(1α,4β)-1-methyl-4-hydroxycyclohexanecarboxylic acid methyl ester | 87787-02-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (1α,4β)-1-methyl-4-hydroxycyclohexanecarboxylic acid methyl ester
• CAS: 87787-02-8
• 化学式: C₉H₁₆O₃
• 分子量: 172.224
• InChiKey: BAGVQRARNBDKOA-XWEPSHTISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  12.0
• 可旋转键数：
  1.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  46.53
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  (1α,4β)-1-methyl-4-hydroxycyclohexanecarboxylic acid methyl ester 在 palladium on activated charcoal copper(I) oxide 、 盐酸 、 lithium aluminium tetrahydride 、 氢溴酸 、 氢气 、 sodium acetate 、 sodium hydride 、 对甲苯磺酸 、 sodium nitrite 作用下， 以 甲醇 、 乙醚 、 乙醇 、 二甲基亚砜 为溶剂， 5.0~35.0 ℃ 、101.33 kPa 条件下， 反应 7.5h， 生成 5-<4-(t-4-hydroxy-1-methyl-r-1-cyclohexylmethoxy)benzyl>-2-imino-4-thiazolidinone
  参考文献：
  名称：

  Studies on antidiabetic agents. IV. Synthesis and activity of the metabolites of 5-(4-(1-methylcyclohexylmethoxy)benzyl)-2,4-thiazolidinedione (ciglitazone).

  摘要：

  合成了在 5-[4-(1-甲基环己基甲氧基)苄基]-2，4-噻唑烷二酮（1，西格列酮）的环己烷环上具有羟基或氧代分子的化合物 2-9，以明确 1 的代谢物的结构，并研究其药理特性。在鉴定出的代谢物中，5-[4-（t-3-羟基-1-甲基-r-1-环己基甲氧基）苄基]-2，4-噻唑烷二酮（7）与 1 相比，表现出极强的抗糖尿病活性。

  DOI：

  10.1248/cpb.32.2267
• 作为产物：
  描述：

  1-甲基环己-3-烯-1-羧酸甲酯 在 sodium hydroxide 、 sodium tetrahydroborate 、 Hg(OAc)4 作用下， 生成 (1α,4β)-1-methyl-4-hydroxycyclohexanecarboxylic acid methyl ester
  参考文献：
  名称：

  Design and Synthesis of Seco-oxysterol Analogs as Potential Inhibitors of 3-Hydroxy-3-methylglutaryl-Coenzyme A (HMG-CoA) Reductase Gene Transcription

  摘要：

  The synthesis and biological activity of a series of seco-oxysterol analogs designed to be inhibitors of transcription of the gene for 3-hydroxy-3-methylglutaryl-Coenzyme A reductase (HMGR) are described. The compound possessing the most significant activity, [1 alpha(E),4 beta]-3-[2-(4-hydroxy- 1-methylcyclohexyl)ethenyl]-alpha,alpha-dimethylbenzenepentanol (4, U-88156), inhibited (IC50 = 10 mu M) the expression of beta-galactosidase (beta-gal) in a transfected human HepG2 cell line wherein the beta-gal gene was driven by a 5 kB segment of the promoter for hamster HMGR. Furthermore, using wild-type HepG2 cells, it was shown that 10 mu M: 4 reduced HMGR mRNA levels by 73% while stimulating LDL-receptor activity by 47%. In the same system, the related oxysterol, 25-hydroxycholesterol (1), at 10 mu M lowered both HMGR mRNA levels and LDL-receptor activity by 58% and 64%, respectively. Overall HMGR activity in wild-type HepG2 cells was inhibited 30% by 4 at 10 mu M. These findings collectively demonstrate that a secooxysterol analog is capable of regulating HMGR gene expression and that this regulation can occur without a concomitant attenuation of the level of LDL-receptor activity.

  DOI：

  10.1021/jm00041a013

文献信息

• IRAK INHIBITORS AND USES THEREOF
  申请人：NIMBUS IRIS, INC.

