53186-45-1

Usage

Uses

Used in Pharmaceutical Industry:
4-(4-aminobutyl)amino-7-chloroquinoline is used as an anticancer agent for its ability to inhibit the growth of cancer cells. It has shown promising results in preclinical studies, making it a candidate for further research and development in cancer treatment.
Used in Antimalarial Applications:
In addition to its anticancer properties, 4-(4-aminobutyl)amino-7-chloroquinoline also exhibits antimalarial activity. It is being investigated for its potential to combat malaria, offering a possible therapeutic solution for this widespread disease.

InChI:InChI=1/C13H16ClN3/c14-10-3-4-11-12(16-7-2-1-6-15)5-8-17-13(11)9-10/h3-5,8-9H,1-2,6-7,15H2,(H,16,17)

Upstream product

• 86-98-6 4,7-dichloroquinoline 
• 110-60-1 1,4-diaminobutane 

Downstream Products

• 324761-30-0 C₃₆H₃₈ClN₃O₃ 
• 1207449-65-7 C₂₇H₃₇ClN₈ 
• 1207449-58-8 C₂₈H₃₃ClN₈O₃ 
• 1207449-70-4 C₂₈H₂₇ClN₈ 
• 1322044-09-6 3-(4-((7-chloroquinolin-4-yl)amino)butyl)-2-(4-hydroxy-3-methoxyphenyl)thiazolidin-4-one 
• 1322043-95-7 3-(4-(7-chloroquinolin-4-ylamino)butyl)-2-(3,4-dimethoxyphenyl) thiazolidin-4-one 
• 1319718-30-3 C₄₄H₅₇ClN₄O₇ 
• 1360748-87-3 1-(4-(7-chloroquinolin-4-ylamino)butylamino)-3-(4-(2-fluorophenyl)piperazin-1-yl)propan-2-ol 
• 1376766-41-4 5-ethoxycarbonyl-6-methyl-4-phenyl-2-[4-(7-chloroquinolin-4-ylamino)butylamino]pyrimidine 
• 1376766-56-1 5-isopropyloxycarbonyl-6-methyl-4-(2-nitrophenyl)-2-[4-(7-chloroquinolin-4-ylamino)butylamino]pyrimidine 
• 1392513-38-0 C₄₁H₄₇ClN₆O₆Si 

Relevant academic research and scientific papers

Pentacycloundecylamines and conjugates thereof as chemosensitizers and reversed chloroquine agents

The control of malaria has been complicated by increased resistance of the malaria parasite to existing antimalarials such as chloroquine (CQ). Herein, we report the ability of NGP1-01, the prototype pentacycloundecylamine (PCU), to reverse CQ resistance (>50%) and act as a chemosensitizer. Based on this finding we set out to synthesize a small series of novel agents comprising of a PCU moiety as the reversal agent conjugated to a CQ-like aminoquinoline (AM) molecule and evaluate the potential of these PCU-AM derivatives as reversed CQ agents. PCU-AM derivatives 1-3 showed anti-plasmodial IC50 values in the ranges of 3.74-17.6 nM and 27.6-253.5 nM against CQ-sensitive (D10) and CQ-resistant strains (Dd2) of Plasmodium falciparum, respectively. Compound 1 presented with the best antiplasmodial activity at low nM concentrations against both strains and was found to be 5 fold more active against the resistant strain than CQ. Compound 1 can be considered as a lead compound to develop reversed CQ agents with improved pharmacodynamic and pharmacokinetic properties.

Targeting Asexual and Sexual Blood Stages of the Human Malaria Parasite P. falciparum with 7-Chloroquinoline-Based 1,2,3-Triazoles

Novel 4-amino-7-chloroquinoline-based 1,2,3-triazole hybrids were synthesised in good yields by CuI-catalysed Huisgen 1,3-dipolar cycloaddition reactions of 2-azido-N-(7-chloroquinolin-4-ylaminoalkyl)acetamides with various terminal alkynes. Th

Incorporation of Fluorinated Pyridine in the Side Chain of 4-Aminoquinolines: Synthesis, Characterization and Antibacterial Activity

A series of hybrid of 4-aminoquinoline and fluorinated pyridine derivatives were synthesized and their chemical structure were confirmed by 19 F-NMR, 1 H-NMR, 13 C-NMR and FT-IR. All compounds were tested against one Gram-positive and one Gram-negative bacteria to assess their in vitro antibacterial activity. Compounds 10a, 10b, 11a and 12b showed moderate antibacterial activity against Gram-positive bacterium, Staphylococcus aureus.

Application of multicomponent reactions to antimalarial drug discovery. Part 2: New antiplasmodial and antitrypanosomal 4-aminoquinoline γ- and δ-lactams via a 'catch and release' protocol

A parallel synthesis of a new series of 4-aminoquinoline γ- and δ-lactams synthesized via the Ugi 3-component 4-centre multicomponent reaction is described. The basicity of the quinoline nitrogen was exploited in the purification of compounds via a 'catch and release' protocol. Yields ranging from 60% to 77% and purities as high as 96% were obtained. Compound 29, the most active against a chloroquine-resistant W2 strain of Plasmodium falciparum with an IC50 of 0.096 μM, also inhibited recombinant falcipain-2 in vitro (IC50 = 17.6 μM). Compound 17 inhibited the growth of Trypanosoma brucei with an ED50 of 1.44 μM whilst exhibiting a favourable therapeutic index of 409 against a human KB cell line.

