6584-12-9Relevant academic research and scientific papers
Tailored-design Synthesis of Sulfapyrimidine Derivatives
Azzam, Rasha A.
, p. 619 - 627 (2019/01/04)
In this paper, we report an efficient and convenient approach for the synthesis of tailored-design target sulfapyrimidine derivatives expected to show remarkable antimicrobial activities. The approach is based on reacting arylsulfonyl guanidine with α,β-unsaturated carbonyl compounds to afford N-(4,6-diarylpyrimidin-2-yl)arylsulfonamide or with ylidene derivatives to afford N-(6-aryl-5-cyanopyrimidin-2-yl)arylsulfonamide, N-(4-amino-5-cyano-6-(methylthio)-pyrimidin-2-yl)-arylsulfonamide, and N-(5-cyanopyrimidin-2-yl)arylsulfonamide compounds through Michael addition reaction. The structure of the newly synthesized compounds was confirmed from spectral data and elemental analysis.
Synthesis of Guanidine Derivatives and molecular recognition
Qi, Yanxing,Gao, Haixiang,Yang, Min,Xia, Chun-Gu,Suo, Jishuan
, p. 1073 - 1079 (2007/10/03)
Five Guanidine Derivatives bearing acyl group were synthesized by the reaction of acyl chloride with 1,1,3,3-tetramethylguanidine. Their structures were confirmed by IR, 1H-NMR, EI-MS, HRMS and elementary analysis. One of them (4a) was also cha
Protease inhibitors: Synthesis and QSAR study of novel classes of nonbasic thrombin inhibitors incorporating sulfonylguanidine and O- methylsulfonylisourea moieties at P1
Supuran, Claudiu T.,Scozzafava, Andrea,Briganti, Fabrizio,Clare, Brian W.
, p. 1793 - 1806 (2007/10/03)
Using benzamidine as a lead molecule, two series of alkyl/aralkyl/arylsulfonylguanidines/sulfonyl-O-methylisoureas have been prepared and assayed as inhibitors of two serine proteases, thrombin and trypsin. The study showed that sulfaguanidine and its corresponding O- methylisourea derivative possess moderate but intrinsically selective thrombin inhibitory properties, with K(I)'s around 100 nM against thrombin and 1350-1500 nM against trypsin. Further elaboration of these two molecules afforded compounds that inhibited thrombin with K(I)'s in the range of 12-50 nM, whereas affinity for trypsin remained relatively low. Such compounds were obtained by attaching benzyloxycarbonyl- or 4-toluenesulfonylureido-protected amino acids (such as L- and D-Phe or L-Pro) or dipeptides (such as Phe-Pro, Gly-His, β-Ala-His, or Pro-Gly) to the two leads mentioned above, sulfaguanidine and 4-aminobenzenesulfonyl-O-methylisourea. Thus, the present study proposes two novel approaches for the preparation of high-affinity, specific thrombin inhibitors: two novel S1 anchoring moieties in the already large family of arginine/amidine-based inhibitors and novel peptidomimetic scaffolds obtained by incorporating tosylureido amino acids in the hydrophobic binding site(s). The first one is important for obtaining bioavailable thrombin inhibitors, devoid of the high basicity of the commonly used arginine/amidine-based inhibitors, whereas the second one may lead to improved water solubility of such compounds due to facilitated metal (sodium) salts formation (at the relatively acidic SO2NHCO protons) as well as increased stability at hydrolysis (in vivo). A QSAR study also explained the activity in terms of global properties of the molecules, electronic properties of the sulfonylguanidine/sulfonylisourea moiety, and novel descriptors, the frontier orbital phase angles (FOPA), that account for the directions of the nodes in the π orbitals in the aromatic portion of those of the drugs in which the sulfonyl group was bound to a benzene ring. For thrombin inhibition, the size of the molecule was the dominant influence, while for trypsin inhibition the FOPA was the principal determinant of activity. The dependence of activity on the FOPA variables is perhaps the clearest example of a quantum effect in pharmacology and suggests a promising new tool for drug design.
CARBONIC ANHYDRASE INHIBITORS. 9. INHIBITORS WITH MODIFIED SULFONAMIDO GROUPS AND THEIR INTERACTION WITH THE ZINC ENZYME
Supuran, Claudiu T.,Banciu, Mircea D.
, p. 1345 - 1354 (2007/10/03)
A number of 20 compounds, containing modified sulfonamido groups were prepared and tested as carbonic anhydrase inhibitors on the bovine enzyme. Novel classes of inhibitors were evidenced, and a new mode of binding for bidentate inhibitors was proposed, both for the native and Co(II) substituted enzyme.
