(S)-2-((mesyloxy)methyl)-1,4-benzodioxane | 650597-69-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并二恶烷
• 英文名称: (S)-2-((mesyloxy)methyl)-1,4-benzodioxane
• 英文别名: (2S)-2-mesyloxymethyl-1,4-benzodioxane；(S)-2-mesyloxymethyl-1,4-benzodioxane；(S)-2-(mesyloxymethyl)benzodioxane；(S)-2-methanesulfonyloxymethyl-1,4-benzodioxane；[(3S)-2,3-dihydro-1,4-benzodioxin-3-yl]methyl methanesulfonate
• CAS: 650597-69-6
• 化学式: C₁₀H₁₂O₅S
• 分子量: 244.268
• InChiKey: DKZOUTWWMFKQGK-QMMMGPOBSA-N

物化性质

• 沸点：
  409.5±24.0 °C(Predicted)
• 密度：
  1.332±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  70.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S)-2-((mesyloxy)methyl)-1,4-benzodioxane 在 1,3-丙二醇 sodium azide 、 一水合肼 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 (R)-2,3-二氢-1,4-苯并二恶烷-2-甲胺
  参考文献：
  名称：

  Structure–affinity studies for a novel series of homochiral naphtho and tetrahydronaphtho analogues of α1 antagonist WB-4101

  摘要：

  A number of enantiomeric pairs of naphthodioxane, tetrahydronaphthodioxane and naphthoxy analogues of WB-4101 (1) were designed and synthesized in order to improve the selectivity profile of the parent compound, hopefully in favour of the alpha(1a)-AR with respect to the other two alpha(1), subtypes and the 5-HT1A receptor. The new compounds 2-8 and, in addition, the two enantiomers of 1 were tested in binding assays on the alpha(1a)-AR, alpha(1b)-AR, alpha(1d)-AR, and the 5-HT1A receptor. Two of them, namely the naphtho- and tetrahydronaphthodioxane derivatives (S)-2 and (S)-3, showed lower, but significantly more specific alpha(1a), affinity than (S)-1, while the two enantiomers of the 2-methoxy-1-naphthoxy analogue 6 maintained most of the very high alpha(1a) affinity of (S)-1 and its alpha(1a) versus alpha(1b) selectivity slightly increasing the alpha(1a)/alpha(1d) and alpha(1a)/5HT(1A) affinity ratios. The SAR data were evaluated in the light of known alpha(1), subtype pharmacophores and of the alpha(1a)-AR binding mode of WB-4101 resultant from literature mutagenesis studies disclosing some interesting consonances with these models. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.06.040
• 作为产物：
  描述：

  2-苯甲氧基苯酚 在 palladium on activated charcoal 盐酸 、 氢氧化钾 、 TEA 、 氢气 、 potassium carbonate 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 水 、 乙酸乙酯 、 丙酮 为溶剂， 反应 39.0h， 生成 (S)-2-((mesyloxy)methyl)-1,4-benzodioxane
  参考文献：
  名称：

  Structure–affinity studies for a novel series of homochiral naphtho and tetrahydronaphtho analogues of α1 antagonist WB-4101

  摘要：

  A number of enantiomeric pairs of naphthodioxane, tetrahydronaphthodioxane and naphthoxy analogues of WB-4101 (1) were designed and synthesized in order to improve the selectivity profile of the parent compound, hopefully in favour of the alpha(1a)-AR with respect to the other two alpha(1), subtypes and the 5-HT1A receptor. The new compounds 2-8 and, in addition, the two enantiomers of 1 were tested in binding assays on the alpha(1a)-AR, alpha(1b)-AR, alpha(1d)-AR, and the 5-HT1A receptor. Two of them, namely the naphtho- and tetrahydronaphthodioxane derivatives (S)-2 and (S)-3, showed lower, but significantly more specific alpha(1a), affinity than (S)-1, while the two enantiomers of the 2-methoxy-1-naphthoxy analogue 6 maintained most of the very high alpha(1a) affinity of (S)-1 and its alpha(1a) versus alpha(1b) selectivity slightly increasing the alpha(1a)/alpha(1d) and alpha(1a)/5HT(1A) affinity ratios. The SAR data were evaluated in the light of known alpha(1), subtype pharmacophores and of the alpha(1a)-AR binding mode of WB-4101 resultant from literature mutagenesis studies disclosing some interesting consonances with these models. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.06.040

