35478-73-0

Usage

InChI:InChI=1/C10H15NO3S/c1-3-11(4-2)9-5-7-10(8-6-9)15(12,13)14/h5-8H,3-4H2,1-2H3,(H,12,13,14)

Upstream product

• 91-66-7 N,N-diethylaniline 
• 35478-72-9 o-diethylaminobenzenesulfonic acid 
• 2481-94-9 4-(diethylamino)azobenzene 
• 826-42-6 N,N-diethylaniline N-oxide 
• 76129-30-1 N,N-diethyl-N-phenylammonium hydrogen sulfate 
• 113934-35-3 diethylanilinesulfotrioxide 

Downstream Products

• 35478-72-9 o-diethylaminobenzenesulfonic acid 
• 97-20-1 3-diethylamino-benzenesulfonic acid 
• 90945-15-6 4-(diethylamino)-benzenesulphonyl chloride 
• 91-66-7 N,N-diethylaniline 
• 1021463-03-5 (E,E)-4-methyl-5-{4-[4-(diethylamino)phenyl]sulfonamido}penta-2,4-dienoic acid N-hydroxyamide 
• 1021463-10-4 tert-butyl (E,E)-4-methyl-5-{4-[4-(diethylamino)phenyl]sulfonamido}penta-2,4-dienoate 
• 1021463-12-6 (E,E)-4-methyl-5-{4-[4-(diethylamino)phenyl]sulfonamido}penta-2,4-dienoic acid trifluoroacetate 
• 131998-63-5 5-(4-Diethylamino-benzenesulfonylamino)-pentanoic acid 
• 131998-64-6 1-[4-(diethylamino)benzenesulphonyl]-2-piperidinone 
• 125393-02-4 1-[4-(diethylamino)benzenesulphonyl]-2-pyrrolidinone 

Relevant academic research and scientific papers

COMPOUNDS AND USES THEREOF

There is provided a compound of formula (I) wherein R1a, R2a, R3, X1 to X6, a, b and c have meanings given in the description, which compounds are useful as, or are useful as prodrugs of, inhibitors of HDAC enzyme activity, and thus, in particular, in the treatment of conditions where inhibition of HDAC enzyme activity is required.

New classes of antimuscarinic agents endowed with selective antispasmodic properties. 1-Arylsulfonyl pyrrolidin-2-ones and 2-thiones, 1-arylsulfonyl piperidin-2-ones and 2-thiones and 1-arylsulfonyl hexahydro-2H-azepin-2-one

A series of 1-arylsulfonylpyrrolidin-2-ones (and 2-thiones), 1-aryl sulfonylpiperidin-2-ones (and 2-thiones) and 1-arylsulfonyl hexahydro-2H-azepin-2-one were synthesized and submitted to a battery of binding assays. The compounds showed little or no affinity for the receptors tested other than muscarinic receptors labelled either with [3H]pirenzepine or with [3H]quinuclidinyl benzilate. When tested in the isolated guinea pig ileum, they antagonized the contractions induced by acetylcholine and behaved as competitive muscarinic antagonists. After parenteral administration in mice, most compounds inhibited carbachol-induced diarrhoea but were less effective in counteracting salivation and lacrimation and showed little or no mydriatic action, thus displaying selectivity at the intestinal level. The reference drugs tested, atropine, butyl scopolamine and cimetropium bromide were far less selective. Maximal in vivo activity was obtained by introducing diethylamino or 1-piperidino or 1-hexahydroazepinyl groups in the 4-position of the phenyl ring while the enlargement of a 5- to a 6-membered lactam ring or its conversion into a thiolactam had a less marked effect. The most interesting compounds were further evaluated for their ability to antagonize carbachol-induced colonic hypermotility in the rat and arecoline-induced analgesia in mice. The effect on gastric acid secretion in the rat was also investigated. The overall in vivo data showed that compounds 14, 15, 26 and 27, i.e. those bearing a 1-hexahydroazepinyl group in the 4-position of the phenyl ring, were the most potent and selective compounds. Unlike the reference drugs, they antagonized carbachol-induced diarrhoea and colonic hypermotility at doses (0.6-4 mg/kg i.p.) 1-2 orders of magnitude lower than those needed to counteract carbachol-induced salivation and lacrimation or to induce mydriatic and antisecretory effects. The novelty of these structures and their selectivity of action on smooth muscle are the two key features of this class of antimuscarinics.

