6938-27-8

Usage

Uses

Used in Pharmaceutical Industry:
5-Nitro-1H-quinolin-2-one is used as a synthetic intermediate for the preparation of novel antileishmanial agents targeting Leishmania donovani promastigotes. These agents are crucial in the development of treatments for leishmaniasis, a vector-borne disease caused by protozoan parasites of the genus Leishmania. 5-nitro-1H-quinolin-2-one's unique structure and properties make it a valuable building block in the synthesis of new drugs with potential therapeutic benefits.

InChI:InChI=1/C14H10ClNO3/c1-9-7-12(17)5-6-13(9)16-19-14(18)10-3-2-4-11(15)8-10/h2-8H,1H3

Upstream product

• 607-34-1 5-nitroquinoline 
• 13067-94-2 2-chloro-5-nitroquinoline 
• 116632-28-1 2-bromo-5-nitroquinoline 
• 7613-19-6 5-nitro-quinoline-1-oxide 
• 1116137-62-2 2-chloro-5-nitro-1,2-dihydroquinoline 
• 612-62-4 2-Chloroquinoline 
• 59-31-4 2-hydroxyquinoline 
• 2005-43-8 2-bromoquinoline 
• 91-22-5 quinoline 

Downstream Products

• 61317-32-6 5-amino-quinolin-2-ol 
• 61317-32-6 5-aminoquinolin-2(1H)-one 
• 58130-38-4 5-amino-3,4-dihydro-1H-quinolin-2-one 
• 607377-99-1 2-chloro-5-aminoquinoline 
• 13067-94-2 2-chloro-5-nitroquinoline 
• 77738-80-8 2-methoxy-5-nitroquinoline 

Relevant academic research and scientific papers

N-(4-acetamidophenyl)-5-acetylfuran-2-carboxamide as a novel orally available diuretic that targets urea transporters with improved PD and PK properties

Urea transporters (UTs) have been identified as new targets for diuretics. Functional deletion of UTs led to urea-selective urinary concentrating defects with relative salt sparing. In our previous study, a UT inhibitor with a diarylamide scaffold, which is denoted as 11a, was demonstrated as the first orally available UT inhibitor. However, the oral bioavailability of 11a was only 4.38%, which obstructed its clinical application. In this work, by replacing the nitro group of 11a with an acetyl group, 25a was obtained. Compared with 11a, 25a showed a 10 times stronger inhibitory effect on UT-B (0.14 μM vs. 1.41 μM in rats, and 0.48 μM vs. 5.82 μM in mice) and a much higher inhibition rate on UT-A1. Moreover, the metabolic stability both in vitro and in vivo and the drug-like properties (permeability and solubility) of 25a were obviously improved compared with those of 11a. Moreover, the bioavailability of 25a was 15.18%, which was 3 times higher than that of 11a, thereby resulting in significant enhancement of the diuretic activities in rats and mice. 25a showed excellent potential for development as a promising clinical diuretic candidate for targeting UTs to treat diseases that require long-term usage of diuretics, such as hyponatremia.

Discovery of Benzopyridone-Based Transient Receptor Potential Vanilloid 1 Agonists and Antagonists and the Structural Elucidation of Their Activity Shift

Among a series of benzopyridone-based scaffolds investigated as human transient receptor potential vanilloid 1 (TRPV1) ligands, two isomeric benzopyridone scaffolds demonstrated a consistent and distinctive functional profile in which 2-oxo-1,2-dihydroquinolin-5-yl analogues (e.g., 2) displayed high affinity and potent antagonism, whereas 1-oxo-1,2-dihydroisoquinolin-5-yl analogues (e.g., 3) showed full agonism with high potency. Our computational models provide insight into the agonist-antagonist boundary of the analogues suggesting that the Arg557 residue in the S4-S5 linker might be important for sensing the agonist binding and transmitting signals. These results provide structural insights into the TRPV1 and the protein-ligand interactions at a molecular level.

Palladium-catalyzed synthesis of quinolin-2(1: H)-ones: the unexpected reactivity of azodicarboxylate

Quinolin-2(1H)-one is a useful structure unit present in a wide range of natural products and pharmaceuticals. A Pd(ii)-catalyzed synthesis of quinolin-2(1H)-ones from quinoline N-oxides was developed with azodicarboxylates which act as both the activating agent and oxidant. The reaction proceeded under mild conditions and no protection against air and moisture was needed.

