(S)-N-(3-(2-amino-4-methyl-5,6-dihydro-4H-1,3-oxazin-4-yl)-4-fluorophenyl)-5-chloropicolinamide | 1310373-43-3

• 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: (S)-N-(3-(2-amino-4-methyl-5,6-dihydro-4H-1,3-oxazin-4-yl)-4-fluorophenyl)-5-chloropicolinamide
• 英文别名: 5-chloro-pyridine-2-carboxylic acid [3-((S)-2-amino-4-methyl-5,6-dihydro-4H-[1,3]oxazin-4-yl)-4-fluoro-phenyl]-amide；N-[3-[(4S)-2-amino-4-methyl-5,6-dihydro-1,3-oxazin-4-yl]-4-fluorophenyl]-5-chloropyridine-2-carboxamide
• CAS: 1310373-43-3
• 化学式: C₁₇H₁₆ClFN₄O₂
• 分子量: 362.791
• InChiKey: HIFMUVLULGJLTJ-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  89.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (R)-2-methyl-propane-2-sulfinic acid [(S)-1-(2-fluoro-5-nitro-phenyl)-3-hydroxy-1-methyl-propyl]-amide 在 盐酸 、 palladium 10% on activated carbon 、 氢气 、 4-(4,6-二甲氧基三嗪-2-基)-4-甲基吗啉盐酸盐 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醇 为溶剂， 95.0 ℃ 、101.33 kPa 条件下， 反应 16.5h， 生成 (S)-N-(3-(2-amino-4-methyl-5,6-dihydro-4H-1,3-oxazin-4-yl)-4-fluorophenyl)-5-chloropicolinamide
  参考文献：
  名称：

  BACE1 inhibitors: A head group scan on a series of amides

  摘要：

  A series of amides bearing a variety of amidine head groups was investigated as BACE1 inhibitors with respect to inhibitory activity in a BACE1 enzyme as well as a cell-based assay. Determination of their basicity as well as their properties as substrates of P-glycoprotein revealed that a 2-amino-1,3-oxazine head group would be a suitable starting point for further development of brain penetrating compounds for potential Alzheimer's disease treatment. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.05.003

文献信息

• [EN] AMINO OXAZINE DERIVATIVES<br/>[FR] DÉRIVÉS D'AMINO-OXAZINE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2011070029A1

  公开（公告）日：2011-06-16

  This invention relates to 5,6-dihydro-4H-[1,3]oxazin-2-ylamine compounds of the formula (I) wherein R1 to R5 are as defined in the description and in the claims, as well as pharmaceutically acceptable salts thereof. These compounds are BACE2 inhibitors and can be used as medicaments for the treatment or prevention of diseases such as diabetes.

  这项发明涉及式(I)的5,6-二氢-4H-[1,3]噁嗪-2-胺类化合物，其中R1至R5如描述和权利要求中定义的那样，以及其药用盐。这些化合物是BACE2抑制剂，可用作治疗或预防糖尿病等疾病的药物。
• AMINO OXAZINE DERIVATIVES
  申请人：Banner David

  公开号：US20110144098A1

  公开（公告）日：2011-06-16

  This invention relates to 5,6-dihydro-4H-[1,3]oxazin-2-ylamine compounds of the formula wherein R 1 to R 5 are as defined in the description and in the claims, as well as pharmaceutically acceptable salts thereof. These compounds are BACE2 inhibitors and can be used as medicaments for the treatment or prevention of diseases such as diabetes.

  这项发明涉及式中R1至R5如描述和索赔中所定义的5,6-二氢-4H-[1,3]噁唑啉-2-胺化合物，以及其药学上可接受的盐。这些化合物是BACE2抑制剂，可用作治疗或预防糖尿病等疾病的药物。
• Amino oxazine derivatives
  申请人：Hoffmann-La Roche Inc.

  公开号：US07964594B1

  公开（公告）日：2011-06-21

  This invention relates to 5,6-dihydro-4H-[1,3]oxazin-2-ylamine compounds of the formula wherein R1 to R5 are as defined in the description and in the claims, as well as pharmaceutically acceptable salts thereof. These compounds are BACE2 inhibitors and can be used as medicaments for the treatment or prevention of diseases such as diabetes.

  本发明涉及式中R1至R5如描述和权利要求中定义的5,6-二氢-4H-[1,3]噁唑-2-胺化合物，以及其药学上可接受的盐。这些化合物是BACE2抑制剂，可用作治疗或预防糖尿病等疾病的药物。
• BACE1 inhibitors: A head group scan on a series of amides
  作者：Thomas J. Woltering、Wolfgang Wostl、Hans Hilpert、Mark Rogers-Evans、Emmanuel Pinard、Alexander Mayweg、Martin Göbel、David W. Banner、Jörg Benz、Massimiliano Travagli、Martina Pollastrini、Guido Marconi、Emanuele Gabellieri、Wolfgang Guba、Harald Mauser、Matteo Andreini、Helmut Jacobsen、Eoin Power、Robert Narquizian

  DOI：10.1016/j.bmcl.2013.05.003

  日期：2013.7

  A series of amides bearing a variety of amidine head groups was investigated as BACE1 inhibitors with respect to inhibitory activity in a BACE1 enzyme as well as a cell-based assay. Determination of their basicity as well as their properties as substrates of P-glycoprotein revealed that a 2-amino-1,3-oxazine head group would be a suitable starting point for further development of brain penetrating compounds for potential Alzheimer's disease treatment. (C) 2013 Elsevier Ltd. All rights reserved.
• OXAZINE DERIVATIVES
  申请人：Shionogi & Co., Ltd.

  公开号：US20150166491A1

  公开（公告）日：2015-06-18

  The present invention provides, for example, a compound mentioned below as a medicament for treating or preventing the diseases induced by production, secretion or deposition of amyloid-β proteins. A compound of the formula (I): wherein R 1 , R 2a , R 2b , R 3 , R 4a , R 4b , ring A and the dashed lines are defined in the specification, its pharmaceutically acceptable salt or a solvate thereof.