S-(-)-2-[N-(trifluoroacetyl)amino]-1-(2,5-dimethoxy-4-bromophenyl)-1-propanone | 677277-64-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: S-(-)-2-[N-(trifluoroacetyl)amino]-1-(2,5-dimethoxy-4-bromophenyl)-1-propanone
• 英文别名: (S)-(-)-2-[N-(Trifluoroacetyl)amino]-1-(2,5-dimethoxy-4-bromophenyl)-1-propanone；N-[(2S)-1-(4-bromo-2,5-dimethoxyphenyl)-1-oxopropan-2-yl]-2,2,2-trifluoroacetamide
• CAS: 677277-64-4
• 化学式: C₁₃H₁₃BrF₃NO₄
• 分子量: 384.15
• InChiKey: GGOVTXYKMUNIEC-LURJTMIESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  S-(-)-2-[N-(trifluoroacetyl)amino]-1-(2,5-dimethoxy-4-bromophenyl)-1-propanone 在 二甲基苯基硅烷 、 乙酸酐 、 potassium carbonate 、 三氟乙酸 作用下， 以 甲醇 为溶剂， 反应 6.0h， 生成 (1S,2S)-2-Amino-1-(4-bromo-2,5-dimethoxy-phenyl)-propan-1-ol
  参考文献：
  名称：

  β-Oxygenated Analogues of the 5-HT_2A Serotonin Receptor Agonist 1-(4-Bromo-2,5-dimethoxyphenyl)-2-aminopropane

  摘要：

  Activation of 5-HT2A serotonin receptors represents a novel approach to lowering intraocular pressure. Because 5-HT2A serotonin receptor agonists might also produce undesirable central effects should sufficient quantities enter the brain, attempts were made to identify 5-HT2A serotonin receptor agonists with reduced propensity to penetrate the blood-brain barrier. 1-(4Bromo-2,5-dimethoxyphenyl)-2-aminopropan-1-oI (6), an analogue of the 5-HT2A serotonin receptor agonist 1-(4-bromo-2,5-dimethoxyphenyl)-2-aminopropane (DOB; 1a) bearing a benzylic hydroxyl group, was identified as a candidate structure. Of the four optical isomers of 6, the 1R,2R-isomer (6d; K-i = 0.5 nM) was found to bind at 5-HT2A receptors with an affinity similar to that of R(-)DOB (Ki = 0.2 nM). Like R(-)DOB, 6d behaved as a partial agonist (efficacy ca. 50%) in a 5-HT2-mediated calcium mobilization assay. However, in an in vivo test of central action (i.e., stimulus generalization with rats as subjects), 6d was > 15 times less potent than R(-)DOB. O-Methylation of 6d (i.e., 7d; 5-HT2A K-i = 0.3 nM) resulted in an agent that behaved as a full (93% efficacy) agonist. Intraocular administration of 300,mug of 6d and 7d to ocular hypertensive monkeys was shown to reduce intraocular pressure by 20-27%. Given the route of administration (i.e., topical), and concentrations necessary to reduce intraocular pressure, compounds such as 6d should demonstrate minimal central effects at potentially useful therapeutic doses and offer useful leads for further development.

  DOI：

  10.1021/jm040082s
• 作为产物：
  描述：

  N-(trifluoroacetyl)-L-alanine 在 吡啶 、 草酰氯 、 四氯化钛 作用下， 以 二氯甲烷 为溶剂， 反应 62.0h， 生成 S-(-)-2-[N-(trifluoroacetyl)amino]-1-(2,5-dimethoxy-4-bromophenyl)-1-propanone
  参考文献：
  名称：

  β-Oxygenated Analogues of the 5-HT_2A Serotonin Receptor Agonist 1-(4-Bromo-2,5-dimethoxyphenyl)-2-aminopropane

