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(R)-tert-butyl 4-(2-(4-(biphenyl-4-ylmethoxy)-3-(trifluoromethyl)phenyl)-2-oxoethylcarbamoyl)-2,2,4-trimetyloxazolidine-3-carboxylate

中文名称
——
中文别名
——
英文名称
(R)-tert-butyl 4-(2-(4-(biphenyl-4-ylmethoxy)-3-(trifluoromethyl)phenyl)-2-oxoethylcarbamoyl)-2,2,4-trimetyloxazolidine-3-carboxylate
英文别名
tert-butyl (4R)-2,2,4-trimethyl-4-[[2-oxo-2-[4-[(4-phenylphenyl)methoxy]-3-(trifluoromethyl)phenyl]ethyl]carbamoyl]-1,3-oxazolidine-3-carboxylate
(R)-tert-butyl 4-(2-(4-(biphenyl-4-ylmethoxy)-3-(trifluoromethyl)phenyl)-2-oxoethylcarbamoyl)-2,2,4-trimetyloxazolidine-3-carboxylate化学式
CAS
——
化学式
C34H37F3N2O6
mdl
——
分子量
626.673
InChiKey
YEBQJZAVNVYQCR-MGBGTMOVSA-N
BEILSTEIN
——
EINECS
——
  • 物化性质
  • 计算性质
  • ADMET
  • 安全信息
  • SDS
  • 制备方法与用途
  • 上下游信息
  • 反应信息
  • 文献信息
  • 表征谱图
  • 同类化合物
  • 相关功能分类
  • 相关结构分类

计算性质

  • 辛醇/水分配系数(LogP):
    6.4
  • 重原子数:
    45
  • 可旋转键数:
    10
  • 环数:
    4.0
  • sp3杂化的碳原子比例:
    0.38
  • 拓扑面积:
    94.2
  • 氢给体数:
    1
  • 氢受体数:
    9

上下游信息

  • 上游原料
    中文名称 英文名称 CAS号 化学式 分子量
  • 下游产品
    中文名称 英文名称 CAS号 化学式 分子量

反应信息

  • 作为反应物:
    描述:
    (R)-tert-butyl 4-(2-(4-(biphenyl-4-ylmethoxy)-3-(trifluoromethyl)phenyl)-2-oxoethylcarbamoyl)-2,2,4-trimetyloxazolidine-3-carboxylate六氯乙烷三乙胺三苯基膦 作用下, 以 二氯甲烷 为溶剂, 反应 1.0h, 以79%的产率得到(S)-tert-butyl 4-(5-(4-([1,1'-biphenyl]-4-ylmethoxy)-3-(trifluoromethyl)phenyl)oxazol-2-yl)-2,2,4-trimethyloxazolidine-3-carboxylate
    参考文献:
    名称:
    Discovery of Clinical Candidate GSK1842799 As a Selective S1P1 Receptor Agonist (Prodrug) for Multiple Sclerosis
    摘要:
    To develop effective oral treatment for multiple sclerosis (MS), we discovered a series of alkyl-substituted biaryl amino alcohols as selective S1P(1) modulators. One exemplar is (S)-2-amino-2-(5-(4-(octyloxy)-3-(trifluoromethyl)phenyl) -1,3,4-thiadiazol-2-yl)propan-1-ol (10, GSK1842799). Upon phosphorylation, the compound (10-P) showed subnanomole S1P(1) agonist activity with >1000x selectivity over S1P(3). The alcohol 10 demonstrated good oral bioavailability and rapid in vivo conversion to 10-P. Dosed orally at 0.1 mg/kg, 10 significantly reduced blood lymphocyte counts 6 h postdose, and at 3 mg/kg, 10 achieved efficacy equivalent to FTY720 in the mouse EAE model of MS. Further pharmacokinetic/pharmacodynamic (PK/PD) study with cynomolgus monkeys indicated that, after oral dosing of 10 at 3.8 mg/kg, the active phosphate reached plasma levels that are comparable to FTY-720 phosphate (FTY-P) revealed in human clinical pharmacokinetics studies. On the basis of the favorable in vitro ADME and in vivo PK/PD properties as well as broad toxicology evaluations, compound 10 (GSK1842799) was selected as a candidate for further clinical development.
    DOI:
    10.1021/ml400194r
  • 作为产物:
    参考文献:
    名称:
    Discovery of Clinical Candidate GSK1842799 As a Selective S1P1 Receptor Agonist (Prodrug) for Multiple Sclerosis
    摘要:
    To develop effective oral treatment for multiple sclerosis (MS), we discovered a series of alkyl-substituted biaryl amino alcohols as selective S1P(1) modulators. One exemplar is (S)-2-amino-2-(5-(4-(octyloxy)-3-(trifluoromethyl)phenyl) -1,3,4-thiadiazol-2-yl)propan-1-ol (10, GSK1842799). Upon phosphorylation, the compound (10-P) showed subnanomole S1P(1) agonist activity with >1000x selectivity over S1P(3). The alcohol 10 demonstrated good oral bioavailability and rapid in vivo conversion to 10-P. Dosed orally at 0.1 mg/kg, 10 significantly reduced blood lymphocyte counts 6 h postdose, and at 3 mg/kg, 10 achieved efficacy equivalent to FTY720 in the mouse EAE model of MS. Further pharmacokinetic/pharmacodynamic (PK/PD) study with cynomolgus monkeys indicated that, after oral dosing of 10 at 3.8 mg/kg, the active phosphate reached plasma levels that are comparable to FTY-720 phosphate (FTY-P) revealed in human clinical pharmacokinetics studies. On the basis of the favorable in vitro ADME and in vivo PK/PD properties as well as broad toxicology evaluations, compound 10 (GSK1842799) was selected as a candidate for further clinical development.
    DOI:
    10.1021/ml400194r
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