文献信息

• Fused imidazopyridine derivatives as antihyperlipidemic agents
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US06235731B1

  公开（公告）日：2001-05-22

  A novel compound of the formula: wherein ring Q is an optionally substituted pyridine ring; One of R0, R1 and R2 is —Y0—Z0, and the other tow groups are a hydrogen, a halogen, an optionally substituted hydroxy group, a hydrocarbon group that may be an optionally substituted hydrocarbon group or an acyl group; Y0 is a bond or an optionally substituted bivalent hydrocarbon group; Z0 is a basic group which may be bonded via oxygen, nitrogen, —CO—, —CS—, —SO2N(R3)— (where R3 is hydrogen or an optionally substituted hydrocarbon group), or S(O)n (wherein n is to 0, 1 or 2); ......... is a single bond or a double bond, or a salt thereof, which has an excellent LDL receptor up-regulating, blood-lipids lowering, blood-sugar lowering and diabetic complication-ameliorating activity.

  其中环Q是一个可选择取代的吡啶环； R0、R1和R2中的一个是—Y0—Z0，另外两个基团是氢、卤素、可选择取代的羟基、可能是可选择取代的碳氢基团或酰基； Y0是一个键或一个可选择取代的二价碳氢基团； Z0是一种碱性基团，可以通过氧、氮、—CO—、—CS—、—SO2N(R3)—（其中R3是氢或可选择取代的碳氢基团）或S(O)n（其中n为0、1或2）与之键合； .........是一种单键或双键，或其盐，具有出色的LDL受体上调、降低血脂、降低血糖和改善糖尿病并发症的活性。
• WB4101-Related Compounds:  New, Subtype-Selective α₁-Adrenoreceptor Antagonists (or Inverse Agonists?)
  作者：Marco Pallavicini、Roberta Budriesi、Laura Fumagalli、Pierfranco Ioan、Alberto Chiarini、Cristiano Bolchi、Maria Paola Ugenti、Simona Colleoni、Marco Gobbi、Ermanno Valoti

  DOI：10.1021/jm060358r

  日期：2006.11.30

  Our previous structure-affinity relationship study had considered the enantiomers of the naphthodioxane, tetrahydronaphthodioxane, and 2-methoxy-1-naphthoxy analogues ( compounds 1, 3, and 2, respectively) of 2-(2,6-dimethoxyphenoxyethylaminomethyl)-1,4-benzodioxane, the well-known alpha(1)-adrenoceptor (alpha(1)-AR) antagonist WB4101, showing that such modifications significantly modulate the affinity and selectivity profile for alpha(1)-AR subtypes and 5-HT1A receptor. Here, we extend investigations to antagonist activity enclosing new enantiomeric pairs, namely those of the methoxytetrahydronaphthoxy and methoxybiphenyloxy WB4101 analogues (4 and 5-7, respectively) and of a double- modified WB4101 derivative ( 8) resulting from hybridization between 2 and 3. We found that (S)-2 is a very potent (pA(2) 10.68) and moderately selective alpha(1D)-AR antagonist and the hybrid (S)-8 is a potent (pA(2) 7.98) and highly selective alpha(1A)-AR antagonist. Both of these compounds and (S)-WB4101 seem to act as inverse agonists in a vascular model. The results, which generally validate the logic we followed in designing these eight compounds, are acceptably rationalized by comparative SAR analysis of binding and functional affinities.
• A short entry to enantiopure 2-substituted 1,4-benzodioxanes by efficient resolution methods
  作者：Cristiano Bolchi、Laura Fumagalli、Barbara Moroni、Marco Pallavicini、Ermanno Valoti

