1-(4-methoxyphenyl)-3-(2-oxo-2,3-dihydro-1H-indol-5-yl)-urea | 1172464-50-4

• 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-(4-methoxyphenyl)-3-(2-oxo-2,3-dihydro-1H-indol-5-yl)-urea
• 英文别名: 1-(4-Methoxyphenyl)-3-(2-oxoindolin-5-yl)urea；1-(4-methoxyphenyl)-3-(2-oxo-1,3-dihydroindol-5-yl)urea
• CAS: 1172464-50-4
• 化学式: C₁₆H₁₅N₃O₃
• 分子量: 297.313
• InChiKey: ZXDJBWDMNZBVCU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  79.5
• 氢给体数：
  3
• 氢受体数：
  3

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  5-氨基-1,3-二氢吲哚-2-酮	5-amino-1,3-dihydro-2H-indol-2-one	20876-36-2	C8H8N2O	148.164

反应信息

• 作为反应物：
  描述：

  5-(3-硝基苯基)糠醛 、 1-(4-methoxyphenyl)-3-(2-oxo-2,3-dihydro-1H-indol-5-yl)-urea 在 四氢吡咯 作用下， 以 乙醇 为溶剂， 以95%的产率得到(E)-1-(4-methoxyphenyl)-3-{3-[5-(3-nitrophenyl)-furan-2-ylmethylene]-2-oxo-2,3-dihydro-1H-indol-5-yl}urea
  参考文献：
  名称：

  Synthesis and structure–activity relationship of 6-arylureido-3-pyrrol-2-ylmethylideneindolin-2-one derivatives as potent receptor tyrosine kinase inhibitors

  摘要：

  A series of new ureidoindolin-2-one derivatives were synthesized and evaluated as inhibitors of receptor tyrosine kinases. Investigation of structure-activity relationships at positions 5, 6, and 7 of the oxindole skeleton led to the identification of 6-ureido-substituted 3-pyrrolemethylidene-2-oxindole derivatives that potently inhibited both the vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) families of receptor tyrosine kinases. Several derivatives showed potency against the PDGFR inhibiting both its enzymatic and cellular functions in the single-digit nanomolar range. Among them, compound 35 was a potent inhibitor against tyrosine kinases, including VEGFR and PDGFR families, as well as Aurora kinases. Inhibitor 36 (non-substituted on the pyrrole or phenyl ring) had a moderate pharmacokinetic profile and completely inhibited tumor growth initiated with the myeloid leukemia cell line, MV4-11, in a subcutaneous xenograft model in BALB/c nude mice. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.05.021
• 作为产物：
  描述：

  5-氨基-1,3-二氢吲哚-2-酮 、 对甲氧基苯异氰酸酯 以 甲醇 、 二氯甲烷 为溶剂， 以95%的产率得到1-(4-methoxyphenyl)-3-(2-oxo-2,3-dihydro-1H-indol-5-yl)-urea
  参考文献：
  名称：

  Synthesis and structure–activity relationship of 6-arylureido-3-pyrrol-2-ylmethylideneindolin-2-one derivatives as potent receptor tyrosine kinase inhibitors

  摘要：

  A series of new ureidoindolin-2-one derivatives were synthesized and evaluated as inhibitors of receptor tyrosine kinases. Investigation of structure-activity relationships at positions 5, 6, and 7 of the oxindole skeleton led to the identification of 6-ureido-substituted 3-pyrrolemethylidene-2-oxindole derivatives that potently inhibited both the vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) families of receptor tyrosine kinases. Several derivatives showed potency against the PDGFR inhibiting both its enzymatic and cellular functions in the single-digit nanomolar range. Among them, compound 35 was a potent inhibitor against tyrosine kinases, including VEGFR and PDGFR families, as well as Aurora kinases. Inhibitor 36 (non-substituted on the pyrrole or phenyl ring) had a moderate pharmacokinetic profile and completely inhibited tumor growth initiated with the myeloid leukemia cell line, MV4-11, in a subcutaneous xenograft model in BALB/c nude mice. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.05.021

文献信息

• [EN] SMALL MOLECULE GRB2 STABILIZERS FOR RAS MAP KINASE INHIBITION<br/>[FR] STABILISATEURS GRB2 À PETITES MOLÉCULES POUR INHIBITION DE LA MAP KINASE RAS
  申请人：UNIV TEXAS

  公开号：WO2020186202A1

  公开（公告）日：2020-09-17

  The present disclosure compounds of the formula (I-A) or (I), wherein the variables are defined herein, as well as pharmaceutical compositions thereof. The present disclosure also provides methods for the use of said compounds and/or pharmaceutical compositions, such as in the treatment of cancer. The present disclosure also provides methods for the use of compounds of the formula (III), wherein the variables are defined herein.

  本公开涉及公式（I-A）或（I）的化合物，其中变量在此定义，以及其制药组合物。本公开还提供了使用所述化合物和/或制药组合物的方法，例如用于治疗癌症。本公开还提供了使用公式（III）的化合物的方法，其中变量在此定义。
• SMALL MOLECULE GRB2 STABILIZERS FOR RAS MAP KINASE INHIBITION
  申请人：Board of Regents, The University of Texas System

  公开号：US20220151991A1

  公开（公告）日：2022-05-19

  The present disclosure compounds of the formula (I-A) or (I), wherein the variables are defined herein, as well as pharmaceutical compositions thereof. The present disclosure also provides methods for the use of said compounds and/or pharmaceutical compositions, such as in the treatment of cancer. The present disclosure also provides methods for the use of compounds of the formula (III), wherein the variables are defined herein.
• Synthesis and structure–activity relationship of 6-arylureido-3-pyrrol-2-ylmethylideneindolin-2-one derivatives as potent receptor tyrosine kinase inhibitors
  作者：Rahul R. Khanwelkar、Grace Shiahuy Chen、Hsiao-Chun Wang、Chao-Wu Yu、Chiung-Hua Huang、On Lee、Chih-Hung Chen、Chrong-Shiong Hwang、Ching-Huai Ko、Nien-Tzu Chou、Mai-Wei Lin、Ling-mei Wang、Yen-Chun Chen、Tzong-Hsiung Hseu、Chia-Ni Chang、Hui-Chun Hsu、Hui-Chi Lin、Ying-Chu Shih、Shuen-Hsiang Chou、Hsiang-Wen Tseng、Chih-Peng Liu、Chia-Mu Tu、Tsan-Lin Hu、Yuan-Jang Tsai、Ji-Wang Chern

  DOI：10.1016/j.bmc.2010.05.021

  日期：2010.7

  A series of new ureidoindolin-2-one derivatives were synthesized and evaluated as inhibitors of receptor tyrosine kinases. Investigation of structure-activity relationships at positions 5, 6, and 7 of the oxindole skeleton led to the identification of 6-ureido-substituted 3-pyrrolemethylidene-2-oxindole derivatives that potently inhibited both the vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) families of receptor tyrosine kinases. Several derivatives showed potency against the PDGFR inhibiting both its enzymatic and cellular functions in the single-digit nanomolar range. Among them, compound 35 was a potent inhibitor against tyrosine kinases, including VEGFR and PDGFR families, as well as Aurora kinases. Inhibitor 36 (non-substituted on the pyrrole or phenyl ring) had a moderate pharmacokinetic profile and completely inhibited tumor growth initiated with the myeloid leukemia cell line, MV4-11, in a subcutaneous xenograft model in BALB/c nude mice. (C) 2010 Elsevier Ltd. All rights reserved.