13947-20-1Relevant articles and documents
Mixed ligand palladium(II) complexes of N-hydroxy-methylsaccharin (Sac-CH2OH): Synthesis, characterization and biological studies
Al-Jibori, Subhi A.,Al-Janabi, Ahmed S.,Basak-Modi, Sucharita,Mohamed, Samar S.,Schmidt, Harry
, p. 917 - 921 (2015)
Reaction of Na2PdCl4 with two equivalents of N-hydroxymethylsaccharin (Sac-CH2OH) in the presence of NEt3 afforded trans-[Pd(κ2-Sac-CH2O)2]. Further reaction of [Pd(κ2-Sac-CH2O)2] with one equivalent of diphosphine (L2), Ph2P(CH2) n PPh2, (n = 1, dppm; 2, dppe and 3, dppp), Ph2P(S)(CH2)P(S)Ph2 (dppmS2) or Ph2P(O)(CH2)2P(O)Ph2 (dppeO2) afforded mixed ligand complexes [Pd(κ1-Sac-CH2O)2(L2)], while reaction with two equivalents of Ph3P, Ph3PO or Ph3PS (L) gave trans-[Pd(κ1-Sac-CH2O)2(L)2]. The N-hydroxymethylsaccharinate anion acts as a monodentate ligand, coordinating to the palladium center through the hydroxymethyl oxygen atom. The complexes were characterized by physico-chemical and spectroscopic methods. In addition, the free ligand N-hydroxymethylsaccharin and some of the complexes were screened in vitro for antibacterial activity.
Synthesis, antimycobacterial and antitumor activities of new (1,1-dioxido-3-oxo-1,2-benzisothiazol-2(3H)-yl)methyl N,N-disubstituted dithiocarbamate/O-alkyldithiocarbonate derivatives
Guezel, Oezlen,Salman, Aydin
, p. 7804 - 7815 (2006)
Reaction of 2-chloromethylsaccharin with substituted potassium dithiocarbamates and substituted potassium dithiocarbonates furnished (1,1-dioxido-3-oxo-1,2-benzisothiazol-2(3H)-yl)methyl N,N-disubstituted dithiocarbamates (4-15) and (1,1-dioxido-3-oxo-1,2-benzisothiazol-2(3H)-yl)methyl O-alkyldithiocarbonates (16-20). The new derivatives were evaluated for in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv. Compounds 4-13, 15, and 16-20 described herein showed moderate to good inhibitory activity. In particular, seven analogs 4, 5, 6, 13, and 7, 8, and 12 exhibited excellent MIC values of 1.56 and 0.78 μg/mL, respectively. Compounds 4, 5, 10, 12, 13, and 16 were selected and screened for antitumor activity. Among the tested compounds, 4 and 5 were found to be cytotoxic, especially against leukemia cell lines CCRF-CEM, HL-60(TB), RPMI-8226, and SR with log10 GI50 values lower than -6.69, and against non-small cell lung cancer NCI-H522 cell line with log10 GI50 values lower than -6.31. Compound 10 was cytotoxic against leukemia cell line HL-60(TB), whereas 16 displayed favorable cytotoxicity against ovarian cancer cell line OVCAR-3 with log10 GI50 values of -6.31 and -7.45, respectively.
A prodrug approach to increasing the oral potency of a phenolic drug. 1. Synthesis, characterization, and stability of an O-(imidomethyl) derivative of 17β-estradiol
Patel,Prankerd,Sloan
, p. 1477 - 1481 (1994)
An O-(saccharinylmethyl) prodrug was synthesized to improve the poor oral potency of the phenolic drug 17β-estradiol. This O-(imidomethyl) type of prodrug was designed to undergo chemical hydrolysis and to be a poor substrate for enzymatic hydrolysis. At 37 °C, it was found to exhibit half- lives of about 13 min in 50% methanol:pH 7.0 (v/v) phosphate buffer, about 3 min in rat plasma, about 15 min in human plasma, and about 50 min in 20% rat liver homogenate. Introduction of the enzyme poison tetraethyl pyrophosphate or the protein denaturant sodium fluoride into rat plasma had no significant effect on the half-life. Thus, the observed increased rate of hydrolysis in biological media is not due to enzymatic catalysis but to a nonspecific solventlike effect. The fact that the rate of hydrolysis in the methanol:buffer exhibited a first-order dependence on the hydroxide ion concentration and that the rate of hydrolysis increased with increasing methanol concentrations up to 70% supported an S(N)2 mechanism of hydrolysis for the prodrug. These results suggest that an O-(imidomethyl) type prodrug is insensitive to enzymatic catalysis of hydrolysis yet may hydrolyze quickly enough to release 17β-estradiol faster than 17β-estradiol is conjugated and excreted.
