2-[1-(Cyclohexylmethyl)piperidin-4-yl]ethan-1-ol | 141430-54-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 2-[1-(Cyclohexylmethyl)piperidin-4-yl]ethan-1-ol
• 英文别名: 2-[1-(cyclohexylmethyl)piperidin-4-yl]ethanol
• CAS: 141430-54-8
• 化学式: C₁₄H₂₇NO
• mdl: MFCD23708534
• 分子量: 225.374
• InChiKey: DHZUZLGOIMDYOX-UHFFFAOYSA-N

物化性质

• 沸点：
  331.2±15.0 °C(Predicted)
• 密度：
  0.968±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  23.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-[1-(Cyclohexylmethyl)piperidin-4-yl]ethan-1-ol 在 2-叔丁基-1,1,3,3-四甲基胍 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 10.0h， 生成 8-[(6-Bromo-1,3-benzodioxol-5-yl)thio]-9-{2-[1-(cyclohexylmethyl)piperidin-4-yl]ethyl}-9H-purin-6-amine
  参考文献：
  名称：

  Discovery of (2S)-1-[4-(2-{6-Amino-8-[(6-bromo-1,3-benzodioxol-5-yl)sulfanyl]-9H-purin-9-yl}ethyl)piperidin-1-yl]-2-hydroxypropan-1-one (MPC-3100), a Purine-Based Hsp90 Inhibitor

  摘要：

  Modulation of Hsp90 (heat shock protein 90) function has been recognized as an attractive approach for cancer treatment, since many cancer cells depend on Hsp90 to maintain cellular homeostasis. This has spurred the search for small-molecule Hsp90 inhibitors. Here we describe our lead optimization studies centered on the purine-based Hsp90 inhibitor 28a containing a piperidine moiety at the purine N9 position. In this study, key SAR was established for the piperidine N-substituent and for the congeners of the 1,3-benzodioxole at C8. These efforts led to the identification of orally bioavailable 28g that exhibits good in vitro profiles and a characteristic molecular biomarker signature of Hsp90 inhibition both in vitro and in vivo. Favorable pharmacokinetic properties along with significant antitumor effects in multiple human cancer xenograft models led to the selection of 28g (MPC-3100) as a clinical candidate.

  DOI：

  10.1021/jm3004619
• 作为产物：
  描述：

  4-哌啶乙醇 、 环己烷基甲醛 在 三乙酰氧基硼氢化钠 作用下， 以 二氯甲烷 为溶剂， 生成 2-[1-(Cyclohexylmethyl)piperidin-4-yl]ethan-1-ol
  参考文献：
  名称：

  Discovery of (2S)-1-[4-(2-{6-Amino-8-[(6-bromo-1,3-benzodioxol-5-yl)sulfanyl]-9H-purin-9-yl}ethyl)piperidin-1-yl]-2-hydroxypropan-1-one (MPC-3100), a Purine-Based Hsp90 Inhibitor

  摘要：

  Modulation of Hsp90 (heat shock protein 90) function has been recognized as an attractive approach for cancer treatment, since many cancer cells depend on Hsp90 to maintain cellular homeostasis. This has spurred the search for small-molecule Hsp90 inhibitors. Here we describe our lead optimization studies centered on the purine-based Hsp90 inhibitor 28a containing a piperidine moiety at the purine N9 position. In this study, key SAR was established for the piperidine N-substituent and for the congeners of the 1,3-benzodioxole at C8. These efforts led to the identification of orally bioavailable 28g that exhibits good in vitro profiles and a characteristic molecular biomarker signature of Hsp90 inhibition both in vitro and in vivo. Favorable pharmacokinetic properties along with significant antitumor effects in multiple human cancer xenograft models led to the selection of 28g (MPC-3100) as a clinical candidate.

  DOI：

  10.1021/jm3004619

文献信息

• N-HYDROCARBYL-4-SUBSTITUTED PIPERIDINES, THEIR PREPARATION AND USE AS CALCIUM BLOCKING AGENTS
  申请人：SMITH KLINE & FRENCH LABORATORIES LIMITED

  公开号：EP0542846A1

  公开（公告）日：1993-05-26
• US6743777B1
  申请人：——

  公开号：US6743777B1

  公开（公告）日：2004-06-01
• US7790744B2
  申请人：——

  公开号：US7790744B2

  公开（公告）日：2010-09-07
• [EN] N-HYDROCARBYL-4-SUBSTITUTED PIPERIDINES, THEIR PREPARATION AND USE AS CALCIUM BLOCKING AGENTS
  申请人：SMITH KLINE & FRENCH LABORATORIES LIMITED

  公开号：WO1992002502A1

  公开（公告）日：1992-02-20

  (EN) Compounds of structure (I) in which R is C1-8alkyl(phenyl)p, C2-8alkenyl(phenyl)p, C2-8alkenyl(phenyl)p, C3-8cycloalkyl or C1-8alkylC3-8cycloalkyl; p is 0 to 2; n is 0 to 6; A is a bond, oxygen, sulphur or NR1; R1 is hydrogen, C1-8alkyl or phenylC1-4alkyl; m is 0 to 3; and Ar is aryl or heteroaryl, each of which may be optionally substituted, and salts thereof; processes for preparing said compounds, pharmaceutical compositions containing them and their use in therapy, in particular as calcium blocking agents.(FR) Composés de la structure (I) dans laquelle R représente C1-8 alkyle(phényle)p, C2-8 alkényle(phényle)p, C2-8 alcényle(phényle)p, C3-8 cycloalkyle ou C1-8 alkyle C3-8 cycloalkyle; p est compris entre 0 et 2; n est compris entre 0 et 6; A représente une liaison, oxygène, soufre ou NR1; R1 représente hydrogène, C1-8 alkyle ou phényle C1-4 alkyle; m est compris entre 0 et 3; et Ar représente aryle ou hétéroaryle, chacun d'entre eux pouvant être éventuelement substitués, ainsi que leurs sels; procédés de préparation desdits composés (I), compositions pharmaceutiques qui les contiennent et leur utilisation thérapeutique, notamment comme agents de blocage du calcium.