2-({2-[(2-tert-butoxycarbonylaminothiazole-4-carbonyl)amino]thiazole-4-carbonyl}amino)thiazole-4-carboxylic acid ethyl ester | 292071-59-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-({2-[(2-tert-butoxycarbonylaminothiazole-4-carbonyl)amino]thiazole-4-carbonyl}amino)thiazole-4-carboxylic acid ethyl ester
• 英文别名: 2-({2-[(2-tert-Butoxycarbonylamino-thiazole-4-carbonyl)-amino]-thiazole-4-carbonyl}-amino)-thiazole-4-carboxylic acid ethyl ester；ethyl 2-[[2-[[2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazole-4-carbonyl]amino]-1,3-thiazole-4-carbonyl]amino]-1,3-thiazole-4-carboxylate
• CAS: 292071-59-1
• 化学式: C₁₉H₂₀N₆O₆S₃
• 分子量: 524.602
• InChiKey: SMGXGKYYZGVLFO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  34
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  246
• 氢给体数：
  3
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  2-({2-[(2-tert-butoxycarbonylaminothiazole-4-carbonyl)amino]thiazole-4-carbonyl}amino)thiazole-4-carboxylic acid ethyl ester 在 水 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 三氟乙酸 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 28.34h， 生成
  参考文献：
  名称：

  用于组装 HIV-1 TAR RNA 结合配体的靶向叠氮-炔环加成。

  摘要：

  高度保守的 HIV-1 反式激活反应元件 (TAR) 与反式激活蛋白 Tat 结合，并促进潜伏状态下的病毒复制。通过选择性靶向 TAR RNA 来抑制 Tat-TAR 相互作用已被用作开发有效抗病毒药物的策略。因此，HIV-1 TAR RNA 代表了治疗干预的范例系统。在此，我们使用生物素标记的 TAR RNA 从反应性叠氮化物和炔构建块池中组装其自己的配体。为了确定配体的结合位点和选择性，使用对照核苷酸（TAR DNA 和不带凸出的 TAR RNA）模板进一步进行了原位环加成。使用链霉亲和素珠从生物素标记的靶模板中分离出命中的三唑连接的噻唑拟肽产品。 TAR RNA 产生的主要三唑先导物可能结合在凸起区域，显示出对 TAR RNA 而非 TAR DNA 的特异性，并抑制 Tat-TAR 相互作用。

  DOI：

  10.1002/anie.202003461
• 作为产物：
  描述：

  2-BOC-氨基噻唑-4-羧酸 在 水 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 44.34h， 生成 2-({2-[(2-tert-butoxycarbonylaminothiazole-4-carbonyl)amino]thiazole-4-carbonyl}amino)thiazole-4-carboxylic acid ethyl ester
  参考文献：
  名称：

  用于组装 HIV-1 TAR RNA 结合配体的靶向叠氮-炔环加成。

  摘要：

  高度保守的 HIV-1 反式激活反应元件 (TAR) 与反式激活蛋白 Tat 结合，并促进潜伏状态下的病毒复制。通过选择性靶向 TAR RNA 来抑制 Tat-TAR 相互作用已被用作开发有效抗病毒药物的策略。因此，HIV-1 TAR RNA 代表了治疗干预的范例系统。在此，我们使用生物素标记的 TAR RNA 从反应性叠氮化物和炔构建块池中组装其自己的配体。为了确定配体的结合位点和选择性，使用对照核苷酸（TAR DNA 和不带凸出的 TAR RNA）模板进一步进行了原位环加成。使用链霉亲和素珠从生物素标记的靶模板中分离出命中的三唑连接的噻唑拟肽产品。 TAR RNA 产生的主要三唑先导物可能结合在凸起区域，显示出对 TAR RNA 而非 TAR DNA 的特异性，并抑制 Tat-TAR 相互作用。

  DOI：

  10.1002/anie.202003461

文献信息

• Alkyl 4- [4- (5-Oxo-2,3,5, 11A-Tetrahydo-5H-Pyrrolo [2, 1-C] [1,4] Benzodiazepine-8-Yloxy) -Butyrylamino]-1H-Pyrrole-2-Carboxylate Derivatives and Related Compounds For the Treatment of a Proliferative Disease
  申请人：Howard Philip Wilson

  公开号：US20080214525A1

  公开（公告）日：2008-09-04

  A compound of formula (I); or a salt or solvate thereof, wherein: the dotted line indicates the optional presence of a double bond between C2 and C3; R 2 is selected from —H, —OH, =0, ═CH 2 , —CN, —R, OR, halo, ═CH—R, O—SO 2 —R, CO 2 R and COR; R 7 is selected from H, R, OH, OR, SH, SR, NH 2 , NHR, NRR′, nitro, Me 3 Sn and halo, where R and R′ are independently selected from optionally substituted C 1-7 alkyl, C 3-20 heterocyclyl and C 5-20 aryl groups; R 10 and R 11 either together form a double bond, or are selected from H and YR Y , where Y is selected from O, S and NH and R is H or C 1-7 alkyl or H and SO x M, where x is 2 or 3 and M is a monovalent pharmaceutically acceptable cation; each X is independently a heteroarylene group; n is from 1 to 6; and R E is C 1-4 alkyl. The compound is useful for the treatment of proliferative diseases.

