(2E)-5,5-dimethyl-2-hexenamide | 1359767-12-6

• 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: (2E)-5,5-dimethyl-2-hexenamide
• 英文别名: (E)-5,5-dimethylhex-2-enamide
• CAS: 1359767-12-6
• 化学式: C₈H₁₅NO
• 分子量: 141.213
• InChiKey: XLGJFIJMYVCFIK-SNAWJCMRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  10
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  43.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (2E)-5,5-dimethyl-2-hexenamide 在 二异丁基氢化铝 、 四乙基氟化铵水合物 、 potassium carbonate 、 三乙胺 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 31.83h， 生成 methyl (S)-2-tert-butoxycarbonyl-7-(2-{2-[(1E)-4,4-dimethylpent-1-enyl]-5-methyloxazol-4-yl}ethoxy)-1,2,3,4-tetrahydroisoquinoline-3-carboxylate
  参考文献：
  名称：

  Novel (S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acids: Peroxisome proliferator-activated receptor γ selective agonists with protein-tyrosine phosphatase 1B inhibition

  摘要：

  A novel series of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives were synthesized and (S)-2-[(2E,4E)- hexadienoyl]-7-(2-(5-methyl-2-[( 1E)-5-methylhexen-1-yl]oxazol-4-yl]ethoxy)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (14i) was identified as a potent human peroxisome proliferator-activated receptor gamma (PPAR gamma) selective agonist (EC(50) = 0.03 mu M) and human protein-tyrosine phosphatase 1B (PTP-1B) inhibitor (IC(50) = 1.18 mu M). C(max) after oral administration of 14i at 10 mg/kg was 2.2 mu g/ml (4.5 mu M) in male SD rats. Repeated administration of 14i and rosiglitazone for 14 days dose-dependently decreased plasma glucose levels, ED(50) = 4.3 and 23 mg/kg/day, respectively, in male KK-A(y) mice. In female SD rats, repeated administration of 14i at 12.5-100 mg/kg/day for 28 days had no effect on the hematocrit value (Ht) and red blood cell count (RBC), while rosiglitazone significantly decreased them from 25 mg/kg/day. In conclusion, 14i showed about a fivefold stronger hypoglycemic effect and fourfold or more weaker hemodilution effect than rosiglitazone, indicating that 14i is 20-fold or more safer than rosiglitazone. Compound 14i is a promising candidate for an efficacious and safe anti-diabetic drug targeting PPAR gamma and PTP-1B. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.11.035
• 作为产物：
  描述：

  (E)-5,5-dimethylhex-2-enoyl chloride 在 氨 作用下， 以 水 为溶剂， 反应 2.0h， 生成 (2E)-5,5-dimethyl-2-hexenamide
  参考文献：
  名称：

  Novel (S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acids: Peroxisome proliferator-activated receptor γ selective agonists with protein-tyrosine phosphatase 1B inhibition

  摘要：

  A novel series of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives were synthesized and (S)-2-[(2E,4E)- hexadienoyl]-7-(2-(5-methyl-2-[( 1E)-5-methylhexen-1-yl]oxazol-4-yl]ethoxy)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (14i) was identified as a potent human peroxisome proliferator-activated receptor gamma (PPAR gamma) selective agonist (EC(50) = 0.03 mu M) and human protein-tyrosine phosphatase 1B (PTP-1B) inhibitor (IC(50) = 1.18 mu M). C(max) after oral administration of 14i at 10 mg/kg was 2.2 mu g/ml (4.5 mu M) in male SD rats. Repeated administration of 14i and rosiglitazone for 14 days dose-dependently decreased plasma glucose levels, ED(50) = 4.3 and 23 mg/kg/day, respectively, in male KK-A(y) mice. In female SD rats, repeated administration of 14i at 12.5-100 mg/kg/day for 28 days had no effect on the hematocrit value (Ht) and red blood cell count (RBC), while rosiglitazone significantly decreased them from 25 mg/kg/day. In conclusion, 14i showed about a fivefold stronger hypoglycemic effect and fourfold or more weaker hemodilution effect than rosiglitazone, indicating that 14i is 20-fold or more safer than rosiglitazone. Compound 14i is a promising candidate for an efficacious and safe anti-diabetic drug targeting PPAR gamma and PTP-1B. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.11.035

文献信息

• Purinone Derivatives as Tyrosine Kinase Inhibitors
  申请人：Principia Biopharma Inc.

