ethyl 2,2-dimethylnonanoate | 93476-25-6

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: ethyl 2,2-dimethylnonanoate
• 英文别名: 2,2-Dimethyl-pelargonsaeure-ethylester
• CAS: 93476-25-6
• 化学式: C₁₃H₂₆O₂
• 分子量: 214.348
• InChiKey: ZTTMCPHTRBZLKY-UHFFFAOYSA-N

物化性质

• 沸点：
  71 °C(Press: 3 Torr)
• 密度：
  0.8629 g/cm3

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  15
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  ethyl 2,2-dimethylnonanoate 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 生成 2,2-二甲基壬烷-1-醇
  参考文献：
  名称：

  Potent Anandamide Analogs:  The Effect of Changing the Length and Branching of the End Pentyl Chain

  摘要：

  To examine the effect of changing the length and branching of the end pentyl chain (C5H11) of anandamide (AN), various analogs 1a-h and 2a-f were synthesized from either the known aldehyde ester 6a or from the alcohol 6b and tested for their pharmacological activity. A reproducible procedure was developed for the conversion of arachidonic acid to 6a or 6b in gram quantities (overall yield 15%). The appropriate tetraene esters 7 were prepared by carrying out a Wittig reaction, between 6a and the ylide generated from the phosphonium salt of the appropriate alkyl halide or between the ylide of 6d (prepared from 6a --> 6b --> 6c --> 6d) and the appropriate alkyl aldehydes. They were then hydrolyzed to the corresponding acids and transformed into AN analogs 1 via their acid chlorides then treated with excess ethanolamine. alpha-Alkylation of esters 7 gave compounds 8 which were hydrolyzed to the corresponding acids. These acids via their acid chlorides and subsequent treatment with excess fluoroethylamine gave the target compounds 2. In this way analogs 1e and 2a-c were synthesized from 6d while all the remaining analogs were prepared from 6a. In order to assess the optimal length of the alkyl terminus, analogs 1a-d were prepared and showed moderately high affinities (18-55 nM). However analogs 1a-c failed to produce significant pharmacological effects at doses up to 30 mg/kg. Analog 1d was found to be a weak partial agonist. The reason for the lack of activity in 1a-c is presently not clear. Like the THCs, the branching of the end pentyl chain in AN (1e-h) increased potency both in in vitro and in vivo activities; the dimethylheptyl (DMH) analog 1e was the most potent in the series. Similar alkyl substitutions were carried out in the fluoro-2-methylanandamide series (2a-f), and all of these analogs had high receptor affinities (1-14 nM), the DMH analog 2a being the most potent. With a few exceptions they showed robust pharmacological effects, and AN-like profiles, It was shown that the SAR of the end pentyl chain in AN is very similar to that of THCs. However, the magnitude of enhanced potency observed when the side chain of THC was changed from straight to branched was not observed when the end chain of AN was similarly changed.

  DOI：

  10.1021/jm970212f
• 作为产物：
  描述：

  1-溴代庚烷 、 异丁酸乙酯 在 lithium diisopropyl amide 作用下， 生成 ethyl 2,2-dimethylnonanoate
  参考文献：
  名称：

  Potent Anandamide Analogs:  The Effect of Changing the Length and Branching of the End Pentyl Chain

