(1R,2R)-2-acetylcyclopropane-1-carboxylic acid | 18180-59-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 酮酸及其衍生物
• 英文名称: (1R,2R)-2-acetylcyclopropane-1-carboxylic acid
• CAS: 18180-59-1；60212-43-3
• 化学式: C₆H₈O₃
• 分子量: 128.128
• InChiKey: HYILWFYAUMCTTP-CRCLSJGQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  9
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 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：

  (1R,2R)-2-acetylcyclopropane-1-carboxylic acid 在 barium dihydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 48.0h， 生成 (1R,2R)-2-(1-amino-1-carboxyethyl)cyclopropane-1-carboxylic acid
  参考文献：
  名称：

  2-Substituted (2SR)-2-Amino-2-((1SR,2SR)-2-carboxycycloprop-1-yl)glycines as Potent and Selective Antagonists of Group II Metabotropic Glutamate Receptors. 1. Effects of Alkyl, Arylalkyl, and Diarylalkyl Substitution

  摘要：

  In this paper, we describe the synthesis of a series of a-substituted analogues of the potent and selective group II metabotropic glutamate receptor (mGluR) agonist (1S,1'S,2'S)-carboxy-cyclopropylglycine (2, L-CCG 1). Incorporation of a substituent on the amino acid carbon converted the agonist 2 into antagonist. Ail of the compounds were prepared and tested as a series of four isomers, i.e., two racemic diastereomers. We explored alkyl substitution, both normal and terminally branched; phenylalkyl and diphenylalkyl substitution; and a variety of aromatic and carbocyclic surrogates for phenyl. Affinity for group II mGluRs was measured using [H-3]glutamic acid (Glu) binding in rat forebrain membranes. Antagonist activity was confirmed for these compounds by measuring their ability to antagonize (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid-induced inhibition of forskolin-stimulated cyclic-AMP in RGT cells transfected with human mGluR2 and mGluR3. We found that while alkyl substitution provided no increase in affinity relative to 2, phenylethyl and diphenylethyl substitution, as in 105 and 109, respectively, were quite beneficial, The affinity of 109 was further enhanced when the two aromatic rings were joined by an oxygen or sulfur atom to form the tricyclic xanthylmethyl and thioxanthylmethyl amino acids 113 and 114, respectively. Amino acid 113, with an IC50 of 0.10 mu M in the [H-3]Glu binding assay, was 52-fold more patent than 2, whose IC50 was 0.47 mu M.

  DOI：

  10.1021/jm970497w
• 作为产物：
  描述：

  反-1,2-环丙烷二羧酸二乙酯 在 sodium hydroxide 、 copper(l) iodide 、 氯化亚砜 作用下， 以 乙醇 为溶剂， 反应 7.5h， 生成 (1R,2R)-2-acetylcyclopropane-1-carboxylic acid
  参考文献：
  名称：

  2-Substituted (2SR)-2-Amino-2-((1SR,2SR)-2-carboxycycloprop-1-yl)glycines as Potent and Selective Antagonists of Group II Metabotropic Glutamate Receptors. 1. Effects of Alkyl, Arylalkyl, and Diarylalkyl Substitution

  摘要：

  In this paper, we describe the synthesis of a series of a-substituted analogues of the potent and selective group II metabotropic glutamate receptor (mGluR) agonist (1S,1'S,2'S)-carboxy-cyclopropylglycine (2, L-CCG 1). Incorporation of a substituent on the amino acid carbon converted the agonist 2 into antagonist. Ail of the compounds were prepared and tested as a series of four isomers, i.e., two racemic diastereomers. We explored alkyl substitution, both normal and terminally branched; phenylalkyl and diphenylalkyl substitution; and a variety of aromatic and carbocyclic surrogates for phenyl. Affinity for group II mGluRs was measured using [H-3]glutamic acid (Glu) binding in rat forebrain membranes. Antagonist activity was confirmed for these compounds by measuring their ability to antagonize (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid-induced inhibition of forskolin-stimulated cyclic-AMP in RGT cells transfected with human mGluR2 and mGluR3. We found that while alkyl substitution provided no increase in affinity relative to 2, phenylethyl and diphenylethyl substitution, as in 105 and 109, respectively, were quite beneficial, The affinity of 109 was further enhanced when the two aromatic rings were joined by an oxygen or sulfur atom to form the tricyclic xanthylmethyl and thioxanthylmethyl amino acids 113 and 114, respectively. Amino acid 113, with an IC50 of 0.10 mu M in the [H-3]Glu binding assay, was 52-fold more patent than 2, whose IC50 was 0.47 mu M.

