tert-butyl N-{2,2-dimethyl-5-[(methylsulfanyl)methyl]-1,3-dioxan-5-yl}carbamate | 1010701-36-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: tert-butyl N-{2,2-dimethyl-5-[(methylsulfanyl)methyl]-1,3-dioxan-5-yl}carbamate
• 英文别名: tert-butyl 2,2-dimethyl-5-(methylthiomethyI)-1,3-dioxan-5-ylcarbamate；tert-butyl 2,2-dimethyl-5-(methylthiomethyl)-1,3-dioxan-5-ylcarbamate；tert-butyl N-[2,2-dimethyl-5-(methylsulfanylmethyl)-1,3-dioxan-5-yl]carbamate
• CAS: 1010701-36-6
• 化学式: C₁₃H₂₅NO₄S
• 分子量: 291.412
• InChiKey: QRYCMZORZWXSDW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  82.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl N-{2,2-dimethyl-5-[(methylsulfanyl)methyl]-1,3-dioxan-5-yl}carbamate 在 盐酸 、 水 作用下， 以 甲醇 为溶剂， 反应 0.17h， 以81%的产率得到2-amino-2-[(methylsulfanyl)methyl]propane-1,3-diol hydrochloride
  参考文献：
  名称：

  Transition state analogue inhibitors of human methylthioadenosine phosphorylase and bacterial methylthioadenosine/S-adenosylhomocysteine nucleosidase incorporating acyclic ribooxacarbenium ion mimics

  摘要：

  Several acyclic hydroxy-methylthio-amines with 3-5 carbon atoms were prepared and coupled via a methylene link to 9-deazaadenine. The products were tested for inhibition against human MTAP and Escherichia coli and Neisseria meningitidis MTANs and gave K-i values as low as 0.23 nM. These results were compared to those obtained with 1st and 2nd generation inhibitors (1S)-1-(9-deazaadenin-9-yl)-1,4-dideoxy-1,4-imino-5-methylthio-D-ribitol (MT-Immucillin-A, 3) and (3R,4S)-1-[9-deazaadenin-9-yl)methyl]3-hydroxy-4-methylthiomethylpyrrolidine (MT-DADMe-Immucillin-A, 4). The best inhibitors were found to exhibit binding affinities of approximately 2- to 4-fold those of 3 but were significantly weaker than 4. Cleavage of the 2,3 carbon-carbon bond in MT-Immucillin-A (3) gave an acyclic product (79) with a 21,500 fold loss of activity against E. coli MTAN. In another case, N-methylation of a side chain secondary amine resulted in a 250-fold loss of activity against the same enzyme [(+/-)-65 vs (+/-)-68]. The inhibition results were also contrasted with those acyclic derivatives previously prepared as inhibitors for a related enzyme, purine nucleoside phosphorylase (PNP), where some inhibitors in the latter case were found to be more potent than their cyclic counterparts. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.07.006
• 作为产物：
  描述：

  tert-butyl N-[5-(hydroxymethyl)-2,2-dimethyl-1,3-dioxan-5-yl]carbamate 在 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.5h， 生成 tert-butyl N-{2,2-dimethyl-5-[(methylsulfanyl)methyl]-1,3-dioxan-5-yl}carbamate
  参考文献：
  名称：

  Transition state analogue inhibitors of human methylthioadenosine phosphorylase and bacterial methylthioadenosine/S-adenosylhomocysteine nucleosidase incorporating acyclic ribooxacarbenium ion mimics

