ethyl 2-(4-fluorophenyl)-1-[(4-methylphenyl)sulfonyl]-2,5-dihydro-1H-pyrrole-3-carboxylate

• 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: ethyl 2-(4-fluorophenyl)-1-[(4-methylphenyl)sulfonyl]-2,5-dihydro-1H-pyrrole-3-carboxylate
• 英文别名: Ethyl 2-(4-fluorophenyl)-1-(4-methylphenyl)sulfonyl-2,5-dihydropyrrole-3-carboxylate
• 化学式: C₂₀H₂₀FNO₄S
• 分子量: 389.448
• InChiKey: PGVPVPHDVZSVDM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  72.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl 2-(4-fluorophenyl)-1-[(4-methylphenyl)sulfonyl]-2,5-dihydro-1H-pyrrole-3-carboxylate 在 盐酸 、 platinum(IV) oxide 、 potassium tert-butylate 、 氢气 、 碳酸氢钠 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 70.0 ℃ 、310.27 kPa 条件下， 反应 73.0h， 生成 cis-1-acetyl-2-(4-fluorophenyl)pyrrolidine-3-carboxylic acid
  参考文献：
  名称：

  Discovery of Novel, Potent, and Selective Inhibitors of 3-Phosphoinositide-Dependent Kinase (PDK1)

  摘要：

  Analogues substituted with various amines at the 6-position of the pyrazine ring on (4-amino-7-isopropyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)pyrazin-2-ylmethanone were discovered as potent and selective inhibitors of PDK1 with potential as anticancer agents. An early lead with 2-pyridine-3-ylethylamine as the pyrazine substituent showed moderate potency and selectivity. Structure-based drug design led to improved potency and selectivity against PI3K alpha through a combination of cyclizing the ethylene spacer into a saturated, five-membered ring and substituting on the 4-position of the aryl ring with a fluorine. ADME properties were improved by lowering the lipophilicity with heteroatom replacements in the saturated, five-membered ring. The optimized analogues have a PDK1 K-i of 1 nM and >100-fold selectivity against PI3K/AKT-pathway kinases. The cellular potency of these analogues was assessed by the inhibition of AKT phosphorylation (T308) and by their antiproliferation activity against a number of tumor cell lines.

  DOI：

  10.1021/jm201019k
• 作为产物：
  描述：

  2,3-丁二烯酸乙酯 、 (E)-N-(4-fluorobenzylidene)-4-methylbenzenesulfonamide 在 (η⁵-C5H5)Re(NO)(PPh3)(CH2PPh3) 作用下， 以 苯 为溶剂， 反应 24.0h， 以90%的产率得到ethyl 2-(4-fluorophenyl)-1-[(4-methylphenyl)sulfonyl]-2,5-dihydro-1H-pyrrole-3-carboxylate
  参考文献：
  名称：

  A promising new catalyst family for enantioselective cycloadditions involving allenes and imines: chiral phosphines with transition metal–CH2–P: linkages

  摘要：

  The racemic thenium-containing phosphine (eta(5)-C5H5)Re(NO)(PPh3)(CH2PPh3) (3) catalyzes the [3+2] cycloaddition of H2C=C=CHCO2Et and N-tosyl imines ArCH=NTs in C6H6 (RT, 1 d, 20 mol %) to give 2-aryl-3-carbethoxy-3-pyrrolines (Ar=p-C6H4X (X = H, NO2, OMe, Me, Cl, Br), 2-furyl; 95-84% isolated). Similar reactions with enantiopure (S)-3 are conducted in C6H5Cl at -30 degrees C (8 d) to maximize enantio selectivities (60-51% ee; 93-90% isolated). (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2006.07.005

文献信息

• [EN] COMPOUNDS, COMPOSITIONS, AND METHODS FOR MODULATING CALCIUM ION HOMEOSTASIS<br/>[FR] COMPOSÉS, COMPOSITIONS ET PROCÉDÉS DE MODULATION DE L'HOMÉOSTASIE DES IONS CALCIUM
  申请人：UNIV CALIFORNIA

  公开号：WO2021163493A1

  公开（公告）日：2021-08-19

  The present disclosure relates to compounds that are capable of modulating calcium ion homeostasis and treating disorders related thereto. The disclosure further relates to methods of making the aforementioned compounds.

  本公开涉及能够调节钙离子稳态并治疗相关疾病的化合物。此外，本公开还涉及制备上述化合物的方法。
• Discovery of Novel, Potent, and Selective Inhibitors of 3-Phosphoinositide-Dependent Kinase (PDK1)
  作者：Sean T. Murphy、Gordon Alton、Simon Bailey、Sangita M. Baxi、Benjamin J. Burke、Thomas A. Chappie、Jacques Ermolieff、RoseAnn Ferre、Samantha Greasley、Michael Hickey、John Humphrey、Natasha Kablaoui、John Kath、Steven Kazmirski、Michelle Kraus、Stan Kupchinsky、John Li、Laura Lingardo、Matthew A. Marx、Dan Richter、Steven P. Tanis、Khanh Tran、William Vernier、Zhi Xie、Min-Jean Yin、Xiao-Hong Yu

  DOI：10.1021/jm201019k

  日期：2011.12.22

  Analogues substituted with various amines at the 6-position of the pyrazine ring on (4-amino-7-isopropyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)pyrazin-2-ylmethanone were discovered as potent and selective inhibitors of PDK1 with potential as anticancer agents. An early lead with 2-pyridine-3-ylethylamine as the pyrazine substituent showed moderate potency and selectivity. Structure-based drug design led to improved potency and selectivity against PI3K alpha through a combination of cyclizing the ethylene spacer into a saturated, five-membered ring and substituting on the 4-position of the aryl ring with a fluorine. ADME properties were improved by lowering the lipophilicity with heteroatom replacements in the saturated, five-membered ring. The optimized analogues have a PDK1 K-i of 1 nM and >100-fold selectivity against PI3K/AKT-pathway kinases. The cellular potency of these analogues was assessed by the inhibition of AKT phosphorylation (T308) and by their antiproliferation activity against a number of tumor cell lines.
• A promising new catalyst family for enantioselective cycloadditions involving allenes and imines: chiral phosphines with transition metal–CH2–P: linkages
  作者：Alexander Scherer、J.A. Gladysz

  DOI：10.1016/j.tetlet.2006.07.005

  日期：2006.9

  The racemic thenium-containing phosphine (eta(5)-C5H5)Re(NO)(PPh3)(CH2PPh3) (3) catalyzes the [3+2] cycloaddition of H2C=C=CHCO2Et and N-tosyl imines ArCH=NTs in C6H6 (RT, 1 d, 20 mol %) to give 2-aryl-3-carbethoxy-3-pyrrolines (Ar=p-C6H4X (X = H, NO2, OMe, Me, Cl, Br), 2-furyl; 95-84% isolated). Similar reactions with enantiopure (S)-3 are conducted in C6H5Cl at -30 degrees C (8 d) to maximize enantio selectivities (60-51% ee; 93-90% isolated). (c) 2006 Elsevier Ltd. All rights reserved.