NMR study of the tautomeric behavior of N -(α-Aminoalkyl)tetrazoles
Katritzky, Alan R.,El-Gendy, Bahaa El-Dien M.,Draghici, Bogdan,Hall, C. Dennis,Steel, Peter J.
scheme or table, p. 6468 - 6476 (2010/12/24)
N-(α-Aminoalkyl)tetrazoles exist in solution as equilibrium mixtures of N1 and N2 tautomers. The position of equilibrium depends significantly on the polarity of the solvent and the substituents in the tetrazole ring. Interconversion between individual tautomers is shown to proceed via tight ion-pair intermediates in which intramolecular recombination is faster than the intermolecular crossover since the latter probably requires solvent separation of ion-pair intermediates.
Facile one-pot synthesis of 4-hydroxy-2-methyl-(2H)-1,2-benzothiazine-3- sulfonic acid 1,1-dioxide
Siddiqui, Waseeq A.,Ahmad, Saeed,Khan, Islam Ullah,Siddiqui, Hamid Latif,Weaver, George W.
, p. 767 - 773 (2007/10/03)
We report a convenient synthesis of 4-hydroxy-2-methyl-(2H)-1,2- benzothiazine-3-sulfonic acid-1,1-dioxide (6a) prepared in a novel one-pot reaction. The synthesis involves two transformations starting from 2-methyl-2H-1,2-benzothiazin-4-(3H)-one 1,1-dioxide (7) with an overall yield better than that from the stepwise process, as well as the alternate procedure starting from saccharin (1). One-pot synthesis of an important intermediate, saccharin-N-methane sulfonic acid (4), is also described. Copyright Taylor & Francis Group, LLC.
Synthesis of soft alkyl phenolic ether prodrugs using Mitsunobu chemistry
Majumdar, Susruta,Juntunen, Juha,Sivendran, Sashi,Bharti, Neelam,Sloan
, p. 8981 - 8982 (2007/10/03)
The synthesis of soft alkyl phenolic ether prodrugs in excellent yields has been reported by coupling a phenol with a hydroxymethylimide using Mitsunobu chemistry. The imides used in this study include saccharin, phthalimide, succinimide and two other compounds containing acidic imide-like N-H groups, benzotriazole, and imidazole.
Mechanism of Hydrolysis of O-Imidomethyl Derivatives of Phenols
Getz, John J.,Prankerd, Richard J.,Sloan, Kenneth B.
, p. 4913 - 4918 (2007/10/02)
Three series of O-imidomethyl derivatives of para-substituted phenolic compounds were synthesized and their rates of hydrolysis were studied.Saccharin, phthalimide, and succinimide served as the imide portions of the derivatives.Their rates of hydrolysis were found to be first order with respect to hydroxide from pH 7.0 to 10 or 11 and dependent on the acidity (leaving group potential) of both the imide and the phenol portions.The more acidic the imide or the phenol, the faster the rate of hydrolysis.However, the rates of hydrolysis were more sensitive to the acidity of the phenol.Trapping experiments with cyanide also suggested that the phenol anion was functioning as the leaving group in what is apparently an SN2 reaction.An amide derivative was found to hydrolyze more slowly than predicted from the analogous series and the pKa of the amide.This result is apparently due partially stereoelectronic constraints in the imide series that cause the CH2-O bond to be oriented more nearly perpendicular to the plane of the C(=O)N group and hence more accessible to nucleophilic attack.
Reaction of N-Hydroxymethylsaccharin with Aliphatic Carboxylic Acid Derivatives: Synthesis of N-Acylsaccharins and N-(Saccharinylmethyl) Aliphatic Carboxylates
Choi, Sam-Young,Lee, Sang-Gyeong,Yoon, Yong-Jin,Kim, Kyu-Wan
, p. 1073 - 1076 (2007/10/02)
N-Acylsaccharins and N-(saccharinylmethyl)aliphatic carboxylates were synthesized from N-hydroxymethylsaccharin and aliphatic carboxylic acid chlorides (or anhydrides).
Synthesis and Antibacterial Activity of 2,2'-Dithiobis(benzamide) Derivatives against Mycobacterium Species
Okachi, Ryo,Niino, Hideki,Kitaura, Kozo,Mineura, Kazuyuki,Nakamizo, Yoshinobu,et al.
, p. 1772 - 1779 (2007/10/02)
A series of compounds, which are analogues of 2,2'-dithiobis(benzamide), were synthesized and tested for in vitro antibacterial activity against Mycobacterium tuberculosis H37Rv including resistant strains against streptomycin, kanamycin, or isonicotinic acid hydrazide.MICs of these compounds against a typical mycobacteria, Mycobacterium kansasii and Mycobacteruim intracellulare were also examined.Structure-activity relationships were found in a series of (acyloxy)alkyl ester derivatives depending upon the length of alkyl carbon chain.The MIC of the most potent compound , 2,2'-dithiobisbenzamide> was superior or at least equivalent to streptomycin, kanamycin, and ethanbutol.All the compounds showed no cross-resistance between the current antitubercular agents.
