The scientific introduction of the term "isostere" by Langmuir in 1919 and its application to biological activity by Friedman in 1951 is one of the cornerstone concepts in modern MedChem . Despite the seeming simplicity of the concept, its practical using sometimes seriously limited by synthetic accessibility of corresponding speculatively generated isostere-structures. As an example of the statement the "benzene isosteres story" could be highlighted . Therefore, the generating of isosteric structures, which could be easily obtained by the changing of readily accessible starting materials using the general approach to parent structure is promising for modern MedChem. For example, the isosteric replacement of C=O with SO2 was widely used in peptide chemistry via exchanging of the corresponding amino acids to sulpha analogues . Besides, the abovementioned isosteric replacement also was used in more sophisticated structures including cyclic ones (Figure , A) . Among these compounds, some examples bear NS(O)2N sequence instead of NC(O)N ones. Logically, we can explore "classical" reactions in which urea is used for the NC(O)N installation for the replacement of the latter to (H2NSO2NH2). Moreover, such examples of using H2NSO2NH2 as 1,3-binucleophile is already existing . Thus, it was a great surprise for us, that the simple switch from urea to sulfamide in the classical well-known multicomponent reaction, like Biginelli , was unknown for today (Figure ). Since Monastrol's discovery in 1999 threecomponent Biginelli condensation became one of the most widespread reactions in MedChem utilizing urea derivatives . Accordingly, our amazing has been even more when only two papers described the synthesis of thiadiazine-1,1-dioxides from sulfamide via a Biginelli-like approach, while using "non-classical" cyclization partners. In one, the thiadiazine-1,1-dioxide's core was obtained using the recyclization of an 8-member adduct of 2 molecules NH2SO2NH2 and 2 molecules (EtO)2CHCH2CO2Et with aryl aldehyde. This method was developed in a course of evaluation of SO2 isosteric replacement in analogous of Biginelli-type compound MAL1-127, active in a Model of Huntington's Disease . Another paper obtained the bicyclic structure with a specific methyleneactive component -hexane-1,3-dione. (Figure ). Finally, Bolm and co-workers described the Biginelli-type reaction with sulfonimidamides leading to 2,3-dihydro-1,2,6-thiadiazine 1-oxides under solvent-free mechanochemical conditions catalyzed by AcOH or Yb(OTf)3 . Based on such starting points, we decided to systematically study this reaction using sulfamide derivatives as one of the cyclization partners and taking into account our previous successful experience in expanding the Biginelli reaction's scope .