1,12-dodecamethylene bis[(4-ethoxycarbonylmethyl)thiazol-5-yl] | 321915-89-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1,12-dodecamethylene bis[(4-ethoxycarbonylmethyl)thiazol-5-yl]
• 英文别名: dodecamethylenebis[5-(4-ethoxycarbonyl-methyl)thiazole]；Ethyl 2-[5-[12-[4-(2-ethoxy-2-oxoethyl)-1,3-thiazol-5-yl]dodecyl]-1,3-thiazol-4-yl]acetate
• CAS: 321915-89-3
• 化学式: C₂₆H₄₀N₂O₄S₂
• 分子量: 508.747
• InChiKey: LHHAWGRCDCRTQI-UHFFFAOYSA-N

物化性质

• 熔点：
  112-114 °C
• 沸点：
  599.9±45.0 °C(Predicted)
• 密度：
  1.125±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.7
• 重原子数：
  34
• 可旋转键数：
  21
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  135
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  1,12-dodecamethylene bis[(4-ethoxycarbonylmethyl)thiazol-5-yl] 、 溴甲苯 以 乙醇 为溶剂， 反应 48.0h， 以60%的产率得到dodecamethylenebis[5-(1-methyl-4-ethoxycarbonylethyl)-thiazolium] dibromide
  参考文献：
  名称：

  Mono- and Bis-Thiazolium Salts Have Potent Antimalarial Activity

  摘要：

  Three new series comprising 24 novel cationic choline analogues and consisting of mono- or his (N or C-5-duplicated) thiazolium salts have been synthesized. Bis-thiazolium salts showed potent antimalarial activity (much superior to monothiazoliums). Among them, bis-thiazolium salts 12 and 13 exhibited IC50 values of 2.25 nM and 0.65 nM, respectively, against P. falciparum in vitro. These compounds also demonstrated good in vivo activity (ED50 <= 0.22 mg/kg), and low toxicity in mice infected by Plasmodium vinckei.

  DOI：

  10.1021/jm0492608
• 作为产物：
  描述：

  1,12-二溴十二烷 在 溴 、 sodium hydride 作用下， 以 四氢呋喃 、 四氯化碳 、 丙酮 为溶剂， 反应 122.84h， 生成 1,12-dodecamethylene bis[(4-ethoxycarbonylmethyl)thiazol-5-yl]
  参考文献：
  名称：

  Mono- and Bis-Thiazolium Salts Have Potent Antimalarial Activity

  摘要：

  Three new series comprising 24 novel cationic choline analogues and consisting of mono- or his (N or C-5-duplicated) thiazolium salts have been synthesized. Bis-thiazolium salts showed potent antimalarial activity (much superior to monothiazoliums). Among them, bis-thiazolium salts 12 and 13 exhibited IC50 values of 2.25 nM and 0.65 nM, respectively, against P. falciparum in vitro. These compounds also demonstrated good in vivo activity (ED50 <= 0.22 mg/kg), and low toxicity in mice infected by Plasmodium vinckei.

  DOI：

  10.1021/jm0492608

文献信息

• Quaternary bis-ammonium salt precursors and their uses as prodrugs having an antiparasitic activity
  申请人：Vial Henri

