(2R)-2-乙酰氨基-3-(3-氧代丙基硫基)丙酸 | 140226-30-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: (2R)-2-乙酰氨基-3-(3-氧代丙基硫基)丙酸
• 中文别名: 4-{(2S,3S)-3-[(1E,3E,5Z,8Z)-十四碳-1,3,5,8-四烯-1-基]噁丙环-2-基}丁酸
• 英文名称: S-(3-oxopropyl)mercapturic acid
• 英文别名: S-(3-oxopropyl)-N-acetyl-L-cysteine；S-(3-Oxopropyl)-N-acetylcysteine；(2R)-2-acetamido-3-(3-oxopropylsulfanyl)propanoic acid
• CAS: 140226-30-8
• 化学式: C₈H₁₃NO₄S
• 分子量: 219.262
• InChiKey: OOMVCGSUXLINOO-ZETCQYMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  14
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  109
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2R)-2-乙酰氨基-3-(3-氧代丙基硫基)丙酸 在 双氧水 作用下， 以 水 为溶剂， 反应 1.0h， 以96%的产率得到S-(3-oxopropyl)-N-acetyl-L-cysteine S-oxide
  参考文献：
  名称：

  Acrolein Mercapturates: Synthesis, Characterization, and Assessment of Their Role in the Bladder Toxicity of Cyclophosphamide

  摘要：

  Acrolein is the metabolite of cyclophosphamide (CP) believed to be involved in the bladder toxicity associated with this anticancer drug. The mechanism by which this extremely reactive intermediate is delivered to the bladder is not known. Glutathione (GSH) readily conjugates with acrolein, and the acrolein mercapturate S-(3-hydroxypropyl)-N-acetylcysteine (3-hydroxy-PrMCA) has been found in the urine of animals and man given CP. The objectives of this study were to prepare and characterize synthetic standards of the GSH acrolein adduct (3-oxopropyl)glutathione (3-oxoPrGSH), the acrolein mercapturates S-(3-oxopropyl)-N-acetylcysteine (S-oxoPrMCA) and 3-hydroxyPrMCA, and the S-oxidation product of 3-oxoPrMCA (3-oxoPrMCA S-oxide). In addition, the release of acrolein from, and the bladder toxicity of, these conjugates was determined. 3-OxoPrGSH and 3-oxoPrMCA were prepared with a 99% yield by condensing acrolein with GSH and N-acetylcysteine, respectively. 3-HydroxyPrMCA was prepared with a 63% yield by refluxing 3-chloropropanol and N-acetylcysteine in a basic medium. Oxidation of 3-oxoPrMCA with H2O2 was used to prepare 3-oxoPrMCA S-oxide. By decreasing the reaction time to 1 h, and adjusting the ratio of S-oxoPrMCA to H2O2, the yield of 3-oxoPrMCA S-oxide was increased to 96%. The anhydrous aldehyde, 3-oxoPrMCA, afforded characteristic aldehydic proton resonances (H-1 NMR) in deuterated dimethyl sulfoxide. New resonances were observed in deuterated water, indicating a 75% hydration of the aldehyde to the corresponding geminal diol. This phenomenon was enhanced with 3-oxoPrMCA S-oxide where similar to 100% hydration of the aldehyde to the corresponding geminal diol was observed. When incubated at 25 degrees C in 100 mM potassium phosphate buffer containing 1 M KCl, pH 8.0, 3-oxoPrMCA released similar to 6% and 3-oxoPrMCA S-oxide released similar to 16-18% of the theoretical maximum yield of acrolein after 30 min, as indicated by an increase in absorbance at 210 nm and confirmed by trapping this aldehyde as a semicarbazone. There was less than a 2% yield of acrolein from 3-hydroxyPrMCA or 3-oxoPrGSH under similar conditions. At pH 7.4 the release of acrolein from 3-oxoPrMCA and S-oxoPrMCA S-oxide was decreased by 50%. An assay where aldehydes are reacted with m-aminophenol in acid media produced fluorescence consistent with 72%, 46%, 23%, and 1% yields of acrolein from 3-oxoPrMCA S-oxide, 3-oxoPrMCA, 3-oxoPrGSH, and 3-hydroxyPrMCA, respectively. These yields were unaffected by incubation in buffer for up to 2 h. Acrolein, 3-oxoPrMCA S-oxide, S-oxoPrMCA and 3-oxoPrGSH, but not 3-hydroxyPrMCA, damaged the bladder dose-dependently when instilled intravesically in mice at concentrations of 10-20 mM. Potency was acrolein > 3-oxoPrMCA S-oxide > 3-oxoPrMCA > 3-oxoPrGSH. These data support the possibility that a mercapturic acid may be involved in the bladder toxicity of CP.

