(2S)-1,1-bis(6-fluoro-3-pyridyl)-1,2-propanediamine | 357926-92-2

• 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
• 英文名称: (2S)-1,1-bis(6-fluoro-3-pyridyl)-1,2-propanediamine
• 英文别名: (2S)-1,1-bis(6-fluoro-pyridin-3-yl)-1,2-propanediamine；(2S)-1,1-bis(6-fluoropyridin-3-yl)propane-1,2-diamine
• CAS: 357926-92-2
• 化学式: C₁₃H₁₄F₂N₄
• 分子量: 264.278
• InChiKey: RXOLGJCPADQQGG-QMMMGPOBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  77.8
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  吡啶-2,4-二腈 、 (2S)-1,1-bis(6-fluoro-3-pyridyl)-1,2-propanediamine 在 ytterbium(III) triflate 作用下， 以 甲苯 为溶剂， 反应 15.0h， 以46%的产率得到2-[(5S)-4,4-bis(6-fluoro-3-pyridyl)-5-methyl-4,5-dihydro-1H-imidazol-2-yl]-4-pyridinecarbonitrile
  参考文献：
  名称：

  四取代的咪唑啉作为有效和选择性神经肽Y Y5受体拮抗剂的发现：减少人类以太相关基因钾通道结合亲和力和有效的抗肥胖作用

  摘要：

  合成了一系列新型咪唑啉衍生物，并将其评估为神经肽Y（NPY）Y5受体拮抗剂。通过在咪唑啉环的5-位引入取代基并修饰双（4-氟苯基）部分，尝试优化先前报道的咪唑啉导线1a和1b。鉴定了许多没有人类以太相关基因钾通道（hERG）活性的有效衍生物。包括2a在内的选定化合物被证明具有出色的大脑和CSF渗透性。化合物2a对慢性体内研究显示出合适的药代动力学特征，并有效抑制了d -Trp 34NPY诱导的大鼠急性食物摄入。在饮食诱导的肥胖小鼠模型中，口服2a可有效降低体重。

  DOI：

  10.1021/jm900110t
• 作为产物：
  描述：

  (2S)-1-azido-1,1-bis(6-fluoro-3-pyridyl)-2-propanamine 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 2.0h， 以54 mg的产率得到(2S)-1,1-bis(6-fluoro-3-pyridyl)-1,2-propanediamine
  参考文献：
  名称：

  四取代的咪唑啉作为有效和选择性神经肽Y Y5受体拮抗剂的发现：减少人类以太相关基因钾通道结合亲和力和有效的抗肥胖作用

  摘要：

  合成了一系列新型咪唑啉衍生物，并将其评估为神经肽Y（NPY）Y5受体拮抗剂。通过在咪唑啉环的5-位引入取代基并修饰双（4-氟苯基）部分，尝试优化先前报道的咪唑啉导线1a和1b。鉴定了许多没有人类以太相关基因钾通道（hERG）活性的有效衍生物。包括2a在内的选定化合物被证明具有出色的大脑和CSF渗透性。化合物2a对慢性体内研究显示出合适的药代动力学特征，并有效抑制了d -Trp 34NPY诱导的大鼠急性食物摄入。在饮食诱导的肥胖小鼠模型中，口服2a可有效降低体重。

  DOI：

  10.1021/jm900110t

文献信息

• N-substituted-2-oxodihydropyridine derivatives
  申请人：——

  公开号：US20040072874A1

  公开（公告）日：2004-04-15

  A compound of the formula (I): 1 (wherein Ar 1 and Ar 2 are independently aryl or heteroaryl, any of which is optionally substituted by a substituent selected from the group consisting of cyano, halogen, nitro, lower alkyl, halo-lower alkyl, hydroxy-lower alkyl, cyclo-lower alkyl, cyclo (lower alkyl)-lower alkyl, lower alkenyl, lower alkylamino, di-lower alkylamino, lower alkanoylamino, lower alkylsulfonylamino, arylsulfonylamino, hydroxy, lower alkoxy, halo-lower alkoxy, aryloxy, heteroaryloxy, lower alkylthio, carboxyl, formyl, lower alkanoyl, lower alkoxycarbonyl, carbamoyl, lower alkylcarbamoyl, di-lower alkylcarbamoyl, lower alkylsulfonyl, arylsulfonyl, aryl and heteroaryl; R 1 and R 2 are independently lower alkyl, cyclo-lower alkyl, cyclo(lower alkyl)-lower alkyl or lower alkoxy, any of which is optionally substituted by a substituent selected from the group consisting of halogen, lower alkylamino, di-lower alkylamino, lower alkanoylamino, hydroxy, lower alkoxy, formyl, lower alkoxycarbonyl, lower alkylcarbamoyl and di-lower alkylcarbamoyl; R 3 , R 4 and R 5 are independently hydrogen, cyano, halogen or hydroxy, or lower alkyl, lower alkoxy or lower alkylthio, the last three groups being optionally substituted by a substituent selected from the group consisting of halogen, lower alkylamino, di-lower alkylamino, lower alkanoylamino, hydroxy, lower alkoxy, formyl, lower alkoxycarbonyl, lower alkylcarbamoyl and di-lower alkylcarbamoyl), or a salt or ester thereof is useful as a neuropeptide Y receptor antagonist agent and is also useful as an agent for the treatment of bulimia, obesity or diabetes.