  公开号：US20140142099A1

  公开（公告）日：2014-05-22

  The present disclosure provides compounds and pharmaceutically acceptable salts thereof that are tyrosine kinase inhibitors, in particular BLK, BMX, EGFR, HER2, HER4, ITK, TEC, BTK, and TXK and are therefore useful for the treatment of diseases treatable by inhibition of tyrosine kinases such as autoimmune diseases, cancer and inflammatory diseases. Also provided are pharmaceutical compositions containing such compounds and pharmaceutically acceptable salts thereof and processes for preparing such compounds and pharmaceutically acceptable salts thereof.

  本公开提供了一些酪氨酸激酶抑制剂及其药用盐，特别是BLK、BMX、EGFR、HER2、HER4、ITK、TEC、BTK和TXK，因此适用于治疗通过抑制酪氨酸激酶可治疗的疾病，如自身免疫疾病、癌症和炎症性疾病。还提供了含有这些化合物和药用盐的药物组合物，以及制备这些化合物和药用盐的方法。
• [EN] CYTOTOXIC AND ANTI-MITOTIC COMPOUNDS, AND METHODS OF USING THE SAME<br/>[FR] COMPOSÉS CYTOTOXIQUES ET ANTIMITOTIQUES ET LEURS PROCÉDÉS D'UTILISATION
  申请人：CT FOR DRUG RES AND DEV

  公开号：WO2014144871A1

  公开（公告）日：2014-09-18

  Compounds having cytotoxic and/or anti-mitotic activity are disclosed. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed. Also disclosed are compositions having the structure: (T)-(L)-(D), wherein (T) is a targeting moiety, (L) is an optional linker, and (D) is a compound having cytotoxic and/or anti-mitotic activity.

  揭示了具有细胞毒性和/或抗有丝分裂活性的化合物。还揭示了与制备和使用这些化合物相关的方法，以及包含这些化合物的药物组合物。还揭示了具有结构的组合物：(T)-(L)-(D)，其中(T)是靶向基团，(L)是可选的连接物，(D)是具有细胞毒性和/或抗有丝分裂活性的化合物。
• CYTOTOXIC AND ANTI-MITOTIC COMPOUNDS, AND METHODS OF USING THE SAME
  申请人：Centre For Drug Research And Development

  公开号：EP2968440A1

  公开（公告）日：2016-01-20
• Novel (S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acids: Peroxisome proliferator-activated receptor γ selective agonists with protein-tyrosine phosphatase 1B inhibition
  作者：Kazuya Otake、Satoru Azukizawa、Masaki Fukui、Kazuyoshi Kunishiro、Hikaru Kamemoto、Mamoru Kanda、Tomohiro Miike、Masayasu Kasai、Hiroaki Shirahase

  DOI：10.1016/j.bmc.2011.11.035

  日期：2012.1

  A novel series of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives were synthesized and (S)-2-[(2E,4E)- hexadienoyl]-7-(2-(5-methyl-2-[( 1E)-5-methylhexen-1-yl]oxazol-4-yl]ethoxy)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (14i) was identified as a potent human peroxisome proliferator-activated receptor gamma (PPAR gamma) selective agonist (EC(50) = 0.03 mu M) and human protein-tyrosine phosphatase 1B (PTP-1B) inhibitor (IC(50) = 1.18 mu M). C(max) after oral administration of 14i at 10 mg/kg was 2.2 mu g/ml (4.5 mu M) in male SD rats. Repeated administration of 14i and rosiglitazone for 14 days dose-dependently decreased plasma glucose levels, ED(50) = 4.3 and 23 mg/kg/day, respectively, in male KK-A(y) mice. In female SD rats, repeated administration of 14i at 12.5-100 mg/kg/day for 28 days had no effect on the hematocrit value (Ht) and red blood cell count (RBC), while rosiglitazone significantly decreased them from 25 mg/kg/day. In conclusion, 14i showed about a fivefold stronger hypoglycemic effect and fourfold or more weaker hemodilution effect than rosiglitazone, indicating that 14i is 20-fold or more safer than rosiglitazone. Compound 14i is a promising candidate for an efficacious and safe anti-diabetic drug targeting PPAR gamma and PTP-1B. (C) 2011 Elsevier Ltd. All rights reserved.