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At least 19 recordsLinked to original sources
PubMed2006

Pharmacophoric 2-hydroxyalkyl benzenesulfonamide: a single-step synthesis from benzenesulfonamide via hemiaminal.

ortho-Acylation attempt of benzenesulfonamide afforded the corresponding hemiaminal as major product. The in situ reduction of the reaction mixture, reported herein, directly provided 2-hydroxyalkyl benzenesulfonamide, an important pharmacophoric element for designing drug-like scaffolds. Its application is demonstrated through designing a novel series of 1,5-diarylpyrazoles for cyclooxygenase-2 (COX-2) inhibition.

Aldehydes↗
PubMedDate not supplied

2-mercapto N-(azolyl)benzenesulfonamides. VI. Synthesis and anti-HIV activity of some new 2-mercapto-N-(1,2,4-triazol-3-yl)benzenesulfonamide derivatives containing the 1,2,4-triazole moiety fused with a variety of heteroaromatic rings.

A series of 2-mercapto-N-(1,2,4-triazol-3-yl)benzenesulfonamide derivatives containing the triazole moiety fused with a variety of heteroaromatic rings [XVI-XXVIII] was obtained by the reactions of 3-methylthio-1,4-2-benzodithiazine 1,1-dioxide derivatives [Ia-d] with 2-hydrazines [IIa-f]. Some of the intermediate 1,1-dioxide-1,4,2-benzodithiazin-3-ylhydrazines [III-XV] initially formed were also isolated. Preliminary screening data indicated that compounds [XVI-XIX and XXVII] were anti-HIV inactive, whereas other compounds showed a high [XXI and XXIII], fairly high [XXIII and XXVI] or moderate [XX, XXIV, XXV and XXVIII] activity. The compound [XXI] exhibited also high activity against ten selected HIV mutants.

Anti-HIV Agents↗
PubMedDate not supplied

2-Mercapto-N-(azolyl)benzenesulfonamides. V. Syntheses, anti-HIV and anticancer activity of some 4-chloro-2-mercapto-5-methyl-N-(1,2,4- triazolo[4,3-a]pyrid-3-yl)benzenesulfonamides.

A series of 4-chloro-2-mercapto-5-methyl-N- (1,2,4-triazolo[4,3-a]pyrid-3-yl) benzenesulfonamides [IIIa-IIId] was obtained by the reaction of 6-chloro-7-methyl-3-methylthio- 1,4,2-benzodithiazine 1,1-dioxide with some 2-hydrazinopyridines. Preliminary screening data indicated that compounds [IIIa-IIId] exibited moderate or fairly high anti-HIV activity and moderate anticancer activity.

Anti-HIV Agents↗
PubMed2005

N-acetyl-4-[(2-hydroxybenzylidene)amino]benzenesulfonamide monohydrate and N-acetyl-4-[(5-bromo-2-hydroxybenzylidene)amino]benzenesulfonamide monohydrate.

Molecules of the title compounds, C15H14N2O4S.H2O and C15H13BrN2O4S.H2O, adopt an E configuration about the azomethine C=N double bond. In both molecules, the two benzene rings and the azomethine group are practically coplanar, as a result of intramolecular hydrogen bonds involving the hydroxy O atom and azomethine N atom. The angular disposition of the bonds about the S atom deviates significantly from that of a regular tetrahedron. In the crystal structures, both compounds form two-dimensional layers parallel to the (100) plane.

Benzylidene Compounds↗
PubMed2002

The pharmacokinetics of a thiazole benzenesulfonamide beta 3-adrenergic receptor agonist and its analogs in rats, dogs, and monkeys: improving oral bioavailability.