  摘要：

  To examine the effect of changing the length and branching of the end pentyl chain (C5H11) of anandamide (AN), various analogs 1a-h and 2a-f were synthesized from either the known aldehyde ester 6a or from the alcohol 6b and tested for their pharmacological activity. A reproducible procedure was developed for the conversion of arachidonic acid to 6a or 6b in gram quantities (overall yield 15%). The appropriate tetraene esters 7 were prepared by carrying out a Wittig reaction, between 6a and the ylide generated from the phosphonium salt of the appropriate alkyl halide or between the ylide of 6d (prepared from 6a --> 6b --> 6c --> 6d) and the appropriate alkyl aldehydes. They were then hydrolyzed to the corresponding acids and transformed into AN analogs 1 via their acid chlorides then treated with excess ethanolamine. alpha-Alkylation of esters 7 gave compounds 8 which were hydrolyzed to the corresponding acids. These acids via their acid chlorides and subsequent treatment with excess fluoroethylamine gave the target compounds 2. In this way analogs 1e and 2a-c were synthesized from 6d while all the remaining analogs were prepared from 6a. In order to assess the optimal length of the alkyl terminus, analogs 1a-d were prepared and showed moderately high affinities (18-55 nM). However analogs 1a-c failed to produce significant pharmacological effects at doses up to 30 mg/kg. Analog 1d was found to be a weak partial agonist. The reason for the lack of activity in 1a-c is presently not clear. Like the THCs, the branching of the end pentyl chain in AN (1e-h) increased potency both in in vitro and in vivo activities; the dimethylheptyl (DMH) analog 1e was the most potent in the series. Similar alkyl substitutions were carried out in the fluoro-2-methylanandamide series (2a-f), and all of these analogs had high receptor affinities (1-14 nM), the DMH analog 2a being the most potent. With a few exceptions they showed robust pharmacological effects, and AN-like profiles, It was shown that the SAR of the end pentyl chain in AN is very similar to that of THCs. However, the magnitude of enhanced potency observed when the side chain of THC was changed from straight to branched was not observed when the end chain of AN was similarly changed.

  DOI：

  10.1021/jm970212f

文献信息

• 2,5,6,7-tetranor-4,8-inter-m-phenylene PGI.sub.2 derivatives
  申请人：Toray Industries, Inc.

  公开号：US04775692A1

  公开（公告）日：1988-10-04

  Disclosed herein are novel prostaglandin I.sub.2 (PGI.sub.2) derivatives exhibiting excellent in vivo duration and activities, said derivatives being represented by the general formula: ##STR1## wherein R.sub.1, X, R.sub.2 and R.sub.3 are as defined herein.

  本文披露了一种展现出优异体内持续时间和活性的新型前列腺素I.sub.2（PGI.sub.2）衍生物，所述衍生物由以下一般式表示：##STR1##其中R.sub.1、X、R.sub.2和R.sub.3如本文所定义。
• US4775692A
  申请人：——

  公开号：US4775692A

  公开（公告）日：1988-10-04
• [EN] MACROCYLIC INHIBITORS OF HEPATITIS C VIRUS<br/>[FR] INHIBITEURS MACROCYCLIQUES DU VIRUS DE L'HÉPATITE C
  申请人：TIBOTEC PHARM LTD

