(E)-N-Acetyl-S-(1,2,3,4,4-pentachlorobutadienyl)-L-cysteine | 89784-39-4

• 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
• 英文名称: (E)-N-Acetyl-S-(1,2,3,4,4-pentachlorobutadienyl)-L-cysteine
• 英文别名: N-acetyl-S-(1,2,3,4,4-pentachloro-1,3-butadienyl)-L-cysteine；N-acetyl-S-(1,2,3,4,4-pentachlorobuta-1,3-dienyl)-L-cysteine；N-acetyl-S-pentachlorobutadienyl-L-cysteine；S-Pentachlorobutadienyl-N-acetylcysteine；(2R)-2-acetamido-3-[(1E)-1,2,3,4,4-pentachlorobuta-1,3-dienyl]sulfanylpropanoic acid
• CAS: 89784-39-4；169231-00-9
• 化学式: C₉H₈Cl₅NO₃S
• 分子量: 387.498
• InChiKey: HMFZXPFVUQXTHQ-ZPFUWANQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  91.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (E)-N-Acetyl-S-(1,2,3,4,4-pentachlorobutadienyl)-L-cysteine 在 双氧水 作用下， 以 三氟乙酸 为溶剂， 反应 5.0h， 以89%的产率得到N-acetyl-S-(1,2,3,4,4-pentachlorobuta-1,3-dienyl)-L-cysteine sulfoxide
  参考文献：
  名称：

  The Sulfoxidation of the Hexachlorobutadiene Metabolite N-Acetyl-S-(1,2,3,4,4-pentachlorobutadienyl)-L-cysteine Is Catalyzed by Human Cytochrome P450 3A Enzymes

  摘要：

  The sulfoxidation of the mercapturic acid N-acetyl-S-(1,2,3,4,4-pentachlorobuta-1,3-dienyl)-L-cysteine (N-Ac-PCBC), a urinary metabolite of the renal toxin hexachlorobutadiene (HCBD), was studied in human liver microsomes and with purified cDNA expressed human liver cytochrome P450 (P450) enzymes. N-Acetyl-S-(1,2,3,4,4-pentachlorobuta-1,3-dienyl)-L-cysteine sulfoxide (N-Ac-PCBC SO) is a major urinary metabolite of HCBD in male rats; only liver microsomes from male rats catalyze the sulfoxidation of N-Ac-PCBC. Our results presented here show that human liver microsomes from both male and female donors are capable of oxidizing N-Ac-PCBC to the corresponding sulfoxide diastereomers. The correlation of N-Ac-PCBC sulfoxidation with the rates of oxidation of P450 enzyme specific substrates suggests that only P450 3A enzymes oxidize N-Ac-PCBC. Moreover, only gestodene and troleandomycin, two selective inhibitors for P450 of the 3A family, significantly reduced the rates of N-Ac-PCBC sulfoxidation. No reduction in sulfoxidation rates was observed with inhibitors for other P450 enzymes, i.e., diethyldithiocarbamate, 4-methylpyrazole, 7,8-benzoflavone, or sulfaphenazole. Incubations of N-Ac-fCBC with purified and reconstituted recombinant P450s 1A2, 2E1, 3A4, and 3A5 resulted in sulfoxide formation only with P450s 3A4 and 3A5. In summary, these results indicate that P450 from the 3A family may sulfoxidize N-Ac-PCBC. Since these P450 enzymes account for a major fraction of the P450 in human liver and are also present in human kidney, the sulfoxidation reaction may also be expected to occur in humans exposed to HCBD.

  DOI：

  10.1021/tx00049a004

文献信息

• Biotransformation, Excretion, and Nephrotoxicity of the Hexachlorobutadiene Metabolite (<i>E</i>)-<i>N</i>-Acetyl-<i>S</i>-(1,2,3,4,4-pentachlorobutadienyl)-<scp>l</scp>-cysteine Sulfoxide
  作者：Gerhard Birner、Michael Werner、Elisabeth Rosner、Claudia Mehler、Wolfgang Dekant

  DOI：10.1021/tx970216n

  日期：1998.7.1

  observed nephrotoxic effects. A novel metabolite, identified as (E)-N-acetyl-S-(1,2,3,4, 4-pentachlorobutadienyl)-L-cysteine sulfoxide (N-AcPCBC-SO), was described after administration of [14C]HCBD to male Wistar rats. This metabolite is formed by sulfoxidation of N-acetyl-S-(1,2,3,4, 4-pentachlorobutadienyl)-L-cysteine (N-AcPCBC) mediated by cytochrome P450 3A and has been found to be cytotoxic to proximal

  六氯丁三烯-1,3-二烯（HCBD）在啮齿动物中具有肾毒性。其毒性基于多步生物激活途径。通过谷胱甘肽S-转移酶与谷胱甘肽结合形成（E）-S-（1,2,3,4,4-五氯丁二烯基）-L-谷胱甘肽（PCBG），进一步加工成相应的半胱氨酸S-缀合物，最后加工认为反应性硫代乙烯酮的抗氧化剂是所观察到的肾毒性作用的原因。服用[14C]后，描述了一种新的代谢物，称为（E）-N-乙酰基-S-（1,2,3,4,4-五氯丁二烯基）-L-半胱氨酸亚砜（N-AcPCBC-SO）。对雄性Wistar大鼠使用HCBD。该代谢物是由N-乙酰基-S-（1,2,3,4，由细胞色素P450 3A介导的4-五氯丁二烯基）-L-半胱氨酸（N-AcPCBC），并在体外对近端肾小管细胞具有细胞毒性，而没有被β-裂合酶激活。在大鼠体内给予六氯丁二烯时，仅排出亚砜的一种非对映异构体。然而，在大鼠肝微粒体中，形成了两个非对映异构体，（R）
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  公开号：WO2019055825A1

  公开（公告）日：2019-03-21

  The current methods and compositions provide for therapeutic approaches to treating hepatocellular carcinoma (HCC) and other types of cancer including, for example, pancreatic and colon cancer. Accordingly, certain aspects of the disclosure relates to methods and compositions for treating HCC, pancreatic and colon cancer using one or more small molecule inhibitors disclosed herein. In certain embodiments, the small molecule inhibitor is a benzothiazine, a sulfonamide, a thiazolidinone or other chemical compound.

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  申请人：Dentalmed Pharm Holding Ltd.

  公开号：EP2976061B1

  公开（公告）日：2019-10-16
• INHIBITION OF AMINOCYLASE 3 (AA3) IN THE TREATMENT OF CANCER
  申请人：THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

  公开号：US20200206239A1

  公开（公告）日：2020-07-02

  The current methods and compositions provide for therapeutic approaches to treating hepatocellular carcinoma (HCC) and other types of cancer including, for example, pancreatic and colon cancer. Accordingly, certain aspects of the disclosure relates to methods and compositions for treating HCC, pancreatic and colon cancer using one or more small molecule inhibitors disclosed herein. In certain embodiments, the small molecule inhibitor is a benzothiazine, a sulfonamide, a thiazolidinone or other chemical compound.
• [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.