The pharmacokinetics and oral bioavailability of (R)-N-[4-[2-[[2-hydroxy-2-(pyridin-3-yl)ethyl]amino]ethyl]phenyl]-4-[4-[4-(trifluoromethylphenyl]thiazol-2-yl]benzenesulfonamide (1), a 3-pyridyl thiazole benzenesulfonamide beta3-adrenergic receptor agonist, were investigated in rats, dogs, and monkeys. Systemic clearance was higher in rats (approximately 30 ml/min/kg) than in dogs and monkeys (both approximately 10 ml/min/kg), and oral bioavailability was 17, 27, and 4%, respectively. Since systemic clearance was 25 to 40% of hepatic blood flow in these species, hepatic extraction was expected to be low, and it was likely that oral bioavailability was limited either by absorption or a large first-pass effect in the gut. The absorption and excretion of 3H-labeled 1 were investigated in rats, and only 28% of the administered radioactivity was orally absorbed. Subsequently, the hepatic extraction of 1 was evaluated in rats (30%) and monkeys (47%). The low oral bioavailability in rats could be explained completely by poor oral absorption and hepatic first-pass metabolism; in monkeys, oral absorption was either less than in rats or first-pass extraction in the gut was greater. In an attempt to increase oral exposure, the pharmacokinetics and oral bioavailability of two potential prodrugs of 1, an N-ethyl [(R)-N-[4-[2-[ethyl[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]phenyl]-4-[4-[4-(trifluoromethyl)phenyl]thiazol-2-yl]benzenesulfonamide; 2] and a morpholine derivative [(R)-N-[4-[2-[2-(3-pyridinyl)morpholin-4-yl]ethyl]phenyl]-4-[4-[4-(trifluoromethyl)- phenyl]thiazol-2-yl]benzenesulfonamide; 3], were evaluated in monkeys. Conversion to 1 was low (<3%) with both derivatives, and neither entity was an effective prodrug, but the oral bioavailability of 3 (56%) compared with 1 (4%) was significantly improved. The hypothesis that the increased oral bioavailability of 3 was due to a reduction in hydrogen bonding sites in the molecule led to the design of (R)-N-[4-[2-[[2-hydroxy-2-(pyridin-2-yl)ethyl]amino]ethyl]phenyl]-4-[4-(4-trifluoromethylphenyl)thiazol-2-yl]benzenesulfonamide (4), a 2-pyridyl beta3-adrenergic receptor agonist with improved oral bioavailability in rats and monkeys.

Administration, Oral↗
PubMed1979

3-Chloro-4-(phenylsuccinimido)-benzenesulfonamide (GS 385), a new anticonvulsant: its quantitative determination, pharmacokinetics and metabolism using high performance liquid chromatography.

A high-performance liquid chromatographic method (HPLC) involving dual wave length detection was developed for the determination of a new anticonvulsant, 3-chloro-4-(phenylsuccinimido)-benzenesulfonamide (suclofernide, GS 385, Sulfalepsin), and three of its metabolites: 3-chloro-4-(p-hydroxyphenylsuccinimido)-benzenesulfonamide (I), 3-chloro-4-(3'-phenylsuccinamyl)-benzenesulfonamide (II) and 3-chloro-4-(2'-phenylsuccinamyl)-benzenesulfonamide (III). The concentrations of GS 385 in blood samples from epileptic patients under chronic treatment with this drug was found in the range of 8--11 micrograms/ml. Pharmacokinetic curves of GS 385 blood levels in rats receiving single doses of the drug showed a maximum concentration of 22--23 micrograms/ml 1.5 h after oral application. The quantity of GS 385 in rat feces, bile and brain was also estimated. The p-hydroxy (I) and acid (II, III) metabolites of GS 385 were detected in both rat feces and bile, whereas only the acid metabolites were found in rat urine.

Animals↗
PubMed2003

Synthesis and cyclooxygenase-2 inhibiting property of 1,5-diarylpyrazoles with substituted benzenesulfonamide moiety as pharmacophore: Preparation of sodium salt for injectable formulation.

A series of 1,5-diarylpyrazoles having a substituted benzenesulfonamide moiety as pharmacophore was synthesized and evaluated for cyclooxygenase (COX-1/COX-2) inhibitory activities. Through SAR and molecular modeling, it was found that fluorine substitution on the benzenesulfonamide moiety along with an electron-donating group at the 4-position of the 5-aryl ring yielded selectivity as well as potency for COX-2 inhibition in vitro. Among such compounds 3-fluoro-4-[5-(4-methoxyphenyl)-3-trifluoromethyl-1H-1-pyrazolyl]-1-benzenesulfonamide 3 displayed interesting pharmacokinetic properties along with antiinflammatory activity in vivo. Among the sodium salts tested in vivo, 10, the propionyl analogue of 3, showed excellent antiinflammatory activity and therefore represents a new lead structure for the development of injectable COX-2 specific inhibitors.

