亚达唑散 | 79944-58-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并二恶烷
• 中文名称: 亚达唑散
• 中文别名: 咪唑克生；2-(1,4-苯并二烷-2-基)-4,5-二氢-1H-咪唑；2-(1,4-苯并二噁烷-2-基)-4,5-二氢-1H-咪唑
• 英文名称: idazoxan
• 英文别名: 2-(2,3-dihydro-1,4-benzodioxin-2-yl)-4,5-dihydro-1H-imidazole；IDA；2-(1,4-benzodioxan-2-yl)-2-imidazoline；2-(1,4-benzodioxan-2-yl)-imidazoline；2-(1,4-benzodioxanyl)-imidazoline；2-(2,3-dihydro-1,4-benzodioxin-3-yl)-4,5-dihydro-1H-imidazole
• CAS: 79944-58-4
• 化学式: C₁₁H₁₂N₂O₂
• 分子量: 204.228
• InChiKey: HPMRFMKYPGXPEP-UHFFFAOYSA-N

物化性质

• 沸点：
  155-165 °C(Press: 0.1 Torr)
• 密度：
  1.39±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  42.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  亚达唑散 在 氢溴酸 作用下， 生成 2-(1,4-benzodioxan-2-yl)imidazolinium bromide
  参考文献：
  名称：

  Absolute configuration of 2-(1,4-benzodioxan-2-yl)imidazolinium bromide

  摘要：

  The title compound, C11H13N2O2+. Br-, crystallizes in the P2(1)2(1)2(1) space group. The absolute configuration of the therapeutically active molecule idazoxan [2-(1,4-benzodioxan-2-yl)imidazoline] could be resolved in this hydrobromide salt, The asymmetric C atom of the benzodioxanyl group is bonded to an H atom and to a C atom of the imidazolinium ring. (+)-Idazoxan has the S configuration. Packing of molecules in the crystal is stabilized by weak N--H ... Br [N ... Br = 3.226(5) and 3.217 (5) Angstrom] hydrogen bonding.

  DOI：

  10.1107/s0108270198013286
• 作为产物：
  描述：

  2,3-二氢苯并[1,4]二恶烷-2-甲腈 在 盐酸 作用下， 以 乙醚 、 乙醇 为溶剂， 反应 48.0h， 生成 亚达唑散
  参考文献：
  名称：

  α-肾上腺素受体试剂。1.合成一些1,4-苯并二恶烷作为选择性的突触前α2-肾上腺素受体拮抗剂和潜在的抗抑郁药。

  摘要：

  讨论了RX 781094，2-（1,4-苯并二恶烷-2-基）-2-咪唑啉盐酸盐（5）的合理设计，该化合物是新型的α2-肾上腺素受体有效和选择性拮抗剂。在突触前α2肾上腺素受体上起拮抗剂作用的化合物可能是有效的新型抑郁症治疗方法，因为它具有增加中央受体部位去甲肾上腺素浓度的能力。已经研究了芳族和咪唑啉环中取代基的作用，以及用examined官能团或其他杂环系统取代咪唑啉环的作用。尽管有些衍生物确实表现出一定程度的拮抗剂，但这些衍生物都不像5那样有效或具有选择性。发现一些衍生物具有激动剂特性，除23种外，它们更有利于突触后位点。化合物9

  DOI：

  10.1021/jm00360a008

文献信息

• [EN] AZA PYRIDONE ANALOGS USEFUL AS MELANIN CONCENTRATING HORMONE RECEPTOR-1 ANTAGONISTS<br/>[FR] ANALOGUES D'AZAPYRIDONE UTILES COMME ANTAGONISTES DU RÉCEPTEUR 1 DE L'HORMONE CONCENTRANT LA MÉLANINE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2010104818A1

