(R)-2-(tert-butyldimethylsilyloxy)-2-(3-chlorophenyl)acetaldehyde | 153294-02-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (R)-2-(tert-butyldimethylsilyloxy)-2-(3-chlorophenyl)acetaldehyde
• 英文别名: (R)-α-(t-butyldimethylsilyloxy)-α-(3-chlorophenyl)acetaldehyde；(R)-2-[(tert-Butyldimethylsilyl)oxy]-2-(3-chlorophenyl)acetaldehyde；(2R)-2-[tert-butyl(dimethyl)silyl]oxy-2-(3-chlorophenyl)acetaldehyde
• CAS: 153294-02-1
• 化学式: C₁₄H₂₁ClO₂Si
• 分子量: 284.858
• InChiKey: LBCVPYBBUCWRLU-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (R)-2-(tert-butyldimethylsilyloxy)-2-(3-chlorophenyl)acetaldehyde 在 正丁基锂 、 copper(II) sulfate 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 为溶剂， 反应 83.5h， 生成 (R)-N-((1R,2R)-2-(tert-butyldimethylsilyloxy)-2-(3-chlorophenyl)-1-(1-(phenylsulfonyl)-1H-indol-2-yl)ethyl)-2-methylpropane-2-sulfinamide
  参考文献：
  名称：

  [EN] HETEROCYCLIC COMPOUNDS AS MDM2 INHIBITORS FOR THE TREATMENT OF CANCER
  [FR] HETEROCYCLES UTILISES COMME INHIBITEURS DE MDM2 DANS LE TRAITEMENT DU CANCER

  摘要：

  本发明提供了化合物I或II的MDM2抑制剂，或其药用盐，其中上述变量已定义，这些化合物可用作治疗剂，特别用于癌症的治疗。本发明还涉及含有MDM2抑制剂的药物组合物。

  公开号：

  WO2013049250A1
• 作为产物：
  描述：

  (R)-(-)-methyl 2-(3-chlorophenyl)-2-hydroxyacetate 在 咪唑 、 二异丁基氢化铝 作用下， 以 乙醚 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 10.0h， 生成 (R)-2-(tert-butyldimethylsilyloxy)-2-(3-chlorophenyl)acetaldehyde
  参考文献：
  名称：

  [EN] HETEROCYCLIC COMPOUNDS AS MDM2 INHIBITORS FOR THE TREATMENT OF CANCER
  [FR] HETEROCYCLES UTILISES COMME INHIBITEURS DE MDM2 DANS LE TRAITEMENT DU CANCER

  摘要：

  本发明提供了化合物I或II的MDM2抑制剂，或其药用盐，其中上述变量已定义，这些化合物可用作治疗剂，特别用于癌症的治疗。本发明还涉及含有MDM2抑制剂的药物组合物。

  公开号：

  WO2013049250A1

文献信息

• Oxazolidine derivatives having anti-diabetic and anti-obesity
  申请人：Sankyo Company, Limited

  公开号：US05436257A1

  公开（公告）日：1995-07-25

  Compounds of formula (I): ##STR1## wherein: R is an alkyl group; X is oxygen or sulfur; Y is hydrogen atom or --A--COOH, in which A is an alkylene group; Ar is aryl or substituted aryl group; and pharmaceutically acceptable salts and esters thereof, have use in the treatment or prophylaxis of diabetes, obesity, hyperlipemia, hyperglycemia, complications of diabetes, obesity-related hypertension and osteoporosis.

  公式（I）的化合物：其中：R是烷基基团；X是氧或硫；Y是氢原子或--A--COOH，其中A是烷基基团；Ar是芳基或取代芳基基团；以及其药用可接受的盐和酯，在糖尿病、肥胖症、高脂血症、高血糖、糖尿病并发症、肥胖相关高血压和骨质疏松症的治疗或预防中有用。
• Aromatic amino-alcohol derivatives having anti-diabetic and anti-obesity
  申请人：Sankyo Company, Limited

  公开号：US05635534A1

  公开（公告）日：1997-06-03

  Compounds of formula (I): ##STR1## (wherein: R.sup.0 is hydrogen, methyl or hydroxymethyl; R.sup.1 is substituted alkyl; R.sup.2 and R.sup.3 are each hydrogen, halogen, hydroxy, alkoxy, carboxy, alkoxycarbonyl, alkyl, nitro, haloalkyl, or substituted alkyl; X is oxygen or sulfur; and Ar optionally substituted phenyl or naphthyl); and pharmaceutically acceptable salts thereof have a variety of valuable pharmaceutical activities, including anti-diabetic and anti-obesity activities; in addition, they are capable of treating or preventing hyperlipemia and hyperglycemia and, by inhibiting the action of aldose reductase, they can also be effective in the treatment and prevention of complications of diabetes.

  式(I)的化合物：##STR1##（其中：R.sup.0为氢、甲基或羟甲基；R.sup.1为取代的烷基；R.sup.2和R.sup.3分别为氢、卤素、羟基、烷氧基、羧基、烷氧羰基、烷基、硝基、卤代烷基或取代的烷基；X为氧或硫；Ar为可选取代的苯基或萘基）；以及其药学上可接受的盐具有各种有价值的药理活性，包括抗糖尿病和抗肥胖活性；此外，它们能够治疗或预防高脂血症和高血糖症，并通过抑制醛固酮还原酶的作用，也可以在糖尿病并发症的治疗和预防中发挥作用。
• Arylethanolamine derivatives and their use as agonists of atypical
  申请人：Glaxo Wellcome Inc.

