13918-92-8Relevant articles and documents
Conversion of thiols into sulfonyl halogenides under aerobic and metal-free conditions
Jereb, Marjan,Hribernik, Luka
supporting information, p. 2286 - 2295 (2017/07/24)
An environmentally benign, metal-free synthesis of sulfonyl chlorides and bromides from thiols in the presence of ammonium nitrate, an aqueous solution of HCl and HBr and oxygen as a terminal oxidant was developed. The reactivity of various substituted thiophenols, benzylic-, aliphatic- and heteroaromatic thiols was examined. Ammonium nitrate served as a source of nitrogen oxides (NO/NO2), which are the crucial players in a redox-catalytic cycle. Sulfonyl chlorides and bromides were isolated without extraction and "filtered" over a short pad of silica gel; the use of solvents was greatly reduced in comparison with traditional isolation and purification. A "one-pot" protocol for the conversion of thiol into sulfonamide is also demonstrated. Scale-up experiments on the preparation of sulfonyl chloride and bromide are shown. A possible reaction pathway is discussed.
Thermodynamic characterization of new positive allosteric modulators binding to the glutamate receptor A2 ligand-binding domain: Combining experimental and computational methods unravels differences in driving forces
Norholm, Ann-Beth,Francotte, Pierre,Goffin, Eric,Botez, Iuliana,Danober, Laurence,Lestage, Pierre,Pirotte, Bernard,Kastrup, Jette S.,Olsen, Lars,Oostenbrink, Chris
, p. 3404 - 3416 (2015/04/27)
Positive allosteric modulation of the ionotropic glutamate receptor GluA2 presents a potential treatment of cognitive disorders, for example, Alzheimer's disease. In the present study, we describe the synthesis, pharmacology, and thermodynamic studies of a series of monofluoro-substituted 3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxides. Measurements of ligand binding by isothermal titration calorimetry (ITC) showed similar binding affinities for the modulator series at the GluA2 LBD but differences in the thermodynamic driving forces. Binding of 5c (7-F) and 6 (no-F) is enthalpy driven, and 5a (5-F) and 5b (6-F) are entropy driven. For 5d (8-F), both quantities were equal in size. Thermodynamic integration (TI) and one-step perturbation (OSP) were used to calculate the relative binding affinity of the modulators. The OSP calculations had a higher predictive power than those from TI, and combined with the shorter total simulation time, we found the OSP method to be more effective for this setup. Furthermore, from the molecular dynamics simulations, we extracted the enthalpies and entropies, and along with the ITC data, this suggested that the differences in binding free energies are largely explained by the direct ligand-surrounding enthalpies. Furthermore, we used the OSP setup to predict binding affinities for a series of polysubstituted fluorine compounds and monosubstituted methyl compounds and used these predictions to characterize the modulator binding pocket for this scaffold of positive allosteric modulators.
Benzodioxole derivatives, processes for the manufacture thereof and corresponding pharmaceutical compositions
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, (2008/06/13)
The invention relates to novel benzodioxole derivatives of the general formula I STR1 in which R1 represents an unsubstituted or substituted, aliphatic, aromatic or heteroaromatic radical, alk represents an alkylene, alkenylene or alkylidene radical having a maximum of 5 carbon atoms, n1 represents 0, 1 or 2 n2 represents 0 or 1, R2, R3 and R4 each represents, independently of the others, hydrogen, lower alkyl, lower alkoxy or halogen, and A represents the radical --O--R5, wherein R5 represents hydrogen or an unsubstituted or substituted, aliphatic or araliphatic hydrocarbon radical, or A represents the radical STR2 in which either R6 and R7 each represents, independently of the other, hydrogen or lower alkyl, or R6 and R7 are bonded to one another and, together with the adjacent nitrogen atom, represent optionally lower alkyl-substituted tetra- to hexa-methyleneimino, 4-morpholinyl or 1H-tetrazol-1-yl, such as, for example, 5-methyl-6-phenylsulphonyl-1,3-benzodioxole-2-carboxylic acid. The invention relates also to salts of compounds of the general formula I in which A represents OR5 wherein R5 represents hydrogen, with bases, and to acid addition salts of compounds of the general formula I in which the radical R1 has a basic character and to processes for the manufacture of the above compounds and the salts thereof and to pharmaceutical compositions containing them. These novel substances have diuretic and supplementary uricosuric action and may be used, preferably in the form of appropriate pharmaceutical compositions, for the treatment of oedema and hypertension.