Novel 8-nitroquinolin-2(1H)-ones as NTR-bioactivated antikinetoplastid molecules: Synthesis, electrochemical and SAR study

To study the antiparasitic 8-nitroquinolin-2(1H)-one pharmacophore, a series of 31 derivatives was synthesized in 1–5 steps and evaluated in vitro against both Leishmania infantum and Trypanosoma brucei brucei. In parallel, the reduction potential of all molecules was measured by cyclic voltammetry. Structure-activity relationships first indicated that antileishmanial activity depends on an intramolecular hydrogen bond (described by X-ray diffraction) between the lactam function and the nitro group, which is responsible for an important shift of the redox potential (+0.3 V in comparison with 8-nitroquinoline). With the assistance of computational chemistry, a set of derivatives presenting a large range of redox potentials (from ?1.1 to ?0.45 V) was designed and provided a list of suitable molecules to be synthesized and tested. This approach highlighted that, in this series, only substrates with a redox potential above ?0.6 V display activity toward L. infantum. Nevertheless, such relation between redox potentials and in vitro antiparasitic activities was not observed in T. b. brucei. Compound 22 is a new hit compound in the series, displaying both antileishmanial and antitrypanosomal activity along with a low cytotoxicity on the human HepG2 cell line. Compound 22 is selectively bioactivated by the type 1 nitroreductases (NTR1) of L. donovani and T. brucei brucei. Moreover, despite being mutagenic in the Ames test, as most of nitroaromatic derivatives, compound 22 was not genotoxic in the comet assay. Preliminary in vitro pharmacokinetic parameters were finally determined and pointed out a good in vitro microsomal stability (half-life > 40 min) and a 92% binding to human albumin.

Discovery of a new antileishmanial hit in 8-nitroquinoline series

A series of nitrated 2-substituted-quinolines was synthesized and evaluated in vitro toward Leishmania donovani promastigotes. In parallel, the in vitro cytotoxicity of these molecules was assessed on the murine J774 and human HepG2 cell lines. Thus, a very promising antileishmanial hit molecule was identified (compound 21), displaying an IC50 value of 6.6 μM and CC 50 values ≥ 100 μM, conferring quite good selectivity index to this molecule, in comparison with 3 drug-compounds of reference (amphotericin B, miltefosine and pentamidine). Compound 21 also appears as an efficient in vitro antileishmanial molecule against both Leishmania infantum promastigotes and the intracellular L. donovani amastigotes (respective IC50 = 7.6 and 6.5 μM). Moreover, hit quinoline 21 does not show neither significant antiplasmodial nor antitoxoplasmic in vitro activity and though, presents a selective antileishmanial activity. Finally, a structure-activity relationships study enabled to define precisely the antileishmanial pharmacophore based on this nitroquinoline scaffold: 2-hydroxy-8-nitroquinoline.

CONDENSED HETEROCYCLIC COMPOUNDS HAVING 5-HT6 RECEPTOR AFFINITY

The present disclosure provides compounds having affinity for the 5-HT6 receptor which are of the formula (I) wherein R1, A, B, D, E, G, Q, Ar, n, m, and p are as defined herein. The disclosure also relates to methods of preparing such compounds, compositions containing such compounds, and methods of use thereof.

ACYCLIC COMPOUNDS HAVING 5-HT6 RECEPTOR AFFINITY

The present disclosure provides compounds having affinity for the 5-HT6 receptor which are of the formula (I): wherein R1, R2, R5, Q, G, Ar, m, and n are as defined herein. The disclosure also relates to methods of preparing such compounds, compositions containing such compounds, and methods of use thereof.

4'-AMINO CYCLIC COMPOUNDS HAVING 5-HT6 RECEPTOR AFFINITY

The present disclosure provides compounds having affinity for the 5-HT6 receptor which are of the formula (I): formula (I) wherein Cy is selected from formula (Il) and wherein R1, R2, R3, Q, G, Ar, m, n and p are as defined herein. The disclosure also relates to methods of preparing such compounds, compositions containing such compounds, and methods of use thereof.

3' SUBSTITUTED COMPOUNDS HAVING 5-HT6 RECEPTOR AFFINITY

The present disclosure provides compounds having affinity for the 5-HT6 receptor which are of the formula (I): wherein Q, R1, R4, m and Ar are as defined herein. The disclosure also relates to methods of preparing such compounds, compositions containing such compounds, and methods of use thereof.

NOVEL NITROGENATED HETEROCYCLIC COMPOUND AND SALT THEREOF

A nitrogen-containing heterocyclic compound represented by the general formula: wherein the dashed line represents a single bond or a double bond; R1, R2, R3, R4 and R5 independently represent a hydrogen atom, halogen atom, a lower alkyl, aryl, lower alkoxy or monocyclic heterocyclic group which may be substituted or the like; R6 represents a lower alkyl, aryl, monocyclic heterocyclic, bicyclic heterocyclic or tricyclic heterocyclic group which may be substituted; X1 represents a lower alkylene group or the like; X2 represents a lower alkylene, lower alkenylene or lower alkynylene group which may be substituted; X3 represents an oxygen atom, sulfur atom, a sulfinyl group, sulfonyl group or the like; Y1 represents a bivalent cyclic group, containing a nitrogen, which may be substituted or the like; and Z1 represents a nitrogen atom, a carbon atom which may be substituted or the like, or a salt thereof. The compound or salt has a potent antibacterial activity and a high safety, and is therefore useful as an excellent antibacterial agent.