(3R)-6,7-bis (hydroxymethyl)-5-methyl-3-phenyl-1H,3H-pyrrolo [1,2-c]thiazole | 1252613-16-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: (3R)-6,7-bis (hydroxymethyl)-5-methyl-3-phenyl-1H,3H-pyrrolo [1,2-c]thiazole
• 英文别名: [(3R)-7-(hydroxymethyl)-5-methyl-3-phenyl-1,3-dihydropyrrolo[1,2-c][1,3]thiazol-6-yl]methanol
• CAS: 1252613-16-3
• 化学式: C₁₅H₁₇NO₂S
• 分子量: 275.371
• InChiKey: YZIMIQPVZGYIAY-OAHLLOKOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  70.7
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  dimethyl (3R)-5-methyl-3-phenyl-3,4-dihydro-1H-pyrrolo[1,2-a]thiazole-6,7-dicarboxylate 在 lithium aluminium tetrahydride 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 以45%的产率得到(3R)-6,7-bis (hydroxymethyl)-5-methyl-3-phenyl-1H,3H-pyrrolo [1,2-c]thiazole
  参考文献：
  名称：

  Chiral 6-hydroxymethyl-1H,3H-pyrrolo[1,2-c]thiazoles: Novel antitumor DNA monoalkylating agents

  摘要：

  New chiral 1H,3H-pyrrolo[1,2-c]thiazoles were synthesized and screened for their in vitro activity as anti-cancer agents in three human tumor cell lines, colorectal adenocarcinoma, melanoma and breast adenocarcinoma. (R)-6-Hydroxymethyl-5-methyl-3-phenyl-1H,3H-pyrrolo[1,2-c]thiazole and the corresponding benzylcarbamate showed selectivity for breast cancer cell lines with IC(50) values of 24 mu M and 2.2 mu M, respectively. The latter also showed significant activity against colorectal adenocarcinoma cancer cell lines (IC(50) = 8.7 mu M) In contrast, the 7-hydroxymethyl-5-methyl-3-phenyl-1H,3H-pyrrolo[1,2-c] thiazole gave moderate anti-cancer activity. The performance against breast cancer cell lines (IC(50) = 10 mu M) of a potential bisalkylating agent, a (3R)-6,7-bis(hydroxymethyl)-1H,3H-pyrrolo[1,2-c] thiazole, wasn't significantly different from the one observed for the monoalkylating derivatives indicating that the main mechanism of action may in fact be the monoalkylation process. (C) 2010 Elsevier Masson SAS. All rights reserved

  DOI：

  10.1016/j.ejmech.2010.07.029

文献信息

• [EN] "(3S)- AND (3R)-6,7-BIS(HYDROXYMETHYL)-1H,3H-PYRROLO[1,2-C]THIAZOLES AS P53 ACTIVATORS"<br/>[FR] (3S)- ET (3R)-6,7-BIS (HYDROXYMÉTHYL)-1H,3H-PYRROLO[1,2-C]THIAZOLES UTILISÉS COMME ACTIVATEURS DE P53
  申请人：UNIV DE COIMBRA

  公开号：WO2019243906A1

  公开（公告）日：2019-12-26

  The present application relates to compounds of formula I, which are (3S)- and (3R)-6,7-bis(Hydroxymethyl)-1H,3H-pyrrolo[1,2-c]thiazoles. The present application also relates to pharmaceutical compositions comprising said compounds and the use of these compounds in the treatment of conditions influenced by wild-type or mutant p53 forms. More specifically, these compounds represent a completely new chemical family of p53-activating agents and show a higher selectivity towards the p53-pathway compared to the reactivators of p53 currently under clinical trials. For some cancer types these compounds revealed to be more potent than the reactivators of p53 currently under clinical trials. In addition to these advantages, the presently disclosed compounds are not genotoxic and have no apparent undesirable toxic side effects.

  本申请涉及的化合物属于公式I，即(3S)-和(3R)-6,7-双(羟甲基)-1H,3H-吡咯并[1,2-c]噻唑。本申请还涉及包含上述化合物的药物组合物，以及这些化合物在治疗受野生型或突变型p53形式影响的疾病中的用途。更具体地说，这些化合物代表了一种全新的p53激活剂化学家族，并显示出与目前正在临床试验中的p53再活化剂相比更高的选择性作用于p53途径。对于某些癌症类型，这些化合物显示出比目前正在临床试验中的p53再活化剂更强效的作用。除了这些优势外，目前披露的化合物不具有基因毒性，并且没有明显的不良毒性副作用。
• (3S)- AND (3R)-6,7-BIS(HYDROXYMETHYL)-1H,3H-PYRROLO[1,2-C]THIAZOLES AS P53 ACTIVATORS
  申请人：UNIVERSIDADE DE COIMBRA

  公开号：US20210315866A1

  公开（公告）日：2021-10-14

  The present application relates to compounds of formula I, which are (3S)- and (3R)-6,7-bis(Hydroxymethyl)-1H,3H-pyrrolo[1,2-c]thiazoles. The present application also relates to pharmaceutical compositions having the compounds and the use of these compounds in the treatment of conditions influenced by wild-type or mutant p53 forms. More specifically, these compounds represent a completely new chemical family of p53-activating agents and show a higher selectivity towards the p53-pathway compared to the reactivators of p53 currently under clinical trials. For some cancer types these compounds revealed to be more potent than the reactivators of p53 currently under clinical trials. In addition to these advantages, the presently disclosed compounds are not genotoxic and have no apparent undesirable toxic side effects.
• Chiral 6-hydroxymethyl-1H,3H-pyrrolo[1,2-c]thiazoles: Novel antitumor DNA monoalkylating agents
  作者：Maria I.L. Soares、Ana Filipa Brito、Mafalda Laranjo、Ana Margarida Abrantes、M. Filomena Botelho、José A. Paixão、Ana Matos Beja、Manuela Ramos Silva、Teresa M.V.D. Pinho e Melo

  DOI：10.1016/j.ejmech.2010.07.029

  日期：2010.10

  New chiral 1H,3H-pyrrolo[1,2-c]thiazoles were synthesized and screened for their in vitro activity as anti-cancer agents in three human tumor cell lines, colorectal adenocarcinoma, melanoma and breast adenocarcinoma. (R)-6-Hydroxymethyl-5-methyl-3-phenyl-1H,3H-pyrrolo[1,2-c]thiazole and the corresponding benzylcarbamate showed selectivity for breast cancer cell lines with IC(50) values of 24 mu M and 2.2 mu M, respectively. The latter also showed significant activity against colorectal adenocarcinoma cancer cell lines (IC(50) = 8.7 mu M) In contrast, the 7-hydroxymethyl-5-methyl-3-phenyl-1H,3H-pyrrolo[1,2-c] thiazole gave moderate anti-cancer activity. The performance against breast cancer cell lines (IC(50) = 10 mu M) of a potential bisalkylating agent, a (3R)-6,7-bis(hydroxymethyl)-1H,3H-pyrrolo[1,2-c] thiazole, wasn't significantly different from the one observed for the monoalkylating derivatives indicating that the main mechanism of action may in fact be the monoalkylation process. (C) 2010 Elsevier Masson SAS. All rights reserved