  DOI：10.1016/j.tetasy.2003.09.012

  日期：2003.11

  (R)-1,4-Benzodioxane-2-carboxilic acid (R)-1 was obtained by resolution of the racemic acid 1 with stoichiometric or nonstoichiometric (+)-dehydroabietylamine (+)-2 in high chemical yield and enantiomeric excess. (S)-1 was isolated from the mother liquors of the crystallisation of (R)-1-(+)-2 and its enantiomeric excess maximised by recrystallisation procedures involving a precipitation under kinetic control or, alternatively, by conversion into the methyl ester followed by a single crystallisation. The different mechanisms of the two S enrichments is well explained by the binary phase diagrams of the acid and of the ester, which show that the former is a racemic compound, whereas the latter a conglomerate. The DSC analyses were extended to 2-hydroxymethyl- and 2-mesyloxymethyl-1,4-benzodioxane, establishing that the alcohol forms a racemic compound, while its mesyl ester a conglomerate. On the basis of these results, different resolution strategies can be designed to obtain useful homochiral 2-substituted 1,4-benzodioxanes coupling the resolution of I via diastereomeric salt formation with the enantiomeric enrichments by recrystallisations, preferably of its conglomerate forming derivatives. (C) 2003 Elsevier Ltd. All rights reserved.
• QSAR study for a novel series of ortho monosubstituted phenoxy analogues of α1-adrenoceptor antagonist WB4101
  作者：Laura Fumagalli、Cristiano Bolchi、Simona Colleoni、Marco Gobbi、Barbara Moroni、Marco Pallavicini、Alessandro Pedretti、Luigi Villa、Giulio Vistoli、Ermanno Valoti

  DOI：10.1016/j.bmc.2005.01.034

  日期：2005.4

  A number of (S)- and (R)-2-[(2-phenoxyethyl)aminomethyl]-1,4-benzodioxanes unsubstituted or ortho monosubstituted at the phenoxy moiety were synthesized and tested in binding assays on the alpha(1a)-AR, alpha(1b)-AR alpha(1d)-AR and the 5-HT1A receptor. The affinity values of the new compounds 1-16 were compared with those of the enantiomers of the 2,6-dimethoxyphenoxy analogue, the well-known alpha(1) antagonist WB4101, finding that the unsubstituted derivative (S)-1 and the o-methyl, the o-t-butyl, the o-fluoro and the o-methoxy derivatives, (S)-2, (S)-4, (S)-8 and (S)-16, respectively, display a significantly specific 5-HT1A affinity, very close, with the exception of (S)-4, to the almost nanomolar one of (S)-WB4101. Otherwise sensible affinity decreases were recorded for the three alpha(1)-AR subtypes. A classical quantitative structure-activity relationship (Hansch) analysis was successfully applied to compounds (S)-1 to (S)-16 and (S)-WB4101 to rationalize such binding data. (c) 2005 Elsevier Ltd. All rights reserved.
• New Ras CAAX mimetics: Design, synthesis, antiproliferative activity, and RAS prenylation inhibition
  作者：Cristiano Bolchi、Marco Pallavicini、Laura Fumagalli、Nicola Ferri、Alberto Corsini、Chiara Rusconi、Ermanno Valoti

  DOI：10.1016/j.bmcl.2009.07.065

  日期：2009.9

  Mimetics of the C-terminal CAAX tetrapeptide of Ras protein were designed replacing cysteine (C) by 2-hydroxymethylbenzodioxane or 2-aminomethylbenzodioxane, respectively etherified and amidified with 2'-methyl or 2'-methoxy substituted 2-carboxy-4-hydroxybiphenyl and 2,4-dicarboxybiphenyl. These pluri-substituted biphenyl systems, used as internal spacer and AA dipeptide bioisoster, were linked to the methyl ester Of L-methionine, glycine or L-leucine by an amide bond. The resultant twelve pairs of stereoisomers at the dioxane C-2 were tested for anti proliferative effect finding the maximum activity for derivatives with methyleneoxy linker between benzodioxane and 2'-methylbiphenyl. Of these compounds, the one with terminal methionine and S configuration proved a good Ras prenylation inhibitor in a cell-based assay. (C) 2009 Elsevier Ltd. All rights reserved.