Animals↗
PubMed1997

Synthesis and biochemical evaluation of N-(4-phenylthiazol-2-yl)benzenesulfonamides as high-affinity inhibitors of kynurenine 3-hydroxylase.

In this paper we describe the synthesis, structure-activity relationship (SAR), and biochemical characterization of N-(4-phenylthiazol-2-yl)benzenesulfonamides as inhibitors of kynurenine 3-hydroxylase. The compounds 3,4-dimethoxy-N-[4-(3-nitrophenyl)thiazol-2-yl]benzenesulfonamide 16 (IC50 = 37 nM, Ro-61-8048) and 4-amino-N-[4-[2-fluoro-5-(trifluoromethyl)phenyl]-thiazol-2-yl] benzenesulfonamide 20 (IC50 = 19 nM) were found to be high-affinity inhibitors of this enzyme in vitro. In addition, both compounds blocked rat and gerbil kynurenine 3-hydroxylase after oral administration, with ED50's in the 3-5 mumol/kg range in gerbil brain. In a microdialysis experiment in rats, 16 dose dependently increased kynurenic acid concentration in the extracellular hippocampal fluid. A dose of 100 mumol/kg po led to a 7.5-fold increase in kynurenic acid outflow. These new compounds should allow detailed investigation of the pathophysiological role of the kynurenine pathway after neuronal injury.

Animals↗
PubMed1991

Isolation and characterization of cDNA clones for RNA species induced by substituted benzenesulfonamides in corn.

A search of compounds capable of inducing specific gene expression in plants without affecting growth and development led to the examination of changes in the pattern of gene expression in corn after treatment with substituted benzenesulfonamide herbicide safeners. Following hydroponic treatment of corn with the safener N-(aminocarbonyl)-2-chlorobenzenesulfonamide (2-CBSU), the specific induction of new translatable mRNA species was observed. Replicate copies of a cDNA library made using RNA from 2-CBSU-treated corn roots were differentially screened with cDNA probes made from either the same mRNA fraction used for library construction or mRNA isolated from roots treated with 2-chlorobenzenesulfonamide (2-CBSA), an inactive analog of the safener. Colonies showing hybridization only with the probe made using mRNA from 2-CBSU-treated roots were further characterized to assess the specificity of the induction and decay of the corresponding induced RNA species. RNA blot analyses showed two clones, designated In2-1 and In2-2, contained plasmids that hybridized to RNAs that were induced from an undetectable background in corn roots within 30 minutes after treatment with 2-CBSU. Leaf and meristem tissues showed similar inductions of the In2-1 and In2-2 RNA species after a delay of several hours. In addition, both RNA species were induced in corn by foliar application of 2-CBSU. In contrast, neither RNA species was induced following stress treatments of plants. These results indicate a substituted benzenesulfonamide safener might be used with the promoters from the In2-1 and In2-2 genes to develop a new inducible gene expression system for plants.

Amino Acid Sequence↗
PubMed2005

Carbonic anhydrase inhibitors: X-ray crystal structure of a benzenesulfonamide strong CA II and CA IX inhibitor bearing a pentafluorophenylaminothioureido tail in complex with isozyme II.

N-1-(4-Sulfamoylphenyl)-N-4-pentafluorophenyl-thiosemicarbazide was prepared by the reaction of 4-isothiocyanato-benzenesulfonamide with pentafluorophenyl hydrazine, and proved to be an effective inhibitor of several isozymes of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1), such as CA I, II, and IX. Against the physiologically relevant isozymes hCA II and hCA IX, the compound showed inhibition constants in the range of 15-19 nM, whereas it was less effective as a hCA I inhibitor (K(I) of 78 nM). The high-resolution X-ray crystal structure of its adduct with hCA II showed the inhibitor to bind within the hydrophobic half of the enzyme active site, making extensive and strong van der Waals contacts with amino acid residues Gln92, Val121, Phe131, Leu198, Thr200, Pro202, in addition to the coordination of the sulfonamide nitrogen to the Zn(II) ion of the active site, and participation of the SO(2)NH(2) group to a network of hydrogen bonds involving residues Thr199 and Glu106. These results are helpful for the design of better CA II or CA IX inhibitors based on the thioureido-benzenesulfonamide motif, with potential applications as anti-glaucoma or anti-cancer drugs.

