1-Iodo-2-(4-methylideneheptyl)benzene | 745784-80-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-Iodo-2-(4-methylideneheptyl)benzene
• CAS: 745784-80-9
• 化学式: C₁₄H₁₉I
• 分子量: 314.209
• InChiKey: WZZNKNKIILNGQX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  15
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  0
• 氢给体数：
  0
• 氢受体数：
  0

反应信息

• 作为反应物：
  描述：

  1-Iodo-2-(4-methylideneheptyl)benzene 、 一氧化碳 、 2-(三丁基锡烷基)呋喃 在 palladium diacetate 、 三苯基膦 作用下， 以 甲苯 为溶剂， 生成 1-(furan-2-yl)-2-(1-propyl-3,4-dihydro-2H-naphthalen-1-yl)ethanone
  参考文献：
  名称：

  Dissociated Nonsteroidal Glucocorticoid Receptor Modulators; Discovery of the Agonist Trigger in a Tetrahydronaphthalene−Benzoxazine Series

  摘要：

  The tetrahydronaphthalene-benzoxazine glucocorticoid receptor (GR) partial agonist 4b was optimized to produce potent full agonists of GR. Aromatic ring substitution of the tetrahydronaphthalene leads to weak GR antagonists. Discovery of an "agonist trigger" substituent on the saturated ring of the tetrahydronaphthalene leads to increased potency and efficacious GR agonism. These compounds are efficacy selective in an NFkB GR agonist assay ( representing transrepression effects) over an MMTV GR agonist assay ( representing transactivation effects). 52 and 60 have NFkB pIC(50) = 8.92 (105%) and 8.69 (92%) and MMTV pEC(50) = 8.20 (47%) and 7.75 (39%), respectively. The impact of the trigger substituent on agonism is modeled within GR and discussed. 36, 52, and 60 have anti-inflammatory activity in a mouse model of inflammation after topical dosing with 52 and 60, having an effect similar to that of dexamethasone. The original lead was discovered by a manual agreement docking method, and automation of this method is also described.

  DOI：

  10.1021/jm060302x
• 作为产物：
  描述：

  2-IODOBENZYLZINC BROMIDE 在 正丁基锂 、 lithium chloride 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 生成 1-Iodo-2-(4-methylideneheptyl)benzene
  参考文献：
  名称：

  Dissociated Nonsteroidal Glucocorticoid Receptor Modulators; Discovery of the Agonist Trigger in a Tetrahydronaphthalene−Benzoxazine Series

  摘要：

  The tetrahydronaphthalene-benzoxazine glucocorticoid receptor (GR) partial agonist 4b was optimized to produce potent full agonists of GR. Aromatic ring substitution of the tetrahydronaphthalene leads to weak GR antagonists. Discovery of an "agonist trigger" substituent on the saturated ring of the tetrahydronaphthalene leads to increased potency and efficacious GR agonism. These compounds are efficacy selective in an NFkB GR agonist assay ( representing transrepression effects) over an MMTV GR agonist assay ( representing transactivation effects). 52 and 60 have NFkB pIC(50) = 8.92 (105%) and 8.69 (92%) and MMTV pEC(50) = 8.20 (47%) and 7.75 (39%), respectively. The impact of the trigger substituent on agonism is modeled within GR and discussed. 36, 52, and 60 have anti-inflammatory activity in a mouse model of inflammation after topical dosing with 52 and 60, having an effect similar to that of dexamethasone. The original lead was discovered by a manual agreement docking method, and automation of this method is also described.

  DOI：

  10.1021/jm060302x

文献信息

• [EN] COMPOUNDS<br/>[FR] COMPOSÉS
  申请人：GLAXO GROUP LTD

  公开号：WO2004071389A2

  公开（公告）日：2004-08-26

  A compound of formula (I) wherein: n represents an integer 0, 1 or 2; X represents, O, S, NR6a, or CHR6b; R1 represents hydrogen, halogen such as F, Cl or Br, NO2, hydroxy, cyano, -OC1-6 alkoxy such as methoxy, C1-6 alkyl such as methyl, NR8R9 such as NH2, NR8COR9 such as -NHCHO or -NHCOCH3, COOR7 or CONR8R9; R2 represents hydrogen, halogen such as F, Cl, Br, NO2, hydroxy, cyano, -OC1-6 alkoxy such as methoxy, C1-6 alkyl such as methyl, NR8R9 such as NH2, NR8COR9 such as -NHCHO or -NHCOCH3, COOR7 or CONR8R9; R3 represents hydrogen, halogen such as F, Cl, Br, NO2, hydroxy, cyano, -OC1-6 alkoxy such as methoxy, C1-6 alkyl such as methyl, NR8R9 such as NH2, NR8COR9 such as -NHCHO or -NHCOCH3, COOR7, CONR8R9; R4 represents hydrogen, halogen such as F, Cl, Br, NO2, hydroxy, cyano, -OC1-6 alkoxy such as methoxy, C1-6 alkyl such as methyl, NR8R9 such as NH2, NR8COR9 such as -NHCHO or -NHCOCH3, COOR7 or CONR8R9; R5 represents H, C1-6 alkyl, or C1-6 alkenyl; R6a represents hydrogen, C1-6 alkyl, CO2C1-3 alkyl, COC1-3 alkyl or SO2C1-3 alkyl; R6b represents hydrogen, or C1-6 alkyl; R7 represents hydrogen, C1-6 alkyl, C1-3 alkyleneSiC1-3 alkyl such as -CH2CH2Si(CH3)3; R8 and R9 independently represent hydrogen or C1-6 alkyl; including pharmaceutically acceptable esters, amides and carbamates thereof, salts thereof, solvates thereof, and solvates of such pharmaceutically acceptable esters, amides, carbamates and salts.