1-(4-fluorophenyl)piperidin-4-ol | 681481-96-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 1-(4-fluorophenyl)piperidin-4-ol
• CAS: 681481-96-9
• 化学式: C₁₁H₁₄FNO
• 分子量: 195.237
• InChiKey: ROULXCNJEQELQP-UHFFFAOYSA-N

物化性质

• 沸点：
  330.5±37.0 °C(Predicted)
• 密度：
  1.198±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  23.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(4-fluorophenyl)piperidin-4-ol 在 吡啶 、 4-二甲氨基吡啶 、 caesium carbonate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 32.0h， 生成
  参考文献：
  名称：

  Discovery of Potent and Orally Bioavailable Dihydropyrazole GPR40 Agonists

  摘要：

  G protein-coupled receptor 40 (GPR40) has become an attractive target for the treatment of diabetes since it was shown clinically to promote,glucose-stimulated insulin secretion. Herein, we report our efforts to develop highly I selectiveand potent GPR40 agonists with a dual mechanism of action, promoting both ghicose-clependent insulin and incretin secretion. Employing strategies to increase fiolarity and the ratio of sp(3)/sP(2) character of the chemotype, we identified BMS-986118 (compound 4), which showed potent and selective GPR40 agonist activity in vitro. In vivo, compound 4 demonstrated insulinotropic efficacy and GLP-1 secretory effects resulting in improved glucose control in acute animal models.

  DOI：

  10.1021/acs.jmedchem.7b00982
• 作为产物：
  描述：

  4-羟基哌啶 、 对溴氟苯 在 copper(l) iodide 、 potassium carbonate 、 L-脯氨酸 作用下， 以 二甲基亚砜 为溶剂， 反应 16.0h， 以26%的产率得到1-(4-fluorophenyl)piperidin-4-ol
  参考文献：
  名称：

  [EN] INHIBITORS OF DIHYDROCERAMIDE DESATURASE FOR TREATING DISEASE
  [FR] INHIBITEURS DE LA DIHYDROCÉRAMIDE DÉSATURASE POUR LE TRAITEMENT D'UNE MALADIE

  摘要：

  本文披露了二氢神经酰胺脱饱和酶1（Des1）抑制剂化合物和组合物，这些化合物和组合物在治疗疾病方面非常有用，例如代谢紊乱，预期通过抑制Des1对患者具有治疗作用。还提供了在人类或动物受试者中抑制Des1活性的方法。

  公开号：

  WO2019140188A1

文献信息

• [EN] INHIBITORS OF DIHYDROCERAMIDE DESATURASE FOR TREATING DISEASE<br/>[FR] INHIBITEURS DE LA DIHYDROCÉRAMIDE DÉSATURASE POUR LE TRAITEMENT D'UNE MALADIE
  申请人：CENTAURUS THERAPEUTICS

  公开号：WO2019140188A1

  公开（公告）日：2019-07-18

  Disclosed herein are dihydroceramide desaturase 1 (Des1) inhibitor compounds and compositions, which are useful in the treatment of diseases, such as metabolic disorders, where inhibition of Des1 is expected to be therapeutic to a patient. Methods of inhibition of Des1 activity in a human or animal subject are also provided.

  本文披露了二氢神经酰胺脱饱和酶1（Des1）抑制剂化合物和组合物，这些化合物和组合物在治疗疾病方面非常有用，例如代谢紊乱，预期通过抑制Des1对患者具有治疗作用。还提供了在人类或动物受试者中抑制Des1活性的方法。
• 2,3-Dihydro-6-nitroimidazo[2,1-b]oxazoles
  申请人：Tsubouchi Hidetsugu

  公开号：US20060094767A1

  公开（公告）日：2006-05-04

  The present invention provides a 2,3-dihydro-6-nitroimidazo[2,1-b]oxazole compound represented by the following general formula: wherein R 1 represents a hydrogen atom or C1-C6 alkyl group, n represents an integer of 0 to 6, R 2 represents a group —OR 3 or the like, and R 3 represents a hydrogen atom, C1-C6 alkyl group or the like, or R 1 and —(CH 2 ) n R 2 may bind to each other together with carbon atoms adjacent thereto through nitrogen atoms so as to form a spiro ring represented by the general formula (H): wherein R 41 is hydrogen, C1-C6 alkyl group or the like. The present compound has an excellent bactericidal action against Mycobacterium tuberculosis , multi-drug-resistant Mycobacterium tuberculosis , and atypical acid-fast bacteria.

  本发明提供了一种2,3-二氢-6-硝基咪唑并[2,1-b]噁唑化合物，其通式如下：其中，R1代表氢原子或C1-C6烷基，n代表0到6的整数，R2代表—OR3或类似的基团，R3代表氢原子、C1-C6烷基或类似的基团，或者R1和—(CH2)nR2可以通过相邻的碳原子通过氮原子结合在一起形成一个螺环，其通式为（H）：其中，R41为氢、C1-C6烷基或类似的基团。该化合物对结核分枝杆菌、多药耐药结核分枝杆菌和非典型酸性快速细菌具有优异的杀菌作用。
• 2,3-DIHYDRO-6-NITROIMIDAZO 2,1-b OXAZOLES
  申请人：OTSUKA PHARMACEUTICAL CO., LTD.