  公开号：WO2007014919A1

  公开（公告）日：2007-02-08

  [EN] Inhibitors of HCV of formula (I), and the N-oxides, salts, and stereochemically isomeric forms thereof, wherein R¹ is aryl or a saturated, a partially unsaturated or completely unsaturated 5 or 6 membered monocyclic or 8 to 12 membered bicyclic heterocyclic ring system containing one nitrogen, and optionally one to three oxygen, sulfur or nitrogen, wherein said ring system may be optionally substituted; L is a direct bond, -O-. -O-C_1-4alkanediyl-, -O-CO-, -O-C(=O)-NR^5a- or -O-C(=O)-NR^5a-C_1-4alkanediyl-; R² is hydrogen, -OR⁶, -C(O)OR⁶, -C(=O)R⁷, -C(=O)NR^5aR^5b, -C(=O)NHR^5c, -NR^5aR^5b, -NHR^5c, -NHSO_pNR^5aR^5b, -NR^5aSO_pR⁸, or -B(OR⁶)₂; R³ and R⁴ are hydrogen or C_1-6alkyl; or R³ and R⁴ taken together may form a C_3-7cycloalkyl ring; n is 3, 4, 5, or 6; p is 1 or 2; aryl is phenyl, naphthyl, indanyl, or 1,2,3,4-tetrahydronaphthyl, each of which may be optionally substituted Het is a 5 or 6 membered saturated, partially unsaturated or completely unsaturated heterocyclic ring containing 1 to 4 heteroatoms each independently selected from nitrogen, oxygen and sulfur, being optionally condensed with a benzene ring, and wherein the group Het as a whole may be optionally substituted ; pharmaceutical compositions containing compounds (I) and processes for preparing compounds (I). Bioavailable combinations of the inhibitors of HCV of formula (I) with ritonavir are also provided.
  [FR] Inhibiteurs du VHC de formule (I) et N-oxydes, sels et formes isomériques du point de vue stéréochimique de ceux-ci, dans laquelle formule R¹ est un aryle ou un système hétérocyclique monocyclique ayant 5 ou 6 chaînons ou bicyclique ayant 8 à 12 chaînons, saturé, partiellement insaturé ou complètement insaturé, contenant un azote et facultativement un à trois atomes d'oxygène, de soufre ou d'azote, ledit système cyclique pouvant être facultativement substitué ; L est une liaison directe, -O-, un -O-(alcane en C_1-4)diyle-, -O-CO-, -O-C(=O)-NR^5a- ou un -O-C(=O)-NR^5a-(alcane en C_1-4)diyle- ; R² est un hydrogène, -OR⁶, -C(O)OR⁶, -C(=O)R⁷, -C(=O)NR^5aR^5b, -C(=O)NHR^5c, -NR^5aR^5b, -NHR^5c, -NHSO_pNR^5aR^5b, -NR^5aSO_pR⁸ ou -B(OR⁶)₂ ; R³ et R⁴ sont chacun un hydrogène ou un alkyle en C_1-6 ; ou bien R³ et R⁴ pris ensemble peuvent former un cycle cycloalkyle en C_3-7 ; n est 3, 4, 5 ou 6 ; p est 1 ou 2 ; un aryle est un phényle, un naphtyle, un indanyle ou un 1,2,3,4-tétrahydronaphtyle, chacun desquels pouvant être facultativement substitué ; Het est un hétérocycle saturé, partiellement insaturé ou complètement insaturé à 5 ou 6 chaînons contenant 1 à 4 hétéroatomes sélectionnés chacun indépendamment entre l'azote, l'oxygène et le soufre, ledit hétérocycle étant facultativement condensé avec un noyau benzénique et le groupe Het pris dans son ensemble pouvant être facultativement substitué ; compositions pharmaceutiques contenant les composés (I) et procédés servant à préparer les composés (I). L'invention concerne également des associations biodisponibles des inhibiteurs du VHC de formule (I) avec du ritonavir.
• Potent Anandamide Analogs:  The Effect of Changing the Length and Branching of the End Pentyl Chain
  作者：William J. Ryan、W. Kenneth Banner、Jenny L. Wiley、Billy R. Martin、Raj K. Razdan

  DOI：10.1021/jm970212f

  日期：1997.10.1

  To examine the effect of changing the length and branching of the end pentyl chain (C5H11) of anandamide (AN), various analogs 1a-h and 2a-f were synthesized from either the known aldehyde ester 6a or from the alcohol 6b and tested for their pharmacological activity. A reproducible procedure was developed for the conversion of arachidonic acid to 6a or 6b in gram quantities (overall yield 15%). The appropriate tetraene esters 7 were prepared by carrying out a Wittig reaction, between 6a and the ylide generated from the phosphonium salt of the appropriate alkyl halide or between the ylide of 6d (prepared from 6a --> 6b --> 6c --> 6d) and the appropriate alkyl aldehydes. They were then hydrolyzed to the corresponding acids and transformed into AN analogs 1 via their acid chlorides then treated with excess ethanolamine. alpha-Alkylation of esters 7 gave compounds 8 which were hydrolyzed to the corresponding acids. These acids via their acid chlorides and subsequent treatment with excess fluoroethylamine gave the target compounds 2. In this way analogs 1e and 2a-c were synthesized from 6d while all the remaining analogs were prepared from 6a. In order to assess the optimal length of the alkyl terminus, analogs 1a-d were prepared and showed moderately high affinities (18-55 nM). However analogs 1a-c failed to produce significant pharmacological effects at doses up to 30 mg/kg. Analog 1d was found to be a weak partial agonist. The reason for the lack of activity in 1a-c is presently not clear. Like the THCs, the branching of the end pentyl chain in AN (1e-h) increased potency both in in vitro and in vivo activities; the dimethylheptyl (DMH) analog 1e was the most potent in the series. Similar alkyl substitutions were carried out in the fluoro-2-methylanandamide series (2a-f), and all of these analogs had high receptor affinities (1-14 nM), the DMH analog 2a being the most potent. With a few exceptions they showed robust pharmacological effects, and AN-like profiles, It was shown that the SAR of the end pentyl chain in AN is very similar to that of THCs. However, the magnitude of enhanced potency observed when the side chain of THC was changed from straight to branched was not observed when the end chain of AN was similarly changed.