1198-40-9

Basic information

• Product Name: 7-Chloro-4-quinolinamine
• Synonyms: 4-AMINO-7-CHLOROQUINOLINE;7-CHLORO-QUINOLIN-4-YLAMINE;7-chloro-4-quinolinamine;BUTTPARK 22\09-04;7-chloro-4-aminoquinoline;(7-chloro-4-quinolyl)amine;4-QuinolinaMine,7-chloro-;4-amino-7-chloroQUINOLINE:7-chloro-4-quinolinamine
• CAS NO: 1198-40-9
• Molecular Formula: C₉H₇ClN₂
• Molecular Weight: 178.62
• Product Categories: pharmacetical
• Mol File: 1198-40-9.mol
• Article Data: 20

Chemical Properties

• Melting Point: 150-152.5 °C
• Boiling Point: 366.843 °C at 760 mmHg
• Flash Point: 175.66 °C
• Appearance: /
• Density: 1.363 g/cm³
• Vapor Pressure: 1.42E-05mmHg at 25°C
• Refractive Index: 1.712
• Storage Temp.: under inert gas (nitrogen or Argon) at 2–8 °C
• PKA: 7.49±0.50(Predicted)
• CAS DataBase Reference: 7-Chloro-4-quinolinamine(CAS DataBase Reference)
• NIST Chemistry Reference: 7-Chloro-4-quinolinamine(1198-40-9)
• EPA Substance Registry System: 7-Chloro-4-quinolinamine(1198-40-9)

Safety Data

• Hazard Codes: T
• Statements: 25-36
• Safety Statements: 26-45
• RIDADR: UN 2811 6.1 / PGIII
• WGK Germany: 3
• Hazardous Substances Data: 1198-40-9(Hazardous Substances Data)

Usage

Uses

7-Chloroquinolin-4-amine is an aminoquinoline that complexes ferriprotoporphyrin IX (Fe(III)PPIX) and inhibits its conversion to β-hematin (hemozoin).

Synthesis Reference(s)

Journal of the American Chemical Society, 69, p. 704, 1947 DOI: 10.1021/ja01195a501

Synthesis

4-amino-7-chloroquinoline is obtained byreacting 7-chloro-4-hydrazinoquinoline ,sodium borohydride with nickel (II) chloride hexahydrate in methanol.To a suspension of 7-chloro-4-hydrazinoquinoline (1.67 g, 8.6 mmol) and nickel (II) chloride hexahydrate (2.00 g, 8.6 mmol) in methanol (33 ml), sodium borohydride (0.98 g, 25.8 mmol) was added cautiously while stirring the reaction mixture vigorously at room temperature and left to react overnight. The reaction mixture was filtered through celite pad. Water was used to dilute the filtrate layer and then washed with ethyl acetate. The organic layer was dried with magnesium sulphate and concentrated in vacuo to give the title compound as a yellow powder (1.09 g, 72%): mp: 143 – 147 ℃ (Lit.: 147 – 148 ℃) ;vmax/cm-1 3337 s (N-H), 1642 m (C=N), 1609 m and 1575 m (C=N); δH (300 MHz; DMSO-d6) 8.28 (1H, d, J 5.3, C(2)H), 8.19 (1H, d, J 9.1, C(5)H), 7.76 (1H, d, J 1.6, C(8)H), 7.39 (1H, dd, J 9.1, 1.6, C(6)H), 7.03 (2H, s, NH2), 6.57 (1H, d, J 5.3, C(3)H); δC (75 MHz; DMSO-d6) 152.0 (Ar-C), 151.1 (C(2)H), 148.9 (Ar-C), 133.7 (Ar-C), 126.8 (C(8)H), 124.8 (C(5)H), 123.9 (C(6)H), 117.0 (Ar-C), 102.7 (C(3)H); m/z (-ES) 179 (100%, [M+H]- with 35Cl), 181 (35%, [M+H]- with 37Cl); found by +ES 179.0377, C9H8ClN2 ([M+H]+ with 35Cl), requires 179.0371, error 3.3 ppm.

InChI:InChI=1/C9H7ClN2/c10-6-1-2-7-8(11)3-4-12-9(7)5-6/h1-5H,(H2,11,12)

Upstream product

• 86-98-6 4,7-dichloroquinoline 
• 109-83-1 (2-hydroxyethyl)(methyl)amine 
• 98591-57-2 7-chloro-4-iodoquinoline 
• 110-85-0 piperazine 
• 23834-14-2 7-chloro-4-hydrazinoquinoline 
• 69063-03-2 4-azido-7-chloro-quinoline 
• 100-46-9 benzylamine 
• 100-36-7 N,N-diethylethylenediamine 
• 109-73-9 N-butylamine 
• 75-64-9 tert-butylamine 
• 75-31-0 isopropylamine 
• 107-10-8 propylamine 
• 124495-03-0 7-chloro-4-phenoxyquinoline 
• 631-61-8 ammonium acetate 

Downstream Products

• 1104050-93-2 (+/-)-7-chloro-N-{(4-chlorophenyl)[4-(pyrrolidin-1-ylmethyl)phenyl]phenylmethyl}-4-aminoquinoline 
• 1050527-00-8 (+/-)-7-chloro-N-{(4-chlorophenyl)[4-(morpholin-4-ylmethyl)phenyl]methyl}-4-aminoquinoline 
• 54-05-7 (R)-(-)-chloroquine 
• 133092-34-9 4-chloro-5,6,7,8-tetrahydroquinoline 
• 858466-68-9 N-(5,6,7,8-tetrahydroquinolin-4-yl)acetamide 
• 137433-23-9 (R)-Hydroxychloroquine 
• 137433-23-9 (S)-Hydroxychloroquine 

