2-oxo-2-(1',2',3',4'-tetrahydro-1',1',4',4'-tetramethyl-6'-naphthalenyl)acetic acid | 142650-43-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: 2-oxo-2-(1',2',3',4'-tetrahydro-1',1',4',4'-tetramethyl-6'-naphthalenyl)acetic acid
• 英文别名: 2-oxo-2(1',2',3',4',-tetrahydro-1',1',4',4'-tetramethyl-6'-naphthyl)acetic acid；5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthylglyoxylic acid；2-oxo-2-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)acetic acid
• CAS: 142650-43-9
• 化学式: C₁₆H₂₀O₃
• 分子量: 260.333
• InChiKey: QDTVGDHZIDYETA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  54.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-oxo-2-(1',2',3',4'-tetrahydro-1',1',4',4'-tetramethyl-6'-naphthalenyl)acetic acid 在 葡萄糖 、 Candida utilis SC 13983 作用下， 以 甲醇 、 phosphate buffer 为溶剂， 以64%的产率得到(R)-2-hydroxy-2-(1',2',3',4'-tetrahydro-1',1',4',4'-tetramethyl-6'-naphthalenyl)acetic acid
  参考文献：
  名称：

  Enantioselective microbial reduction of 2-oxo-2-(1′,2′,3′,4′-tetrahydro-1′,1′,4′,4′-tetramethyl-6′-naphthalenyl)acetic acid and its ethyl ester

  摘要：

  The chiral ester ethyl (2R)-hydroxy-2-(1',2',3',4'-tetrahydro-1',1',4',4'-tetramethyl-6'-naphthalenyl) acetate 2 and the corresponding acid 4 were prepared as intermediates in the synthesis of the retinoic acid receptor gamma-specific agonist (R)-3-fluoro-4-[[hydroxy(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)acety]amino]benzoic acid 7. Enantioselective reduction of ethyl 2-oxo-2-(1',2',3',4'-tetrahydro-1'.1',4',4'-tetramethyl-6'-naphthalenyl)acetate 1 to alcohol 2 was carried out using Aureobasidium pullulans SC 13849 in 98% yield and with an enantiomeric excess (e.e.) of 96%. Among microorganisms screened for the reduction of 2-oxo-2-(1',2',3',4'-tetrahydro-1',1',4',4'-tetramethyl-6'-naphthalenyl)acetic acid 3 to hydroxy acid 4. Candida maltosa SC 16112 and two strains of Candida utilis (SC 13983, SC 1394) gave reaction yields of >53% with e.e.s. of >96%. (C) 2002 Elsevier Science Ltd, All rights reserved.

  DOI：

  10.1016/s0957-4166(02)00109-x
• 作为产物：
  描述：

  1,1,4,4-四甲基-1,2,3,4-四氢萘 在 lithium hydroxide 、 三氯化铝 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 2.5h， 生成 2-oxo-2-(1',2',3',4'-tetrahydro-1',1',4',4'-tetramethyl-6'-naphthalenyl)acetic acid
  参考文献：
  名称：

  Enantioselective microbial reduction of 2-oxo-2-(1′,2′,3′,4′-tetrahydro-1′,1′,4′,4′-tetramethyl-6′-naphthalenyl)acetic acid and its ethyl ester

  摘要：

  The chiral ester ethyl (2R)-hydroxy-2-(1',2',3',4'-tetrahydro-1',1',4',4'-tetramethyl-6'-naphthalenyl) acetate 2 and the corresponding acid 4 were prepared as intermediates in the synthesis of the retinoic acid receptor gamma-specific agonist (R)-3-fluoro-4-[[hydroxy(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)acety]amino]benzoic acid 7. Enantioselective reduction of ethyl 2-oxo-2-(1',2',3',4'-tetrahydro-1'.1',4',4'-tetramethyl-6'-naphthalenyl)acetate 1 to alcohol 2 was carried out using Aureobasidium pullulans SC 13849 in 98% yield and with an enantiomeric excess (e.e.) of 96%. Among microorganisms screened for the reduction of 2-oxo-2-(1',2',3',4'-tetrahydro-1',1',4',4'-tetramethyl-6'-naphthalenyl)acetic acid 3 to hydroxy acid 4. Candida maltosa SC 16112 and two strains of Candida utilis (SC 13983, SC 1394) gave reaction yields of >53% with e.e.s. of >96%. (C) 2002 Elsevier Science Ltd, All rights reserved.