  化合物的结构式(I):1（其中Ar1和Ar2分别独立地为芳基或杂环芳基，任何一个可以选择性地被来自以下组的取代基取代，该组包括氰基、卤素、硝基、较低烷基、卤代较低烷基、羟基较低烷基、环较低烷基、环（较低烷基）-较低烷基、较低烯基、较低烷基氨基、二较低烷基氨基、较低烷酰氨基、较低烷基磺酰氨基、芳基磺酰氨基、羟基、较低烷氧基、卤代较低烷氧基、芳氧基、杂环芳氧基、较低烷硫基、羧基、甲酰基、较低烷酰基、较低烷氧羰基、氨基甲酰基、较低烷基氨基甲酰基、二较低烷基氨基甲酰基、较低烷基磺酰基、芳基磺酰基、芳基和杂环芳基；R1和R2独立地为较低烷基、环较低烷基、环（较低烷基）-较低烷基或较低烷氧基，任何一个可以选择性地被来自以下组的取代基取代，该组包括卤素、较低烷基氨基、二较低烷基氨基、较低烷酰氨基、羟基、较低烷氧基、甲酰基、较低烷氧羰基、较低烷基氨基甲酰基和二较低烷基氨基甲酰基；R3、R4和R5独立地为氢、氰基、卤素或羟基，或较低烷基、较低烷氧基或较低烷硫基，最后三个基可以选择性地被来自以下组的取代基取代，该组包括卤素、较低烷基氨基、二较低烷基氨基、较低烷酰氨基、羟基、较低烷氧基、甲酰基、较低烷氧羰基、较低烷基氨基甲酰基和二较低烷基氨基甲酰基），或其盐或酯是一种神经肽Y受体拮抗剂药物，也是一种治疗厌食症、肥胖症或糖尿病的药物。
• Novel imidazonline compounds
  申请人：——

  公开号：US20030158418A1

  公开（公告）日：2003-08-21

  Compounds represented by the general formula (I): 1 wherein Ar 1 and Ar 2 are each aryl or heteroaryl; R 1 is lower cycloalkyl, —Ar 3 , or a group of the general formula (a), (b) or (c): 2 and R 2 and R 3 are each hydrogen, lower cycloalkyl, lower alkenyl, or optionally substituted lower alkyl (with the proviso that when R 2 and R 3 are simultaneously hydrogen, Ar 1 , Ar 2 and R 1 do not simultaneously represent unsubstituted phenyl). The compounds are useful as treating agents for various NPY-related diseases, for example, circulatory diseases including hypertension, kidney diseases, cardiac diseases, vasospasm and arteriosclerosis; central nervous system diseases including hyperphagia, depression, anxiety, convulsion, epilepsy, dementia, pain, alcohol dependence, and withdrawal symptoms due to abstinence from drugs; metabolic diseases including obesity, diabetes, hormonal disorders, hypercholesterolemia, and hyperlipidemia; sexual dysfunction and reproductive function disorders; digestive diseases including enterokinetic disorders; respiratory diseases; inflammation; or glaucoma.

  化合物的一般公式(I)代表的化合物，其中Ar1和Ar2分别为芳香族或杂环芳基；R1为较低的环烷基，-Ar3，或一般公式(a)，(b)或(c)的基团；R2和R3分别为氢、较低的环烷基、较低的烯基，或可选择地取代的较低烷基（但当R2和R3同时为氢时，Ar1、Ar2和R1不同时代表未取代的苯基）。这些化合物可用作治疗各种NPY相关疾病的药物，例如循环系统疾病包括高血压、肾脏疾病、心脏疾病、血管痉挛和动脉硬化；中枢神经系统疾病包括过食、抑郁、焦虑、抽搐、癫痫、痴呆、疼痛、酒精依赖以及因戒断药物而引起的戒断症状；代谢性疾病包括肥胖、糖尿病、激素紊乱、高胆固醇血症和高脂血症；性功能障碍和生殖功能障碍；消化系统疾病包括肠动力失调；呼吸系统疾病；炎症；或青光眼。
• Novel imidazoline compounds
  申请人：Sato Nagaaki

