4-((2S,4R)-1-乙酰基-4-((4-氯苯基)氨基)-2-甲基-1,2,3,4-四氢喹啉-6-基)苯甲酸

CAS号：1300031-52-0

CAS号1300031-52-0, 是Epigenetics类化合物, 分子量为434.91, 分子式C25H23ClN2O3, 标准纯度98%, 毕得医药(Bidepharm)提供1300031-52-0批次质检（如NMR, HPLC, GC）等检测报告。

4-((2S,4R)-1-乙酰基-4-((4-氯苯基)氨基)-2-甲基-1,2,3,4-四氢喹啉-6-基)苯甲酸 (请以英文为准,中文仅做参考)

4-((2S,4R)-1-Acetyl-4-((4-chlorophenyl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)benzoic acid , GSK1324726A

货号：BD447299 4-((2S,4R)-1-Acetyl-4-((4-chlorophenyl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)benzoic acid 标准纯度：, 98%

标准纯度	包装	价格	上海	深圳	天津	武汉	成都	VIP价格	数量

检测信息
批次：
纯度：批次查询可见
COA MS HPLC LC-MS Microanalysis

产品名称 :	4-((2S,4R)-1-Acetyl-4-((4-chlorophenyl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)benzoic acid , GSK1324726A
中文名称 :	4-((2S,4R)-1-乙酰基-4-((4-氯苯基)氨基)-2-甲基-1,2,3,4-四氢喹啉-6-基)苯甲酸(请以英文为准,中文仅做参考)
CAS号 :	1300031-52-0
分子式 :	C₂₅H₂₃ClN₂O₃
线性分子式 :	-
分子量 :	434.91
MDL NO :	MFCD28144683
沸点 :	-
Pubchem ID :	52912222
InChIKey :	FAWSUKOIROHXAP-NPMXOYFQSA-N

常用 :

SDS-BD447299

2D :

3D :

【用途一】

计算化学

Physicochemical Properties

Num. heavy atoms	31
Num. arom. heavy atoms	18
Fraction Csp3	0.2
Num. rotatable bonds	5
Num. H-bond acceptors	3.0
Num. H-bond donors	2.0
Molar Refractivity	127.29
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	69.64 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	3.42
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	5.14
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	5.11
Log P_o/w (MLOGP)? MLOGP: Topological method implemented from Moriguchi I. et al. 1992 Chem. Pharm. Bull. Moriguchi I. et al. 1994 Chem. Pharm. Bull. Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.	4.1
Log P_o/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	4.32
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	4.42

Water Solubility

Log S (ESOL)? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-5.87
Solubility	0.000581 mg/ml ; 0.00000134 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Moderately soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-6.35
Solubility	0.000195 mg/ml ; 0.000000449 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Poorly soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-7.79
Solubility	0.00000704 mg/ml ; 0.0000000162 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Poorly soluble

Pharmacokinetics

GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg	High
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg	No
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) and tested on 415 molecules (test set) 10-fold CV: ACC=0.72 / AUC=0.77 External: ACC=0.88 / AUC=0.94	Yes
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.83 / AUC=0.90 External: ACC=0.84 / AUC=0.91	No
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.80 / AUC=0.86 External: ACC=0.80 / AUC=0.87	Yes
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) and tested on 2075 molecules (test set) 10-fold CV: ACC=0.78 / AUC=0.85 External: ACC=0.71 / AUC=0.81	Yes
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) and tested on 1068 molecules (test set) 10-fold CV: ACC=0.79 / AUC=0.85 External: ACC=0.81 / AUC=0.87	No
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) and tested on 2579 molecules (test set) 10-fold CV: ACC=0.77 / AUC=0.85 External: ACC=0.78 / AUC=0.86	Yes
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-5.3 cm/s