  公开号：EP1555267A1

  公开（公告）日：2005-07-20

  The present invention provides a 2,3-dihydro-6-nitroimidazo[2,1-b]oxazole compound represented by the following general formula: wherein R1 represents a hydrogen atom or C1-C6 alkyl group, n represents an integer of 0 to 6, R2 represents a group -OR3 or the like, and R3 represents a hydrogen atom, C1-C6 alkyl group or the like, or R1 and -(CH2)nR2 may bind to each other together with carbon atoms adjacent thereto through nitrogen atoms so as to form a spiro ring represented by the general formula (H): wherein R41 is hydrogen, C1-C6 alkyl group or the like. The present compound has an excellent bactericidal action against Mycobacterium tuberculosis, multi-drug-resistant Mycobacterium tuberculosis, and a typical acid-fast bacteria.

  本发明提供了由以下通式代表的 2，3-二氢-6-硝基咪唑并[2，1-b]恶唑化合物： 其中R1代表氢原子或C1-C6烷基，n代表0至6的整数，R2代表基团-OR3或类似基团，R3代表氢原子、C1-C6烷基或类似基团，或者R1和-(CH2)nR2可以通过氮原子与相邻的碳原子相互结合，从而形成通式(H)代表的螺环： 其中 R41 为氢、C1-C6 烷基或类似基团。本化合物对结核分枝杆菌、多重耐药结核分枝杆菌和典型的耐酸细菌有很好的杀菌作用。
• 2,3-dihydro-6-nitroimidazo[2,1-b]oxazoles compound
  申请人：OTSUKA PHARMACEUTICAL CO., LTD.

  公开号：EP2570418A2

  公开（公告）日：2013-03-20

  The present invention provides a 2,3-dihydro-6-nitroimidazo[2,1-b]oxazole compound represented by the following general formula: wherein R1 represents a hydrogen atom or C1-C6 alkyl group, n represents an integer of 0 to 6, R2 represents a group -OR3 or the like, and R3 represents a hydrogen atom, C1-C6 alkyl group or the like, or R1 and -(CH2)nR2 may bind to each other together with carbon atoms adjacent thereto through nitrogen atoms so as to form a spiro ring represented by the general formula (H): wherein R41 is hydrogen, C1-C6 alkyl group or the like. The present compound has an excellent bactericidal action against Mycobacterium tuberculosis, multi-drug-resistant Mycobacterium tuberculosis, and atypical acid-fast bacteria.

  本发明提供了一种由以下通式表示的 2,3-二氢-6-硝基咪唑并[2,1-b]恶唑化合物： 其中R1代表氢原子或C1-C6烷基，n代表0至6的整数，R2代表基团-OR3或类似基团，R3代表氢原子、C1-C6烷基或类似基团，或者R1和-(CH2)nR2可以通过氮原子与相邻的碳原子相互结合，从而形成通式(H)代表的螺环： 其中 R41 为氢、C1-C6 烷基或类似基团。本化合物对结核分枝杆菌、多重耐药结核分枝杆菌和非典型耐酸菌有很好的杀菌作用。
• 7-Substituted 2-Nitro-5,6-dihydroimidazo[2,1-<i>b</i>][1,3]oxazines: Novel Antitubercular Agents Lead to a New Preclinical Candidate for Visceral Leishmaniasis
  作者：Andrew M. Thompson、Patrick D. O’Connor、Andrew J. Marshall、Vanessa Yardley、Louis Maes、Suman Gupta、Delphine Launay、Stephanie Braillard、Eric Chatelain、Scott G. Franzblau、Baojie Wan、Yuehong Wang、Zhenkun Ma、Christopher B. Cooper、William A. Denny

  DOI：10.1021/acs.jmedchem.7b00034

  日期：2017.5.25

  Within a backup program for the clinical investigational agent pretomanid (PA-824), scaffold hopping from delamanid inspired the discovery of a novel class of potent antitubercular agents that unexpectedly possessed notable utility against the kinetoplastid disease visceral leishmaniasis (VL). Following the identification of delamanid analogue DNDI-VL-2098 as a VL preclinical candidate, this structurally related 7 substituted 2-nitro-5,6-dihydroimidazo [2,1-b][1,3]oxazine class was further explored, seeking efficacious backup compounds with improved solubility and safety. Commencing with a biphenyl lead, bioisosteres formed by replacing one phenyl by pyridine or pyrimidine showed improved solubility and potency, whereas more hydrophilic side chains reduced VL activity. In a Leishmania donovani mouse model, two racemic phenylpyridines (71 and 93) were superior, with the former providing >99% inhibition at 12.5 mg/kg (b.i.d., orally) in the Leishmania infantum hamster model. Overall, the 7R enantiomer of 71 (79) displayed more optimal efficacy, pharmacokinetics, and safety, leading to its selection as the preferred development candidate.