Medicinal chemistry of anthranilic acid derivatives: A mini review

Abstract

Anthranilic acid and its analogues present a privileged profile as pharmacophores for the rational development of pharmaceuticals deliberated for managing the pathophysiology and pathogenesis of various diseases. The substitution on anthranilic acid scaffold provides large compound libraries, which enable a comprehensive assessment of the structure activity relationship (SAR) analysis for the identification of hits and leads in a typical drug development paradigm. Besides, their widespread applications as anti‐inflammatory fenamates, the amide and anilide derivatives of anthranilic acid analogues play a central role in the management of several metabolic disorders. In addition, these derivatives of anthranilic acid exhibit interesting antimicrobial, antiviral and insecticidal properties, whereas the derivatives based on anthranilic diamide scaffold present applications as P‐glycoprotein inhibitors for managing the drug resistance in cancer cells. In addition, the anthranilic acid derivatives serve as the inducers of apoptosis, inhibitors of hedgehog signaling pathway, inhibitors of mitogen activated protein kinase pathway, and the inhibitors of aldo‐keto reductase enzymes. The antiviral derivatives of anthranilic acid focus on the inhibition of hepatitis C virus NS5B polymerase to manifest considerable antiviral properties. The anthranilic acid derivatives reportedly present neuroprotective applications by downregulating the key pathways responsible for the manifestation of neuropathological features and neurodegeneration. Nevertheless, the transition metal complexes of anthranilic acid derivatives offer therapeutic applications in diabetes mellitus, and obesity by regulating the activity of α‐glucosidase. The present review demonstrates a critical analysis of the therapeutic profile of the key derivatives of anthranilic acid and its analogues for the rational development of pharmaceuticals and therapeutic molecules.

Anthranilate Derivative Inhibits Glutamate Release and Glutamate Excitotoxicity In Rats

“…dl-threo-β-benzyloxyaspartate (dl-TBOA), ba lomycin A1, dantrolene, 7-chloro-5-(2-chlorophenyl)-1,5-dihydro-4,1-benzothiazepin-2(3H)-one (CGP37157), and bisindolylmaleimide I (GF109203X) were purchased from Tocris (Bristol, UK). 3,3,3-Dipropylthiadicarbocyanine iodide [DiSC 3 (5)], and fura-2-acetoxymethyl ester (Fura-2-AM) were purchased from Thermo (Waltham, USA). ω-conotoxin GVIA (ω-CgTX GVIA) and ω-agatoxin IVA (ω-Aga IVA) were purchased from Alomone lab (Jerusalem, Israel).…”

“…The synaptosomal membrane potential was assayed with a positively charged membrane potentialsensitive carbocyanine dye DiSC 3 (5). DiSC 3 (5) uorescence was monitored at 2 s intervals and data are expressed in uorescence units [24].…”

“…Anthranilate derivatives have gained much attention in drug discovery and development because of their diverse pharmacological activities, including anti-in ammatory, antiviral, immunosuppressive, anticancer, antithrombotic, antidiabetic, and analgesic activities [5][6][7][8][9][10][11][12][13][14]. Anthranilate derivatives was also reported to have antidepressant and anticonvulsant effects, as described in different animal models [14,15], indicating that they are potential candidates for drug therapy for related diseases such as anxiety, depression, and epilepsy.…”

Bright Side of Fusarium oxysporum: Secondary Metabolites Bioactivities and Industrial Relevance in Biotechnology and Nanotechnology

“…Anthranilates are derivatives of anthranilic acid that constitute an important part of several bio-metabolites and serve as a scaffold for developing remarkable pharmaceuticals for the management of the pathogenesis and pathophysiology of diverse disorders. They possessed impressive bioactivates such as antiviral, antimicrobial, insecticidal, antiinflammatory, anti-diabetic, and anticancer [181]. Compounds 1-21 are anthranilic acid derivatives that had been purified and characterized only from F. oxysporum f. sp.…”

Mild Copper-Catalyzed, l-Proline-Promoted Cross-Coupling of Methyl 3-Amino-1-benzothiophene-2-carboxylate

“…The importance of the aforementioned class of compounds supported our interest in the synthesis of the anthranilic acid analogues in which the thiophene moiety is present as a benzene ring bioisostere [16]. Moreover, N-substituted anthranilic acids are broadly used in the treatment of various diseases, such as arthritis, atypical dermatitis, and bronchial asthma, and they are also described as anti-allergic, analgesic, and anticancer agents [17][18][19][20][21].…”