dimethyl (3R)-5-methyl-3-phenyl-3,4-dihydro-1H-pyrrolo[1,2-a]thiazole-6,7-dicarboxylate | 158446-64-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: dimethyl (3R)-5-methyl-3-phenyl-3,4-dihydro-1H-pyrrolo[1,2-a]thiazole-6,7-dicarboxylate
• 英文别名: dimethyl (3R)-3-phenyl-5 methyl-1H,3H-pyrrolo [1,2-c]thiazole-6,7-dicarboxylate；dimethyl (3R)-5-methyl-3-phenyl-1H-pyrrolo[1,2-c][1,3]thiazole-6,7-dicarboxylate；dimethyl (3R)-5-methyl-3-phenyl-1,3-dihydropyrrolo[1,2-c][1,3]thiazole-6,7-dicarboxylate
• CAS: 158446-64-1
• 化学式: C₁₇H₁₇NO₄S
• 分子量: 331.392
• InChiKey: NCPUAZQBLWRIHM-OAHLLOKOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  82.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  dimethyl (3R)-5-methyl-3-phenyl-3,4-dihydro-1H-pyrrolo[1,2-a]thiazole-6,7-dicarboxylate 在 间氯过氧苯甲酸 作用下， 生成 dimethyl (3R)-5-methyl-2,2-dioxo-3-phenyl-1H,3H-pyrrolo[1,2-c]thiazole-6,7-dicarboxylate
  参考文献：
  名称：

  吡咯并[1,2 - c ]噻唑-2,2-二氧化物衍生的甲基氮杂富烯鎓甲基化物的反应性：官能化吡咯的合成

  摘要：

  从吡咯并[1,2 - c ]噻唑-2,2-二氧化物中挤出二氧化硫，通过生成1-氮杂富烯基甲基化物导致官能化吡咯的合成。密封管反应条件允许合成N-和C-乙烯基吡咯，而由FVP 1,3-二甲基-5-氧代-5 H-吡咯烷嗪-2-羧酸甲酯和4-氧代-1,4-二氢-1-氮杂合成获得了-苯并[ f ] azulene-3-羧酸盐。这些最后的化合物也可以从N-和C-乙烯基吡咯的FVP获得。

  DOI：

  10.1016/j.tetlet.2004.03.111
• 作为产物：
  描述：

  R-2-苯基-噻唑烷-4-羧酸 、 dimethyl acetylenedicarboxylate 在 乙酸酐 作用下， 以75%的产率得到dimethyl (3R)-5-methyl-3-phenyl-3,4-dihydro-1H-pyrrolo[1,2-a]thiazole-6,7-dicarboxylate
  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

• Intermolecular Dipolar Cycloaddition Reactions of 5H,7H-Thiazolo[3,4-c]oxazol-4-ium-1-olates
  作者：Teresa M.V.D. Pinho e Melo、Maria I.L. Soares、Dália M. Barbosa、António M.d'A. Rocha Gonsalves、Ana Matos Beja、José A. Paixão、Manuela Ramos Silva、Luiz Alte da Veiga

  DOI：10.1016/s0040-4020(00)00243-x

  日期：2000.5

  (5R)-3-Methyl-5-phenyl-5H,7H-thiazolo[3,4-c]oxazol-4-ium-1-olate was generated in the presence of a range of dipolarophiles. The intermolecular 1,3-dipolar cycloaddition of this mesoionic species led to the synthesis of chiral 1H-pyrrolo[1,2-c]thiazole derivatives 7a, 7b, 8, 14, 18,19 and 20. In the reaction with methyl and ethyl vinyl ketone, spiro compounds 9 and 15 were also obtained. The structure

  （5R）-3-甲基-5-苯基5H，7H -噻唑并[3,4- Ç的范围dipolarophiles的存在下生成的]恶唑-4-鎓-1-酚盐。导致手性的合成这个介离子物种的分子间的1,3-偶极环加成1H -吡咯并[1,2- c ^ ]噻唑衍生物7A，7B，8，14，18，19和20。在与甲基和乙基乙烯基酮的反应中，还获得了螺化合物9和15。化合物15的结构 通过X射线晶体学测定。
• [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。
• Heterocyclische Verbindungen aus Zuckern, XV: Zur Konfiguration chiraler C-2-substituierter 4-Thiazolidincarbons�uren. Chiralit�tstransfer auf C-3 in 3,4-Dihydro-1H-pyrrolo[1,2-c]thiazolen
  作者：Z. Gy�rgyde�k、L. Szil�gyi、J. Kajt�r、G. Argay、A. K�lm�n

  DOI：10.1007/bf00818164

  日期：1994.2

  5-Substituted 3,4-dihydro-pyrrolo[1,2-c]thiazole-6,7-dicarboxylic acid esters 3 are obtained from 2-substituted-3-acyl-1,3-thiazolidine-4-carboxylic acids, 1 in [3 + 2]-cycloaddition reactions via mesoionic oxazolone (''munchnone'') intermediates. The chirality at C-4 of the starting carboxylic acids 1 is eliminated in the products 3, and the chirality at C-3 (C-2 in the starting carboxylic acids 1) can thus be determined through chiroptical measurements. Several representatives of the ring system 3 have been characterised through H-1- and CD-spectra and the molecular structure of (3S)-3da has been determined by X-ray crystallography.
• Gyoergydeak Z., Szilagyi L., Kajtar J., Argay G., Kalman A., Monatsh. Chem, 125 (1994) N 2, S 189-208
  作者：Gyoergydeak Z., Szilagyi L., Kajtar J., Argay G., Kalman A.

  DOI：——

  日期：——
• (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.