(2R)-2-amino-2-(5-bromo-2-fluorophenyl)-2-cyclopropyl-acetic acid hydrochloride | 1352420-11-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2R)-2-amino-2-(5-bromo-2-fluorophenyl)-2-cyclopropyl-acetic acid hydrochloride
• CAS: 1352420-11-1
• 化学式: C₁₁H₁₁BrFNO₂*ClH
• 分子量: 324.577
• InChiKey: OFOIOUDCDQDHLV-RFVHGSKJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.66
• 重原子数：
  17.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  63.32
• 氢给体数：
  2.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  (2R)-2-amino-2-(5-bromo-2-fluorophenyl)-2-cyclopropyl-acetic acid hydrochloride 在 tetraphosphorus decasulfide 、 二乙胺基三氟化硫 、 sodium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 10.33h， 生成 (5R,6R)-5-(5-bromo-2-fluorophenyl)-5-cyclopropyl-6-fluoromorpholine-3-thione
  参考文献：
  名称：

  1,4-Oxazine β-Secretase 1 (BACE1) Inhibitors: From Hit Generation to Orally Bioavailable Brain Penetrant Leads

  摘要：

  1,4-Oxazines are presented, which show good in vitro inhibition in enzymatic and cellular BACE1 assays. We describe lead optimization focused on reducing the amidine pK(a) while optimizing interactions in the BACE1 active site. Our strategy permitted modulation of properties such as permeation and especially P-glycoprotein efflux. This led to compounds which were orally bioavailable, centrally active, and which demonstrated robust lowering of brain and CSF A beta levels, respectively, in mouse and dog models. The amyloid lowering potential of these molecules makes them valuable leads in the search for new BACE1 inhibitors for the treatment of Alzheimer's disease.

  DOI：

  10.1021/acs.jmedchem.5b01101
• 作为产物：
  描述：

  (5-bromo-2-fluorophenyl)(oxo)acetic acid 在 titanium(IV) isopropylate 、 盐酸 、 氯化亚砜 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 为溶剂， 反应 47.5h， 生成 (2R)-2-amino-2-(5-bromo-2-fluorophenyl)-2-cyclopropyl-acetic acid hydrochloride
  参考文献：
  名称：

  1,4-Oxazine β-Secretase 1 (BACE1) Inhibitors: From Hit Generation to Orally Bioavailable Brain Penetrant Leads

  摘要：

  1,4-Oxazines are presented, which show good in vitro inhibition in enzymatic and cellular BACE1 assays. We describe lead optimization focused on reducing the amidine pK(a) while optimizing interactions in the BACE1 active site. Our strategy permitted modulation of properties such as permeation and especially P-glycoprotein efflux. This led to compounds which were orally bioavailable, centrally active, and which demonstrated robust lowering of brain and CSF A beta levels, respectively, in mouse and dog models. The amyloid lowering potential of these molecules makes them valuable leads in the search for new BACE1 inhibitors for the treatment of Alzheimer's disease.

  DOI：

  10.1021/acs.jmedchem.5b01101