Mono- and bis-thiazolium salts have potent antimalarial activity

Three new series comprising 24 novel cationic choline analogues and consisting of mono- or bis (N or C-5-duplicated) thiazolium salts have been synthesized. Bis-thiazolium salts showed potent antimalarial activity (much superior to monothiazoliums). Among them, bis-thiazolium salts 12 and 13 exhibited IC(50) values of 2.25 nM and 0.65 nM, respectively, against P. falciparum in vitro. These compounds also demonstrated good in vivo activity (ED(50) 相似文献   

Kinetic aspects of the dissolution and partition of diclofenac, alclofenac and their sodium salts

The dissolution and the three-phase partition profiles, vs. time, of diclofenac, alclofenac and their sodium salts have been examined in buffered mediums. The bioavailability of these drugs appears to be mainly controlled by the dissolution. The parameters influencing the higher dissolution rates of the sodium salts relative to the free acids are briefly discussed.     

Tumour inhibitory triazenes: structural requirements for an active metabolite.

A series of aryldialkyltriazenes and some related compounds have been investigated for their anti-tumour properties. Unlike the imidazole-triazenes in clinical use, aryltriazenes are stable in light and do not undergo photodecomposition to toxic diazonium salts. Some of the triazenes investigated had good anti-tumour activity yet did not form diazonium salts under physiological conditions, implying that this pathway is not important for anti-tumour action. Evidence has been obtained that only aryltriazenes that can be metabolized in vivo to an aryl-N³-monomethyltriazene have anti-tumour properties. It was also found that the aryltriazenes were dose-schedule dependent in their anti-tumour action, probably a consequence of their short biological half-lives.     

伯喹有机酸盐的合成及其对疟疾根治作用的实验观察

作者等根据某些药物制成复盐后,可增加疗效或减低毒性,从而用酸碱反应法合成了各种伯喹的有机酸盐。经对鸡疟Plasmodium gallinaceum及鼠疟P.yoelii初筛,以伯喹3,5-二碘水杨酸盐(M 74018)疗效较好,进一步试验证明M 74018对食蟹猴疟原虫(P.cynomolgi)的组织期、对根治子孢子引起的感染以及对孢子增殖作用都有良好的作用,这些作用都比磷酸伯喹稍佳。共毒性则与磷酸伯喹相当。     

Safety, efficacy and extended duration of action of mixed amphetamine salts extended-release capsules for the treatment of ADHD

Stimulant medications have proven to be effective in reducing the core symptoms of hyperactivity, impulsivity and inattention and are considered the first line of therapy for patients with attention-deficit/hyperactivity disorder (ADHD). Mixed amphetamine salts extended-release capsules (MAS XR; Adderall XR, Shire Pharmaceuticals Group) include immediate-release pellets of mixed amphetamine salts that release the first half of the dose upon ingestion and delayed-release pellets that begin to release active drug approximately 4 h later. The MAS XR capsule contains the same 3:1 ratio of dextroamphetamine to levoamphetamine as do mixed amphetamine salts immediate-release tablets (MAS IR; Adderall), Shire Pharmaceuticals Group), and the bioavailability and pharmacokinetic profiles of MAS XR 20 mg are comparable to those with MAS IR 10 mg b.i.d. MAS XR has a rapid onset of action--within 1.5 h--and provides 12 h coverage. The efficacy, safety and extended duration of action of MAS XR have been established through clinical studies in school-age children, adolescents and adults.     

Synthesis and antimicrobial activity of potassium salts of alkylene-N,N′ bis(dithiocarbamic) acids

A series of alkylene-N,N′-bis(dithiocarbamic) acid potassium salts have been synthesized via the interaction of diamines with carbon disulfide in the presence of potassium hydroxide in an aqueous alcohol environment and their antimicrobial properties have been evaluated. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 40, No. 8, pp. 10–11, August, 2006.     

Nonsteroidal antiinflammatory agents. Part 16: Stereomeric 3-aryl-biphenylyl-hydroxy-propionic acids

As part of a wider research project on structure-activity relationships of chiral arylalkanoic acids, stereomeric aryl- biphenylyl-hydroxypropionic acids 3a-d have been prepared and their antiinflammatory activity evaluated. Diastereomeric racemic erythro- and threo-acids have been synthesized by reaction of alpha-lithiated biphenylyl-acetic acid salts with the appropriate aldehyde. They were separated, and after attribution of their relative configuration by 1H-NMR analysis, resolved. The antiinflammatory activities of the enantiomeric potassium salts were determined by the carrageenan test.     

Studies in the cyclobutanedicarboxylic acid field

Some dialkylaminoalkyl esters of-truxillic acid and their bis-quaternary salts have been synthesized, and their properties and pharmacological activity have been studied.Translated from Khimiko-Farmatsevticheskii Zhurnal, No. 4, pp. 3–8, April, 1967.     

