# Synthetic Transformations and Medicinal Significance of 1,2,3-Thiadiazoles Derivatives: An Update
## 2 Synthetic Approaches
### Fungicidal Agents  
The chemical agents that have the potential to control and eradicate fungal infections are termed as fungicides or antifungal drugs [149]. The commercial antifungal agents are chlorothalonil (**65**) which is a non-systemic fungicide [150; 151], fluconazole (**66**) [152] and ketoconazole (**67**) (Figure 26) [153]. As the first example, it is worth bring up oxadiazoles containing thiadiazole derivatives [154]. In this group, two oxadiazole derivatives **141** and **142** (Figure 27) displayed the best antifungal activity against _Puccinia triticina_ at a concentration of 500 \(\mathrm{\SIUnitSymbolMicro\SIUnitSymbolMicro mL}\). Both structures showed a remarkable high growth inhibition activity (98 and 83%, respectively) which was slighter lower than the standard drug chlorothalonil with 100% fungal growth inhibition activity. The remarkable high and excellent antifungal activity of scaffold **141** could lead to the development of novel oxadiazole-based 1,2,3-thiadiazole fungicides [154]. Another example of compounds with good antifungal activities are new structures designed by [PERSON] et al., which are 1,2,4-triazole derivatives substituted with a 1,2,3-thiadiazole ring [82]. One of the synthesized compounds **143** (Figure 28), exhibited remarkably high fungicidal 93.19% against _Corynespora cassicola_, while reference compounds iprodione, validamycin and topsin-M possessed 78.20, 53.52 and 78.75% antifungal activity, respectively. The authors declared that compound containing phenyl group on triazole ring **143** exhibited higher activity, however, the results were different in the case of _Pseudoperonspora cubensis_ as compound **144** containing cyclopropyl group displayed higher activity than that of **143**. The most active compound with regard to _Pseudoperonospora cubensis_ was **144**, which inhibited the growth of this pathogen in 81.62%. However, SAR analysis did not clear the results against _pseudomonas syringae_ pv. _Lachrymans_. Both the scaffolds showed excellent and the highest antifungal potential than all three commercial reference drugs that will lead to the development of promising antifungal agents [82]. Figure 26: Structures of commercial antifungal drugs **138–140**. Figure 27: Novel potent 1,2,3-thiadiazole fungicides **141** and **142**. Less antifungal activity was observed in the derivative **145** (Figure 29) reported by [PERSON] et al. [155]. Its inhibition rates to _Ptytophthora infestans_ (Mont[PERSON] de [PERSON], _Alternaria solani, Gibbrella sunhinetti, Physalospora piricola_ Nose, _Botrytis cinerea, Phytophthora capsaicin_ Leonian, _Cercospora nachidicola, Rhizoctonia solanti_ and _Fusarium oxysporum_ reached 32.3, 17.4, 32.3, 25.8, 43.5%, 36.1, 15.8, 30.3 and 26.9% at 50 \(\upmu\)g/mL respectively. The results indicated that the structural motif **145** proved to be broad-spectrum fungicide because it exhibited significant antifungal activity against different fungal strains [155]. Another group reported the fungicidal properties of 1,2,3-thiadiazole derivatives against _Alternaria solani_ (AS), _Botrytis cinerea_ (BC), _Cercospora anachidicola_ (CA), _Cercospora beticola_ (CB), _Colletotrichum lagenarium_ (CL), _Fusarium oxysporum_ (FO), _Gibbrella zeae_ (GZ), _Macrophoma kuwatsukai_ (MK), _Ptytophthora infestans_(_[PERSON]_ (PI), _Physalospora piricola_ (PP), _Pellicularia sasaki_ ([PERSON]) (PS), _Puccinia triticina Eriks_ (PT) and _Rhizoctonia solanti Kuhn_ (RS) [156]. The most active occurred to be structure **146** (Figure 30) showed potent fungicidal inhibitory activity 84.8, 83.9, 83.3, 78.9, 75.0, 71.4, 70.7, 66.7, 64.7 and 63.6% against PS, PP, RS, PT, FO, CB, PI, AS, CL and CA, respectively. On the other hand, the propyl containing fused 1,2,4-triazole0[1,3,4]thiadiazole **147** (Figure 30) exhibited the best fungicidal inhibition activity 93.0% for FO, 84.9% for BC, 77.8% for PS, 75.8% for PI, 75.0% for GZ, 62.1% for CA, 50.0% for CL, 40.5% for IP, 34.4% for AS and 33.3% for CB.