  DOI：

  10.1016/s0957-4166(02)00109-x
• 作为试剂：
  描述：

  、 ethyl 2-oxo-2-(1',2',3',4'-tetrahydro-1',1',4',4'-tetramethyl-6'-naphthalenyl)acetate 、 乙醇 、 sodium hydroxide 在 乙醚 、 magnesium sulfate 、 2-oxo-2-(1',2',3',4'-tetrahydro-1',1',4',4'-tetramethyl-6'-naphthalenyl)acetic acid 作用下， 以 水 为溶剂， 反应 1.0h， 生成 2-oxo-2-(1',2',3',4'-tetrahydro-1',1',4',4'-tetramethyl-6'-naphthalenyl)acetic acid
  参考文献：
  名称：

  Di(aromatic) compounds and their use in human and veterinary medicine

  摘要：

  以下化学式对应的是二元芳香化合物：##STR1## 其中：Ar代表##STR2## n=1或2或：##STR3## X代表二价基团，Z代表O，S或二价基团，R.sub.1，R.sub.2，R.sub.3，R.sub.4和R.sub.5代表氢原子或不同的有机基团，当R.sub.1是羧酸功能时，该化合物的盐也包括在内。用于人类和兽医药物以及化妆品。

  公开号：

  US05439925A1

文献信息

• Biaromatic amido compounds and pharmaceutical/cosmetic compositions
  申请人：Centre International de Recherches Dermatologiques Galderma

  公开号：US05935585A1

  公开（公告）日：1999-08-10

  Novel pharmaceutically/cosmetically-active biaromatic amido compounds have the structural formula (I): ##STR1## in which Ar is a radical selected from among those of the following formulae (a)-(e): ##STR2## and are useful for the treatment of a wide variety of disease states, whether human or veterinary, for example dermatological, rheumatic, respiratory, cardiovascular and ophthalmological disorders, as well as for the treatment of mammalian skin and hair conditions/disorders.

  新型药用/化妆品活性双芳基酰胺化合物具有结构式(I)：##STR1## 其中Ar是从以下式(a)-(e)中选择的基团：##STR2## 并且适用于治疗各种疾病状态，无论是人类还是兽医，例如皮肤病、风湿病、呼吸系统疾病、心血管疾病和眼科疾病，以及哺乳动物皮肤和毛发状况/疾病的治疗。
• Rary-specific retinobenzoic acid derivatives
  申请人：Bristol-Myers Squibb Company

  公开号：US05624957A1

  公开（公告）日：1997-04-29

  Retinoid-like activity is exhibited by compounds of the formula ##STR1## wherein X is F, Cl, OH or CH.sub.3, Y is H or F, R.sub.1 -R.sub.6 are each independently hydrogen or C.sub.1 -C.sub.6 alkyl, n is an integer of 1 to 4 and R.sub.7 is hydrogen or a carboxyl-protecting group, and pharmaceutically acceptable salts thereof. The compounds of formula I selectively interact with the retinoic acid subtype RAR.gamma. and have been found to lack the liver toxicity associated with systemic administration of non-selective retinoids.

  化合物的公式为##STR1##，其中X为F，Cl，OH或CH.sub.3，Y为H或F，R.sub.1-R.sub.6各自独立地为氢或C.sub.1-C.sub.6烷基，n为1至4的整数，R.sub.7为氢或羧基保护基，以及其药学上可接受的盐。公式I的化合物选择性地与视黄酸亚型RAR.gamma.相互作用，并发现它们缺乏与非选择性视黄酸类似物系统给药相关的肝毒性。
• RARy-specific retinobenzoic acid derivatives
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：EP0747347A1

  公开（公告）日：1996-12-11

  Retinoid-like activity is exhibited by compounds of the formula wherein X is F, Cl, OH or CH3, Y is H or F, R1-R6 are each independently hydrogen or C1-C6 alkyl, n is an integer of 1 to 4 and R7 is hydrogen or a carboxyl-protecting group, and pharmaceutically acceptable salts thereof. The compounds of formula I selectively interact with the retinoic acid subtype RARγ and have been found to lack the liver toxicity associated with systemic administration of non-selective retinoids.

  式中的化合物具有类视黄醇活性 其中 X 是 F、Cl、OH 或 CH3，Y 是 H 或 F，R1-R6 独立地分别是氢或 C1-C6 烷基，n 是 1 至 4 的整数，R7 是氢或羧基保护基团，及其药学上可接受的盐类。式 I 的化合物可选择性地与视黄酸亚型 RARγ 发生作用，并且不存在与全身给药非选择性视黄酸相关的肝毒性。
• A Practical Synthesis of the RAR_γ Agonist, BMS-270394
  作者：Ramakrishnan Chidambaram、Joydeep Kant、Jason Zhu、Jean Lajeunesse、Pierre Sirard、Peter Ermann、Peter Schierling、Peter Lee、David Kronenthal

  DOI：10.1021/op0202134

  日期：2002.9.1

  A novel synthesis of 1 (BMS-270394), a nuclear retinoic acid receptor (RARgamma) agonist, is reported. The synthesis includes an enantioselective reduction of alpha-ketoacid 4 to the corresponding chiral a.-hydroxy acid 7 using a NaBH4/L-tartaric acid mixture and a novel coupling between 7 and an electron-deficient aniline 11 which was activated via N-sulfinyl derivative 15 to form chiral alpha-hydroxy amide 16. The synthesis was completed by a racemization-free hydrolysis of 16 to the corresponding alpha-hydroxy amidoacid 1 using KOPSiMe3 in acetonitrile.
• US06171603B2
  申请人：——

  公开号：——

  公开（公告）日：——