  公开（公告）日：2010-09-16

  MCHR1 antagonists are provided having the following Formula (I): A1 and A2 are independently C or N; E is C or N; Q1, Q2, and Q3 are independently C or N provided that at least one of Q1, Q2, and Q3 is N but not more than one of Q1, Q2, and Q3 is N; D1 is a bond, -CR8R9 X-, -XCR8R9-, -CHR8CHR9-, -CR10=CR10'-, -C≡C-, or 1,2-cyclopropyl; X is O, S or NR11; R1, R2, and R3 are independently selected from the group consisting of hydrogen, halogen, lower alkyl, lower cycloalkyl, -CF3, -OCF3, -OR12 and -SR12; G is O, S or -NR15; D2 is lower alkyl, lower cycloalkyl, lower alkylcycloalkyl, lower cycloalkylalkyl, lower cycloalkoxyalkyl or lower alkylcycloalkoxy or when G is NR15, G and D2 together may optionally form an azetidine, pyrrolidine or piperidine ring; Z1 and Z2 are independently hydrogen, lower alkyl, lower cycloalkyl, lower alkoxy, lower cycloalkoxy, halo, -CF3, -OCONR14R14', -CN, -CONR14R14', -SOR12, -SO2R12, -NR14COR14', -NR14CO2R14', -CO2R12, NR14SO2R12 or COR12; R5, R6, and R7 are independently selected from the group consisting of hydrogen lower alkyl, lower cycloalkyl, -CF3, -SR12, lower alkoxy, lower cycloalkoxy, -CN, -CONR14R14', SOR12, SO2R12, NR14COR14', NR14CO2R12, CO2R12, NR14SO2R12 and -COR12; R8, R9, R10, R10', R11 are independently hydrogen or lower alkyl; R12 is lower alkyl or lower cycloalkyl; R14 and R14' are independently H, lower alkyl, lower cycloalkyl or R14 and R14' together with the N to which they are attached form a ring having 4 to 7 atoms; and R15 is independently selected from the group consisting of hydrogen and lower alkyl. Such compounds are useful for the treatment of MCHR1 mediated diseases, such as obesity, diabetes, IBD, depression, and anxiety.

  MCHR1拮抗剂具有以下化学式（I）：A1和A2独立地为C或N；E为C或N；Q1、Q2和Q3独立地为C或N，但至少其中一个为N，但不超过一个为N；D1为键，-CR8R9 X-，-XCR8R9-，-CHR8CHR9-，-CR10=CR10'-，-C≡C-，或1,2-环丙基；X为O、S或NR11；R1、R2和R3独立地从氢、卤素、低烷基、低环烷基、-CF3、-OCF3、-OR12和-SR12组成的群体中选择；G为O、S或-NR15；D2为低烷基、低环烷基、低烷基环烷基、低环烷基烷基、低环烷氧基烷基或低烷基环烷氧基，或当G为NR15时，G和D2一起可以选择形成氮杂环丙烷、吡咯烷或哌啶环；Z1和Z2独立地为氢、低烷基、低环烷基、低烷氧基、低环烷氧基、卤素、-CF3、-OCONR14R14'、-CN、-CONR14R14'、-SOR12、-SO2R12、-NR14COR14'、-NR14CO2R14'、-CO2R12、NR14SO2R12或COR12；R5、R6和R7独立地从氢、低烷基、低环烷基、-CF3、-SR12、低烷氧基、低环烷氧基、-CN、-CONR14R14'、SOR12、SO2R12、NR14COR14'、NR14CO2R12、CO2R12、NR14SO2R12和-COR12组成的群体中选择；R8、R9、R10、R10'、R11独立地为氢或低烷基；R12为低烷基或低环烷基；R14和R14'独立地为H、低烷基、低环烷基或R14和R14'与其连接的N一起形成具有4至7个原子的环；R15独立地从氢和低烷基组成的群体中选择。这些化合物对于治疗MCHR1介导的疾病，如肥胖症、糖尿病、炎症性肠病、抑郁症和焦虑症非常有用。
• NOVEL GLUCOKINASE ACTIVATORS AND METHODS OF USING SAME
  申请人：Ryono Denis E.

  公开号：US20080009465A1

  公开（公告）日：2008-01-10

  Compounds are provided which are phosphonate and phosphinate activators and thus are useful in treating diabetes and related diseases and have the structure wherein is a heteroaryl ring; R 4 is —(CH 2 ) n -Z-(CH 2 ) m —PO(OR 7 )(OR 8 ), —(CH 2 ) n Z-(CH 2 ) m —PO(OR 7 )R g , —(CH 2 ) n -Z-(CH 2 ) m —OPO(OR 7 )R g , —(CH 2 ) n Z—(CH 2 ) m —OPO(R 9 )(R 10 ), or —(CH 2 ) n Z—(CH 2 ) m —PO(R 9 )(R 10 ); R 5 and R 6 are independently selected from H, alkyl and halogen; Y is R 7 (CH 2 ) s or is absent; and X, n, Z, m, R 4 , R 5 , R 6 , R 7 , and s are as defined herein; or a pharmaceutically acceptable salt thereof. A method for treating diabetes and related diseases employing the above compounds is also provided.