Druglikeness

Lipinski? Lipinski (Pfizer) filter: implemented from Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev. MW ≤ 500 MLOGP ≤ 4.15 N or O ≤ 10 NH or OH ≤ 5	0.0
Ghose? Ghose filter: implemented from Ghose AK. et al. 1999 J. Comb. Chem. 160 ≤ MW ≤ 480 -0.4 ≤ WLOGP ≤ 5.6 40 ≤ MR ≤ 130 20 ≤ atoms ≤ 70	None
Veber? Veber (GSK) filter: implemented from Veber DF. et al. 2002 J. Med. Chem. Rotatable bonds ≤ 10 TPSA ≤ 140	0.0
Egan? Egan (Pharmacia) filter: implemented from Egan WJ. et al. 2000 J. Med. Chem. WLOGP ≤ 5.88 TPSA ≤ 131.6	0.0
Muegge? Muegge (Bayer) filter: implemented from Muegge I. et al. 2001 J. Med. Chem. 200 ≤ MW ≤ 600 -2 ≤ XLOGP ≤ 5 TPSA ≤ 150 Num. rings ≤ 7 Num. carbon > 4 Num. heteroatoms > 1 Num. rotatable bonds ≤ 15 H-bond acc. ≤ 10 H-bond don. ≤ 5	1.0
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat implemented from Martin YC. 2005 J. Med. Chem.	0.56

Medicinal Chemistry

PAINS? Pan Assay Interference Structures: implemented from Baell JB. & Holloway GA. 2010 J. Med. Chem.	0.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	0.0 alert
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	2.0
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties, trained on 12'782'590 molecules and tested on 40 external molecules (r² = 0.94)	3.72

合成路线：*资料仅供科研用途参考，更多细节请参阅原文出处。

1~22 ►

1. 合成：1300031-52-0

1300694-19-2

1300031-52-0

产率

合成条件

实验步骤

87%

Stage #1: With water; sodium hydroxide In ethanol at 20℃; for 2 h;
Stage #2: With hydrogenchloride In dichloromethane; water

实施例6方法24- {（2S.4 /β）-1-乙酰基-4-（4-氯苯基）氨基-2-甲基-1,2,3.4-四氢-6-喹啉合苯甲酸乙基4 - {（2S，4R） -1-乙酰基-4 - [（4-氯苯基）氨基] -2-甲基-1,2,3,4-四氢-6-喹啉基}苯甲酸酯（制备参见实施例158）（5.41g，11.69mmol）将该溶液溶解在乙醇（100mL）中，并将溶液用2M NaOH水溶液（50mL，100mmol）处理。将所得混合物在室温（空气气氛）下搅拌约2小时，然后真空除去大部分乙醇。将得到的黄色溶液用水稀释（导致形成油状黄色沉淀）。将水相用DCM（其不溶解先前形成的沉淀物）洗涤两次，然后用2N盐酸水溶液酸化至pH 1并用AcOEt萃取两次。将合并的AcOEt相用盐水洗涤，使用疏水性玻璃料干燥并真空浓缩。将残留的黄色泡沫用Et 2 O在约1小时内研磨。过滤分离所得固体，用Et2O洗涤并空气干燥，得到4 - {（2S，4 /β）-1-乙酰基-4 - [（4-氯苯基）氨基] -2-甲基-1,2。，3,4-四氢-6-喹啉基}苯甲酸（4.41g，10.1mmol，87％），为乳白色固体.LCMS（高pH）：保留时间1.08min，[MH] - = 433.16

87%

With water; sodium hydroxide In ethanol at 20℃; for 2 h;