Amino Acids↗
PubMed1991

Synthesis and biological evaluation of substituted benzenesulfonamides as novel potent membrane-bound phospholipase A2 inhibitors.

A novel series of 4-[N-methyl-N-[(E)-3-[4-(methylsulfonyl)phenyl]-2- propenoyl]amino]benzenesulfonamides has been prepared and evaluated as membrane-bound phospholipase A2 inhibitors. A structure-activity relationship study indicated that the optimum potency was realized with the N-(phenylalkyl)piperidine derivatives 3 and 4. These compounds inhibited the liberation of arachidonic acid from the rabbit heart membrane fraction with IC30 values of 0.028 and 0.009 microM, respectively. Several compounds (3, 4, and 28), which proved to be potent inhibitors in vitro, significantly reduced the size of myocardial infarction in coronary occluded rats by iv administrations prior to the ligation. N-(1-Benzyl-4-piperidinyl)-4-[N-methyl-N-[(E)-3-[ 4-(methylsulfonyl)phenyl]-2-propenoyl]amino]-benzenesulfonamide (3, ER-3826), which showed the protective in vivo effects at doses higher than 0.3 mg/kg iv, was finally chosen as a leading candidate.

Animals↗
PubMed2006

Molecular structure and conformations of benzenesulfonamide: gas electron diffraction and quantum chemical calculations.

The molecular structure and conformational properties of benzenesulfonamide, C6H5SO2NH2, were studied by gas electron diffraction (GED) and quantum chemical methods (MP2 and B3LYP with different basis sets). The calculations predict the presence of two stable conformers with the NH2 group eclipsing or staggering the SO2 group. The eclipsed form is predicted to be favored by about 0.5 kcal/mol. According to GED, the saturated vapor over solid benzenesulfonamide at a temperature of 150(5) degrees C consists of the eclipsed conformer. The GED intensities, however, possess a very low sensitivity toward the vapor composition, and contributions of the anti conformer of up to 75% (at the 0.05 level of significance) or up to 55% (at the 0.25 level of significance) cannot be excluded. The molecule possesses C(sS) symmetry with the S-N bond perpendicular to the ring plane.

Electrons↗
PubMed2001

QSAR of antineoplastics IV: Hansch analysis of N-(7-indolyl)benzenesulfonamides against KB human nasopharynx carcinoma, colon 38 murine adenocarcinoma and P388 murine leukemia cell lines.

Hansch analysis of recently reported antitumor activities of novel N-(7-indolyl)benzenesulfonamide derivatives against KB human nasopharynx carcinoma, colon 38 murine adenocarcinoma and P388 murine leukemia cell lines reveals that the pattern of receptor interactions in human KB cells differs from that in murine (colon 38 and P388 leukemia) cells. The latter two activities are autocorrelated and show similar receptor specificity. It seems that two binding sites, one interacting with the indole fragment and another with phenyl fragment of the indolylbenzenesulfonamide compounds, are present on the murine cell receptors (colon 38 and P388 leukemia) while only the latter binding site is active on the human KB cell receptors. For the activity against KB cells, a para-methyl or paramethoxy substituent on the phenyl ring of benzenesulfonamide moiety greatly enhances the activity. For the other two activities, a 3-chloro or 3-cyano substituent on indole nucleus enhances activities, while presence of bulkier meta or para substituent on the phenyl ring decreases activities. Presence of an ortho substituent on the phenyl ring appears to be detrimental for all the three activities. Equations generated by both QSAR and QAAR studies are quite robust as evidenced from cross-validation by 'leave-one-out' technique.

Adenocarcinoma↗
PubMed1977

Reactions of benzenesulfonohydrazides and benzenesulfonamides with hydrogen chloride or hydrogen bromide in acetic acid.

