3-甲基苯并[E]苯并咪唑-2-胺 | 35199-58-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 中文名称: 3-甲基苯并[E]苯并咪唑-2-胺
• 英文名称: 2-Amino-3-methyl-naphtho<1.2>imidazol
• 英文别名: 2-amino-3-methylimidazo[1,2-d]naphthalene；3-methyl-3H-naphtho[1,2-d]imidazol-2-ylamine；2-Amino-3-methylnaphtho(1,2-d)imidazole；3-methylbenzo[e]benzimidazol-2-amine
• CAS: 35199-58-7
• 化学式: C₁₂H₁₁N₃
• mdl: MFCD00142856
• 分子量: 197.239
• InChiKey: UDFXLWPBGSMBRA-UHFFFAOYSA-N

物化性质

• 熔点：
  252-253 °C
• 沸点：
  440.4±28.0 °C(Predicted)
• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.083
• 拓扑面积：
  43.8
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  3-甲基苯并[E]苯并咪唑-2-胺 、 O⁶-benzyl-8-bromo-N9-[3',5'-O-(1,1,3,3-tetrakis(isopropyl)-1,3-disiloxanediyl)-β-D-2'-deoxyribofuranosyl]guanine 在 tris-(dibenzylideneacetone)dipalladium(0) 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 0.5h， 生成
  参考文献：
  名称：

  The C8-2′-Deoxyguanosine Adduct of 2-Amino-3-methylimidazo[1,2-d]naphthalene, a Carbocyclic Analogue of the Potent Mutagen 2-Amino-3-methylimidazo[4,5-f]quinoline, Is a Block to Replication in Vitro

  摘要：

  2-Amino-3-methylimidazo[1,2-d]naphthalene (cIQ) is a carbocyclic analogue of the dietary carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in which a naphthalene ring system replaces the quinoline unit of IQ. The activity of cIQ in Ames Salmonella typhimurium tester strain TA98 is known to be 4-5 orders of magnitude lower than IQ. cIQ undergoes efficient bioactivation with rat liver microsomes. The C8-dGuo adduct was formed when calf thymus DNA was treated with the N-hydroxy-cIQ metabolite and either acetic anhydride or extracts from cells that overexpress N-acetyl transferase (NAT). These studies indicate that bioactivation, the stability of the N-hydroxylamine ester, and the reactivity of the nitrenium ion with DNA of cIQ are similar to IQ and that none of these factors account for the differences in mutagenic potency of these analogues in Ames assays. Oligonucleotides were synthesized that contain the C8-dGuo adduct of cIQ in the frameshift-prone CG-dinucleotide repeat unit of the Narl recognition sequence. We have examined the in vitro translesion synthesis of this adduct and have found it to be a strong replication block to Escherichia coli DNA polymerase I, Klenow fragment exo(-) (Kf(-)), E. coli DNA polymerase II exo(-) (pol II-), and Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4). Previous studies by Fuchs and co-workers identified E. coli pol II as the polymerase responsible for two-base deletions of the C8-dGuo adduct of N-acetyl-2-aminofluorene in the Narl sequence. Our observation that pol II is strongly inhibited by the C8-dGuo adduct of cIQ suggests that one of the other SOS inducible polymerases (E. coli pol IV or pol V) is required for its bypass, and this accounts for the greatly attenuated mutagenicity in the Ames assays as compared with IQ.

  DOI：

  10.1021/tx100053n

文献信息

• Toll-like receptor agonists
  申请人：The University of Kansas

  公开号：US10471139B2

  公开（公告）日：2019-11-12

  Compounds described herein can be used for therapeutic purposes. The compounds can be TLR agonists, such as TLR7 or TLR8 agonists. The compounds can be included in pharmaceutical compositions and used for therapies were being a TLR agonist is useful. The pharmaceutical compositions can include any ingredients, such as carries, diluents, excipients, fillers or the like that are common in pharmaceutical compositions. The compounds can be those illustrated or described herein as well as derivative thereof, prodrug thereof, salt thereof, or stereoisomer thereof, or having any chirality at any chiral center, or tautomer, polymorph, solvate, or combinations thereof. As such, the compounds can be used as adjuvants in vaccines as well as for other therapeutic purposes described herein. The compounds can have any one of the formulae. Examples of the compounds can be reviewed in Table 1 and Table A1 for activates.

  本文所述化合物可用于治疗目的。这些化合物可以是 TLR 激动剂，如 TLR7 或 TLR8 激动剂。这些化合物可包含在药物组合物中，用于治疗TLR激动剂有用的疾病。药物组合物可以包括任何成分，例如药物组合物中常见的载体、稀释剂、赋形剂、填料等。化合物可以是本文图示或描述的化合物，也可以是其衍生物、原药、盐或立体异构体，或在任何手性中心具有任何手性的化合物，或同系物、多晶型物、溶胶或其组合。因此，这些化合物可用作疫苗佐剂，也可用于本文所述的其他治疗目的。这些化合物可以具有任意一个式子。化合物的实例可参见表 1 和表 A1 中的活化剂。
• The C8-2′-Deoxyguanosine Adduct of 2-Amino-3-methylimidazo[1,2-<i>d</i>]naphthalene, a Carbocyclic Analogue of the Potent Mutagen 2-Amino-3-methylimidazo[4,5-<i>f</i>]quinoline, Is a Block to Replication in Vitro
  作者：Plamen P. Christov、Goutam Chowdhury、Craig A. Garmendia、Feng Wang、James S. Stover、C. Eric Elmquist、Albena Kozekova、Karen C. Angel、Robert J. Turesky、Michael P. Stone、F. Peter Guengerich、Carmelo J. Rizzo

  DOI：10.1021/tx100053n

  日期：2010.6.21

  2-Amino-3-methylimidazo[1,2-d]naphthalene (cIQ) is a carbocyclic analogue of the dietary carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in which a naphthalene ring system replaces the quinoline unit of IQ. The activity of cIQ in Ames Salmonella typhimurium tester strain TA98 is known to be 4-5 orders of magnitude lower than IQ. cIQ undergoes efficient bioactivation with rat liver microsomes. The C8-dGuo adduct was formed when calf thymus DNA was treated with the N-hydroxy-cIQ metabolite and either acetic anhydride or extracts from cells that overexpress N-acetyl transferase (NAT). These studies indicate that bioactivation, the stability of the N-hydroxylamine ester, and the reactivity of the nitrenium ion with DNA of cIQ are similar to IQ and that none of these factors account for the differences in mutagenic potency of these analogues in Ames assays. Oligonucleotides were synthesized that contain the C8-dGuo adduct of cIQ in the frameshift-prone CG-dinucleotide repeat unit of the Narl recognition sequence. We have examined the in vitro translesion synthesis of this adduct and have found it to be a strong replication block to Escherichia coli DNA polymerase I, Klenow fragment exo(-) (Kf(-)), E. coli DNA polymerase II exo(-) (pol II-), and Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4). Previous studies by Fuchs and co-workers identified E. coli pol II as the polymerase responsible for two-base deletions of the C8-dGuo adduct of N-acetyl-2-aminofluorene in the Narl sequence. Our observation that pol II is strongly inhibited by the C8-dGuo adduct of cIQ suggests that one of the other SOS inducible polymerases (E. coli pol IV or pol V) is required for its bypass, and this accounts for the greatly attenuated mutagenicity in the Ames assays as compared with IQ.