osteoporosis, osteopenia, and male and female sexual dysfunction comprising administering to a patient in need thereof an effective amount of a compound of formula (I).

  本发明提供了以下公式的化合物：公式（I）或其药学上可接受的盐；包含有效量公式（I）化合物与适当载体、稀释剂或赋形剂的制剂；以及治疗生理障碍，特别是虚弱，骨质疏松，骨质疏松症和男女性功能障碍的方法，包括向需要的患者给予公式（I）化合物的有效量。
• Tetrahydrocarbazole derivatives useful as androgen receptor modulators
  申请人：Eli Lilly and Company

  公开号：US07935722B2

  公开（公告）日：2011-05-03

  The present invention provides a compound of the formula: Formula (I) or a pharmaceutically acceptable salt thereof; pharmaceutical compositions comprising an effective amount of a compound of Formula (I) in combination with a suitable carrier, diluent, or excipient; and methods for treating physiological disorders, particularly frailty, osteoporosis, osteopenia, and male and female sexual dysfunction comprising administering to a patient in need thereof an effective amount of a compound of formula (I).

  本发明提供了一个化合物的公式：公式（I）或其药学上可接受的盐；包含公式（I）化合物的有效量与适当载体、稀释剂或赋形剂的药物组合物；以及治疗生理障碍，特别是虚弱、骨质疏松、骨质疏松症和男性和女性性功能障碍的方法，包括向需要治疗的患者施用公式（I）化合物的有效量。