4 - {（2S，4R）-1-乙酰基-4 - [（4-氯苯基）氨基] -2-甲基-1,2,3,4-四氢-6-喹啉基}苯甲酸乙酯（制备见中间体）将17）（5.41g，11.69mmol）溶解在乙醇（100mL）中，并将溶液用NaOH水溶液（2M，50mL，100mmol）处理。将所得混合物在室温（空气气氛）下搅拌约2小时，然后真空除去大部分乙醇。将得到的黄色溶液用水稀释（导致形成油状黄色沉淀）。将水相用DCM洗涤两次（其不溶解先前形成的沉淀物），然后用盐酸（2N）酸化至pH 1并用EtOAc（x2）萃取。将合并的EtOAc相用盐水洗涤，干燥（疏水性玻璃料）并真空浓缩。将残留的黄色泡沫用Et 2 O在约1小时内研磨。过滤分离所得固体，用Et2O洗涤并空气干燥，得到4 - {（2S，4 /β）-1-乙酰基-4 - [（4-氯苯基）氨基] -2-甲基-1,2 ，3,4-四氢-6-喹啉基}苯甲酸（4.41g，10.1mmol，87％），为乳白色固体。 LCMS（HpH），保留时间1.08分钟，[M-H] - = 433

87%

With water; sodium hydroxide In ethanol at 20℃; for 2 h;

87%

With water; sodium hydroxide In ethanol at 20℃; for 2 h;

中间体18 4 - {（2S，4R）-1-乙酰基-4 - [（4-氯苯基）氨基] -2-甲基-1,2,3,4-四氢-6-喹啉基}苯甲酸[01] [ 0200] 4 - {（2S，4R）-1-乙酰基-4 - [（4-氯苯基）氨基] -2-甲基-1,2,3,4-四氢-6-喹啉基}苯甲酸乙酯（用于制备）将中间体17）（5.41g，11.69mmol）溶解在乙醇（100mL）中，并将溶液用NaOH水溶液（2M，50mL，100mmol）处理。将所得混合物在室温（空气气氛）下搅拌约2小时，然后真空除去大部分乙醇。将得到的黄色溶液用水稀释（导致形成油状黄色沉淀）。将水相用DCM洗涤两次（其不溶解先前形成的沉淀物），然后用盐酸（2N）酸化至pH 1并用EtOAc（×2）萃取。将合并的EtOAc相用盐水洗涤，干燥（疏水性玻璃料）并真空浓缩。将残留的黄色泡沫用Et 2 O在约1小时内研磨。过滤分离所得固体，用Et 2 O洗涤并空气干燥，得到4 - {（2S，4R）-1-乙酰基-4 - [（4-氯苯基）氨基] -2-甲基-1,2,3 ，4-四氢-6-喹啉基}苯甲酸（4.41g，10.1mmol，87％），为乳白色固体。 LCMS（HpH），保留时间1.08分钟，[M-H] - = 433

参考文献：

[1] Patent: WO2011/54848, 2011, A1. Location in patent: Page/Page column 113
[2] Patent: WO2012/143413, 2012, A1. Location in patent: Page/Page column 41
[3] Patent: WO2012/143415, 2012, A1. Location in patent: Page/Page column 38-39
[4] Patent: US2014/39006, 2014, A1. Location in patent: Paragraph 0199-0200
[5] Journal of Medicinal Chemistry, 2014, vol. 57, # 19, p. 8111 - 8131

