Isoquinolines: Important Cores in Many Marketed and Clinical Drugs

Abstract

Background: Isoquinoline analogs are an important, structurally diverse class of compounds that are extensively used as pharmaceuticals. Derivatives containing the isoquinoline scaffold have become a focus of therapeutic research because of their wide range of biological characteristics. Examples of these drugs, many of which are in clinical application or at the pre-clinical stage, are used to treat a broad swathe of ailments, such as tumors, respiratory diseases, infections, nervous system diseases, cardiovascular and cerebrovascular diseases, endocrine and metabolic diseases. Methods: Data were collected from PubMed, Web of Science, and SciFinder, through searches of drug names. Results: At least 38 isoquinoline-based therapeutic drugs are in clinical application or clinical trials, and their chemical structure and pharmacokinetics are described in detail. Conclusion: The isoquinoline ring is a privileged scaffold which is often preferred as a structural basis for drug design, and plays an important role in drug discovery. This review provides a guide for pharmacologists to find effective preclinical/clinical drugs and examines recent progress in the application of the isoquinoline scaffold.

The Application of Microwaves, Ultrasounds, and Their Combination in the Synthesis of Nitrogen-Containing Bicyclic Heterocycles

“…Isoquinoline, a structural isomer of quinoline, is a nitrogen-containing heterocyclic aromatic compound which is composed of a benzene ring fused to a pyridine ring. As compounds containing an isoquinoline scaffold have been found to possess a wide range of biological and pharmacological activities [ 95 , 96 , 97 , 98 , 99 , 100 , 101 ], their synthesis has aroused considerable attention from the scientific community. To further explore the importance of this scaffold, new synthetic methodologies, and the modification of traditional procedures, such as the Bischler–Napieralski and Pictet–Spengler [ 102 ] and Pomeranz–Fritsch reactions [ 103 ], were developed.…”

Copper(II) Complexes with 1-(Isoquinolin-3-yl)heteroalkyl-2-ones: Synthesis, Structure and Evaluation of Anticancer, Antimicrobial and Antioxidant Potential

“…Isoquinoline-containing compounds are of scientific interest due to their fluorescent properties and broad spectrum of biological activities including antihypertensive [ 53 ], anti-inflammatory and analgesic [ 54 ] or antioxidant [ 55 ] activities, as well as their ability to act as antidepressant and antipsychotic [ 56 ] agents. Moreover, the importance of isoquinoline scaffold in drug design [ 57 , 58 ] has also led to the development of bioactive compounds with antimalarial [ 59 ], antifungal and antibacterial effects [ 60 , 61 ]. In addition, isoquinoline derivatives constitute an important source of novel anticancer agents that may exert their biological activities through various mechanisms such as apoptosis, DNA fragmentation, the inhibition of tubulin polymerization, induced cell cycle arrest and the interruption of cell migration [ 62 , 63 ].…”

Synthesis of Isoquinolines via the [4+2] Cycloaddition Reaction of Oxazoles and Arynes

“…[4] The isoquinoline core is found in many bioactive natural products and drugs used for the treatment of several diseases. [5] For example, papaverine, a natural product with vasodilatory activity, and dimethisoquin and 2,2'hexadecamethylenediisoquinolinium dichloride, two synthetic drugs with anesthetic and antifungal activities, respectively. [6] Consequently, several synthetic approaches to produce isoquinoline derivatives have been reported in the literature due to their pharmacological importance.…”

“…[11] Other publications have reported the reaction of oxazoles with benzyne generated at higher temperatures. [12,13] In 1980, Reddy and Bhatt reported the reaction of trisubstituted oxazoles with benzyne, formed from anthranilic acid and isoamyl nitrite in refluxing 1,4-dioxane (101 °C), affording 1 : 1 benzyne/oxazole Diels-Alder adducts (2), which rapidly underwent retro-Diels-Alder elimination of nitriles, leading to the formation of isobenzofurans (5). The addition of a second benzyne provided 2 : 1 adducts (bicyclic ethers) (7).…”