methyl 3-(4-isothiocyanatophenyl)propanoate

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: methyl 3-(4-isothiocyanatophenyl)propanoate
• 英文别名: Methyl 3-(4-isothiocyanatophenyl)propanoate
• 化学式: C₁₁H₁₁NO₂S
• 分子量: 221.28
• InChiKey: AMUHANUXSNXMIW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  70.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 3-(4-isothiocyanatophenyl)propanoate 、 4-溴邻苯二胺 在 N-cylcohexylcarbodiimide, N'-methyl-polystyrene resin 作用下， 以 二氯甲烷 为溶剂， 反应 16.5h， 生成
  参考文献：
  名称：

  Selectively Targeting T- and B-Cell Lymphomas: A Benzothiazole Antagonist of α₄β₁ Integrin

  摘要：

  Current cancer chemotherapeutic agents clinically deployed today are designed to be indiscriminately cytotoxic, however. achieving selective targeting of cancer malignancies would allow for improved diagnostic and chemotherapeutic tools. Integrin alpha(4)beta(1), a heterodimeric cell surface receptor, is believed to have a low-affinity conformation in resting normal lymphocytes and an activated high-affinity conformation in cancerous cells, specifically T- and B-cell lymphomas. This highly attractive yet poorly understood receptor has been selectively targeted with the bisaryl urea peptidomimetic antagonist 1. However. concerns regarding its preliminary pharmacokinetic (PK) profile provided an impetus to change the pharmacophore from a bisaryl urea to a 2-arylaminobenzothiazole moiety, resulting in an analogue with improved physicochemical properties, solubility, and kidney:tumor ratio while maintaining potency (6; IC50 = 53 pM). The results presented herein utilized heterocyclic and solid-phase chemistry, cell adhesion assay, and in vivo optical imaging using the cyanine dye Cy5.5 conjugate.

  DOI：

  10.1021/jm800313f
• 作为产物：
  描述：

  硫光气 、 3-(4-氨基苯基)丙酸甲酯 在 三乙胺 作用下， 以 乙酸乙酯 为溶剂， 反应 12.5h， 以90%的产率得到methyl 3-(4-isothiocyanatophenyl)propanoate
  参考文献：
  名称：

  Highly Potent, Water Soluble Benzimidazole Antagonist for Activated α₄β₁ Integrin

  摘要：

  The cell surface receptor alpha(4)beta(1), integrin, activated constitutively in lymphoma, can be targeted with the bisaryl urea peptidomimetic antagonist 1 (LLP2A). However, concerns on its preliminary pharmacokinetc (PK) profile provided an impetus to change the pharmacophore from a bisaryl urea to a 2-arylaminobenzimidazole moiety, resulting in improved solubility while maintaining picomolar potency [5 (KLCA4); IC50 = 305 pM]. With exceptional solubility, this finding has the potential for improving PK to help diagnose and treat lymphomas.

  DOI：

  10.1021/jm070790o

文献信息

• Highly Potent, Water Soluble Benzimidazole Antagonist for Activated α₄β₁ Integrin
  作者：Richard D. Carpenter、Mirela Andrei、Edmond Y. Lau、Felice C. Lightstone、Ruiwu Liu、Kit S. Lam、Mark J. Kurth

  DOI：10.1021/jm070790o

  日期：2007.11.1

  The cell surface receptor alpha(4)beta(1), integrin, activated constitutively in lymphoma, can be targeted with the bisaryl urea peptidomimetic antagonist 1 (LLP2A). However, concerns on its preliminary pharmacokinetc (PK) profile provided an impetus to change the pharmacophore from a bisaryl urea to a 2-arylaminobenzimidazole moiety, resulting in improved solubility while maintaining picomolar potency [5 (KLCA4); IC50 = 305 pM]. With exceptional solubility, this finding has the potential for improving PK to help diagnose and treat lymphomas.
• Heterocyclic Ligands for Integrin Imaging and Therapy
  申请人：Carpenter Richard D.

  公开号：US20100310455A1

  公开（公告）日：2010-12-09

  The present invention provides α 4 β 1 integrin ligands that display high binding affinity, specificity, and stability. The ligands comprise a peptide having n independently selected amino acids, wherein at least one amino acid is an unnatural amino acid or a D-amino acid, and wherein n is an integer of from 3 to 20. Methods are provided for administering the ligands for treating cancer, inflammatory diseases, and autoimmune diseases. Also provided are methods for administering the ligands for imaging a tumor, organ, or tissue in a subject.
• US8486370B2
  申请人：——

  公开号：US8486370B2

  公开（公告）日：2013-07-16
• [EN] HETEROCYCLIC LIGANDS FOR INTEGRIN IMAGING AND THERAPY<br/>[FR] LIGANDS HÉTÉROCYCLIQUES D'INTÉGRINE, IMAGERIE ET THÉRAPIE
  申请人：UNIV CALIFORNIA

  公开号：WO2008031016A2

  公开（公告）日：2008-03-13

  [EN] The present invention provides a ₄ß₁ integrin ligands that display high binding affinity, specificity, and stability. The ligands comprise a peptide having n independently selected amino acids, wherein at least one amino acid is an unnatural amino acid or a D-amino acid, and wherein n is an integer of from 3 to 20. Methods are provided for administering the ligands for treating cancer, inflammatory diseases, and autoimmune diseases. Also provided are methods for administering the ligands for imaging a tumor, organ, or tissue in a subject.
  [FR] La présente invention fournit des ligands d'intégrine ₄b₁ affichant une affinité, une spécificité et une stabilité de liaison élevées. Les ligands comprennent un peptide ayant n acides aminés sélectionnés indépendamment, au moins un acide aminé étant un acide aminé non naturel ou un acide aminé D, et n étant un entier de 3 à 20. Des procédés sont fournis pour administrer les ligands pour traiter le cancer, des maladies inflammatoires et des maladies auto-immunes. Des procédés sont également fournis pour administrer les ligands pour visualiser une tumeur, un organe, ou un tissu chez un sujet.
• Selectively Targeting T- and B-Cell Lymphomas: A Benzothiazole Antagonist of α₄β₁ Integrin
  作者：Richard D. Carpenter、Mirela Andrei、Olulanu H. Aina、Edmond Y. Lau、Felice C. Lightstone、Ruiwu Liu、Kit S. Lam、Mark J. Kurth

  DOI：10.1021/jm800313f

  日期：2009.1.8

  Current cancer chemotherapeutic agents clinically deployed today are designed to be indiscriminately cytotoxic, however. achieving selective targeting of cancer malignancies would allow for improved diagnostic and chemotherapeutic tools. Integrin alpha(4)beta(1), a heterodimeric cell surface receptor, is believed to have a low-affinity conformation in resting normal lymphocytes and an activated high-affinity conformation in cancerous cells, specifically T- and B-cell lymphomas. This highly attractive yet poorly understood receptor has been selectively targeted with the bisaryl urea peptidomimetic antagonist 1. However. concerns regarding its preliminary pharmacokinetic (PK) profile provided an impetus to change the pharmacophore from a bisaryl urea to a 2-arylaminobenzothiazole moiety, resulting in an analogue with improved physicochemical properties, solubility, and kidney:tumor ratio while maintaining potency (6; IC50 = 53 pM). The results presented herein utilized heterocyclic and solid-phase chemistry, cell adhesion assay, and in vivo optical imaging using the cyanine dye Cy5.5 conjugate.