  公开号：US20130231328A1

  公开（公告）日：2013-09-05

  The present invention provides compounds, compositions thereof, and methods of using the same.

  本发明提供了化合物、其组合物以及使用它们的方法。
• [EN] IRAK INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS D'IRAK ET LEURS UTILISATIONS
  申请人：NIMBUS IRIS INC

  公开号：WO2013106535A9

  公开（公告）日：2014-09-04
• US9212190B2
  申请人：——

  公开号：US9212190B2

  公开（公告）日：2015-12-15
• Design and Synthesis of Seco-oxysterol Analogs as Potential Inhibitors of 3-Hydroxy-3-methylglutaryl-Coenzyme A (HMG-CoA) Reductase Gene Transcription
  作者：Scott D. Larsen、Charles H. Spilman、Yoshi Yagi、Dac M. Dinh、Karen L. Hart、Gerard F. Hess

  DOI：10.1021/jm00041a013

  日期：1994.7

  The synthesis and biological activity of a series of seco-oxysterol analogs designed to be inhibitors of transcription of the gene for 3-hydroxy-3-methylglutaryl-Coenzyme A reductase (HMGR) are described. The compound possessing the most significant activity, [1 alpha(E),4 beta]-3-[2-(4-hydroxy- 1-methylcyclohexyl)ethenyl]-alpha,alpha-dimethylbenzenepentanol (4, U-88156), inhibited (IC50 = 10 mu M) the expression of beta-galactosidase (beta-gal) in a transfected human HepG2 cell line wherein the beta-gal gene was driven by a 5 kB segment of the promoter for hamster HMGR. Furthermore, using wild-type HepG2 cells, it was shown that 10 mu M: 4 reduced HMGR mRNA levels by 73% while stimulating LDL-receptor activity by 47%. In the same system, the related oxysterol, 25-hydroxycholesterol (1), at 10 mu M lowered both HMGR mRNA levels and LDL-receptor activity by 58% and 64%, respectively. Overall HMGR activity in wild-type HepG2 cells was inhibited 30% by 4 at 10 mu M. These findings collectively demonstrate that a secooxysterol analog is capable of regulating HMGR gene expression and that this regulation can occur without a concomitant attenuation of the level of LDL-receptor activity.
• Studies on antidiabetic agents. IV. Synthesis and activity of the metabolites of 5-(4-(1-methylcyclohexylmethoxy)benzyl)-2,4-thiazolidinedione (ciglitazone).
  作者：TAKASHI SOHDA、KANJI MEGURO、YUTAKA KAWAMATSU

  DOI：10.1248/cpb.32.2267

  日期：——

  Compounds 2-9 possessing a hydroxy or an oxo moiety on the cyclohexane ring of 5-[4-(1-methylcyclohexylmethoxy) benzyl]-2, 4-thiazolidinedione (1, ciglitazone) were synthesized to clarify the structure of the metabolites of 1 and for studies of their pharmacological properties. Of the metabolites identified, 5-[4-(t-3-hydroxy-1-methyl-r-1-cyclohexylmethoxy) benzyl]-2, 4-thiazolidinedione (7) exhibited extremely potent antidiabetic activity compared to 1. Stereoselective syntheses of 3- or 4-hydroxy-1-methylcyclohexanecarboxylic acids required for the preparation of 3'- or 4'-hydroxylated compounds (6, 7 or 3, 4, respectively) are described.

  合成了在 5-[4-(1-甲基环己基甲氧基)苄基]-2，4-噻唑烷二酮（1，西格列酮）的环己烷环上具有羟基或氧代分子的化合物 2-9，以明确 1 的代谢物的结构，并研究其药理特性。在鉴定出的代谢物中，5-[4-（t-3-羟基-1-甲基-r-1-环己基甲氧基）苄基]-2，4-噻唑烷二酮（7）与 1 相比，表现出极强的抗糖尿病活性。