benzyl (3S,4R)-3-fluoro-4-hydroxypiperidine-1-carboxylate | 1147112-65-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: benzyl (3S,4R)-3-fluoro-4-hydroxypiperidine-1-carboxylate
• 英文别名: cis-1-Cbz-3-fluoro-4-hydroxypiperidine
• CAS: 1147112-65-9
• 化学式: C₁₃H₁₆FNO₃
• 分子量: 253.273
• InChiKey: RKRKELORNFODMN-NWDGAFQWSA-N

物化性质

• 沸点：
  393.4±42.0 °C(Predicted)
• 密度：
  1.26±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  benzyl (3S,4R)-3-fluoro-4-hydroxypiperidine-1-carboxylate 在 palladium 10% on activated carbon 、 氢气 、 potassium carbonate 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 二甲基亚砜 为溶剂， 100.0 ℃ 、101.33 kPa 条件下， 反应 25.0h， 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：

  3-氟-1-甲基哌啶-4-酮 在 L-Selectride 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以90.476%的产率得到
  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

文献信息

• 6,7-DIHYDRO-5H-PYRROLO[3,4-B]PYRIDIN-5-ONE ALLOSTERIC MODULATORS OF THE M4 MUSCARINIC ACETYLCHOLINE RECEPTOR
  申请人：BAO JIANMING

  公开号：US20170183342A1

  公开（公告）日：2017-06-29

  The present invention is directed to 6,7-dihydro-5H-pyrrolo[3,4-b]pyridine-5-one compounds which are allosteric modulators of the M4 muscarinic acetylcholine receptor. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which M4 muscarinic acetylcholine receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which M4 muscarinic acetylcholine receptors are involved.

  本发明涉及6,7-二氢-5H-吡咯[3,4-b]吡啶-5-酮化合物，这些化合物是M4毒蕈碱乙酰胆碱受体的变构调节剂。本发明还涉及在本申请中描述的化合物在潜在治疗或预防神经和精神障碍和疾病中的应用，其中涉及M4毒蕈碱乙酰胆碱受体。本发明还涉及包含这些化合物的组合物。本发明还涉及这些组合物在潜在预防或治疗涉及M4毒蕈碱乙酰胆碱受体的疾病的应用。
• [EN] INHIBITORS OF RENAL OUTER MEDULLARY POTASSIUM CHANNEL<br/>[FR] INHIBITEURS DU CANAL POTASSIQUE MÉDULLAIRE EXTERNE RÉNAL
  申请人：MERCK SHARP & DOHME

  公开号：WO2016127358A1

  公开（公告）日：2016-08-18

  Disclosed are compounds of Formula I and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.

  公开的是Formula I的化合物及其药学上可接受的盐，这些化合物是ROMK (Kir1.1)通道的抑制剂。这些化合物可用作利尿剂和/或钠利尿剂，并用于治疗和预防包括高血压、心力衰竭和慢性肾脏疾病在内的心血管疾病以及与过多盐分和水分潴留有关的疾病。
• [EN] PHENYL-HETEROARYL DERIVATIVES AND METHODS OF USE THEREOF<br/>[FR] DÉRIVÉS DE PHÉNYL-HÉTÉROARYLE ET PROCÉDÉS D'UTILISATION DE CEUX-CI
  申请人：TRANSTECH PHARMA INC

  公开号：WO2011103091A1

  公开（公告）日：2011-08-25

  The present invention provides phenyl-heteroaryl derivatives of Formula (I) and pharmaceutically acceptable salts thereof. These compounds are useful in the treatment of RAGE-mediated diseases such as Alzheimer's Disease. The present invention further relates to methods for the preparation of compounds of Formula (I) and pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising such compounds, and the use of such compounds and/or pharmaceutical compositions in treating RAGE-mediated diseases.

  本发明提供了式（I）的苯基-杂环芳基衍生物及其药学上可接受的盐。这些化合物在治疗RAGE介导的疾病，如阿尔茨海默病方面是有用的。本发明还涉及制备式（I）化合物及其药学上可接受的盐的方法，包括含有这些化合物的药物组合物，以及在治疗RAGE介导的疾病中使用这些化合物和/或药物组合物的用途。
• [EN] HETEROARYL PIPERIDINE ETHER ALLOSTERIC MODULATORS OF THE M4 MUSCARINIC ACETYLCHOLINE RECEPTOR<br/>[FR] MODULATEURS ALLOSTÉRIQUES D'ÉTHER DE PIPÉRIDINE D'HÉTÉROARYLE DU RÉCEPTEUR DE L'ACÉTYLCHOLINE MUSCARINIQUE M4
  申请人：MERCK SHARP & DOHME

  公开号：WO2018118734A1

  公开（公告）日：2018-06-28

  The present invention is directed to heteroarylpiperidine ether compounds which are allosteric modulators of the M4 muscarinic acetylcholine receptor. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which M4 muscarinic acetylcholine receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which M4 muscarinic acetylcholine receptors are involved.

  本发明涉及异芳基哌啶醚化合物，其为M4肌氨酸乙酰胆碱受体的变构调节剂。本发明还涉及所述化合物在潜在的治疗或预防M4肌氨酸乙酰胆碱受体参与的神经和精神障碍和疾病中的用途。本发明还涉及包含这些化合物的组合物。本发明还涉及这些组合物在潜在的预防或治疗M4肌氨酸乙酰胆碱受体参与的疾病中的用途。
• [EN] N-(HETEROARYL) QUINAZOLIN-2-AMINE DERIVATIVES AS LRRK2 INHIBITORS, PHARMACEUTICAL COMPOSITIONS, AND USES THEREOF<br/>[FR] DÉRIVÉS DE N-HÉTÉROARYL INDAZOLE UTILISÉS EN TANT QU'INHIBITEURS DE LRRK2, COMPOSITIONS PHARMACEUTIQUES ET LEURS UTILISATIONS
  申请人：MERCK SHARP & DOHME

  公开号：WO2021080929A1

  公开（公告）日：2021-04-29

  The present invention is directed to substituted certain N-(heteroaryl)quinazolin-2-amine derivatives of Formula (I): and pharmaceutically acceptable salts thereof, wherein J, R3, and R4, are as defined herein, which are potent inhibitors of LRRK2 kinase and may be useful in the treatment or prevention of diseases in which the LRRK2 kinase is involved, such as Parkinson's Disease and other diseases and disorders described herein. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of diseases, such as Parkinson's disease, in which LRRK-2 kinase is involved.

  本发明涉及Formula (I)中的某些取代N-(杂环芳基)喹唑啉-2-胺衍生物及其药学上可接受的盐，其中J、R3和R4如本文所定义，这些化合物是LRRK2激酶的有效抑制剂，可能在治疗或预防LRRK2激酶参与的疾病中发挥作用，如帕金森病和本文所述的其他疾病和疾病。该发明还涉及包含这些化合物的药物组合物以及在预防或治疗帕金森病等LRRK-2激酶参与的疾病中使用这些化合物和组合物。