Benzenesulfonohydrazides capable of yielding a sulfinic acid intermediate by virtue of a basic nitrogen atom in the second position of the hydrazide moiety produced thiosulfonates when treated with 1 N hydrogen chloride in acetic acid and produced disulfides when treated with 1 N hydrogen bromide in the same solvent. In two cases, a crystalline mixture of P-nitrophenyl p-nitrobenzenethiosulfonate and bis(p-nitrophenyl) disulfide was isolated from the hydrogen chloride reactions. No reaction product was obtained from either the hydrogen chloride or hydrogen bromide reaction with benzenesulfonohydrazides that were unable to form a sulfinic acid intermediate. Reduction of benzenesulfonamides to disulfides appeared to be possible only with hydrogen bromide in acetic acid. No thiosulfonate was isolated from the treatments of benzenesulfonamides with 1 N hydrogen chloride in acetic acid. p-Nitrophenyl p-nitrobenzenethiosulfonate and p-bromophenyl p-bromobenzenethiosulfonate exhibited some antimicrobial activities against Gram-positive bacteria. The latter compound also showed analgesic properties in the phenylquinone test.

Acetates↗
PubMed2006

Carbonic anhydrase inhibitors. Selective inhibition of human tumor-associated isozymes IX and XII and cytosolic isozymes I and II with some substituted-2-mercapto-benzenesulfonamides.

A series of 2-mercapto-substituted-benzenesulfonamides has been prepared by a unique two-step procedure starting from the corresponding 2-chloro-substituted benzenesulfonamides. Compounds bearing an unsubstituted mercapto group and the corresponding S-benzoyl derivatives were investigated as inhibitors of four isoforms of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1), i.e., the cytosolic, ubiquitous isozymes CA I and II, as well as the transmembrane, tumor associated isozymes CA IX and XII. These derivatives were medium potency hCA I inhibitors (K(I)s in the range of 1.5-5.7 microM), two derivatives were strong hCA II inhibitors (K(I)s in the range of 15-16 nM), whereas the others showed weak activity. These compounds inhibited hCA IX with inhibition constants in the range 160-1950 nM and hCA XII with inhibition constants in the range 1.2-413 nM. Some of these derivatives showed a certain degree of selectivity for inhibition of the tumor-associated over the cytosolic isoforms, being thus interesting leads for the development of potentially novel applications in the management of hypoxic tumors which overexpress CA IX and XII.

Carbonic Anhydrase Inhibitors↗
PubMed2001

Two isomorphous benzenesulfonamide crystal structures determined by intermolecular C-H...O, C-H...pi and C-H...Cl interactions.

The title compounds, N-[5-(4-chlorophenyl)furan-2-ylmethyl]-4-methyl-N-(prop-2-ynyl)benzenesulfonamide, (Ia), and N-[5-(2-chlorophenyl)furan-2-ylmethyl]-4-methyl-N-(prop-2-ynyl)benzenesulfonamide, (Ib), both C(21)H(18)ClNO(3)S, have isomorphous crystal structures. The crystal packing is mainly determined by intermolecular C-H...O and C-H...pi interactions. These interactions are very similar in (Ia) and (Ib). Additional intermolecular C-H...Cl interactions appear less important and are different in (Ia) and (Ib). The different positions of the Cl atoms result in small variations of the crystal packing of the two compounds.

Journal Article↗
PubMedDate not supplied

The isolation and identification of 14C-sulfamethazine (4-amino-n-(4,6-dimethyl-2-pyrimidinyl)[14C]benzenesulfonamide) metabolites in the tissues and excreta of swine.

Pigs were given a single oral dose of 14C-sulfamethazine (4-amino-N(I4,6-dimethyl-2-pyrimidinyl)[14C]benzenesulfonamide). Approximately 78% of the 14C was eliminated in the urine and 18% was eliminated in the feces within 192 hr after dosing. The percentage of the 14C remaining in the animals after dosing was as follows: 6 hr, 88%; 24 hr, 49%; 48 hr, 14%; 192 hr, less than 1%. The 14C-labeled compounds in the tissues and excreta were isolated by solvent extraction and by conventional and high-pressure liquid chromatography, and then derivatized and characterized by infrared and mass-spectral analysis. Chemical structures were confirmed by synthesis. The major 14C-labeled compounds in the skeletal muscle, liver and kidney were identified as sulfamethazine, N4-acetylsulfamethazine, the N4-glucose conjugate of sulfamethazine, and N-(4,6-dimethyl-2-pyrimidinyl)benzenesulfonamide (desaminosulfamethazine). The major 14C-labeled compounds in the urine and feces were identified as sulfamethazine and N4-acetylsulfamethazine.

Animals↗