(S)-(-)-1-chloro-3-(4-iodo-2-methylphenoxy)-3-phenylpropane | 146304-03-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (S)-(-)-1-chloro-3-(4-iodo-2-methylphenoxy)-3-phenylpropane
• 英文别名: [S]-(-)-1-chloro-3-phenyl-3-(4-iodo-2-methylphenoxy)propane；1-[(1S)-3-chloro-1-phenylpropoxy]-4-iodo-2-methylbenzene
• CAS: 146304-03-2
• 化学式: C₁₆H₁₆ClIO
• 分子量: 386.66
• InChiKey: BJGHHFOFZSUCFN-INIZCTEOSA-N

物化性质

• 沸点：
  437.2±45.0 °C(predicted)
• 密度：
  1.500±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (S)-(-)-1-chloro-3-(4-iodo-2-methylphenoxy)-3-phenylpropane 、 甲胺 以 乙醇 、 水 为溶剂， 反应 3.0h， 以48%的产率得到(S)-N-methyl-3-(4-iodo-2-methylphenoxy)-3-phenylpropanamine
  参考文献：
  名称：

  Iodinated tomoxetine derivatives as selective ligands for serotonin and norepinephrine uptake sites

  摘要：

  In order to develop selective radioactive ligands for the study of presynaptic monoamine uptake sites, iodinated derivatives of tomoxetine were synthesized and evaluated in radioligand binding assays. Iodotomoxetine derivatives showed high affinity for serotonin (5-HT) uptake sites using a rat cortical membrane preparation. Compound 1R,(R)-(-)-N-methyl-3-(4-iodo-2-methylphenoxy)-3-phenylpropanamine, was the most potent and showed high stereoselectivity for 5-HT uptake sites (K(i), R isomer = 0.65 nM, S isomer = 13.9 nM). Changing the position of the methyl group or eliminating the methyl group at the phenoxy ring resulted in a loss of stereoselectivity. Substitution of the methyl group of tomoxetine with iodine gave the R and S isomers of N-methyl-3-(2-iodophenoxy)-3-phenylpropanamine 4R and 4S. These compounds displayed stereoselectivity for the norepinephrine (NE) (K(i) values = 0.24 and 9.35 nM for R and S isomers, respectively). The in vitro binding data suggest that 1R and 4R are potential radioiodinated ligands for pharmacological studies of 5-HT and NE uptake sites, respectively.

  DOI：

  10.1021/jm00101a029
• 作为产物：
  描述：

  4-碘-2-甲基苯酚 、 (R)-(+)-3-氯-1-苯基-1-丙醇 在 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 为溶剂， 生成 (S)-(-)-1-chloro-3-(4-iodo-2-methylphenoxy)-3-phenylpropane
  参考文献：
  名称：

  Iodinated tomoxetine derivatives as selective ligands for serotonin and norepinephrine uptake sites

  摘要：

  In order to develop selective radioactive ligands for the study of presynaptic monoamine uptake sites, iodinated derivatives of tomoxetine were synthesized and evaluated in radioligand binding assays. Iodotomoxetine derivatives showed high affinity for serotonin (5-HT) uptake sites using a rat cortical membrane preparation. Compound 1R,(R)-(-)-N-methyl-3-(4-iodo-2-methylphenoxy)-3-phenylpropanamine, was the most potent and showed high stereoselectivity for 5-HT uptake sites (K(i), R isomer = 0.65 nM, S isomer = 13.9 nM). Changing the position of the methyl group or eliminating the methyl group at the phenoxy ring resulted in a loss of stereoselectivity. Substitution of the methyl group of tomoxetine with iodine gave the R and S isomers of N-methyl-3-(2-iodophenoxy)-3-phenylpropanamine 4R and 4S. These compounds displayed stereoselectivity for the norepinephrine (NE) (K(i) values = 0.24 and 9.35 nM for R and S isomers, respectively). The in vitro binding data suggest that 1R and 4R are potential radioiodinated ligands for pharmacological studies of 5-HT and NE uptake sites, respectively.

  DOI：

  10.1021/jm00101a029
• 作为试剂：
  描述：

  (R)-(+)-3-氯-1-苯基-1-丙醇 、 4-碘-2-甲基苯酚 、 三苯基膦 、 N-ethoxycarbonyliminocarbamate 在 (S)-(-)-1-chloro-3-(4-iodo-2-methylphenoxy)-3-phenylpropane 作用下， 以 四氢呋喃 为溶剂， 反应 15.0h， 以gave 1.58 g (69%) of Compound 12 as a thick pale yellow liquid的产率得到(S)-(-)-1-chloro-3-(4-iodo-2-methylphenoxy)-3-phenylpropane
  参考文献：
  名称：

  Serotonin reuptake inhibitors for S.P.E.C.T. imaging

  摘要：

  本发明涉及一种新的CNS神经递质系统的化合物，特别是神经递质5-羟色胺，其化学式为##STR1##其中，U、V、W、X、Y和Z中的每一个独立地选择自氢、卤素、C.sub.1-C.sub.4烷基、C.sub.1-C.sub.4烷基上取代一个或多个卤素原子和羟基基团、C.sub.1-C.sub.4烷氧基、C.sub.1-C.sub.4烷氧基上取代一个或多个卤素原子和羟基基团、C.sub.1-C.sub.6杂环、C.sub.1-C.sub.4硫代烷基、NR.sub.3R.sub.4；--R.sub.5--A--R.sub.6；和--A--R.sub.7；CN；SO.sub.2R.sub.8；--NHCONH.sub.2；和C（O）NR.sub.3R.sub.4；其中，R.sub.1、R.sub.2、R.sub.3和R.sub.4中的每一个独立地选择自氢和C.sub.1-C.sub.4烷基；R.sub.5和R.sub.6中的每一个独立地为C.sub.1-C.sub.6烷基；R.sub.7选择自H、C.sub.1-C.sub.6烷基、C.sub.1-C.sub.6杂环或--A--R.sub.5；R.sub.8选择自C.sub.1-C.sub.4烷基和NR.sub.3R.sub.4；A选择自S、N和O；要求U、V、W、X、Y和Z中至少一个为卤素原子；以及其药学上可接受的盐。