  公开号：US20060135559A1

  公开（公告）日：2006-06-22

  Compounds represented by the general formula (I): wherein Ar 1 and Ar 2 are each aryl or heteroaryl; R 1 is lower cycloalkyl, —Ar 3 , or a group of the general formula (a), (b) or (c): and R 2 and R 3 are each hydrogen, lower cycloalkyl, lower alkenyl, or optionally substituted lower alkyl (with the proviso that when R 2 and R 3 are simultaneously hydrogen, Ar 1 , Ar 2 and R 1 do not simultaneously represent unsubstituted phenyl). The compounds are useful as treating agents for various NPY-related diseases, for example, circulatory diseases including hypertension, kidney diseases, cardiac diseases, vasospasm and arteriosclerosis; central nervous system diseases including hyperphagia, depression, anxiety, convulsion, epilepsy, dementia, pain, alcohol dependence, and withdrawal symptoms due to abstinence from drugs; metabolic diseases including obesity, diabetes, hormonal disorders, hypercholesterolemia, and hyperlipidemia; sexual dysfunction and reproductive function disorders; digestive diseases including enterokinetic disorders; respiratory diseases; inflammation; or glaucoma.

  化合物的通式(I)表示为：其中Ar1和Ar2均为芳基或杂环芳基；R1为较低的环烷基，-Ar3，或通式(a)、(b)或(c)的一种基团：而R2和R3均为氢、较低的环烷基、较低的烯基或可选取代的较低烷基（前提是当R2和R3同时为氢时，Ar1、Ar2和R1不同时表示未取代的苯基）。这些化合物可用作治疗各种NPY相关疾病的治疗剂，例如循环系统疾病，包括高血压、肾脏疾病、心脏疾病、血管痉挛和动脉硬化；中枢神经系统疾病，包括过度进食、抑郁症、焦虑症、惊厥、癫痫、痴呆、疼痛、酒精依赖和戒断症状；代谢性疾病，包括肥胖、糖尿病、内分泌失调、高胆固醇血症和高脂血症；性功能障碍和生殖功能障碍；消化系统疾病，包括肠动力失调；呼吸系统疾病；炎症；或青光眼。
• NOVEL IMIDAZOLINE COMPOUNDS
  申请人：BANYU PHARMACEUTICAL CO., LTD.

  公开号：EP1264826A1

  公开（公告）日：2002-12-11

  Compounds represented by the general formula (I): wherein Ar1 and Ar2 are each aryl or heteroaryl; R1 is lower cycloalkyl, -Ar3, or a group of the general formula (a), (b) or (c): or and R2 and R3 are each hydrogen, lower cycloalkyl, lower alkenyl, or optionally substituted lower alkyl (with the proviso that when R2 and R3 are simultaneously hydrogen, Ar1, Ar2 and R1 do not simultaneously represent unsubstituted phenyl). The compounds are useful as treating agents for various NPY-related diseases, for example, circulatory diseases including hypertension, kidney diseases, cardiac diseases, vasospasm and arteriosclerosis; central nervous system diseases including hyperphagia, depression, anxiety, convulsion, epilepsy, dementia, pain, alcohol dependence, and withdrawal symptoms due to abstinence from drugs; metabolic diseases including obesity, diabetes, hormonal disorders, hypercholesterolemia, and hyperlipidemia; sexual dysfunction and reproductive function disorders; digestive diseases including enterokinetic disorders; respiratory diseases; inflammation; or glaucoma.

  通式 (I) 所代表的化合物： 其中 Ar1 和 Ar2 分别是芳基或杂芳基；R1 是低级环烷基、-Ar3 或通式 (a)、(b) 或 (c) 的基团： 或 以及 R2 和 R3 各为氢、低级环烷基、低级烯基或任选取代的低级烷基（但当 R2 和 R3 同时为氢时，Ar1、Ar2 和 R1 不能同时代表未取代的苯基）。这些化合物可用于治疗各种与 NPY 相关的疾病，例如循环系统疾病，包括高血压、肾脏疾病、心脏病、血管痉挛和动脉硬化；中枢神经系统疾病，包括食欲亢进、抑郁、焦虑、抽搐、癫痫、痴呆、疼痛、酒精依赖和戒毒引起的戒断症状；代谢性疾病，包括肥胖症、糖尿病、内分泌紊乱、高胆固醇血症和高脂血症；性功能障碍和生殖功能障碍；消化系统疾病，包括肠动力障碍；呼吸系统疾病；炎症；或青光眼。
• N-SUBSTITUTED-2-OXODIHYDROPYRIDINE DERIVATIVES AS NPY ANTAGONISTS
  申请人：BANYU PHARMACEUTICAL CO., LTD.

  公开号：EP1546133B1

  公开（公告）日：2010-03-17