methyl N-(2,2-dimethylbut-3-enoyl)-2-methylalaninate | 1240304-76-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: methyl N-(2,2-dimethylbut-3-enoyl)-2-methylalaninate
• 英文别名: Methyl 2-(2,2-Dimethylbut-3-enamido)-2-methylpropanoate；methyl 2-(2,2-dimethylbut-3-enoylamino)-2-methylpropanoate
• CAS: 1240304-76-0
• 化学式: C₁₁H₁₉NO₃
• 分子量: 213.277
• InChiKey: BFZNKOMNKAPXRZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl N-(2,2-dimethylbut-3-enoyl)-2-methylalaninate 在 palladium diacetate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三(邻甲基苯基)磷 、 sodium hydroxide 作用下， 以 甲醇 、 氯仿 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 1.5h， 生成 (2R,3R,4R,5S,6S)-2-(acetoxymethyl)-6-(5-(4-((E)-4-((1-((2-amino-2-methylpropyl)amino)-2-methyl-1-oxopropan-2-yl)amino)-3,3-dimethyl-4-oxobut-1-en-1-yl)-2-methylbenzyl)-4-isopropyl-2-methoxyphenyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate
  参考文献：
  名称：

  Discovery of potent, low-absorbable sodium-dependent glucose cotransporter 1 (SGLT1) inhibitor SGL5213 for type 2 diabetes treatment

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2018.12.015
• 作为产物：
  描述：

  2,2-二甲基-3-丁烯酸 在 草酰氯 、 三乙胺 作用下， 以 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 生成 methyl N-(2,2-dimethylbut-3-enoyl)-2-methylalaninate
  参考文献：
  名称：

  4-ISOPROPYL-6-METHOXYPHENYL GLUCITOL COMPOUND

  摘要：

  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：

  公开号：

  US20130165645A1

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-ISOPROPYLPHENYL GLUCITOL COMPOUNDS AS SGLT1 INHIBITORS
  申请人：Kakinuma Hiroyuki

  公开号：US20110306759A1

  公开（公告）日：2011-12-15

  The present invention provides 4-isopropylphenyl glucitol compounds which have no tendency to accumulate in the body and which inhibit SGLT1 activity to suppress postprandial hyperglycemia (or impaired glucose tolerance) through suppression of glucose absorption in the small intestine, whereby the compounds, for example, can suppress the onset of diabetes and metabolic syndrome or can treat these diseases. A 4-isopropylphenyl glucitol compound represented by the following formula (I) or a pharmaceutically acceptable salt thereof: wherein R 1 represents a hydrogen atom, etc., R 2 represents a methyl group, etc., R 3 represents a C 1-4 alkyl group substituted with an amino group(s), etc., and R 4 represents a hydrogen atom, etc.

  本发明提供了4-异丙基苯基葡萄糖醇化合物，其没有在体内积累的趋势，并通过抑制小肠中的葡萄糖吸收来抑制SGLT1活性，从而抑制餐后高血糖（或糖耐量受损），例如，这些化合物可以抑制糖尿病和代谢综合征的发生或治疗这些疾病。化合物由以下式（I）表示：其中R1表示氢原子等，R2表示甲基基团等，R3表示C1-4烷基基团，该基团被氨基团等取代，R4表示氢原子等，或其药学上可接受的盐。
• 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