  公开号：US06048872A1

  公开（公告）日：2000-04-11

  The present invention relates to phenethanolamine derivatives of formula (I) wherein R.sup.1 represents an aryl group optionally substituted by one or more substituents selected from halogen, hydroxy, C.sub.1-6 -alkoxy, C.sub.1-6 -alkyl, nitro, cyano, hydroxymethyl and trifluoromethyl; R.sup.2 represents hydrogen or C.sub.1-6 -alkyl; R.sup.3 represents a group (A) where the ring is substituted by one to four further substituents selected from C.sub.1-6 -alkyl, halogen, trifluoromethyl, and C.sub.1-6 -alkoxy; or R.sup.3 represents a group (B) where the aromatic ring is optionally substituted by up to three further substituents selected from C.sub.1-6 -alkyl, halogen, trifluoromethyl, and C.sub.1-6 -alkoxy; R.sup.4 represents hydrogen, or C.sub.1-6 -alkyl; R.sup.5 represents ZCH.sub.2 CO.sub.2 H wherein Z represents a bond, or O; Y represents (CH.sub.2).sub.n where n is 1-3; and physiologically acceptable derivatives thereof; to process for their preparation; and their use in the treatment of conditions susceptible of amelioration by an atypical beta-adrenoceptor agonist.

  本发明涉及公式（I）的苯乙醇胺衍生物，其中R.sup.1代表芳基基团，该基团可以选择地被卤素、羟基、C.sub.1-6-烷氧基、C.sub.1-6-烷基、硝基、氰基、羟甲基和三氟甲基中的一个或多个取代基取代; R.sup.2代表氢或C.sub.1-6-烷基; R.sup.3代表一个(A)基团，其中环被选择自C.sub.1-6-烷基、卤素、三氟甲基和C.sub.1-6-烷氧基的一个到四个进一步取代基取代; 或R.sup.3代表一个(B)基团，其中芳香环可以选择地被最多三个进一步的C.sub.1-6-烷基、卤素、三氟甲基和C.sub.1-6-烷氧基取代; R.sup.4代表氢或C.sub.1-6-烷基; R.sup.5代表ZCH.sub.2CO.sub.2H，其中Z代表键或O; Y代表(CH.sub.2).sub.n，其中n为1-3; 以及其生理上可接受的衍生物的制备方法; 以及它们在通过非典型β-肾上腺素受体激动剂改善的情况的治疗中的用途。
• Synthesis and Evaluation of Potent and Selective β₃ Adrenergic Receptor Agonists Containing Acylsulfonamide, Sulfonylsulfonamide, and Sulfonylurea Carboxylic Acid Isosteres
  作者：David E. Uehling、Kelly H. Donaldson、David N. Deaton、Clifton E. Hyman、Elizabeth E. Sugg、David G. Barrett、Robert G. Hughes、Barbara Reitter、Kim K. Adkison、Mary E. Lancaster、Frank Lee、Robert Hart、Mark A. Paulik、Bryan W. Sherman、Timothy True、Conrad Cowan

  DOI：10.1021/jm0101500

  日期：2002.1.1

  Starting from phenethanolamine aniline leads 3a and 3b, we have identified a series of functionally potent and selective beta(3) adrenergic receptor (AR) agonists containing acylsulfonamide, sulfonylsulfonamide, or sulfonylurea groups within the aniline phenethanolamine series. In beta(3) beta(2), and beta(1) AR cAMP functional assays, 3a and other right-hand side (RHS) carboxylate analogues were found to be full agonists that were modestly selective against beta(1) or beta(2) ARs, while analogues lacking RHS acid functionality were active at beta(3) AR but not selective. Replacement of the carboxylate with acylthiazole and acylmethylsulfone gave potent, but only modestly selective, compounds. Increasing the size of the RHS sulfonamide substituent with phenyl or p-toluene afforded compounds with good potency and functional selectivity (beta(3) AR pEC(50) greater than 8; beta(1) and beta(2) AR selectivity greater than 40- and 500-fold, respectively). Our SAR studies suggest that the potency and selectivity profile of the best analogues reported here is a result of both the steric bulk and acidity of the RHS sulfonamide NH group. Although all of the analogues had a pharmacokinetic half-life of less than 2 h, acylsulfonamides 43 and 44 did show moderately low clearance in dogs. These two compounds were further evaluated by thermographic imaging in mice and were found to produce a robust thermogenic response via oral administration.
• [EN] HETEROCYCLIC COMPOUNDS AS MDM2 INHIBITORS FOR THE TREATMENT OF CANCER<br/>[FR] HETEROCYCLES UTILISES COMME INHIBITEURS DE MDM2 DANS LE TRAITEMENT DU CANCER
  申请人：AMGEN INC

  公开号：WO2013049250A1

  公开（公告）日：2013-04-04

  The present invention provides MDM2 inhibitor compounds of Formula I or II, or the pharmaceutically acceptable salts thereof, wherein the variables are defined above, which compounds are useful as therapeutic agents, particularly for the treatment of cancers. The present invention also relates to pharmaceutical compositions that contain an MDM2 inhibitor.

  本发明提供了化合物I或II的MDM2抑制剂，或其药用盐，其中上述变量已定义，这些化合物可用作治疗剂，特别用于癌症的治疗。本发明还涉及含有MDM2抑制剂的药物组合物。