2,2-二甲基-3-羟基-1-茚满酮 | 59269-93-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 中文名称: 2,2-二甲基-3-羟基-1-茚满酮
• 英文名称: 3-hydroxy-2,2-dimethylindan-1-one
• 英文别名: 3-Hydroxy-2,2-dimethyl-1-indanone；3-hydroxy-2,2-dimethyl-3H-inden-1-one
• CAS: 59269-93-1
• 化学式: C₁₁H₁₂O₂
• mdl: MFCD09907921
• 分子量: 176.215
• InChiKey: YATVHPCKCBERKE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.363
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2,2-二甲基-3-羟基-1-茚满酮 在 咪唑 、 manganese(IV) oxide 、 lithium aluminium tetrahydride 、 偶氮二甲酸二叔丁酯 、 三苯基膦 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.5h， 生成 3-[5-(tert-butyldimethylsilanyloxymethyl)imidazol-1-yl]-2,2-dimethylindan-1-one
  参考文献：
  名称：

  Structure–Activity Relationships, Pharmacokinetics, and in Vivo Activity of CYP11B2 and CYP11B1 Inhibitors

  摘要：

  CYP11B2, the aldosterone synthase, and CYP11B1, the cortisol synthase, are two highly homologous enzymes implicated in a range of cardiovascular and metabolic diseases. We have previously reported the discovery of LCI699, a dual CYP11B2 and CYP11B1 inhibitor that has provided clinical validation for the lowering of plasma aldosterone as a viable approach to modulate blood pressure in humans, as well normalization of urinary cortisol in Cushing's disease patients. We now report novel series of aldosterone synthase inhibitors with single-digit nanomolar cellular potency and excellent physicochemical properties. Structure-activity relationships and optimization of their oral bioavailability are presented. An illustration of the impact of the age of preclinical models on pharmacokinetic properties is also highlighted. Similar biochemical potency was generally observed against CYP11B2 and CYP11B1, although emerging structure-selectivity relationships were noted leading to more CYP11B1-selective analogs.

  DOI：

  10.1021/acs.jmedchem.5b00407
• 作为产物：
  描述：

  2-碘苯甲醛 在 palladium diacetate 三乙胺 、 三苯基膦 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 15.75h， 生成 2,2-二甲基-3-羟基-1-茚满酮
  参考文献：
  名称：

  腈的Carpalpallading：通过Pd催化ω-（2-碘芳基）烷腈和相关化合物的环化反应合成苯并酮和环戊烯酮。

  摘要：

  已经开发出一种通过腈的分子内碳弹头化合成2，2-二取代的苯并环酮的有效方法。取代的3-（2-碘芳基）丙烷腈的环化以高收率提供茚满酮。该反应与多种官能团相容。该方法已经扩展到四氢萘酮和环戊烯酮的合成。

  DOI：

  10.1021/jo0262006

文献信息

• 1,2-Shift of a Carboxyl Group in aWagner-Meerwein Rearrangement
  作者：Daniel Berner、D. Philip Cox、Hans Dahn

  DOI：10.1002/hlca.19820650713

  日期：1982.11.3

  (isolated yield: 40–44%). Using monolabelled [3-13C]-1a (1a*) and doubly labelled [1,3-13C2]-1a (1a**), the migration of HOOC (or a mechanistically equivalent group) was proved; a cross experiment established the intramolecular character of the rearrangement. By following the reaction at low temperature in an NMR. spectrometer, the formation of intermediates and side products was demonstrated.

  在0°下在SO 2 C1F中用HSO 3 F处理时，将3-羟基-2,2-二甲基-3-苯基丙酸（1a）转化为2-苯基-3-甲基-2-丁烯酸（2a））（单产：40–44％）。使用monolabelled [3- 13 C] - 1A（1A *）和双标记的[1,3- 13 Ç 2 ] - 1A（1A **），HOOC的迁移（或机理上等效基团）被证明; 交叉实验确定了重排的分子内特性。通过在NMR下在低温下追踪反应。光谱仪，证明了中间体和副产物的形成。
• Synthesis of benzocyclic ketones via palladium-catalyzed cyclization of ω-(2-iodoaryl)alkanenitriles
  作者：Alexandre A. Pletnev、Richard C. Larock

  DOI：10.1016/s0040-4039(02)00247-2

  日期：2002.3

  An efficient procedure for the synthesis of 2,2-disubstituted benzocyclic ketones by intramolecular carbopalladation of nitriles has been developed. The cyclization of substituted 3-(2-iodoaryl)propanenitriles affords indanones in high yields. The reaction is compatible with a wide variety of functional groups. This chemistry has been extended to the synthesis of tetralones, a 9-fluorenone and a cyclopentenone