  化合物的公式（I）；或其盐或溶剂化物，其中：虚线表示C2和C3之间的双键是可选的；R2选择自-H，-OH，=0，═CH2，-CN，-R，OR，卤基，═CH-R，O-SO2-R，CO2R和COR；R7选择自H，R，OH，OR，SH，SR，NH2，NHR，NRR'，硝基，Me3Sn和卤基，其中R和R'独立选择自可选取代的C1-7烷基，C3-20杂环基和C5-20芳基基团；R10和R11要么一起形成双键，要么选择自H和YRY，其中Y选择自O，S和NH，R为H或C1-7烷基或H和SOxM，其中x为2或3，M为一价的药用可接受阳离子；每个X独立地是杂芳基基团；n为1至6；以及RE为C1-4烷基。该化合物可用于治疗增殖性疾病。
• Alkyl 4- [4- (5-oxo-2,3,5, 11a-tetrahydo-5H-pyrrolo [2, 1-c] [1,4] benzodiazepine-8-yloxy)-butyrylamino]-1H-pyrrole-2-carboxylate derivatives and related compounds for the treatment of a proliferative disease
  申请人：Howard Philip Wilson

  公开号：US08637664B2

  公开（公告）日：2014-01-28

  A compound of formula (I); or a salt or solvate thereof, wherein: the dotted line indicates the optional presence of a double bond between C2 and C3; R2 is selected from —H, —OH, =0, ═CH2, —CN, —R, OR, halo, ═CH—R, O—SO2—R, CO2R and COR; R7 is selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR′, nitro, Me3Sn and halo, where R and R′ are independently selected from optionally substituted C1-7 alkyl, C3-20 heterocyclyl and C5-20 aryl groups; R10 and R11 either together form a double bond, or are selected from H and YRY, where Y is selected from O, S and NH and R is H or C1-7 alkyl or H and SOxM, where x is 2 or 3 and M is a monovalent pharmaceutically acceptable cation; each X is independently a heteroarylene group; n is from 1 to 6; and RE is C1-4 alkyl. The compound is useful for the treatment of proliferative diseases.

  化合物的式子（I）或其盐或溶剂化物，其中：虚线表示C2和C3之间的双键是可选的；R2从—H，—OH，=0，═CH2，—CN，—R，OR，卤素，═CH—R，O—SO2—R，CO2R和COR中选择；R7从H，R，OH，OR，SH，SR，NH2，NHR，NRR'，硝基，Me3Sn和卤素中选择，其中R和R'分别从选择性取代的C1-7烷基，C3-20杂环基和C5-20芳基中独立选择；R10和R11要么一起形成双键，要么从H和YRY中选择，其中Y从O，S和NH中选择，R是H或C1-7烷基或H和SOxM，其中x为2或3，M是单价的药用可接受阳离子；每个X都是独立的杂芳基基团；n为1到6；RE是C1-4烷基。该化合物用于治疗增生性疾病。
• In vitro activity and mode of action of distamycin analogues against African trypanosomes
  作者：Jaime Franco、Andrea Medeiros、Diego Benítez、Karen Perelmuter、Gloria Serra、Marcelo A. Comini、Laura Scarone

  DOI：10.1016/j.ejmech.2016.12.002

  日期：2017.1

  Distamycin, a natural polyamide containing three heterocycle rings with a polar end, has inspired several groups to prepare synthetic analogues, which proved to have anti-trypanosomal and anti-tumoral activity. We describe the synthesis of bi and tri thiazoles amides that harbor different substitutions at their ends and the evaluation of their anti-Trypanosoma brucei activity. The most active compound 10b showed better biological activity (EC50 310 nM and selectivity index 16) than the control drug nifurtimox (EC50 15 mu M and selectivity index 10). Studies on the mode of action show that the parasiticidal activity of lob originates from disruption of lysosomal homeostasis, which is followed by release of redox active iron, an increase in oxidizing species and collapse of cell membrane integrity. In this respect, our study suggests that non-charged lipophylic distamycins destabilize cell membranes. (C) 2017 Elsevier Masson SAS. All rights reserved.
• An Extended Pyrrolobenzodiazepine–Polyamide Conjugate with Selectivity for a DNA Sequence Containing the ICB2 Transcription Factor Binding Site
  作者：Federico Brucoli、Rachel M. Hawkins、Colin H. James、Paul J. M. Jackson、Geoff Wells、Terence C. Jenkins、Tom Ellis、Minal Kotecha、Daniel Hochhauser、John A. Hartley、Philip W. Howard、David E. Thurston

  DOI：10.1021/jm4001852

  日期：2013.8.22

  The binding of nuclear factor Y (NF-Y) to inverted CCAAT boxes (ICBs) within the promoter region of DNA topoisomerase II alpha results in control of cell differentiation and cell cycle progression. Thus, NF-Y inhibitory small molecules could be employed to inhibit the replication of cancer cells. A library of pyrrolobenzodiazepine (PBD) C8-conjugates consisting of one PBD unit attached to tri-heterocyclic polyamide fragments was designed and synthesized. The DNA-binding affinity and sequence selectivity of each compound were evaluated in DNA thermal denaturation and DNase I footprinting assays, and the ability to inhibit binding of NF-Y to ICB1 and ICB2 was studied using an electrophoretic mobility shift assay (EMSA). 3a was found to be a potent inhibitor of NF-Y binding, exhibiting a 10-fold selectivity for an ICB2 site compared to an ICB1-containing sequence, and showing low nanomolar cytotoxicity toward human tumor cell lines. Molecular modeling and computational studies have provided details of the covalent attachment process that leads to formation of the PBD-DNA adduct, and have allowed the preference of 3a for ICB2 to be rationalized.
• ALKYL 4- [4- (5-OXO-2, 3, 5, 11A-TETRAHYD0-5H-PYRR0L0 [2, 1-C][1, 4]BENZODIAZEPINE-8-YLOXY) -BUTYRYLAMINO]-1H-PYRROLE-2-CARBOXYLATE DERIVATIVES AND RELATED COMPOUNDS FOR THE TREATMENT OF A PROLIFERATIVE DISEASE
  申请人：Spirogen Limited

  公开号：EP1931671B1

  公开（公告）日：2009-04-08