(R,R)-MK 499 | 161799-18-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: (R,R)-MK 499
• 英文别名: [35S]-MK 499；MK 499；(+)-N-<1'-(6-Cyano-1,2,3,4-tetrahydro-2(R)-naphthalenyl)-3,4-dihydro-4(R)-hydroxyspiro<2H-1-benzopyran-2,4'-piperidin>-6-yl>methanesulfonamide；N-[(4R)-1'-[(2R)-6-cyano-1,2,3,4-tetrahydronaphthalen-2-yl]-4-hydroxyspiro[3,4-dihydrochromene-2,4'-piperidine]-6-yl]methanesulfonamide；35-S MK499；MK-499；OM3KJ27Ats
• CAS: 161799-18-4
• 化学式: C₂₅H₂₉N₃O₄S
• 分子量: 467.589
• InChiKey: NIYGLRKUBPNXQS-FYYLOGMGSA-N

物化性质

• 沸点：
  659.9±65.0 °C(Predicted)
• 密度：
  1.39±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  33
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  111
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (R,R)-MK 499 在 2,6-二甲基吡啶 、 sodium hydroxide 、 2-甲基-2-丙硫醇钠盐 、 sodium hydride 、 cesium fluoride 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 24.0h， 生成 N-[1'-(6-cyano-1,2,3,4-tetrahydro-2(R)-naphthalenyl)-3,4-dihydro-4(R)-trimethylsilyloxyspiro[2H-1-benzopyran-2,4'-piperidin]-6-yl]amine
  参考文献：
  名称：

  Synthesis of the first sulfur-35-labeled hERG radioligand

  摘要：

  The synthesis of the first high specific activity S-35-labeled hERG radioligand, [S-35]MK-0499, for use in HTS assays of drug candidates for hERG interaction is described. The radioligand is prepared by [S-35]sulfonylation of a high diastereomeric excess (de) aniline precursor prepared from unlabeled MK-0499. (C) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.12.021
• 作为产物：
  描述：

  N-<1'-(6-Cyano-1,2,3,4-tetrahydronaphth-2(R)-yl)-3,4-dihydro-4-oxospiro<2H-1-benzopyran-2,4'-piperidin>-6-yl>methanesulfonamide 在 甲醇 、 dimethyl sulfide borane 、 e chiral oxazaborolidine-BH₃ complex (0.1 mole) 、 异丙醇 作用下， 生成 (R,R)-MK 499
  参考文献：
  名称：

  An improved method for chiral oxazaborolidine-catalyzed reduction of 4-chromanone analogs and MK-0499

  摘要：

  Addition of isopropanol to the stoichiometric reduction of ketones 4-8 using oxazborolidine-borane complex 3 or the oxazaborolidine-catalyzed reduction of 4-chromanone analogs (1, 7-9) enhances the enantioselectivity of the reduction.

  DOI：

  10.1016/s0040-4039(00)78232-3

文献信息

• Radioligand and binding assay
  申请人：——

  公开号：US20020034730A1

  公开（公告）日：2002-03-21

  The present invention is directed to the radioligand compound, [ 35 S]-radiolabeled (+)-N-[1′-(6-cyano-1,2,3,4-tetrahydro-2(R)-naphthalenyl)-3,4-dihydro-4(R)-hydoxyspiro[2H-1-benzopyran-2,4′-piperidin]-6-yl]methanesulfonamide. Also within the scope of this invention is a method for identifying compounds that bind to the I Kr channel, and may have antiarrhythmic activity.

  本发明涉及放射配体化合物，即[35S]-放射标记的(+)-N-[1′-(6-氰基-1,2,3,4-四氢-2(R)-萘基)-3,4-二氢-4(R)-羟基螺[2H-1-苯并吡喃-2,4′-哌啶]-6-基]甲磺酰胺。本发明还涵盖了一种用于识别与IKr通道结合并可能具有抗心律失常活性的化合物的方法。
• Asymmetric Synthesis of MK-0499
  作者：David M. Tschaen、Lee Abramson、Dongwei Cai、Richard Desmond、Ulf-H. Dolling、Lisa Frey、Sandor Karady、Yao-Jun Shi、Thomas R. Verhoeven

  DOI：10.1021/jo00119a008

  日期：1995.7

  Described herein is an efficient asymmetric synthesis of the potent antiarrhthymia agent MK-0499. The route is convergent and is highlighted by two stereoselective reactions. A ruthenium-catalyzed, enantioselective hydrogenation of an enamide was developed for the preparation of the key amine intermediate. Oxazaborolidine-mediated ketone reduction was utilized to establish the alcohol stereochemistry. Optimization of this chemistry led to an IPA modified reduction method which provides enhanced stereoselectivity.
• Effects of triethylamine in asymmetric reduction using oxazaborolidine reagents
  作者：Dongwei Cai、David Tschaen、Y.-J. She、Thomas R. Verhoeven、Robert A. Reamer、Allan W. Douglas

  DOI：10.1016/s0040-4039(00)73672-0

  日期：1993.5

  In the presence of triethylamine, the reduction of ketones using stoichiometric amounts of oxazaborolidineborane complex (OAB.BH3) shows increased enantioselectivity.
• DRUG DELIVERY DEVICE
  申请人：MERCK & CO. INC.

  公开号：EP0668758A1

  公开（公告）日：1995-08-30
• RADIOLIGAND AND BINDING ASSAY
  申请人：Merck & Co., Inc.

  公开号：EP1311300B1

  公开（公告）日：2008-02-27