  DOI：

  10.1021/jm970497w

文献信息

• ZumHunsdiecker-Abbau von 2-Acylcyclopropancarbonsäuren
  作者：Friedrich Hammerschmidt、Erich Zbiral

  DOI：10.1007/bf01046438

  日期：1977.11
• [EN] COMPOUNDS AND COMPOSITIONS FOR TREATING HIV INFECTIONS
  申请人：SCHERING CORPORATION

  公开号：WO1993012138A1

  公开（公告）日：1993-06-24

  (EN) The use of a compound respresented by formula (I) in the manufacture of a medicament for treating a mammal infected with human immunodeficiency virus, acquired immune deficiency syndrome caused by human immunodeficiency virus or acquired immunodeficiency syndrome-related complex caused by immunodeficiency virus, and stereochemical isomers and pharmaceutically acceptable salts thereof. In formula (I), W = (C1-C5) alkyl, NHR3 or OR1; B = two hydrogens, a double bond, >O, or >S; Q = R3 or AA; Z = NHR3, OR1 or AA; R1 = H, or (C1-C5) alkyl; R2 = H, CH3, -(CH2)sNHR3 or -(CH2)sAA; R3 = H or (C1-C5) alkyl or (C1-C6); alkanoyl n = 1 to 3; s = 0 to 3; q = 0 or 1; AA = a natural or unnatural-(L)- amino acid moiety; the asterisk (*) carbon atom indicate an asymmetric center; and the wavy line $(1,4)$ represents a single bond to place the (1) moiety in the $i(cis)- or $i(trans)-configuration relative to the (2) moiety except when B is two hydrogens; with the proviso that in formula (I) when B = >O, n = q = 1, W = NH2, R2 = R1 = R3 = H, Z = OH and the wavy line has the trans-configuration, then Q ¸ CO-CH(NH2)CH3.(FR) Cette invention concerne l'utilisation d'un composé de formule (I) pour fabriquer un médicament destiné à traiter un mammifère contaminé par le virus de déficience immunitaire humaine (VIH), le syndrome de déficience immunitaire acquise provoqué par le VIH ou le complexe lié au syndrome de déficience immunitaire acquise provoqué par le virus de déficience immunitaire. Ledit composé est représenté par la formule (I). Cette invention concerne également des isomères stéréochimiques et leurs sels pharmaceutiquement acceptables. Dans la formule (I), W représente alkyle (C1-C5), NHR3 ou OR1; B représente deux atomes d'hydrogène, une double liaison, >O, ou >S; Q représente R3 ou AA; Z représente NHR3, OR1 ou AA; R1 représente H, ou alkyle (C1-C5); R2 représente H, CH3, -(CH2)sNHR3 ou -(CH2)sAA; R3 représente H ou alkyle (C1-C5) ou alcanoyle (C1-C6); n est compris entre 1 et 3; s est compris entre 0 et 3; q est compris entre 0 et 1; AA représente une fraction d'acide aminé -(L)- naturel ou non; l'astérisque (*) atome de carbone indique un centre asymétrique; et la ligne ondulée $(1,4)$ représente une liaison simple servant à placer la fraction (1) dans la configuration $i(cis)- ou $i(trans)- par rapport à la fraction (2) sauf lorsque B représente deux atomes d'hydrogène; à condition que dans la formule (I) lorsque B est >0, n = q = 1, W = NH2, R2 = R1 = R3 = H, Z = OH et la ligne ondulée a la configuration trans, alors Q ¸ CO-CH(NH2)CH3.
• 2-Substituted (2<i>SR</i>)-2-Amino-2-((1<i>SR</i>,2<i>SR</i>)-2-carboxycycloprop-1-yl)glycines as Potent and Selective Antagonists of Group II Metabotropic Glutamate Receptors. 1. Effects of Alkyl, Arylalkyl, and Diarylalkyl Substitution
  作者：Paul L. Ornstein、Thomas J. Bleisch、M. Brian Arnold、Rebecca A. Wright、Bryan G. Johnson、Darryle D. Schoepp

  DOI：10.1021/jm970497w

  日期：1998.1.1

  In this paper, we describe the synthesis of a series of a-substituted analogues of the potent and selective group II metabotropic glutamate receptor (mGluR) agonist (1S,1'S,2'S)-carboxy-cyclopropylglycine (2, L-CCG 1). Incorporation of a substituent on the amino acid carbon converted the agonist 2 into antagonist. Ail of the compounds were prepared and tested as a series of four isomers, i.e., two racemic diastereomers. We explored alkyl substitution, both normal and terminally branched; phenylalkyl and diphenylalkyl substitution; and a variety of aromatic and carbocyclic surrogates for phenyl. Affinity for group II mGluRs was measured using [H-3]glutamic acid (Glu) binding in rat forebrain membranes. Antagonist activity was confirmed for these compounds by measuring their ability to antagonize (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid-induced inhibition of forskolin-stimulated cyclic-AMP in RGT cells transfected with human mGluR2 and mGluR3. We found that while alkyl substitution provided no increase in affinity relative to 2, phenylethyl and diphenylethyl substitution, as in 105 and 109, respectively, were quite beneficial, The affinity of 109 was further enhanced when the two aromatic rings were joined by an oxygen or sulfur atom to form the tricyclic xanthylmethyl and thioxanthylmethyl amino acids 113 and 114, respectively. Amino acid 113, with an IC50 of 0.10 mu M in the [H-3]Glu binding assay, was 52-fold more patent than 2, whose IC50 was 0.47 mu M.