Relevant articles and documents

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Synthesis, in vitro antimalarial activity and cytotoxicity of novel 4-aminoquinolinyl-chalcone amides

A series of 4-aminoquinolinyl-chalcone amides 11-19 were synthesized through condensation of carboxylic acid-functionalized chalcone with aminoquinolines, using 1,1′-carbonyldiimidazole as coupling agent These compounds were screened against the chloroquine sensitive (3D7) and chloroquine resistant (W2) strains of Plasmodium falciparum Their cytotoxicity towards the WI-38 cell line of normal human fetal lung fibroblast was determined All compounds were found active, with IC50 values ranging between 0.04-0.5 μM and 0.07-1.8 μM against 3D7 and W2, respectively They demonstrated moderate to high selective activity towards the parasitic cells in the presence of mammalian cells However, amide 15, featuring the 1,6-diaminohexane linker, despite possessing predicted unfavourable aqueous solubility and absorption properties, was the most active of all the amides tested It was found to be as potent as CQ against 3D7, while it displayed a two-fold higher activity than CQ against the W2 strain, with good selective antimalarial activity (SI = 435) towards the parasitic cells During this study, amide 15 was thus identified as the best drug-candidate to for further investigation as a potential drug in search for new, safe and effective antimalarial drugs

Antimalarials. 8-chloro-4-(2'-n,n-dibutylamino-1'-hydroxyethyl)benzo[h]-1,6-naphthyridine.

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Structural specificity of chloroquine-hematin binding related to inhibition of hematin polymerization and parasite growth

Considerable data now support the hypothesis that chloroquine (CQ)- hematin binding in the parasite food vacuole leads to inhibition of hematin polymerization and parasite death by hematin poisoning. To better understand the structural specificity of CQ-hematin binding, 13 CQ analogues were chosen and their hematin binding affinity, inhibition of hematin polymerization, and inhibition of parasite growth were measured. As determined by isothermal titration calorimetry (ITC), the stoichiometry data and exothermic binding enthalpies indicated that, like CQ, these analogues bind to two or more hematin μ-oxo dimers in a cofacial π-π sandwich-type complex. Association constants (K(a)'s) ranged from 0.46 to 2.9 x 105 M-1 compared to 4.0 x 105 M-1 for CQ. Remarkably, we were not able to measure any significant interaction between hematin μ-oxo dimer and 11, the 6-chloro analogue of CQ. This result indicates that the 7-chloro substituent in CQ is a critical structural determinant in its binding affinity to hematin μ-oxo dimer. Molecular modeling experiments reinforce the view that the enthalpically favorable π-π interaction observed in the CQ-hematin μ-oxo dimer complex derives from a favorable alignment of the out-of-plane π-electron density in CQ and hematin μ-oxo dimer at the points of intermolecular contact. For 4- aminoquinolines related to CQ, our data suggest that electron-withdrawing functional groups at the 7-position of the quinoline ring are required for activity against both hematin polymerization and parasite growth and that chlorine substitution at position 7 is optimal. Our results also confirm that the CQ diaminoalkyl side chain, especially the aliphatic tertiary nitrogen atom, is an important structural determinant in CQ drug resistance. For CQ analogues 1-13, the lack of correlation between K(a) and hematin polymerization IC50 values suggests that other properties of the CQ-hematin μ-oxo dimer complex, rather than its association constant alone, play a role in the inhibition of hematin polymerization. However, there was a modest correlation between inhibition of hematin polymerization and inhibition of parasite growth when hematin polymerization IC50 values were normalized for hematin μ-oxo dimer binding affinities, adding further evidence that antimalarial 4-aminoquinolines act by this mechanism.

Novel Aminoquinoline Derivatives Significantly Reduce Parasite Load in Leishmania infantum Infected Mice

In this Letter, a detailed analysis of 30 4-aminoquinoline-based compounds with regard to their potential as antileishmanial drugs has been carried out. Ten compounds demonstrated IC50 50 1 μM against intramacrophage L. infantum amastigotes. Two compounds showed dose-dependent enhancement of NO and ROS production by bone marrow-derived macrophages and remarkable reduction of parasite load in vivo, with advantage of being short-term and orally active. To the best of our knowledge, this is the first example of 4-amino-7-chloroquinoline derivatives active in Leishmania infantum infected mice.

Functionalized acridin-9-yl phenylamines protected neuronal HT22 cells from glutamate-induced cell death by reducing intracellular levels of free radical species

The in vitro neuronal cell death model based on the HT22 mouse hippocampal cell model is a convenient means of identifying compounds that protect against oxidative glutamate toxicity which plays a role in the development of certain neurodegenerative diseases. Functionalized acridin-9-yl-phenylamines were found to protect HT22 cells from glutamate challenge at submicromolar concentrations. The Aryl1-NHAryl2 scaffold that is embedded in these compounds was the minimal pharmacophore for activity. Mechanistically, protection against the endogenous oxidative stress generated by glutamate did not involve up-regulation of glutathione levels but attenuation of the late stage increases in mitochondrial ROS and intracellular calcium levels. The NH residue in the pharmacophore played a crucial role in this regard as seen from the loss of neuroprotection when it was structurally modified or replaced. That the same NH was essential for radical scavenging in cell-free and cell-based systems pointed to an antioxidant basis for the neuroprotective activities of these compounds.