5'-hydroxyltenatoprazole | 223713-85-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并吡啶类
• 英文名称: 5'-hydroxyltenatoprazole
• 英文别名: 5'-hydroxytenatoprazole；5'-OH Tenatoprazole；[4-methoxy-6-[(5-methoxy-1H-imidazo[4,5-b]pyridin-2-yl)sulfinylmethyl]-5-methylpyridin-3-yl]methanol
• CAS: 223713-85-7
• 化学式: C₁₆H₁₈N₄O₄S
• 分子量: 362.409
• InChiKey: BLBBZXMQVSPFRX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  129
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  泰妥拉唑 在 G₁T mutant of CYP₁₀₂A₁ 作用下， 反应 0.5h， 生成 5'-hydroxyltenatoprazole 、 5'-hydroxyltenatoprazole sulfide
  参考文献：
  名称：

  테나토프라졸 대사체 및 이의 제조방법

  摘要：

  这项发明涉及一种产生tenatoprazole的新代谢物5'-羟基tenatoprazole和5'-羟基tenatoprazole磺酰化物的野生型CYP102A1突变体，该突变体是细菌细胞色素P450酶野生型CYP102A1的点突变体，将野生型CYP102A1的点突变体的血红素区域和野生型CYP102A1的自然变异体的还原酶融合成嵌合体CYP102A1，利用嵌合体CYP102A1和嵌合体CYP102A1的点突变体作为酶，可以选择性地大量生产5'-羟基tenatoprazole和5'-羟基tenatoprazole磺酰化物通过将tenatoprazole氧化。

  公开号：

  KR101958346B1

文献信息

• Regioselective hydroxylation pathway of tenatoprazole to produce human metabolites by Bacillus megaterium CYP102A1
  作者：Thien-Kim Le、Gun-Su Cha、Hyun-Hee Jang、Thi Huong Ha Nguyen、Tiep Thi My Doan、Young Ju Lee、Ki Deok Park、Yumi Shin、Dong-Hyun Kim、Chul-Ho Yun

  DOI：10.1016/j.procbio.2019.09.014

  日期：2019.12

  Tenatoprazole, a proton pump inhibitor drug candidate, is developed as an acid inhibitor to treat gastric acid hypersecretion disorders, such as gastric ulcer and reflux esophagitis. Tenatoprazole is known to be metabolized to three major metabolites tenatoprazole sulfone, 5'-hydroxylated metabolite, and tenatoprazole sulfide in human livers mainly by CYP2C19 and CYP3A4. In this study, an enzymatic strategy for the production of human metabolites of tenatoprazole was developed using bacterial P450 enzymes. A set of CYP102A1 mutants catalyzed the regioselective hydroxylation reactions of tenatoprazole. The major product of tenatoprazole by CYP102A1 is 5'-OH tenatoprazole, a major human metabolite produced by human CYP2C19 and CYP3A4. As another major metabolite of tenatoprazole, tenatoprazole sulfide is formed via a non-enzymatic conversion without a P450 system. In addition, 5'-OH tenatoprazole sulfide was found as a minor metabolite, which can be formed via a 5'-hydroxylation reaction of tenatoprazole sulfide by CYP102A1 and/or a non-enzymatic reduction of 5'-OH tenatoprazole to a sulfide form. Chemical synthesis of the 5'-OH tenatoprazole is not currently possible. In conclusion, an enzymatic synthesis of 5'-OH tenatoprazole, a major human metabolite of tenatoprazole, was developed by using mutants of CYP102A1 from Bacillus megaterium as a biocatalyst and tenatoprazole as a substrate.