  摘要：

  Several acyclic hydroxy-methylthio-amines with 3-5 carbon atoms were prepared and coupled via a methylene link to 9-deazaadenine. The products were tested for inhibition against human MTAP and Escherichia coli and Neisseria meningitidis MTANs and gave K-i values as low as 0.23 nM. These results were compared to those obtained with 1st and 2nd generation inhibitors (1S)-1-(9-deazaadenin-9-yl)-1,4-dideoxy-1,4-imino-5-methylthio-D-ribitol (MT-Immucillin-A, 3) and (3R,4S)-1-[9-deazaadenin-9-yl)methyl]3-hydroxy-4-methylthiomethylpyrrolidine (MT-DADMe-Immucillin-A, 4). The best inhibitors were found to exhibit binding affinities of approximately 2- to 4-fold those of 3 but were significantly weaker than 4. Cleavage of the 2,3 carbon-carbon bond in MT-Immucillin-A (3) gave an acyclic product (79) with a 21,500 fold loss of activity against E. coli MTAN. In another case, N-methylation of a side chain secondary amine resulted in a 250-fold loss of activity against the same enzyme [(+/-)-65 vs (+/-)-68]. The inhibition results were also contrasted with those acyclic derivatives previously prepared as inhibitors for a related enzyme, purine nucleoside phosphorylase (PNP), where some inhibitors in the latter case were found to be more potent than their cyclic counterparts. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.07.006

文献信息

• ACYCLIC AMINE INHIBITORS OF 5-METHYTIOADENOSINE PHOSPHORYLASE AND NUCLEOSIDASE
  申请人：Clinch Keith

  公开号：US20110046167A1

  公开（公告）日：2011-02-24

  The present invention relates to compounds of the general formula (I) which are inhibitors of 5′-methylthioadenosine phosphorylase or 5′-methylthioadenosine nucleosidase. The invention also relates to the use of these compounds in the treatment of diseases or conditions in which it is desirable to inhibit 5′-methylthioadenosine phosphorylase or 5′-methylthioadenosine nucleosidase including cancer, and to pharmaceutical compositions containing the compounds.

  本发明涉及一般公式（I）的化合物，它们是5'-甲基硫腺苷磷酸化酶或5'-甲基硫腺苷核苷酸酶的抑制剂。本发明还涉及使用这些化合物治疗希望抑制5'-甲基硫腺苷磷酸化酶或5'-甲基硫腺苷核苷酶的疾病或病况，包括癌症，并且涉及含有这些化合物的药物组合物。
• Acyclic amine inhibitors of nucleoside phosphorylases and hydrolases
  申请人：Clinch Keith

  公开号：US20110130412A1

  公开（公告）日：2011-06-02

  The invention relates to compounds of the general formula (I) which are inhibitors of purine nucleoside phosphorylases (PNPs) and/or nucleoside hydrolases (NHs). The invention also relates to the use of these compounds in the treatment of diseases and infections including cancer, bacterial infections, protozoal infections, and T-cell mediated disease and to pharmaceutical compositions containing the compounds.

  本发明涉及一般式(I)的化合物，其为嘌呤核苷酸磷酸酯酶（PNP）和/或核苷酸水解酶（NH）的抑制剂。本发明还涉及这些化合物在治疗疾病和感染，包括癌症，细菌感染，原虫感染和T细胞介导的疾病中的使用，以及含有这些化合物的制药组合物。
• Acyclic amine inhibitors of 5-methytioadenosine phosphorylase and nucleosidase
  申请人：Clinch Keith

  公开号：US08383636B2

  公开（公告）日：2013-02-26

  The present invention relates to compounds of the general formula (I) which are inhibitors of 5′-methylthioadenosine phosphorylase or 5′-methylthioadenosine nucleosidase. The invention also relates to the use of these compounds in the treatment of diseases or conditions in which it is desirable to inhibit 5′-methylthioadenosine phosphorylase or 5′-methylthioadenosine nucleosidase including cancer, and to pharmaceutical compositions containing the compounds.

  本发明涉及通式（I）的化合物，其为5'-甲基硫腺苷磷酸酶或5'-甲基硫腺苷核苷酸酶的抑制剂。本发明还涉及这些化合物在治疗需要抑制5'-甲基硫腺苷磷酸酶或5'-甲基硫腺苷核苷酸酶的疾病或病况，包括癌症方面的应用，以及含有这些化合物的制药组合物。
• WO2008/30119
  申请人：——

  公开号：——

  公开（公告）日：——
• WO2008/30118
  申请人：——

  公开号：——

  公开（公告）日：——