  公开号：

  US05320825A1

文献信息

• US5320825A
  申请人：——

  公开号：US5320825A

  公开（公告）日：1994-06-14
• Iodinated tomoxetine derivatives as selective ligands for serotonin and norepinephrine uptake sites
  作者：Sumalee Chumpradit、Mei Ping Kung、Chitchanum Panyachotipun、Vichukorn Prapansiri、Catherine Foulon、Brian P. Brooks、Stephen A. Szabo、Shanaz Tejani-Butt、Alan Frazer、Hank F. Kung

  DOI：10.1021/jm00101a029

  日期：1992.11

  In order to develop selective radioactive ligands for the study of presynaptic monoamine uptake sites, iodinated derivatives of tomoxetine were synthesized and evaluated in radioligand binding assays. Iodotomoxetine derivatives showed high affinity for serotonin (5-HT) uptake sites using a rat cortical membrane preparation. Compound 1R,(R)-(-)-N-methyl-3-(4-iodo-2-methylphenoxy)-3-phenylpropanamine, was the most potent and showed high stereoselectivity for 5-HT uptake sites (K(i), R isomer = 0.65 nM, S isomer = 13.9 nM). Changing the position of the methyl group or eliminating the methyl group at the phenoxy ring resulted in a loss of stereoselectivity. Substitution of the methyl group of tomoxetine with iodine gave the R and S isomers of N-methyl-3-(2-iodophenoxy)-3-phenylpropanamine 4R and 4S. These compounds displayed stereoselectivity for the norepinephrine (NE) (K(i) values = 0.24 and 9.35 nM for R and S isomers, respectively). The in vitro binding data suggest that 1R and 4R are potential radioiodinated ligands for pharmacological studies of 5-HT and NE uptake sites, respectively.
• Serotonin reuptake inhibitors for S.P.E.C.T. imaging
  申请人：Trustees of the University of Pennsylvania

  公开号：US05320825A1

  公开（公告）日：1994-06-14

  Disclosed are novel compounds for CNS neurotransmitter systems, especially for the neurotransmitter serotonin, which have the formula ##STR1## where each of U, V, W, X, Y and Z is independently selected from the group consisting of hydrogen; halogen; C.sub.1 -C.sub.4 alkyl; C.sub.1 -C.sub.4 alkyl substituted with one or more moieties selected from halogen atoms and hydroxy groups; C.sub.1 -C.sub.4 alkoxy; C.sub.1 -C.sub.4 alkoxy substituted with one or more moieties selected from halogen atoms and hydroxy groups; C.sub.1 -C.sub.6 heterocycles; C.sub.1 -C.sub.4 thioalkyl; NR.sub.3 R.sub.4 ; --R.sub.5 --A --R.sub.6 ; and --A--R.sub.7 ; CN; SO.sub.2 R.sub.8 ; --NHCONH.sub.2 ; and C(O)NR.sub.3 R.sub.4 ; each of R.sub.1, R.sub.2, R.sub.3 and R.sub.4 is independently selected from the group consisting of hydrogen and C.sub.1 -C.sub.4 alkyl; each of R.sub.5 and R.sub.6 is independently a C.sub.1 -C.sub.6 alkyl; R.sub.7 is selected from the group consisting of H, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 heterocycles or --A--R.sub.5 ; R.sub.8 is selected from the group consisting of C.sub.1 -C.sub.4 alkyl and NR.sub.3 R.sub.4 ; A is selected from the group consisting of S, N and O; provided that at least one of U, V, W, X, Y and Z is a halogen atom; and pharmaceutically acceptable salts thereof.

  本发明涉及用于中枢神经系统神经递质，特别是神经递质血清素的新化合物，其化学式为##STR1##其中U、V、W、X、Y和Z中的每一个都独立地选自以下组：氢；卤素；C.sub.1-C.sub.4烷基；C.sub.1-C.sub.4烷基，其上取代有一个或多个从卤素原子和羟基中选择的基团；C.sub.1-C.sub.4烷氧基；C.sub.1-C.sub.4烷氧基，其上取代有一个或多个从卤素原子和羟基中选择的基团；C.sub.1-C.sub.6杂环；C.sub.1-C.sub.4硫代烷基；NR.sub.3R.sub.4；--R.sub.5--A--R.sub.6；和--A--R.sub.7；CN；SO.sub.2R.sub.8；--NHCONH.sub.2；和C（O）NR.sub.3R.sub.4；其中R.sub.1、R.sub.2、R.sub.3和R.sub.4中的每一个都独立地选自以下组：氢和C.sub.1-C.sub.4烷基；R.sub.5和R.sub.6中的每一个都独立地是C.sub.1-C.sub.6烷基；R.sub.7选自以下组：H，C.sub.1-C.sub.6烷基，C.sub.1-C.sub.6杂环或--A--R.sub.5；R.sub.8选自以下组：C.sub.1-C.sub.4烷基和NR.sub.3R.sub.4；A选自以下组：S、N和O；前提是U、V、W、X、Y和Z中至少有一个是卤素原子；以及其药学上可接受的盐。