  已经开发了一种通过腈的分子内碳弹孔法合成2,2-二取代的苯并环酮的有效方法。取代的3-（2-碘芳基）丙腈的环化以高收率提供茚满酮。该反应与多种官能团相容。该化学反应已扩展到四氢萘酮，9-芴酮和环戊烯酮的合成。
• Wittig-Horner Reaction of Dimethyl Phthalide-3-phosphonates with Ketones: Synthesis of 3-Ylidenephthalides and Their Conversion to 2,2-Disubstituted Indan-1,3-diones Including Spirocyclic Compounds
  作者：Mitsuaki Watanabe、Hitoshi Morimoto、Maya Tomoda、Umeka Iwanaga

  DOI：10.1055/s-1994-25642

  日期：——

  The Wittig-Horner reaction of dimethyl phthalide-3-phosphonates with various ketones was investigated under the conditions: lithium bis(trimethylsilyl)amide (LHMDS) or sodium hydride in tetrahydrofuran, and cesium carbonate in isopropyl alcohol. The sequential treatment of the 3-ylidenephthalides with diisobutylaluminium hydride (DIBAL-H) and pyridinium dichromate (PDC) afforded 2,2-disubstituted indan-1,3-dione derivatives in modest to high overall yields.

  研究了邻苯二甲酸二甲酯-3-膦酸盐与各种酮的 Wittig-Horner 反应，反应条件为：四氢呋喃中的双(三甲基硅)酰胺锂 (LHMDS) 或氢化钠，以及异丙醇中的碳酸铯。用氢化二异丁基铝（DIBAL-H）和重铬酸吡啶鎓（PDC）依次处理 3- 亚基酞，可以得到 2,2-二取代的茚-1,3-二酮衍生物，总产率从低到高不等。
• ORGANIC COMPOUNDS
  申请人：Adams Christopher

  公开号：US20100048562A1

  公开（公告）日：2010-02-25

  The present invention provides a compound of formula I: said compound is inhibitor of aldosterone synthase (CYP11B2), and/or 11 beta-hydroxylase (CYP11B1), and/or aromatase, and thus can be employed for the treatment of a disorder or disease mediated by aldosterone synthase, aromatase, or CYP11B1. Accordingly, the compound of formula I can be used in treatment of hypokalemia, hypertension, congestive heart failure, renal failure, in particular, chronic renal failure, restenosis, atherosclerosis, syndrome X, obesity, nephropathy, post-myocardial infarction, coronary heart diseases, increased formation of collagen, fibrosis and remodeling following hypertension and endothelial dysfunction. Finally, the present invention also provides a pharmaceutical composition.

  本发明提供了一种公式I的化合物：该化合物是醛固酮合成酶（CYP11B2）和/或11β-羟化酶（CYP11B1）和/或芳香化酶的抑制剂，因此可用于治疗由醛固酮合成酶、芳香化酶或CYP11B1介导的疾病或疾病。因此，公式I的化合物可用于治疗低钾血症、高血压、充血性心力衰竭、肾衰竭，特别是慢性肾衰竭、再狭窄、动脉粥样硬化、X综合征、肥胖症、肾病、心肌梗死后、冠心病、胶原形成增加、高血压和内皮功能障碍后的纤维化和重塑。最后，本发明还提供了一种制药组合物。
• Organic compounds
  申请人：Novartis AG

  公开号：US08153674B2

  公开（公告）日：2012-04-10

  The present invention provides a compound of formula (I): said compound is inhibitor of aldosterone synthase, and thus can be employed for the treatment of a disorder or disease mediated by aldosterone synthase. Accordingly, the compound of formula I can be used in treatment of hypokalemia, hypertension, congestive heart failure, renal failure, in particular, chronic renal failure, restenosis, atherosderosis, syndrome X, obesity, nephropathy, post-myocardial infarction, coronary heart diseases, increased formation of collagen, cardiac fibrosis and remodeling following hypertension and endothelial dysfunction. Finally, the present invention also provides a pharmaceutical composition.

  本发明提供了一种式(I)的化合物：该化合物是醛固酮合酶的抑制剂，因此可用于治疗由醛固酮合酶介导的疾病或疾病。因此，式I的化合物可用于治疗低钾血症，高血压，充血性心力衰竭，肾衰竭，特别是慢性肾衰竭，再狭窄，动脉粥样硬化，X综合症，肥胖症，肾病，心肌梗死后，冠心病，胶原形成增多，高血压和内皮功能障碍后的心脏纤维化和重塑。最后，本发明还提供了一种制药组合物。