盐类及盐基类在醋酐中的滴定

在非水溶液中的酸硷滴定,近年来得到广泛的发展和应用.研究单独以醋酐或与其他溶剂混合作溶剂以滴定盐基性化合物,最近引起了分析工作者们的注意,Riddick 认为是酸硷非水滴定中近年来发展的三大方向之一,但关于这方面的工作尚做得不多.作者等认为醋酐作为盐类及盐基类在非水溶液中滴定的溶剂,有其独到的优点,许多盐基度     

Synthesis and antiarrhythmic activity of new biologically active potassium and magnesium donors

A series of new biologically active substances have been synthesized on the basis of glutamic acid, pyridoxalphosphate, and glycerophosphate to serve as ligands for potassium, calcium, and magnesium donors. General procedures for the synthesis and physicochemical characterization of the synthesized compounds are described. The synthesized compounds showed high antiarrhythmic activity in tests on rats and rabbits. The most active compounds (glutamic acid salts) were comparable in activity with the reference drugs and panangin and asparcam. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 41, No. 12, pp. 12–15, December, 2007.     

Water-in-Oil Microemulsions Containing Medium-chain Fatty Acids/Salts: Formulation and Intestinal Absorption Enhancement Evaluation

Purpose. Water-in-oil (w/o) microemulsions have been developed which, in addition to non-ionic medium-chain glycerides, incorporate ionic lipids, primarily medium-chain fatty acids, such as caprylic (C₈) capric (C₁₀) and lauric (C₁₂) acids and their corresponding sodium salts. The absorption enhancing activity of w/o microemulsions incorporating these lipids was evaluated in the rat using Calcein (MW = 623) a water-soluble and poorly absorbed marker molecule. Methods. Phase diagrams were constructed where C₈/C₁₀ or C₁₂ fatty acids were treated as lipophilic surfactants and their sodium salts as hydrophilic ones. The anesthetised rat model was employed to evaluate Calcein absorption upon a single intraduodenal administration from a solution and the various w/o microemulsions. Results. A wide range of clear and transparent w/o microemulsions were obtained at ambient temperature either in liquid or solid form when a fixed blend of medium chain fatty acid/salt was titrated by a fixed ratio of the oil containing the oil-soluble mono- and diglycerides and deionized water or physiological saline. Upon intraduodenal administration in the anesthetised rat, the absorption of Calcein was improved from about 2% in aqueous solution up to about 37% in w/o microemulsions. Solid and liquid formulations were equally effective in improving bioavailability. The absorption enhancement activity of the fatty acids/salts followed the order C₈ C₁₀ > C₁₂. Absorption enhancement of Calcein was significantly reduced in the absence or presence of low levels of C₈/C₁₀ mono-/diglycerides. Conclusions. These results further support the use of medium-chain glycerides and fatty acids/salts in microemulsion formulations to improve intestinal absorption of water-soluble compounds.     

Investigation of “Bath Salts” Use Patterns Within an Online Sample of Users in the United States

“Bath salts” are synthetic stimulant “legal highs” that have recently been banned in the US. Epidemiological data regarding bath salts use are limited. In the present study, 113 individuals in the US reporting use of bath salts completed an anonymous, online survey characterizing demographic, experiential, and psychological variables. Respondents were more often male, 18–24 years old, and Caucasian/White with some college education. Past-year use was typically low (≤ 10 days), but marked by repeated dosing. Intranasal was the most frequently reported administration route and subjective effects were similar to other stimulants (e.g., cocaine, amphetamines). Bath salts use was associated with increased sexual desire and sexual HIV risk behavior, and met DSM-5 diagnostic criteria for disordered use in more than half of respondents. Bath salts use persists in the US despite federal bans of cathinone-like constituents. Self-reported stimulant-like effects of bath salts suggest their use as substitutes for traditional illicit stimulants. Data revealed more normative outcomes vis-à-vis extreme accounts by media and medical case reports. However, indications of product abuse potential and sexual risk remain, suggesting bath salts pose potential public health harm.     

Conformations, DNA binding parameters, and antileukemic activity of certain cytotoxic protoberberine alkaloids.

The tetrahydroprotoberberine alkaloids 5 and 7 possessing a trans-quinolizidine conformation display in vitro KB cytotoxicities in contrast to their corresponding diastereomers 4 and 6 which exist in the cis-quinolizidine conformation and are much less toxic. The DNA-binding parameters of these compounds as well as the protoberberine salts 1, 8, and 9 have been examined by equilibrium dialysis. Only the quaternary salts bind to DNA. The alcohol 5 showed low in vivo activity against leukemia P388 systems, while the quaternary salts 8 and 9 proved to be toxic to the host.     

Potent antimalarial activity of 2-aminopyridinium salts, amidines, and guanidines

We describe the design, synthesis, and antimalarial activity of 60 bis-tertiary amine, bis-2(1 H)-imino-heterocycle, bis-amidine, and bis-guanidine series. Bis-tertiary amines with a linker from 12 to 16 methylene groups were active against the in vitro growth of Plasmodium falciparum within the 10 (-6)-10 (-7) M concentration range. IC 50 decreased by 2 orders of magnitude for bis-2-aminopyridinium salts, bis-amidines, and bis-guanidines (27 compounds with IC 50 < 10 nM). Increasing the alkyl chain length from 6 to 12 methylene groups led to increased activity, while beyond this antimalarial activity decreased. Antimalarial activities appear to be strictly related to the basicity of the cationic head with an optimal p K a over 12.5. Maximal activity occurs for bis-2-aminopyridinium, two C-duplicated bis-amidines, and three bis-guanidines, with IC 50 values lower than 1 nM. In comparison to similar quaternary ammonium salts, amidinium compounds have distinct structural requirements for antimalarial activity and likely additional binding opportunities on account of their hydrogen-bond-forming properties.     