4-N-, 4-S-, and 4-O-chloroquine analogues: Influence of side chain length and quinolyl nitrogen pKa on activity vs chloroquine resistant malaria

Using predictions from heme-quinoline antimalarial complex structures, previous modifications of chloroquine (CQ), and hypotheses for chloroquine resistance (CQR), we synthesize and assay CQ analogues that test structure-function principles. We vary side chain length for both monoethyl and diethyl 4-N CQ derivatives. We alter the pKa of the quinolyl N by introducing alkylthio or alkoxy substituents into the 4 position and vary side chain length for these analogues. We introduce an additional titratable amino group to the side chain of 4-O analogues with promising CQR strain selectivity and increase activity while retaining selectivity. We solve atomic resolution structures for complexes formed between representative 4-N, 4-S, and 4-O derivatives vs μ-oxo dimeric heme, measure binding constants for monomeric vs dimeric heme, and quantify hemozoin (Hz) formation inhibition in vitro. The data provide additional insight for the design of CQ analogues with improved activity vs CQR malaria.

Antimalarial and anti-inflammatory activities of new chloroquine and primaquine hybrids: Targeting the blockade of malaria parasite transmission

Malaria is a disease that requires new drugs not only to fight Plasmodium but also to reduce symptoms of infection such as fever and inflammation. A series of 21 hybrid compounds were designed from chloroquine (CQ) and primaquine (PQ) linked to the pharmacophoric group present in phenylacetic anti-inflammatory drugs. These compounds were designed to have dual activity: namely, to be capable of killing Plasmodium and still act on the inflammatory process caused by malaria infection. The compounds were assayed with nine different biological methods. The carbonylated CQ derivative 6 (n = 3; R1 = Cl) was more potent than CQ in vitro, and 8 (n = 4; R1 = H) reduced P. berghei parasitemia up to 37% on day 7. The carbonylated PQ derivative 17 (R = Br) was slightly less potent than PQ. The gem-difluoro PQ derivative 20 (R = Cl) exhibited high transmission blockade of the malaria sporogonic cycle in mosquitoes. Compounds 6 and 20 dose-dependently reduced nitric oxide (NO) production and inhibited TNFα production by LPS-stimulated J774A.1 macrophages. Our results indicate a viable and interesting approach in planning new chemical entities that act as transmission-blocking drugs for treating malaria caused by P. falciparum and P. vivax and the anti-inflammatory process related to this disease.

Coupling the antimalarial cell penetrating peptide TP10 to classical antimalarial drugs primaquine and chloroquine produces strongly hemolytic conjugates

Recently, we disclosed primaquine cell penetrating peptide conjugates that were more potent than parent primaquine against liver stage Plasmodium parasites and non-toxic to hepatocytes. The same strategy was now applied to the blood-stage antimalarial chl

Design and synthesis of new antimalarial agents from 4-aminoquinoline

This study describes the synthesis of new 4-aminoquinoline derivatives and evaluation of their activity against a chloroquine sensitive strain of P. falciparum in vitro and chloroquine resistant N-67 strain of P. yoelii in vivo. All the analogues were found to form strong complex with hematin and inhibit the β-hematin formation in vitro. These results suggest that these compounds act on heme polymerization target.

Modulation of human mammary cell sensitivity to paclitaxel by new quinoline sulfonamides

Sulfonamide derivatives of chloroquine and primaquine were synthesised and evaluated against both paclitaxel-sensitive and paclitaxel-resistant mammarian cancer cell lines. All derivatives exhibited at least 96% MDR reversal activity when co-administered with paclitaxel at 5 μM. The best compound, a chloroquine derivative, exhibited 99% MDR reversal activity when co-administered with paclitaxel at 1 μM. Molecular modelling studies reveal that these derivatives share a common pharmacophore with taxane MDR reversal agents.

4-Aminoquinoline-pyrimidine-aminoalkanols: Synthesis, in vitro antimalarial activity, docking studies and ADME predictions

Twenty-four new 4-aminoquinoline-pyrimidine hybrids containing a terminal aliphatic amino-alcohol chain were synthesized and assessed for their antimalarial activity against chloroquine-sensitive (D6) and chloroquine-resistant (W2) strains of Plasmodium falciparum. All of the compounds displayed potent antiplasmodial activities (IC50 values in the range of 0.05-10.47 μM) with no appreciable cytotoxicity towards mammalian cells, up to the highest tested concentration of 12 μM. Molecular docking studies of the most active compounds (8b-8f, 8u and 8v) with both wild type and quadruple mutant Pf-DHFR-TS were performed, which exhibited interactions comparable to conventional folate inhibitors. ADME predictions also revealed favourable pharmacokinetic parameters for the synthesized hybrids, which warrants their suitability for development as potent antimalarials.