ISOMERIC TRANSFORMATIONS OF AMINOSULFONIC ACIDS OF THE BENZENE SERIES IN MIXTURES OF SULFURIC AND ACETIC ACIDS

The isomerization rate of aminosulfonic acids in anhydrous binary mixtures of sulfuric and acetic acids is lower than in aqueous sulfuric acid solutions but higher than in 100percent sulfuric acid.This is explained by the differences in the structure and activity of the proton carriers during desulfonation.The rate of transformation of the labile isomers into the meta isomers increases with increase in the acidity of the medium, and this is due to the increase in the resulfonation rate of the protonating molecules of the amines formed during the desulfonation of the aminosulfonic acids.The effect of mercuric sulfate on the isomeric transformations of aminosulfonic acids is explained by the mercuration of the protonated molecules of the amines, which takes place at higher rates than their sulfonation and leads to the formation of the meta-mercury derivatives of the amines.The latter are than converted into the m-aminosulfonic acids by the action of concentrated sulfuric acid.

KINETICS OF SULFONATION OF AMINES OF THE BENZENE SERIES WITH SULFUR TRIOXIDE

The sulfonation of amines of the benzene series with sulfur trioxide in dichloroethane is described by a third-order kinetic equation for an irreversible process, and first order is observed with respect to the compound being sulfonated and second with respect to the sulfur trioxide.The unprotonated molecules of the amines undergo sulfonation, and this leads to the production of the para-aminosulfonic acids with small amounts of the ortho isomers.The reaction mechanism involves electrophilic reaction of the unprotonated amine molecule with the sulfur trioxide dimer S2O6 and subsequent dissociation of the obtained pyrosulfonate with the production of the amino sulfonic acid and sulfur trioxide.

KINETICS OF THE SULFONATION OF AMINES OF THE BENZENE SERIES BY CHLOROSULFONIC ACID

The kinetics of the sulfonation of amines of the benzene series by an equimolar amount of chlorosulfonic acid in o-dichlorobenzene were studied.It was shown that the sulfonation of aniline and N-alkylanilines is described by a second-order kinetic equation for irreversible reactions.The sulfonation of N,N-dialkylanilines by chlorosulfonic acid is described by a first-order kinetic equation for irreversible reactions.The observed relationships are explained by different mechanism for the sulfonation of amines of the benzene series by chlorosulfonic acid.The sulfonation of aniline and N-alkalynilines takes place by direct reaction between the unprotonated molecules of the amines and the HSO3(1+) ion, whereas in the reaction of chlorosulfonic acid with N,N-dialkylanilines complexes of the N,N-dialkylanilines with sulfur trioxide (dialkylanilinesulfotrioxides) are formed initially and then rearrange to the corresponding para-aminosulfonic acids.

REARRANGEMENT OF PHENYL- AND N-ALKYLPHENYLAMMONIUM HYDROGEN SULFATES IN ORGANIC SOLVENTS

The kinetics of the rearrangement of phenyl- and N-alkylphenylammonium hydrogen sulfates in halogen-containing organic solvents were investigated in closed systems and with the removal of the water produced in the reaction.The isomeric composition of the obtained aminobenzenesulfonic acids was also studied.The rearrangement is described by a second-order kinetic equation.The reaction mechanism involves thermal dissociation of the phenyl- and N-alkylphenylammonium hydrogen sulfates at high temperatures to amines (bases) and sulfuric acid, followed by direct sulfonation of the amines (bases) by the sulfuric acid with the formation mostly of para-aminosulfonic acids of the benzene series.

KINETIC OF THE SULFONATION OF AMINES OF THE BENZENE SERIES WITH SULFURIC ACID

The kinetics of the sulfonation of primary, secondary, and tertiary amines of the benzene series with 80-99.7percent sulfuric acid were investigated.It was shown that the unprotonated and protonated forms of the amines, which are present in equilibrium, undergo sulfonation.The effective reaction rate constants and the activation energies for the sulfonation of the unprotonated and protonated molecules of the amines were calculated.The reaction mechanism and the structure of the transition state are discussed.