1-iodo-4-isopropyl-2-methoxybenzene | 1240304-64-6

• 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-4-isopropyl-2-methoxybenzene
• 英文别名: 1-iodo-2-methoxy-4-(propan-2-yl)benzene；1-iodo-2-methoxy-4-propan-2-ylbenzene
• CAS: 1240304-64-6
• 化学式: C₁₀H₁₃IO
• 分子量: 276.117
• InChiKey: UJJTVYBIFNPFGA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  1

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  1-iodo-4-isopropyl-2-methoxybenzene 在 sodium tetrahydroborate 、 18-冠醚-6 、 potassium carbonate 、 三乙胺 、 tin(ll) chloride 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 生成 9-(5-iodo-2-isopropyl-4-methoxybenzyl)-N⁶-methyl-9H-purine-2,6-diamine
  参考文献：
  名称：

  Evaluation of adenine as scaffold for the development of novel P2X3 receptor antagonists

  摘要：

  Ligands that selectively block P2X3 receptors localized on nociceptive sensory fibres may be useful for the treatment of chronic pain conditions including neuropathic pain, migraine, and inflammatory pain. With the aim at exploring the suitability of adenine moiety as a scaffold for the development of antagonists of this receptor, a series of 9-benzyl-2-aminoadenine derivatives were designed and synthesized. These new compounds were functionally evaluated at rat or human P2X3 receptors expressed in human embryonic kidney (HEK) cells and on native P2X3 receptors from mouse trigeminal ganglion sensory neurons using patch clamp recording under voltage clamp configuration. The new molecules behaved as P2X3 antagonists, as they rapidly and reversibly inhibited (IC50 in the low micromolar range) the membrane currents induced via P2X3 receptor activation by the full agonist alpha,beta-methyleneATP. Introduction of a small lipophilic methyl substituent at the 6-amino group enhanced the activity, in comparison to the corresponding unsubstituted derivative, resulting in the 9-(5-iodo-2-isopropyl-4-methoxybenzyl)-N-6-methyl-9H-purine-2,6-diamine (24), which appears to be a good antagonist on recombinant and native P2X3 receptors with IC50 = 1.74 +/- 0.21 mu M. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.04.037
• 作为产物：
  描述：

  2-(3-甲氧基苯基)-2-丙醇 在 palladium 10% on activated carbon 、 对甲苯磺酸一水合物 、 氢气 、 甲酸铵 、 四丁基硝酸铵 、 三氟乙酸酐 、 potassium iodide 、 sodium nitrite 作用下， 以 甲醇 、 二氯甲烷 、 水 、 溶剂黄146 、 乙腈 为溶剂， 20.0 ℃ 、379.22 kPa 条件下， 反应 8.5h， 生成 1-iodo-4-isopropyl-2-methoxybenzene
  参考文献：
  名称：

  Evaluation of adenine as scaffold for the development of novel P2X3 receptor antagonists

  摘要：

  Ligands that selectively block P2X3 receptors localized on nociceptive sensory fibres may be useful for the treatment of chronic pain conditions including neuropathic pain, migraine, and inflammatory pain. With the aim at exploring the suitability of adenine moiety as a scaffold for the development of antagonists of this receptor, a series of 9-benzyl-2-aminoadenine derivatives were designed and synthesized. These new compounds were functionally evaluated at rat or human P2X3 receptors expressed in human embryonic kidney (HEK) cells and on native P2X3 receptors from mouse trigeminal ganglion sensory neurons using patch clamp recording under voltage clamp configuration. The new molecules behaved as P2X3 antagonists, as they rapidly and reversibly inhibited (IC50 in the low micromolar range) the membrane currents induced via P2X3 receptor activation by the full agonist alpha,beta-methyleneATP. Introduction of a small lipophilic methyl substituent at the 6-amino group enhanced the activity, in comparison to the corresponding unsubstituted derivative, resulting in the 9-(5-iodo-2-isopropyl-4-methoxybenzyl)-N-6-methyl-9H-purine-2,6-diamine (24), which appears to be a good antagonist on recombinant and native P2X3 receptors with IC50 = 1.74 +/- 0.21 mu M. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.04.037

文献信息

• 4-ISOPROPYL-6-METHOXYPHENYL GLUCITOL COMPOUND
  申请人：Kakinuma Hiroyuki

  公开号：US20130165645A1

  公开（公告）日：2013-06-27

  A compound, which inhibits SGLT1 (sodium-dependent glucose transporter 1) activity to suppress absorption of glucose or the like, thereby suppressing abnormal glucose tolerance or postprandial hyperglycemia in diabetes, is provided. Specifically, a 4-isopropyl-6-methoxyphenyl glucitol compound represented by the following formula (I), or a pharmaceutically acceptable salt thereof, is provided:

  提供了一种化合物，它抑制SGLT1（钠依赖型葡萄糖转运蛋白1）的活性，从而抑制葡萄糖等物质的吸收，进而抑制糖尿病患者的异常葡萄糖耐量或餐后高血糖。具体来说，提供了下列式（I）所代表的4-异丙基-6-甲氧基苯基葡糖醇化合物，或其药用可接受的盐：
• CRYSTAL FORM OF 4-ISOPROPYLPHENYL GLUCITOL COMPOUND AND PROCESS FOR PRODUCTION THEREOF
  申请人：Kimura Yoshihiro

  公开号：US20130144050A1

  公开（公告）日：2013-06-06

  A highly stable crystal of (1S)-1,5-anhydro-1-[5-(4-(1E)-4-[(1-[2-(dimethylamino)ethyl]amino}-2-methyl-1-oxopropan-2-yl)amino]-3,3-dimethyl-4-oxobut-1-en-1-yl}benzyl)-2-methoxy-4-(propan-2-yl)phenyl]-D-glucitol, and a process for producing the crystal are provided. Specifically, an ethanolate having the following physical properties, and a plurality of other crystal forms transformed from the ethanolate are provided: (a) Having peaks at 2θ=5.9 degrees, 17.1 degrees, 17.6 degrees and 21.5 degrees in X-ray powder diffraction (Cu—Kα); (b) Showing characteristic absorption bands at 3538 cm −1 , 3357 cm −1 , 2964 cm −1 , 1673 cm −1 , 1634 cm −1 and 1505 cm −1 in an infrared absorption spectrum; and (c) Having a melting point in a vicinity of 111° C.

  提供了(1S)-1,5-脱水-1-[5-(4-(1E)-4-[(1-[2-(二甲氨基)乙基]氨基}-2-甲基-1-氧代丙酰基)氨基]-3,3-二甲基-4-氧代丁-1-烯-1-基}苯甲基)-2-甲氧基-4-(异丙基)苯基]-D-葡萄糖醇的高度稳定的晶体以及制备该晶体的方法。具体而言，提供了以下物理性质的乙醇酸盐和从乙醇酸盐转化而来的多种晶体形式：(a) 在X射线粉末衍射(Cu-Kα)中，在2θ=5.9度、17.1度、17.6度和21.5度处具有峰；(b) 在红外吸收光谱中显示出3538 cm−1、3357 cm−1、2964 cm−1、1673 cm−1、1634 cm−1和1505 cm−1的特征吸收带；以及(c) 具有接近111℃的熔点。
• 4-Isopropyl-6-methoxyphenyl glucitol compound
  申请人：Taisho Pharmaceutical Co., Ltd.

  公开号：EP2607360B1

  公开（公告）日：2015-08-19
• [EN] 4 -ISOPROPYLPHENYL GLUCITOL COMPOUNDS AS SGLT1 INHIBITORS<br/>[FR] COMPOSÉS DE 4-ISOPROPYLPHÉNYL GLUCITOL COMME INHIBITEURS DE SGLT1
  申请人：TAISHO PHARMA CO LTD

  公开号：WO2010095768A8

  公开（公告）日：2011-08-04
• Discovery of potent, low-absorbable sodium-dependent glucose cotransporter 1 (SGLT1) inhibitor SGL5213 for type 2 diabetes treatment
  作者：Shoichi Kuroda、Yohei Kobashi、Takahiro Oi、Kenichi Kawabe、Fumiyasu Shiozawa、Lisa Okumura-Kitajima、Mami Sugisaki-Kitano、Fusayo Io、Koji Yamamoto、Hiroyuki Kakinuma

  DOI：10.1016/j.bmc.2018.12.015

  日期：2019.1

  A new series of C-phenyl D-glucitol derivatives was designed and synthesized, and their SGLT1 inhibitory potency and absorbability were evaluated. We also investigated whether kidney drug retention could be avoided by creating molecules with different excretion pathways. To achieve a class of molecules with low absorption and that were excreted in bile, optimized synthesis was performed to bring the ClogP value and the topological polar surface area to within the appropriate ranges. Compounds 34d and 34j were poorly absorbed, but the absorbed compounds were mainly excreted in bile. Thus, smaller amounts of persistent residue in the kidneys were observed. Since 34d exerted a glucose-lowering effect at a dose of 0.3 mg/kg (p.o.) in SD rats, this compound (SGL5213) could be a clinical candidate for the treatment of type 2 diabetes.