6,9-dioxa-3-thiaspiro[4.4]nonanecarboxylic acid | 508213-64-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 6,9-dioxa-3-thiaspiro[4.4]nonanecarboxylic acid
• 英文别名: 1,4-Dioxa-7-thiaspiro[4.4]nonane-9-carboxylic acid；1,4-dioxa-7-thiaspiro[4.4]nonane-9-carboxylic acid
• CAS: 508213-64-7
• 化学式: C₇H₁₀O₄S
• 分子量: 190.22
• InChiKey: GQOSAGOHVFATAS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  81.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6,9-dioxa-3-thiaspiro[4.4]nonanecarboxylic acid 在 草酰氯 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  Design of Inhibitors of Scytalone Dehydratase: Probing Interactions with an Asparagine Carboxamide

  摘要：

  Among the active-site residues of scytalone dehydratase, the side-chain carboxamide of asparagine 131 has the greatest potential for strong electrostatic interactions. Structure-based inhibitor design aimed at enhancing interactions with this residue led to the synthesis of a series of highly potent inhibitors that have a five- or six-membered ring containing a carbonyl functionality for hydrogen bonding. To achieve a good orientation for hydrogen bonding, the inhibitors incorporate a phenyl substituent that displaces a phenylalanine residue away from the five- or six-membered rings. Without the phenyl substituent, inhibitor binding potency is diminished by three orders of magnitude. Larger K, values of a site-directed mutant (Asn131Ala) of scytalone dehydratase in comparison to those of wild-type enzyme validate the design concept. The most potent inhibitor (K-i = 15 pM) contains a tetrahydrothiophenone that can form a single hydrogen bond with the asparagine carboxamide. Inhibitors with a butyrolactam that can form two hydrogen bonds with the asparagine carboxamide demonstrate excellent in vivo fungicidal activity. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00272-9
• 作为产物：
  描述：

  4-氧四氢噻酚-3-羧酸甲酯 在 sodium hydroxide 、 对甲苯磺酸 作用下， 以 甲醇 、 苯 为溶剂， 生成 6,9-dioxa-3-thiaspiro[4.4]nonanecarboxylic acid
  参考文献：
  名称：

  Design of Inhibitors of Scytalone Dehydratase: Probing Interactions with an Asparagine Carboxamide

  摘要：

  Among the active-site residues of scytalone dehydratase, the side-chain carboxamide of asparagine 131 has the greatest potential for strong electrostatic interactions. Structure-based inhibitor design aimed at enhancing interactions with this residue led to the synthesis of a series of highly potent inhibitors that have a five- or six-membered ring containing a carbonyl functionality for hydrogen bonding. To achieve a good orientation for hydrogen bonding, the inhibitors incorporate a phenyl substituent that displaces a phenylalanine residue away from the five- or six-membered rings. Without the phenyl substituent, inhibitor binding potency is diminished by three orders of magnitude. Larger K, values of a site-directed mutant (Asn131Ala) of scytalone dehydratase in comparison to those of wild-type enzyme validate the design concept. The most potent inhibitor (K-i = 15 pM) contains a tetrahydrothiophenone that can form a single hydrogen bond with the asparagine carboxamide. Inhibitors with a butyrolactam that can form two hydrogen bonds with the asparagine carboxamide demonstrate excellent in vivo fungicidal activity. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00272-9

文献信息

• Design of Inhibitors of Scytalone Dehydratase: Probing Interactions with an Asparagine Carboxamide
  作者：Gregory S Basarab、Douglas B Jordan、Troy C Gehret、Rand S Schwartz

  DOI：10.1016/s0968-0896(02)00272-9

  日期：2002.12

  Among the active-site residues of scytalone dehydratase, the side-chain carboxamide of asparagine 131 has the greatest potential for strong electrostatic interactions. Structure-based inhibitor design aimed at enhancing interactions with this residue led to the synthesis of a series of highly potent inhibitors that have a five- or six-membered ring containing a carbonyl functionality for hydrogen bonding. To achieve a good orientation for hydrogen bonding, the inhibitors incorporate a phenyl substituent that displaces a phenylalanine residue away from the five- or six-membered rings. Without the phenyl substituent, inhibitor binding potency is diminished by three orders of magnitude. Larger K, values of a site-directed mutant (Asn131Ala) of scytalone dehydratase in comparison to those of wild-type enzyme validate the design concept. The most potent inhibitor (K-i = 15 pM) contains a tetrahydrothiophenone that can form a single hydrogen bond with the asparagine carboxamide. Inhibitors with a butyrolactam that can form two hydrogen bonds with the asparagine carboxamide demonstrate excellent in vivo fungicidal activity. (C) 2002 Elsevier Science Ltd. All rights reserved.