Some new alkamino esters of quinuclidine-, piperidine- and pyridinecarboxylic acids

Some new alkamino esters of quinuclidine-2-carboxylic, 1,6-dimethylpiperidine-2-carboxylic and 6-methylpyridine-2-carboxylic acid and their quaternary salts have been synthesized for pharmacological study. The methods of synthesis for some alkamino alcohols are described.Translated from Khimiko-Farmatsevticheskii Zhurnal, No. 3, pp. 48–51, March, 1967.     

Pharmacological properties of esters of 1-alkyl-2-hydroxyalkylpyrrolidine and their quaternary derivatives

A series of esters of 1-alkyl-2-hydroxyalkylpyrrolidine and their quaternary derivatives have been shown to possess significant anti-acetylcholine activity. The benzilic acid esters were the most active, followed by xanthene-9-carboxylic acid, fluorene-9-carboxylic acid and diphenylacetic acid esters in that order. The quaternary derivatives were more active than their corresponding tertiary compounds both in vivo and in vitro. The most active compound of the series tested in vivo was (1-methylpyrrolid-2-yl)methyl benzilate methiodide and was as potent as atropine. There was a progressive decrease in anti-acetylcholine activity and a proportional increase in local anaesthetic activity as the number of carbon atoms was increased from 1 to 3 in the pyrrolidyl side-chain of the tertiary salts of the benzilic acid ester series. Likewise increasing the size of the group on the nitrogen atom led to a decrease in anti-acetylcholine activity and an increase in local anaesthetic activity. Quaternization of the tertiary salts resulted in a loss of local anaesthetic activity. Most of the compounds tested possessed some antihistamine properties, while papaverine-like activity was confined to the tertiary salts only. No significant neuromuscular blocking activity was evident.     

Basic esters and amides of substituted cinnamic acids and their analogs

For comparative pharmacological studies, a series of quaternary salts of basic esters of cinnamic acid and of their derivatives, homologs, and analogs have been obtained. Among the compounds tested the highest curare-like activity was shown by the methiodides of the-dimethylaminobutyl esters of cinnamic acid and also by methoxy-and p-nitro-substituted cinnamic acids. The quaternary salts of the corresponding amides or esters containing lypophilic groups were considerably less active.Translated from Khimiko-Farmatsevticheskii Zhurnal, No. 4, pp. 20–25, April, 1967.     

Sulphonation of 2,6-dimethoxynaphthalene. Reaction mechanisms and products

Protonation and sulphonation mechanism of 2,6-DMON is described. The products of their sulphonation, the sodium and barium salts of 2,6-DMON-4-monosulphonic acid and of 2,6-DMON-4,7-disulphonic acid have been prepared and characterized.     

5124例腹泻患者临床治疗效果回顾性分析

目的:研究腹泻临床治疗方法及其效果,为腹泻的治疗提供依据。方法:对2011年中国知网学术文献总库中收录的关于腹泻临床治疗的文献进行总结,并按照国际用药调研指标体系中的特定疾病用药指标进行分类,对临床效果进行分析。结果:文献共计报道5124例腹泻治疗病例,其中使用口服补液盐1458例,占28.5%;使用止泻药1080例,占21.1%;使用抗生素996例,占19.4%;使用微生态调节剂649例,占12.7%;使用其他疗法941例,占18.4%。口服补液盐使用率明显高于另外4组,差异有统计学意义(P<0.05)。使用口服补液盐的临床总有效率最高(84.7%),其次为使用抗生素治疗,总有效率66.4%,微生态制剂以及止泻药的总有效率分别为50.5%和48.9%,口服补液盐的临床效果明显好于另外4组,差异有统计学意义(P<0.05)。结论:腹泻的治疗以口服补液盐为主,其次为止泻药和抗生素治疗,既有单独治疗方案,也有联合治疗的报道。从治疗结果上看,应用口服补液盐临床总有效率高,治疗效果好,值得在临床中广泛应用。     

Derivatives of 2-mercaptobenzenesulphonamide. VIII. Synthesis and some pharmacological properties of 1,3-dialkyl-2-(4-chloro-2-carboxyalkylthio-5-methylbenzenesulphonyl) guanidines

Synthesis of 1,3-dialkyl-2-(4-chloro-2-carboxyalkylthio-5-methylbenzenesulphonyl)guanidines (IX-XVII) and their easily soluble in water sodium (Xa-XIVa, XVIIa) or 2,6-dimethylpiperidine salts (XIb, XVIIb) have been described. The results of preliminary pharmacological examinations such as acute toxicity and influence on circulatory system have been presented.