  公开号：US06972343B1

  公开（公告）日：2005-12-06

  The invention concerns drug precursors with antimalarial effect, characterised in that it consists in quaternary bis-ammonium salts of general formula (I) wherein A and A′, identical or different, are respectively either a group A1 and A′1 of formula (1) wherein n=2 to 4; R′1 is hydrogen, C1-C5 alkyl, optionally substituted by an aryl, a hydroxy, an alkoxy, wherein the alkyl comprises 1 to 5 C, or aryloxy and W is halogen or a nucleofuge group; or a group A2 which represents formyl-CHO, or acetyl-COCH3. B and B′, identical or different, represent respectively either the group B1 and B′1, if A and A′ respectively represent A1, A′1, B1, B′1 representing a group R1 which has the same definition as R′1 above, but cannot be a hydrogen atom; or respectively the groups B2 and B′2, if A and A′ represent A2, B2 or B′2 being the group R1 as defined above, or a group of formula (2) wherein —Ra is RS— or RCO—, wherein R is a C1-C6 alkyl, substituted if required, a phenyl or benzyl, wherein the phenyl is substituted if required, the latter being optionally substituted; R2 is hydrogen, C1-C5 alkyl, or a —CH2-COO— (C1-C5)alkyl group; and R3 is hydrogen, C1-C5 alkyl or alkenyl, substituted if required, a phosphate, an alkoxy wherein the alkyl is a C1-C3 alkyl, or aryloxy; or an alkyl (or arylcarbonyloxy; or R2 and R3 form together a cycle with 5 or 6 C; R and R3 can be bound to form a cycle. ± represents: either a single bond when A and A′ represent A1 and A′1: or when A and A′ represent A2, and B2 and B′2 Represent (3) either, when A and A′ are —CHO or —COCH3 and B2 and B′2 are R1, a group of formula (4) or a group of formula (5) wherein (a) represents a bond towards Z and (b) a bond towards the nitrogen atom. Z is a C9-C21 alkyl, if required with insertion of one or several bonds, and/or one or several heteroatoms O and/or S and/or several aromatic cycles, and the pharmaceutically acceptable salts of said compounds. Said precursors and cyclized thiazolium derivatives are useful as antiparasitic medicines in particular antimalarial and antibabesiosis.

  该发明涉及具有抗疟疾作用的药物前体，其特征在于它由通式(I)的季铵双盐组成，其中A和A′，相同或不同，分别是通式(1)的A1和A′1基团，其中n=2至4；R′1是氢，C1-C5烷基，可选地被芳基、羟基、烷氧基（其中烷基包括1至5个碳）、芳氧基取代，W是卤素或亲核离去基；或者是代表甲酰基-CHO或乙酰基-COCH3的A2基团。B和B′，相同或不同，分别代表A和A′分别表示A1、A′1、B1、B′1的情况下的B1和B′1基团，其中B1、B′1代表与上述R′1相同定义的R1基团，但不能是氢原子；或者分别代表A和A′表示A2的情况下的B2和B′2基团，其中B2或B′2是如上定义的R1基团，或者是通式(2)的基团，其中-Ra是RS-或RCO-，其中R是C1-C6烷基，必要时取代，苯基或苄基，其中苯基在必要时取代，后者是可选地取代的；R2是氢、C1-C5烷基，或者是—CH2-COO-(C1-C5)烷基；R3是氢、C1-C5烷基或烯烃基，必要时取代，磷酸酯、烷氧基（其中烷基是C1-C3烷基）或芳氧基；或者是烷基（或芳基羰基氧基；或者R2和R3共同形成一个含有5或6个碳的环；R和R3可以结合形成一个环。±表示：当A和A′表示A1和A′1时，是单键；或者当A和A′表示A2，B2和B′2表示(3)时，当A和A′为—CHO或—COCH3，B2和B′2为R1时，是通式(4)的基团或通式(5)的基团，其中(a)表示朝向Z的键，(b)表示朝向氮原子的键。Z是C9-C21烷基，必要时插入一个或多个键，和/或一个或多个杂原子O和/或S，和/或几个芳香环，以及所述化合物的药学上可接受的盐。所述前体和环化噻唑衍生物作为抗寄生虫药物，特别是抗疟疾和抗巴贝斯病的药物是有用的。
• Mono- and Bis-Thiazolium Salts Have Potent Antimalarial Activity
  作者：Abdallah Hamzé、Eric Rubi、Pascal Arnal、Michel Boisbrun、Carole Carcel、Xavier Salom-Roig、Marjorie Maynadier、Sharon Wein、Henri Vial、Michèle Calas

  DOI：10.1021/jm0492608

  日期：2005.5.1

  Three new series comprising 24 novel cationic choline analogues and consisting of mono- or his (N or C-5-duplicated) thiazolium salts have been synthesized. Bis-thiazolium salts showed potent antimalarial activity (much superior to monothiazoliums). Among them, bis-thiazolium salts 12 and 13 exhibited IC50 values of 2.25 nM and 0.65 nM, respectively, against P. falciparum in vitro. These compounds also demonstrated good in vivo activity (ED50 <= 0.22 mg/kg), and low toxicity in mice infected by Plasmodium vinckei.