  提供了磷酸酯和磷酸酯激活剂，因此在治疗糖尿病和相关疾病方面非常有用，并具有以下结构： 其中 是杂环芳基环； R 4 为—(CH 2 ) n -Z-(CH 2 ) m —PO(OR 7 )(OR 8 )、—(CH 2 ) n Z-(CH 2 ) m —PO(OR 7 )R g 、—(CH 2 ) n -Z-(CH 2 ) m —OPO(OR 7 )R g 、—(CH 2 ) n Z—(CH 2 ) m —OPO(R 9 )(R 10) 或—(CH 2 ) n Z—(CH 2 ) m —PO(R 9 )(R 10) ； R 5 和R 6 分别选择自H、烷基和卤素； Y为R 7 (CH 2 ) s 或不存在；以及 X、n、Z、m、R 4 、R 5 、R 6 、R 7 和s如本文所定义；或其药用盐。 还提供了一种利用上述化合物治疗糖尿病和相关疾病的方法。
• [EN] NEW BENZIMIDAZOLE DERIVATIVES<br/>[FR] NOUVEAUX DÉRIVÉS DE BENZIMIDAZOLE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2010043513A1

  公开（公告）日：2010-04-22

  The invention is concerned with novel benzimidazole derivatives of formula (I) wherein R1 to R6 are as defined in the description and in the claims, as well as physiologically acceptable salts and esters thereof. These compounds can be used as medicaments.

  这项发明涉及式(I)的新型苯并咪唑衍生物，其中R1至R6如描述和索赔中所定义，以及其生理上可接受的盐和酯。这些化合物可用作药物。
• [EN] 4-PHENOXY-NICOTINAMIDE OR 4-PHENOXY-PYRIMIDINE-5-CARBOXAMIDE COMPOUNDS<br/>[FR] COMPOSÉS DE 4-PHÉNOXYNICOTINAMIDE OU DE 4-PHÉNOXY-PYRIMIDINE-5-CARBOXAMIDE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2011089099A1

  公开（公告）日：2011-07-28

  This invention relates to novel phenyl amide or pyridyl amide derivatives of the formula (I), wherein A1, A2, B1, B2 and R1 to R11 are as defined in the description and in the claims, as well as pharmaceutically acceptable salts thereof. These compounds are GPBAR1 agonists and can be used as medicaments for the treatment of diseases such as type II diabetes.

  这项发明涉及公式（I）中的新型苯基酰胺或吡啶基酰胺衍生物，其中A1、A2、B1、B2和R1至R11如描述和索赔中所定义，并且其药学上可接受的盐。这些化合物是GPBAR1激动剂，可用作治疗疾病如2型糖尿病的药物。
• [EN] NOVEL CYCLIC BENZIMIDAZOLE DERIVATIVES USEFUL ANTI-DIABETIC AGENTS<br/>[FR] NOUVEAUX AGENTS ANTIDIABÉTIQUES UTILES AVEC DES DÉRIVÉS DE BENZIMIDAZOLE CYCLIQUES
  申请人：MERCK SHARP & DOHME

  公开号：WO2010051176A1

  公开（公告）日：2010-05-06

  Novel compounds of the structural formula (I) are activators of AMP-protein kinase and are useful in the treatment, prevention and suppression of diseases mediated by the AMPK-activated protein kinase. The compounds of the present invention are useful in the treatment of Type 2 diabetes, hyperglycemia, metabolic syndrome, obesity, hypercholesterolemia, and hypertension.

  结构式（I）的新化合物是AMP-蛋白激酶的激活剂，可用于治疗、预防和抑制由AMPK激活的蛋白激酶介导的疾病。本发明的化合物对于治疗2型糖尿病、高血糖、代谢综合征、肥胖、高胆固醇血症和高血压是有用的。