  DOI：

  10.1021/tx00046a005
• 作为产物：
  描述：

  N-乙酰-L-半胱氨酸 、 丙烯醛 以 水 为溶剂， 以99%的产率得到(2R)-2-乙酰氨基-3-(3-氧代丙基硫基)丙酸
  参考文献：
  名称：

  Acrolein Mercapturates: Synthesis, Characterization, and Assessment of Their Role in the Bladder Toxicity of Cyclophosphamide

  摘要：

  Acrolein is the metabolite of cyclophosphamide (CP) believed to be involved in the bladder toxicity associated with this anticancer drug. The mechanism by which this extremely reactive intermediate is delivered to the bladder is not known. Glutathione (GSH) readily conjugates with acrolein, and the acrolein mercapturate S-(3-hydroxypropyl)-N-acetylcysteine (3-hydroxy-PrMCA) has been found in the urine of animals and man given CP. The objectives of this study were to prepare and characterize synthetic standards of the GSH acrolein adduct (3-oxopropyl)glutathione (3-oxoPrGSH), the acrolein mercapturates S-(3-oxopropyl)-N-acetylcysteine (S-oxoPrMCA) and 3-hydroxyPrMCA, and the S-oxidation product of 3-oxoPrMCA (3-oxoPrMCA S-oxide). In addition, the release of acrolein from, and the bladder toxicity of, these conjugates was determined. 3-OxoPrGSH and 3-oxoPrMCA were prepared with a 99% yield by condensing acrolein with GSH and N-acetylcysteine, respectively. 3-HydroxyPrMCA was prepared with a 63% yield by refluxing 3-chloropropanol and N-acetylcysteine in a basic medium. Oxidation of 3-oxoPrMCA with H2O2 was used to prepare 3-oxoPrMCA S-oxide. By decreasing the reaction time to 1 h, and adjusting the ratio of S-oxoPrMCA to H2O2, the yield of 3-oxoPrMCA S-oxide was increased to 96%. The anhydrous aldehyde, 3-oxoPrMCA, afforded characteristic aldehydic proton resonances (H-1 NMR) in deuterated dimethyl sulfoxide. New resonances were observed in deuterated water, indicating a 75% hydration of the aldehyde to the corresponding geminal diol. This phenomenon was enhanced with 3-oxoPrMCA S-oxide where similar to 100% hydration of the aldehyde to the corresponding geminal diol was observed. When incubated at 25 degrees C in 100 mM potassium phosphate buffer containing 1 M KCl, pH 8.0, 3-oxoPrMCA released similar to 6% and 3-oxoPrMCA S-oxide released similar to 16-18% of the theoretical maximum yield of acrolein after 30 min, as indicated by an increase in absorbance at 210 nm and confirmed by trapping this aldehyde as a semicarbazone. There was less than a 2% yield of acrolein from 3-hydroxyPrMCA or 3-oxoPrGSH under similar conditions. At pH 7.4 the release of acrolein from 3-oxoPrMCA and S-oxoPrMCA S-oxide was decreased by 50%. An assay where aldehydes are reacted with m-aminophenol in acid media produced fluorescence consistent with 72%, 46%, 23%, and 1% yields of acrolein from 3-oxoPrMCA S-oxide, 3-oxoPrMCA, 3-oxoPrGSH, and 3-hydroxyPrMCA, respectively. These yields were unaffected by incubation in buffer for up to 2 h. Acrolein, 3-oxoPrMCA S-oxide, S-oxoPrMCA and 3-oxoPrGSH, but not 3-hydroxyPrMCA, damaged the bladder dose-dependently when instilled intravesically in mice at concentrations of 10-20 mM. Potency was acrolein > 3-oxoPrMCA S-oxide > 3-oxoPrMCA > 3-oxoPrGSH. These data support the possibility that a mercapturic acid may be involved in the bladder toxicity of CP.

