N-cyclohex-1-en-1-yl-2-[formyl(methyl)amino]-2-(1-phenylcyclopropyl)acetamide | 676630-42-5

• 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: N-cyclohex-1-en-1-yl-2-[formyl(methyl)amino]-2-(1-phenylcyclopropyl)acetamide
• 英文别名: N-(cyclohexen-1-yl)-2-[formyl(methyl)amino]-2-(1-phenylcyclopropyl)acetamide
• CAS: 676630-42-5
• 化学式: C₁₉H₂₄N₂O₂
• 分子量: 312.412
• InChiKey: JEWBZNCWBIPOCS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  49.4
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-cyclohex-1-en-1-yl-2-[formyl(methyl)amino]-2-(1-phenylcyclopropyl)acetamide 在 盐酸 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 (E)-(S)-4-({(S)-3,3-Dimethyl-2-[2-methylamino-2-(1-phenyl-cyclopropyl)-acetylamino]-butyryl}-methyl-amino)-2,5-dimethyl-hex-2-enoic acid ethyl ester
  参考文献：
  名称：

  Synthesis and Biological Activity of Analogues of the Antimicrotubule Agent N,β,β-Trimethyl-l-phenylalanyl-N-[(1S,2E)-3-carboxy-1-isopropylbut-2-enyl]- N¹,3-dimethyl-l-valinamide (HTI-286)

  摘要：

  Hemiasterlin (1), a tripeptide isolated from marine sponges, induces microtubule depolymerization and mitotic arrest in cells. HTI-286 (2), an analogue from an initial study of the hemiasterlins, is presently in clinical trials. In addition to its potent antitumor effects, 2 has the advantage of circumventing the P-glycoprotein-mediated resistance that hampers the efficacy of other antimicrotubule agents such as paclitaxel and vincristine in animal models. This paper describes an in-depth study of the structure-activity relationships of analogues of 2, their effects on microtubule polymerization, and their in vitro and in vivo anticancer activity. Regions of the molecule necessary for potent activity are identified. Groups tolerant of modification, leading to novel analogues, are reported. Potent analogues identified through in vivo studies in tumor xenograft models include one superior analogue, HTI-042 (48).

  DOI：

  10.1021/jm040056u
• 作为产物：
  描述：

  甲酸 、 1-苯基环丙烷甲醛 、 异氰基环己烯 、 甲胺 以 甲醇 、 水 为溶剂， 反应 18.25h， 以1.23 g的产率得到N-cyclohex-1-en-1-yl-2-[formyl(methyl)amino]-2-(1-phenylcyclopropyl)acetamide
  参考文献：
  名称：

  Synthesis and Biological Activity of Analogues of the Antimicrotubule Agent N,β,β-Trimethyl-l-phenylalanyl-N-[(1S,2E)-3-carboxy-1-isopropylbut-2-enyl]- N¹,3-dimethyl-l-valinamide (HTI-286)

  摘要：

  Hemiasterlin (1), a tripeptide isolated from marine sponges, induces microtubule depolymerization and mitotic arrest in cells. HTI-286 (2), an analogue from an initial study of the hemiasterlins, is presently in clinical trials. In addition to its potent antitumor effects, 2 has the advantage of circumventing the P-glycoprotein-mediated resistance that hampers the efficacy of other antimicrotubule agents such as paclitaxel and vincristine in animal models. This paper describes an in-depth study of the structure-activity relationships of analogues of 2, their effects on microtubule polymerization, and their in vitro and in vivo anticancer activity. Regions of the molecule necessary for potent activity are identified. Groups tolerant of modification, leading to novel analogues, are reported. Potent analogues identified through in vivo studies in tumor xenograft models include one superior analogue, HTI-042 (48).

  DOI：

  10.1021/jm040056u

文献信息

• Method of treating resistant tumors
  申请人：Wyeth Holdings Corporation

  公开号：US20040121965A1

  公开（公告）日：2004-06-24

  The invention provides a method of treating or inhibiting the growth of or eradicating a tumor in a mammal in need thereof wherein said tumor is resistant to at least one chemotherapeutic agent which method comprises providing to said mammal an effective amount of a compound of Formula II or a pharmaceutically acceptable salt thereof.

  本发明提供了一种治疗或抑制哺乳动物体内对至少一种化疗药物产生耐药性的肿瘤生长或根除肿瘤的方法，该方法包括向该哺乳动物提供有效量的公式II化合物或其药学上可接受的盐。
• [EN] METHOD OF TREATING RESISTANT TUMORS<br/>[FR] METHODE DE TRAITEMENT DE TUMEURS RESISTANTES
  申请人：WYETH CORP

  公开号：WO2004026293A2

  公开（公告）日：2004-04-01

  The invention provides a method of treating or inhibiting the growth of or eradicating a tumor in a mammal in need thereof wherein said tumor is resistant to at least one chemotherapeutic agents which method comprises providing to said mammal an effective amount of a compound of Formula II or a pharmaceutically acceptable salt thereof.
• Synthesis and Biological Activity of Analogues of the Antimicrotubule Agent <i>N</i>,β,β-Trimethyl-<scp>l</scp>-phenylalanyl-<i>N</i>-[(1<i>S</i>,2<i>E</i>)-3-carboxy-1-isopropylbut-2-enyl]- <i>N</i>¹,3-dimethyl-<scp>l</scp>-valinamide (HTI-286)
  作者：Arie Zask、Gary Birnberg、Katherine Cheung、Joshua Kaplan、Chuan Niu、Emily Norton、Ronald Suayan、Ayako Yamashita、Derek Cole、Zhilian Tang、Girija Krishnamurthy、Robert Williamson、Gulnaz Khafizova、Sylvia Musto、Richard Hernandez、Tami Annable、Xiaoran Yang、Carolyn Discafani、Carl Beyer、Lee M. Greenberger、Frank Loganzo、Semiramis Ayral-Kaloustian

  DOI：10.1021/jm040056u

  日期：2004.9.1

  Hemiasterlin (1), a tripeptide isolated from marine sponges, induces microtubule depolymerization and mitotic arrest in cells. HTI-286 (2), an analogue from an initial study of the hemiasterlins, is presently in clinical trials. In addition to its potent antitumor effects, 2 has the advantage of circumventing the P-glycoprotein-mediated resistance that hampers the efficacy of other antimicrotubule agents such as paclitaxel and vincristine in animal models. This paper describes an in-depth study of the structure-activity relationships of analogues of 2, their effects on microtubule polymerization, and their in vitro and in vivo anticancer activity. Regions of the molecule necessary for potent activity are identified. Groups tolerant of modification, leading to novel analogues, are reported. Potent analogues identified through in vivo studies in tumor xenograft models include one superior analogue, HTI-042 (48).