Quinoline‐derivatives as privileged scaffolds for medicinal and pharmaceutical chemists: A comprehensive review

Abstract

The quinoline scaffolds are privileged for their numerous biological activities in the pharmaceutical field. This moiety constitutes a well‐known space in several marketed preparations. The quinoline scaffolds gained attention in modern days being an important chemical moiety in the identification, designing, and synthesis of novel potent derivatives. The current review is developed to shine the light on critical and significant insights on the quinoline derivatives possessing diverse biological activities such as analgesic, anti‐inflammatory, antialzheimer, anti‐convulsant, anti‐oxidant, antimicrobial, anti‐cancer activities and so on. A detailed summary of quinoline ring from its origin to the recent advancements regarding its synthesis, green chemistry approaches, patented methods, and its marketed drugs is presented in the review. We attempted to review the literature compiling the critical information that has potential to encourage fellow researchers and scientists for the design and development of quinoline scaffold based active molecules that have improved therapeutic performance along with profound pharmacological properties.

Quinolines: Privileged Scaffolds for Developing New Anti‐neurodegenerative Agents

“…It is yellow in color with molecular formula C 9 H 7 N. Its basic pK a is 9.5 and the acidic pK b is 4.85 [23,24] . Quinoline is a flexible heterocyclic scaffold with a wide range of applications in medicine [25] . Many compounds having quinoline skeletons are utilized in therapeutic practice to treat a variety of human illnesses and problems [26,27] .…”

“…[23,24] Quinoline is a flexible heterocyclic scaffold with a wide range of applications in medicine. [25] Many compounds having quinoline skeletons are utilized in therapeutic practice to treat a variety of human illnesses and problems. [26,27] Quinolines exhibit important biological properties like ant-malarial, [28] anti-microbial, [29] anti-mycobacterial, [30] anti-depressant, antiviral, anti-convulsant, [31] anti-cancer, [32] anti-inflammatory effects and antihypertensive, [33] and are widely used in the treatment of bone joint, respiratory, and urinary tract infections (see figure 4).…”

Gram Scale Synthesis of Membrane-Active Antibacterial 4-Quinolone Lead Compound

“…The combined organic layers were dried (Na 2 SO 4 ), filtered, and concentrated under reduced pressure. Purification by silica gel flash chromatography (0−20% EtOAc/hexane) afforded the title compound (1.43 g, 85%, 6:1 inseparable mixture of regioisomers) as an amorphous white solid: R f = 0.7 (20% EtOAc/hexane); 1 H NMR (400 MHz, CD 3 OD, 6:1 inseparable mixture of regioisomers) δ 8.51 (d, J = 1.1 Hz, 1H, minor), 8.36 (s, 1H, major), 8.20 (s, 1H, minor), 8.12 (d, J = 1.1 Hz, 1H, major), 7.62−7.60 (m, 4H, major + minor), 7.56−7.51 (m, 4H, major + minor), 7.45−7.36 (m, 8H, major + minor), 5.49 (s, 2H, major), 5.48 (s, 2H, minor); 13 C{ 1 H}NMR (151 MHz, CD 3 OD, only signals corresponding to major isomer are given) δ 165.2, 151.8 (q, J = 34.5 Hz), 150.5, 137.8, 136.0, 133.5 (q, J = 33.0 Hz), 131.0 (q, J = 3.1 Hz), 129.8, 129.7, 128.3 (q, J = 3.5 Hz), 124.2 (q, J = 261.1 Hz), 123.7, 121.6 (q, J = 264.5 Hz), 118.8, 101.9, 73.4; 19 F NMR (376 MHz, CD 3 OD) δ −58.1 (minor), −64.8 (major), −69.8 (minor), −69.9 (major); FTIR (cm −1 ) 1439, 1321, 1017, 960; HRMS (ESI) m/z [M + H] + calcd for C 18 H 11 F 6 NOBr + 449.9923, found 449.9964 (error 8.2 ppm). (11).…”

“…Purification by silica gel flash chromatography (0−40% EtOAc/hexane) afforded the title compound (0.15 g, 89%) as an amorphous off-white solid: R f = 0.3 (40% EtOAc/hexane); 1 The structure was unambiguously confirmed by X-ray crystallography (the crystal was grown in EtOAc solvent at room temperature). We could not obtain useful 13 C NMR due to extensive line broadening caused by the 14 N nitrogen quadrupole moment, 19 F− 13 C coupling of the trifluoromethyl groups, and prototropic tautomerism in the quinoline ring despite extensive solvent screening.…”

“…11,12 Quinolines and related heterocycles, chemical classes under which DNAC-2 can be classified, are privileged motifs in medicinal chemistry and provide scaffolds amenable to multiparametric hit-to-lead optimization of potency, drug disposition properties, and therapeutic index. 13,14 Indeed, extensive explorations of structure−activity relationship (SAR) studies of DNAC-2 in collaboration with our group recently led to the identification of a novel class of 5arylamino-4-quinolones including a promising lead compound 1. 12 Quinolone 1 showed mechanistic congruence with the hit quinolinol, leading to partial membrane depolarization and also affecting the morphology of the S. aureus membrane while displaying a >128-fold improvement in antibacterial activity as measured by the minimum inhibitory concentration (MIC) compared to DNAC-2.…”