2,4-dimethyl-3-phenylpyrrole-5-carbaldehyde | 105256-84-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 2,4-dimethyl-3-phenylpyrrole-5-carbaldehyde
• 英文别名: 3,5-dimethyl-4-phenyl-1H-pyrrole-2-carbaldehyde；2-formyl-3,5-dimethyl-4-phenylpyrrole
• CAS: 105256-84-6
• 化学式: C₁₃H₁₃NO
• 分子量: 199.252
• InChiKey: CLFCFEDWQJAZDC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  32.9
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1-methyl-2-(5-methylpyrrol-2-yl)pyrrole 、 2,4-dimethyl-3-phenylpyrrole-5-carbaldehyde 在 盐酸 作用下， 以 乙醇 为溶剂， 反应 0.33h， 以61%的产率得到2,4,10,12-tetramethyl-3-phenylprodigiosene hydrochloride
  参考文献：
  名称：

  Brown, David; Griffiths, David; Rider, Margaret E., Journal of the Chemical Society. Perkin transactions I, 1986, p. 455 - 464

  摘要：

  DOI：
• 作为产物：
  描述：

  O-ethyl-3,5-dimethyl-4-phenyl-1H-pyrrole-2-carbothioate 在 Raney nickel 作用下， 以 水 、 丙酮 为溶剂， 生成 2,4-dimethyl-3-phenylpyrrole-5-carbaldehyde
  参考文献：
  名称：

  2-硫代酸酯吡咯的合成和反应性：制备 2-甲酰基吡咯的途径†

  摘要：

  2-官能化吡咯表现出相当大的合成实用性。在此，报道了 2-硫代酯 (-C(S)OR) 吡咯的合成和反应性。2-硫代酯吡咯是使用克诺尔型方法从脂肪族起始原料合成的。使用 RANEY® 镍一步将 2-硫代酯吡咯还原为相应的 2-甲酰基吡咯或氘代甲酰基变体，从而消除了转化克诺尔通常需要的常用水解/脱羧/甲酰化步骤-型2-羧酸酯吡咯转化为2-甲酰基吡咯。2-硫代酯吡咯被证明能够耐受典型的官能团相互转化，而母体2-羧酸酯吡咯的相互转化已为人所知。

  DOI：

  10.1039/c9ra07527e

文献信息

• 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.
• Novel acylureidoindolin-2-one derivatives as dual Aurora B/FLT3 inhibitors for the treatment of acute myeloid leukemia
  作者：Ajit Dhananjay Jagtap、Pei-Teh Chang、Jia-Rong Liu、Hsiao-Chun Wang、Nagendra B. Kondekar、Li-Jiuan Shen、Hsiang-Wen Tseng、Grace Shiahuy Chen、Ji-Wang Chern

  DOI：10.1016/j.ejmech.2014.07.108

  日期：2014.10

  A series of 6-acylureido derivatives containing a 3-(pyrrol-2-ylmethylidene)indolin-2-one scaffold were synthesized as potential dual Aurora B/FLT3 inhibitors by replacing the 6-arylureido moiety in 6-arylureidoindolin-2-one-based multi-kinase inhibitors. (Z)-N-(2-(pyrrolidin-l-yl)ethyl)-5-((6-(3-(2-fluoro-4-methoxybenzoyflureido)-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide (54) was identified as a dual Aurora B/FLT3 inhibitor (IC50 = 0.4 nM and 0.5 nM, respectively). Compound 54 also exhibited potent cytotoxicity with single-digit nanomolar IC50 values against the FLT3 mutant-associated human acute myeloid leukemia (AML) cell lines MV4-11 (FLT3-ITD) and MOLM-13 (FLT3-ITD). Compound 54 also specifically induced extrinsic apoptosis by inhibiting the phosphorylation of the Aurora B and FLT3 pathways in MOLM-13 cells. Compound 54 had a moderate pharmacokinetic profile. The mesylate salt of 54 efficiently inhibited tumor growth and reduced the mortality of BALB/c nude mice (subcutaneous xenograft model) that had been implanted with AML MOLM-13 cells. Compound 54 is more potent than sunitinib not only against FLT3-WT AML cells but also active against sunitinib-resistant FLT3-ITD AML cells. This study demonstrates the significance of dual Aurora B/FLT3 inhibitors for the development of potential agents to treat AML. (C) 2014 Elsevier Masson SAS. All rights reserved.
• [EN] OXINDOLE COMPOUNDS FOR USE AS MAP4K1 INHIBITORS<br/>[FR] COMPOSÉS D'OXINDOLE DESTINÉS À ÊTRE UTILISÉS EN TANT QU'INHIBITEURS DE MAP4K1
  申请人：ICHNOS SCIENCES S A

  公开号：WO2020070332A1

  公开（公告）日：2020-04-09

  The invention relates to novel inhibitors of MAP4K1 (HPK1), useful for the treatment of diseases or disorders characterized by characterized dysregulation of the signal transduction pathways associated with MAPK activation, including hyperproliferative diseases, diseases of immune system dysfunction, inflammatory disorders, neurological diseases, and cardiovascular diseases. The invention further relates to pharmaceutical compositions comprising the same and methods of treatment of said diseases and disorders. (Formula I)