2. 合成：1300031-52-0

1300031-70-2

1300031-52-0

产率

合成条件

实验步骤

147 mg

With water; sodium hydroxide In ethanol for 1 h; Reflux

将中间体8（320mg，0.73mmol）在EtOH（10ml）和1N NaOH（1.5ml，1.5mmol）中的溶液加热至回流。 1小时后，tlc监测表明反应完成。将粗混合物蒸发，将残余物溶于水（10mL）中。通过加入1N HCl溶液进行pH = 3的混合物的酸化。用EtOAc（3×25mL）萃取有机物质，合并有机相，用盐水洗涤，用Na 2 SO 4干燥。在真空浓缩后，将残余物溶于DCM /己烷混合物中，过滤后得到红色固体。将化合物在EtOAC中重结晶，过滤并用i-Pr 2 O洗涤。将得到的白色粉末溶解在MeOH / H 2 O中，浓缩至干燥并用H 2 O吸收。最后过滤沉淀物，得到标题化合物，为白色粉末（147mg），mp：275℃.HFRMS计算值C 25 H 23 N 2 O 3 Cl（M-H） - 433.1319，实测值：433.1299。 Rt：2.21分钟.1 H NMR（300MHz，氯仿-d）δppm1.2（d，3H）1.35（m，1H）2.3（s，3H）2.7（m，1H）4.25（dd， 1 H）4.95（m，1H）6.65（d，2 H）7.15（d，2 H）7.25（s，1 H）7.55（m，4 H），8.15（d，2H）[α] D =在EtOAc重结晶阶段测量+ 395（c = 0.96g / cl，EtOH）。使用具有叔丁基甲基氧化物的Chiralpak IA（250x4.6mm 5mm）柱，通过HPLC作为第一峰在4.51min洗脱标题化合物（ MTBE）+ 0.1％TFA /乙醇：90/10作为流动相。施加1ml / mn的流速，并注入10mL用1mg标题化合物在1ml洗脱液中稀释制备的样品。用210和254nM UV波长进行化合物的检测。另一种对映体在5.92分钟时脱落。

参考文献：

[1] Patent: WO2011/54848, 2011, A1. Location in patent: Page/Page column 112-113
[2] Patent: EP2955524, 2015, A2. Location in patent: Paragraph 0124; 0125

3. 合成：1300031-52-0

1300031-98-4

1300031-52-0

参考文献：

[1] Patent: WO2012/143413, 2012, A1
[2] Patent: WO2012/143415, 2012, A1
[3] Patent: US2014/39006, 2014, A1
[4] Journal of Medicinal Chemistry, 2014, vol. 57, # 19, p. 8111 - 8131
[5] Patent: WO2011/54848, 2011, A1

骨架产品推荐

历史浏览记录

摩尔计算器

浓度
x
体积
x
分子量
=
质量

浓度 x 体积 x 分子量 = 质量

合成路线

1. 合成：1300031-52-0

1300694-19-2

1300031-52-0

产率

合成条件

实验参考步骤

87%

Stage #1: With water; sodium hydroxide In ethanol at 20℃; for 2 h;
Stage #2: With hydrogenchloride In dichloromethane; water

87%

With water; sodium hydroxide In ethanol at 20℃; for 2 h;

87%

With water; sodium hydroxide In ethanol at 20℃; for 2 h;

87%

With water; sodium hydroxide In ethanol at 20℃; for 2 h;

参考文献：

2. 合成：1300031-52-0

1300031-70-2

1300031-52-0

产率

合成条件

实验参考步骤

147 mg

With water; sodium hydroxide In ethanol for 1 h; Reflux

参考文献：

[1] Patent: WO2011/54848, 2011, A1. Location in patent: Page/Page column 112-113
[2] Patent: EP2955524, 2015, A2. Location in patent: Paragraph 0124; 0125

3. 合成：1300031-52-0

1300031-98-4

1300031-52-0

参考文献：

4. 合成：1300031-52-0

1300031-95-1

1300031-52-0

参考文献：

5. 合成：1300031-52-0

1300031-94-0

1300031-52-0

参考文献：

6. 合成：1300031-52-0

1300695-49-1

1300031-52-0

参考文献：

7. 合成：1300031-52-0

1300695-51-5

1300031-52-0

参考文献：

8. 合成：1300031-52-0

106-40-1

1300031-52-0

参考文献：

[1] Patent: EP2955524, 2015, A2
[2] Patent: WO2011/54848, 2011, A1

9. 合成：1300031-52-0

N/A

1300031-52-0

参考文献：

[1] Patent: EP2955524, 2015, A2
[2] Patent: WO2011/54848, 2011, A1

10. 合成：1300031-52-0

1300031-74-6

1300031-52-0

参考文献：

[1] Patent: EP2955524, 2015, A2
[2] Patent: WO2011/54848, 2011, A1

11. 合成：1300031-52-0

108-86-1

1300031-52-0

参考文献：