  DOI：

  10.1021/tx00046a005

文献信息

• COMBINATIONS OF N-ACETYL CYSTEINE DERIVATIVES AND CRANBERRY POLYPHENOLS IN COMPOSITIONS AND METHODS FOR PREVENTING AND TREATING PERIODONTAL DISEASES AND PERI-IMPLATITIS
  申请人：Dentalmed Pharm Holding Ltd.

  公开号：EP2976061B1

  公开（公告）日：2019-10-16
• DIAGNOSTIC TEST FOR DISTINGUISHING THE SMOKING STATUS OF A SUBJECT
  申请人：PHILIP MORRIS PRODUCTS S.A.

  公开号：US20200141933A1

  公开（公告）日：2020-05-07

  There is disclosed herein a device for determining the smoking status of a subject, wherein said device comprises a plurality of different specific binding molecules deposited to a solid phase to detect specifically the presence of two or three tobacco smoke exposure biomarkers in a biological sample, said biomarkers consisting of: (i) cotinine and total 4-(methylnitrosamino)-1-(3-, pyridyl)-1-butanol (NNAL); (ii) cotinine and N-acetyl-S-[2-carboxyethyl]-L-cysteine (CEMA); or (iii) cotinine and NNAL and CEMA.
• [EN] COMBINATIONS OF N-ACETYL CYSTEINE DERIVATIVES AND CRANBERRY POLYPHENOLS IN COMPOSITIONS AND METHODS FOR PREVENTING AND TREATING PERIODONTAL DISEASES AND PERI-IMPLATITIS<br/>[FR] COMBINAISON DE DÉRIVÉS DE N-ACÉTYLCYSTÉINE ET DE POLYPHÉNOLS DE CANNEBERGE DANS DES COMPOSITIONS ET DES PROCÉDÉS POUR PRÉVENIR ET TRAITER DES MALADIES PARODONTIQUES ET UNE PÉRI-IMPLANTITE
  申请人：DENTALMED PHARM HOLDING LTD

  公开号：WO2014147613A1

  公开（公告）日：2014-09-25

  The present invention relates to combined compositions comprising a combination of N-acetyl cysteine (NAC), or any derivatives thereof, and polyphenols, specifically cranberry polyphenols. The invention further provides methods and uses of said combined compositions for treating and preventing periodontal diseases, specifically gingivitis, periodontitis and peri-implantitis.
• [EN] COMPOSITIONS AND METHODS FOR TREATING OSTEOLYSIS<br/>[FR] COMPOSITIONS ET PROCÉDÉS DE TRAITEMENT DE L'OSTÉOLYSE
  申请人：UNIV RAMOT

  公开号：WO2021181379A1

  公开（公告）日：2021-09-16

  The present invention relates to methods for treating inflammation-induced and/or aseptic osteolysis. In particular, the methods comprise the use of analogs of vasoactive intestinal peptide (VIP) and pituitary adenylyl cyclase activating polypeptide (PACAP) in osteolysis in periodontal or other diseases and conditions.
• [EN] PHARMACEUTICAL COMPOSITIONS COMPRISING AMPHIPHILIC PEPTIDES AND METHODS OF USE THEREOF<br/>[FR] COMPOSITIONS PHARMACEUTIQUES COMPRENANT DES PEPTIDES AMPHIPHILES ET LEURS PROCÉDÉS D'UTILISATION
  申请人：BONE SCI BIO LTD

  公开号：WO2021191903A1

  公开（公告）日：2021-09-30

  Pharmaceutical compositions comprising amphiphilic peptides are provided. The pharmaceutical compositions are useful in treating or preventing various orthopedic and dental-related infectious and/or inflammatory conditions.