# Synthetic Transformations and Medicinal Significance of 1,2,3-Thiadiazoles Derivatives: An Update
## 2 Synthetic Approaches
### Antiviral Agents
Anti-TMV activity of synthesized scaffolds and reference drugs decreases in order of **98** > inamycin >**97** > **95** > **96** > ribavirin while the protection effect decreased in order of inamycin > **97** > **96** > **95** > ribavirin > **98**. Compound **98** display a higher inhibition potential, i.e., 48.73% as compared to innamycin and ribavirin. The SAR study showed that the **2-fluorophenyl substituent** derivative **97** displayed the **best protection effect** among the synthesized congeners as well as from the ribavirin reference drug. The protection effect decreased in order of **inamycin >**2-fluorophenyl >** cyclopropyl >** isopropyl >** ribavirin > **4-ethylphenyl**. Overall the scaffold **97** proved to be a promising therapeutic agent, which has a better protection effect as well as the best anti-TMV activity [84]. carbohydrazide 1,2,3-thiadiazole (**99**; Figure 8) showed potent direct anti-TMV activity with 58.72% and 61.03% induction potencies at 50 \(\upmu\)g/mL when compared with reference drugs, ninamycin and tiadinil. Both the standard reference drugs, ninamycin and tiadinil, exhibited anti-TMV activity (54.93% and 7.94%) and induction activity (18.58% and 59.25%) respectively in vivo at 50 \(\upmu\)g/mL concentration. The scaffold **99** showed remarkably and significant higher antiviral potential than the standard reference drugs. The excellent anti-TMV activity of analogue **99** was due to the presence of thiophene moiety as compare to all the other tested compounds. The structural motif **99** showed significantly higher induction activity (61.03%) more than the induction activities of reference drugs, ninamycin and tiadinil (18.58%) and (59.25%), respectively. So the derivative **99** proved to be a plant elicitor and anti-TMV agent simultaneously [108]. Another example of compounds with anti-TMV activity are structures **100** and **101** with a 1,3,4-oxadiazole ring (Figure 9) [109]. They showed potent curative, inactivation and protection effects against TMV. The derivative **100** displayed curative rate 54.1%, inactivation rate 90.3% and protection rate 52.8% while the compound **101** showed 47.1, 85.5 and 46.4% curative, inactivation and protection rates, respectively. The ninganamycin was used as a standard reference drug, exhibiting a 56.1% curative rate, 92.5% inactivation rate and 59.3% protection rate. The incorporation of 1,3,4-oxadiazole moiety in the skeleton of 1,2,3-thiadiazoles significantly increased the anti-TMV activity [109]. Other promising anti-TMV agents **102** and **103** were presented by [PERSON] et al. (Figure 10) [83]. The substituted 1,2,3-thiadiazole-4-carboxamide scaffold **102** exhibited the best antiviral curative activity of 60 and 47%, at 500 and 100 \(\upmu\)g/mL concentrations, while the standard tiadinil showed curative activity 58 and 46% at 500 and 100 \(\upmu\)g/mL concentrations, respectively. Compound **103** showed its potent protective effect 76 and 71% at 500 and 100 \(\upmu\)g/mL concentrations in comparison with the standard drug tiadinil, which displayed protective 75 and 57% at 500 and 100 \(\upmu\)g/mL. The structure **103** marked a higher protective effect than the tiadinil and **102** at 100 \(\upmu\)g/mL concentration. The enhanced protective potential of **103** was dose-dependent and due to the presence of hyroxyphenyl moiety. The fluorophenyl, chlorophenyl and hyroxyphenyl functionalities contributed to better efficacy that led to a future investigation to develop promising anti-TMV agents [83]. Figure 8: Antiviral 1,2,3-thiadiazole scaffold **99**. Figure 9: 1,2,3-thiadiazoles **100** and **101** with anti-TMV activity. 1,2,3-Thiadiazole acetanilide hybrid structures prepared by [PERSON] et al. were screened for their antiviral activity against HIV-1 [110].