methyl 2-methyl-5-oxo-7-phenyl-4-(4-phenylphenyl)-4,6,7,8-tetrahydro-1H-quinoline-3-carboxylate | 1217598-92-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: methyl 2-methyl-5-oxo-7-phenyl-4-(4-phenylphenyl)-4,6,7,8-tetrahydro-1H-quinoline-3-carboxylate
• CAS: 1217598-92-9
• 化学式: C₃₀H₂₇NO₃
• 分子量: 449.549
• InChiKey: SQSABQNRVFVKDA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  5-phenyl-cyclohexane-1,3-dione 、 乙酰乙酸甲酯 、 对苯基苯甲醛 在 ammonium acetate 、 碘 作用下， 以 乙醇 为溶剂， 生成 methyl 2-methyl-5-oxo-7-phenyl-4-(4-phenylphenyl)-4,6,7,8-tetrahydro-1H-quinoline-3-carboxylate
  参考文献：
  名称：

  Synthesis and SAR of b-Annulated 1,4-Dihydropyridines Define Cardiomyogenic Compounds as Novel Inhibitors of TGFβ Signaling

  摘要：

  A medium-throughput murine embryonic stem cell (mESC)-based high-content screening of 17000 small molecules for cardiogenesis led to the identification of a b-annulated 1,4-dihydropyridine (1,4-DHP) that inhibited transforming growth factor beta (TGF beta)/Smad signaling by clearing the type II TGF beta receptor from the cell surface. Because this is an unprecedented mechanism of action, we explored the series' structure-activity relationship (SAR) based on TGF beta inhibition, and evaluated SAR aspects for cell-surface clearance of TGF beta receptor II (TGFBR2) and for biological activity in mESCs. We determined a pharmacophore and generated 1,4-DHPs with IC(50)s for TGF beta inhibition in the nanomolar range (e.g., compound. 28, 170 nM). Stereochemical consequences of a chiral center at the 4-position was evaluated, revealing 10- to 15-fold more potent TGF beta inhibition for the (+)- than the (-) enantiomer. This stereopreference was not observed for the low level inhibition against Activin A signaling and was reversed for effects on calcium handling in HL-1 cells.

  DOI：

  10.1021/jm301144g

文献信息

• COMPOUNDS FOR STEM CELL DIFFERENTIATION
  申请人：Mercola Mark

  公开号：US20110281356A1

  公开（公告）日：2011-11-17

  Methods and small molecule compounds for stem cell differentiation are provided. One example of a class of compounds that may be used is represented by the compound of Formula I: or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 5′ , R 6 , R 6′ , R 7 , R 7′ are as described herein.

  提供了用于干细胞分化的方法和小分子化合物。可以使用的化合物类别之一的示例由公式I所表示的化合物组成：或其药学上可接受的盐或溶剂，其中R1，R2，R3，R4，R5，R5'，R6，R6'，R7，R7'如本文所述。
• SMALL MOLECULE COMPOUNDS FOR STEM CELL DIFFERENTIATION
  申请人：Mercola Mark

  公开号：US20100159596A1

  公开（公告）日：2010-06-24

  Methods and small molecule compounds for stem cell differentiation are provided. One example of a class of compounds that may be used is represented by the compound having the structure IA or IB in the form of free base or a pharmaceutically acceptable salt, hydrate, solvate or N-oxide thereof: R 1 is independently hydrogen or (C 1 -C 6 )alkyl; R 2 is independently hydrogen, (C 1 -C 6 )alkyl, aryl, or heteroaryl; R 2′ is independently hydrogen, (C 1 -C 6 )alkyl, CF 3 or C 2 F 5 ; R 3 is independently (C 1 -C 6 )alkyl, aryl, 2-tetrahydrofurylmethyl, an aliphatic tertiary amine, or 4-methoxybenzyl; or R 2 and R 3 may be joined together to form a 5 or 6 member ring lactone; R 4 is independently hydrogen, (C 1 -C 6 )alkyl, a 2- or 4-R 5 -substituted aromatic ring selected from a 4-R 5 -phenyl or a 2-R 5 -5-pyridyl, aryl, heteroaryl, aliphatic tertiary amine or halogen; and R 5 , R 5′ , R 6 , R 6′ , R 7 , R 7′ , are each independently hydrogen, (C 1 -C 6 )alkyl, aryl, optionally substituted phenyl, heteroaryl, a heterocyclic ring, an aliphatic tertiary amine, or halogen.

  提供干细胞分化的方法和小分子化合物。可以使用的一类化合物的一个示例由结构IA或IB表示，以自由碱基或其药学上可接受的盐，水合物，溶剂或N-氧化物的形式存在：R1独立地是氢或（C1-C6）烷基; R2独立地是氢，（C1-C6）烷基，芳基或杂环芳基; R2'独立地是氢，（C1-C6）烷基，CF3或C2F5; R3独立地是（C1-C6）烷基，芳基，2-四氢呋喃甲基，脂肪族三级胺或4-甲氧基苄基; 或者R2和R3可以结合形成5或6元环内酯; R4独立地是氢，（C1-C6）烷基，2-或4-R5-取代的芳环，选自4-R5-苯基或2-R5-5-吡啶基，芳基，杂环芳基，脂肪族三级胺或卤素; R5，R5'，R6，R6'，R7，R7'独立地是氢，（C1-C6）烷基，芳基，可选取代的苯基，杂环芳基，杂环环，脂肪族三级胺或卤素。
• US9012217B2
  申请人：——

  公开号：US9012217B2

  公开（公告）日：2015-04-21
• Synthesis and SAR of <i>b</i>-Annulated 1,4-Dihydropyridines Define Cardiomyogenic Compounds as Novel Inhibitors of TGFβ Signaling
  作者：Dennis Schade、Marion Lanier、Erik Willems、Karl Okolotowicz、Paul Bushway、Christine Wahlquist、Cynthia Gilley、Mark Mercola、John R. Cashman

  DOI：10.1021/jm301144g

  日期：2012.11.26

  A medium-throughput murine embryonic stem cell (mESC)-based high-content screening of 17000 small molecules for cardiogenesis led to the identification of a b-annulated 1,4-dihydropyridine (1,4-DHP) that inhibited transforming growth factor beta (TGF beta)/Smad signaling by clearing the type II TGF beta receptor from the cell surface. Because this is an unprecedented mechanism of action, we explored the series' structure-activity relationship (SAR) based on TGF beta inhibition, and evaluated SAR aspects for cell-surface clearance of TGF beta receptor II (TGFBR2) and for biological activity in mESCs. We determined a pharmacophore and generated 1,4-DHPs with IC(50)s for TGF beta inhibition in the nanomolar range (e.g., compound. 28, 170 nM). Stereochemical consequences of a chiral center at the 4-position was evaluated, revealing 10- to 15-fold more potent TGF beta inhibition for the (+)- than the (-) enantiomer. This stereopreference was not observed for the low level inhibition against Activin A signaling and was reversed for effects on calcium handling in HL-1 cells.