4-({4-[(4-tert-butoxycarbonylamino-1-methyl-1H-imidazole-2-carbonyl)amino]-1-methyl-1H-imidazole-2-carbonyl}amino)-1-methyl-1H-imidazole-2-carboxylic acid ethyl ester | 292071-81-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-({4-[(4-tert-butoxycarbonylamino-1-methyl-1H-imidazole-2-carbonyl)amino]-1-methyl-1H-imidazole-2-carbonyl}amino)-1-methyl-1H-imidazole-2-carboxylic acid ethyl ester
• 英文别名: ethyl-1-methyl-4-({1-methyl-4-[((4-tert-butoxycarbonyl)amino-1-methyl-1H-imidazole-2-carbonyl)-amino]-1H-imidazole-2-carbonyl}-amino)-1H-imidazole-2-carboxylate；Ethyl 1-methyl-4-[[1-methyl-4-[[1-methyl-4-[(2-methylpropan-2-yl)oxycarbonylamino]imidazole-2-carbonyl]amino]imidazole-2-carbonyl]amino]imidazole-2-carboxylate；ethyl 1-methyl-4-[[1-methyl-4-[[1-methyl-4-[(2-methylpropan-2-yl)oxycarbonylamino]imidazole-2-carbonyl]amino]imidazole-2-carbonyl]amino]imidazole-2-carboxylate
• CAS: 292071-81-9
• 化学式: C₂₂H₂₉N₉O₆
• 分子量: 515.529
• InChiKey: XSSJSBAIEBVOQC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  37
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  176
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  4-({4-[(4-tert-butoxycarbonylamino-1-methyl-1H-imidazole-2-carbonyl)amino]-1-methyl-1H-imidazole-2-carbonyl}amino)-1-methyl-1H-imidazole-2-carboxylic acid ethyl ester 在 四氢吡咯 、 盐酸 、 4-二甲氨基吡啶 、 四(三苯基膦)钯 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 0.5h， 生成 ethyl 4-{[4-(4-(7-methoxy-5-oxo-2,3,5,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-8-yloxy)butyrylamino-1-methyl-1H-imidazole-2-carbonylamino)-1-methyl-1H-imidazole-2-carbonyl]amino}-1-methyl-1H-imidazole-2-carboxylate
  参考文献：
  名称：

  An Extended Pyrrolobenzodiazepine–Polyamide Conjugate with Selectivity for a DNA Sequence Containing the ICB2 Transcription Factor Binding Site

  摘要：

  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.

  DOI：

  10.1021/jm4001852
• 作为产物：
  描述：

  4-叔丁氧羰基氨基-1-甲基-1H-咪唑-2-甲酸 在 盐酸 、 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 360.5h， 生成 4-({4-[(4-tert-butoxycarbonylamino-1-methyl-1H-imidazole-2-carbonyl)amino]-1-methyl-1H-imidazole-2-carbonyl}amino)-1-methyl-1H-imidazole-2-carboxylic acid ethyl ester
  参考文献：
  名称：

  An Extended Pyrrolobenzodiazepine–Polyamide Conjugate with Selectivity for a DNA Sequence Containing the ICB2 Transcription Factor Binding Site

  摘要：

  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.

  DOI：

  10.1021/jm4001852

文献信息

• [EN] SEQUENCE SELECTIVE PYRROLE AND IMIDAZOLE POLYAMIDE METALLOCOMPLEXES<br/>[FR] MÉTALLOCOMPLEXES POLYAMIDES DE PYRROLE ET IMIDAZOLE SELECTIFS VIS-A-VIS DE SEQUENCES
  申请人：UNIV WESTERN SYDNEY

  公开号：WO2005033077A1

  公开（公告）日：2005-04-14

  The present invention relates to sequence selective compounds for targeting therapeutic or diagnostic groups to polynucleotides. More particularly, the present invention relates to sequence selective targeting of metallocomplexes, such as metallodrugs and metallodiagnostics, to polynucleotides.

  本发明涉及用于将治疗或诊断组靶向到多核苷酸的序列选择性化合物。更具体地说，本发明涉及将金属配合物（如金属药物和金属诊断试剂）的序列选择性靶向到多核苷酸。
• 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。
• Sequence Selective Pyrrole and Imidazole Polyamide Metallocomplexes
  申请人：Jaramillo David

  公开号：US20070265240A1

  公开（公告）日：2007-11-15

  The present invention relates to sequence selective compounds for targeting therapeutic or diagnostic groups to polynucleotides. More particularly, the present invention relates to sequence selective targeting of metallocomplexes, such as metallodrugs and metallodiagnostics, to polynucleotides.

  本发明涉及用于将治疗或诊断药物组选择性地定向到多核苷酸的序列选择性化合物。更具体地，本发明涉及将金属配合物（如金属药物和金属诊断剂）的序列选择性定向到多核苷酸。
• SEQUENCE SELECTIVE PYRROLE AND IMIDAZOLE POLYAMIDE METALLOCOMPLEXES
  申请人：University of Western Sydney

  公开号：EP1678133A1

  公开（公告）日：2006-07-12
• EP1678133A4
  申请人：——

  公开号：EP1678133A4

  公开（公告）日：2008-06-18