  摘要：

  Activation of 5-HT2A serotonin receptors represents a novel approach to lowering intraocular pressure. Because 5-HT2A serotonin receptor agonists might also produce undesirable central effects should sufficient quantities enter the brain, attempts were made to identify 5-HT2A serotonin receptor agonists with reduced propensity to penetrate the blood-brain barrier. 1-(4Bromo-2,5-dimethoxyphenyl)-2-aminopropan-1-oI (6), an analogue of the 5-HT2A serotonin receptor agonist 1-(4-bromo-2,5-dimethoxyphenyl)-2-aminopropane (DOB; 1a) bearing a benzylic hydroxyl group, was identified as a candidate structure. Of the four optical isomers of 6, the 1R,2R-isomer (6d; K-i = 0.5 nM) was found to bind at 5-HT2A receptors with an affinity similar to that of R(-)DOB (Ki = 0.2 nM). Like R(-)DOB, 6d behaved as a partial agonist (efficacy ca. 50%) in a 5-HT2-mediated calcium mobilization assay. However, in an in vivo test of central action (i.e., stimulus generalization with rats as subjects), 6d was > 15 times less potent than R(-)DOB. O-Methylation of 6d (i.e., 7d; 5-HT2A K-i = 0.3 nM) resulted in an agent that behaved as a full (93% efficacy) agonist. Intraocular administration of 300,mug of 6d and 7d to ocular hypertensive monkeys was shown to reduce intraocular pressure by 20-27%. Given the route of administration (i.e., topical), and concentrations necessary to reduce intraocular pressure, compounds such as 6d should demonstrate minimal central effects at potentially useful therapeutic doses and offer useful leads for further development.

  DOI：

  10.1021/jm040082s

文献信息

• Beta-hydroxyphenylalkylamines and their use for treating glaucoma
  申请人：Glennon A. Richard

  公开号：US20060106106A1

  公开（公告）日：2006-05-18

  β-hydroxyphenylalkylamines and their use for lowering and controlling ocular hypertension and treating glaucoma are disclosed.

  本发明揭示了β-羟基苯基烷胺及其用于降低和控制眼压和治疗青光眼的用途。
• BETA-HYDROXYPHENYLALDYLAMINES AND THEIR USE FOR TREATING GLAUCOMA
  申请人：Virginia Commonwealth University

  公开号：EP1558238A2

  公开（公告）日：2005-08-03
• EP1558238A4
  申请人：——

  公开号：EP1558238A4

  公开（公告）日：2006-08-30
• [EN] beta-HYDROXYPHENYLALDYLAMINES AND THEIR USE FOR TREATING GLAUCOMA<br/>[FR] 20040408See references of EP 1558238A4
  申请人：UNIV VIRGINIA COMMONWEALTH

  公开号：WO2004028451A2

  公开（公告）日：2004-04-08

  β-hydroxyphenylalkylamines and their use for lowering and controlling ocular hypertension and treating glaucoma are disclosed.
• β-Oxygenated Analogues of the 5-HT_2A Serotonin Receptor Agonist 1-(4-Bromo-2,5-dimethoxyphenyl)-2-aminopropane
  作者：Richard A. Glennon、Mikhail L. Bondarev、Nantaka Khorana、Richard Young、Jesse A. May、Mark R. Hellberg、Marsha A. McLaughlin、Najam A. Sharif

  DOI：10.1021/jm040082s

  日期：2004.11.1

  Activation of 5-HT2A serotonin receptors represents a novel approach to lowering intraocular pressure. Because 5-HT2A serotonin receptor agonists might also produce undesirable central effects should sufficient quantities enter the brain, attempts were made to identify 5-HT2A serotonin receptor agonists with reduced propensity to penetrate the blood-brain barrier. 1-(4Bromo-2,5-dimethoxyphenyl)-2-aminopropan-1-oI (6), an analogue of the 5-HT2A serotonin receptor agonist 1-(4-bromo-2,5-dimethoxyphenyl)-2-aminopropane (DOB; 1a) bearing a benzylic hydroxyl group, was identified as a candidate structure. Of the four optical isomers of 6, the 1R,2R-isomer (6d; K-i = 0.5 nM) was found to bind at 5-HT2A receptors with an affinity similar to that of R(-)DOB (Ki = 0.2 nM). Like R(-)DOB, 6d behaved as a partial agonist (efficacy ca. 50%) in a 5-HT2-mediated calcium mobilization assay. However, in an in vivo test of central action (i.e., stimulus generalization with rats as subjects), 6d was > 15 times less potent than R(-)DOB. O-Methylation of 6d (i.e., 7d; 5-HT2A K-i = 0.3 nM) resulted in an agent that behaved as a full (93% efficacy) agonist. Intraocular administration of 300,mug of 6d and 7d to ocular hypertensive monkeys was shown to reduce intraocular pressure by 20-27%. Given the route of administration (i.e., topical), and concentrations necessary to reduce intraocular pressure, compounds such as 6d should demonstrate minimal central effects at potentially useful therapeutic doses and offer useful leads for further development.