Quinoline-based small molecules have been explored and being developed as anti-inflammatory agents targeting several pharmacological targets namely Phosphodiesterase 4 (PDE4), Transient Receptor Potential Vanilloid 1 (TRPV1), TNF-α converting enzyme (TACE) and Cyclooxygenase (COX). Efforts on Structure Activity Relationship (SAR) studies revealed that the pharmacological activities and target specificities of these quinoline derivatives were mainly dependent on the nature and position of substituent(s) present on the quinoline ring. For example, quinolines having carboxamide moiety displayed TRPV1 antagonism whereas that with carboxylic acid showed COX-inhibition. Similarly, quinolines possessing aniline moiety at C-4, aryl group at C-8 and oxazole ring at C-5 showed PDE4 inhibition. These quinoline derivatives were synthesized by using various synthetic approaches like Pd-mediated C-C (e.g. Suzuki, Sonogashira type coupling etc.) or C-N (the Buchwald-Hartwig type coupling) or C-S bond formation, AlCl₃ induced C-C bond formation, traditional amide bond formation or amination, formation of ether linkage or additional heterocyclic rings. All these efforts resulted in the discovery of several quinoline-based anti-inflammatory agents for the potential treatment of acute as well as chronic inflammatory diseases.

An iodine-catalyzed four-component reaction of 1,3-dicarbonyl compounds, amines, aldehydes and nitroalkanes afforded polysubstituted pyrroles under a metal free condition. Simplicity, low cost and good yields are the key features of this methodology. The mechanism of this four component process is discussed and structural elaboration of one of the compounds synthesized using Suzuki and Sonogashira coupling is presented.

Background: The indole framework is considered as one of the privileged structures in the area of medicinal chemistry and drug discovery because compounds containing this framework have shown to possess a remarkable ability to bind with many receptors or proteins with high affinity. It is therefore not surprising that the indole nucleus is a frequently found moiety in many bioactive agents or drugs. Indole derivatives have also been explored or studied for their anti-tubercular properties for a long time. The growth inhibition of Mycobacterium tuberculosis (MTB) in vitro and in vivo by the gut microbiota metabolite indole propionic acid (IPA) is one of the recent examples. Notably, tuberculosis (TB), an intractable disease and a major cause of death worldwide, has caused an alarming rise in the number of TB cases recently because of two main reasons, i.e., a several-fold rise among HIV-infected patients and increased drug resistance by some bacterial strains. Thus, the identification of new agents or potential drugs against TB is urgently needed. Methods: While the specific pharmacological target or mechanism of action (MOA) for antitubercular activities has been reported for many indole derivatives, the MOA is not well defined or known for a number of indole derivatives though they were found to be active against MTB. In the current review article, we have focused on both types of indole derivatives that have shown activities against MTB. The indoles with known MOA are further segregated based on this pharmacological target reported or indicated whereas other indoles are classified based on the type of anti-TB properties shown by them. The literature for the last 20 years as well as related to up to date knowledge and information was searched on Pubmed, Google Scholar, MEDLINE, and various other databases until August 2020. Results: A diverse range of functionalized indole derivatives, such as indole-based alkaloids, simple indoles, fused indoles, amide/peptide derivatives of indole, isatin derivatives, etc., have been reported to possess anti-tubercular activities. The anti-tubercular activities, in silico studies (if reported) and the chemical syntheses (in most of the cases) of representative indole derivatives are presented briefly in the current article. The papers referenced by this review allow a deep analysis of the status of the indole-based anti-tubercular agents explored over the past two decades. Conclusion: This review aims at stimulating renewed interest and effort in the discovery and development of new indole-based agents or potential drugs for the treatment of TB. The emergence of modern methods, especially those based on transition metal-catalyzed reactions, has opened up tremendous opportunities in the area of indole synthesis. The desired goal would be to have utilized these modern methodologies for the identification of potent and promising agents to fight against MTB.

A sequential Pd-mediated multi-component reaction followed by Suzuki or Heck or Sonogashira coupling in a single pot has been developed for the synthesis of functionalized pyrroles as potential inhibitors of PDE4.

Neuropathic pain affects 26 million patients worldwide resulting in a worldwide healthcare cost over $ 3 billion per year. Despite the availability of an impressive arsenal of powerful drugs for the effective management of pain, there remains a great medical need for new medicines to treat pain. While little is known about the proteins that detect noxious stimuli (especially those of a physical nature), vanilloid receptor, an excitatory ion channel expressed by nociceptors, has been identified as molecular target for the development of recent therapies to treat pain. Initially, the focus was on the development of TRPV1 agonists e.g. capsaicin and resiniferatoxin (RTX) as analgesic agents through the desensitization/ denervation approach. While various formulations of capsaicin are either marketed or are currently under development, this approach is often hindered by the pain and discomfort experienced on initial treatment. Thus, TRPV1 antagonists are being evaluated as promising drug candidates to inhibit the transmission of nociceptive signals from the periphery to the CNS and to block other pathological states associated with this receptor. Since the discovery of capsazepine as the first TRPV1 antagonist, multiple classes of antagonists has been reported that can be broadly classified as urea/amide-based and non-urea/non-amide-based agents. However, depending on their chemical structures all these agents can be grouped as benzenesulfonamides, cinnamides, ureas, thio-ureas, amides, benzimidazoles, and piperazine carboxamides, N-aryl-cinnamides etc. The present review will focus on all these antagonists as an emerging class of novel, analgesic, antiinflammatory agents that have been reported in the literature over the last several years and the status of the developmental candidates in various stages of clinical trials.