Antiradiation Agents Research Articles

Synthesis and radioprotective properties of 2-arylethylammonium salts of sulfinic acids

The synthesis of new aliphatic analogs of the 2-phenylethylammonium salt of 2-phenylethylamide of o-sulfinobenzoic acid was accomplished. This furthered the study of the influence of sulfinic acid on anti-radiation activity and the search for more effective anti-radiation agents. Various compounds were synthesized, including fluorinated salts and unfluorinated analogs for comparitive tests. The toxicity of the compounds investigated was studied using white hybrid mice. It was determined that the combination of 1,2-oxathiolan-5-on-2-oxides with arylethylamines permits a decrease in the toxicity of the latter with the retention (or increase) of their radioprotective activity. Among the alkanesulfinates studied, the most promising anti-radiation compounds are C-arylethylamides based on isobutyric acid. 5 refs., 2 tabs.

Preliminary Study on Antiradiation Effect of Kuei-Pi-Tang

In order to evaluate the potential action of Kuei-Pi-Tang as an antiradiation agent, colony forming units of bone marrow cells in the spleen (CFUs) were used. Different sequences of X-ray irradiation with or without Kuei-Pi-Tang administration in the groups of ICR strain mice were intraperitoneally injected 10mg/20g or 20mg/20g, once a day, for consecutive seven days before or after 4Gy X-ray irradiation. After the different treatments, whole blood was collected from the tail endings to observe the fluctuation of leukocytes, erythrocytes and thrombocytes. The administration of 20mg/20g was more effective than that of 10mg/20g. Lower radiosensitivity was observed with the treatment of 20mg/20g of Kui-Pi-Tang than that of 10mg/20g. The injection of Kuei-Pi-Tang accelerated the recovery of blood cell counts of leukocytes, erythrocytes and thrombocytes in mice irradiated with 4Gy, especially for leukocytes under the treatments with 20mg/20g of Kuei-Pi-Tang administered after irradiation.

ChemInform Abstract: Sulfinic Acids and Related Compounds. Part 22. Derivatives of 2‐Hydroxyethanesulfinic Acid.

AbstractIn order to develop a convergent synthesis of antiradiation agents the disulfide (VII), which has modest stability, is produced via the relatively stable sulfinate salt (V) (purity ca. 83‐95%).

S-[2-[(2'-carbamoylethyl)amino]ethyl] phosphorothioate and related compounds as potential antiradiation agents

A reinvestigation of the radiation protection activity of S-[2-[(2'-carbamylethyl)amino]ethyl] lithium hydrogen phosphorothioate (4a) revealed that this compound possessed good (70% protection at a dose of 600 mg/kg) activity. The thione and imino bioisosteres of 4, S-[2-(2'-thiocarbamylethylamino)ethyl] lithium hydrogen phosphorothioate (13a) and S-[2-(2'-amidinoethylamino)ethyl] phosphorothioic acid (18b) showed 100% protection at doses of 300 and 150 mg/kg, respectively. The N-methyl (4b) and tert-butyl (4c) analogues of amide 4a, the N-methyl (13b) analogue of the thioamide 13a, the N-methyl (18a) analogue of amidine (18b), and the cyclic amidine S-[2-[[2'-(4,5-dihydroimidozoyl)ethyl]amino]ethyl] lithium hydrogen phosphorothioate (21) all showed 80% protection at the highest dose tested.

Synthesis of S-phosphinylmethylisothioureas and an evaluation of their radioprotective activity

A large number of various S-derivatives of thiourea exhibit the property of elevating an organism's resistance to radioactivity [i0, ii]. Therefore the search for effective radioprotective agents among the isothiourea salts has been proceeding quite actively [13]. Noted with interest is the fact that phosphorus compounds, mainly derivatives of thiophosphoric, phosphoric, and phosphonic acids, also appear to be antiradiation agents [8, ii, 13]. At the same time, the radioprotective activity of phosphine oxides has not been investigated although in a number of cases they are known to be less toxic than other phosphorus compounds [12].

Activité radioprotectrice chez la Souris de composés thiazolidiniques dérivés de la cystéamine et de la mercapto-2 propylamine

2- and 2,5-substituted thiazolidine derivatives have been evaluated as potential anti-radiation agents in mice. Comparison with anti-radiation agent controls, shows the interest of this series: good activity at low doses ( LD 50 1 8 ), low toxicity and duration of the radioprotective effects varied according to the compound. Some thiazolidines are more active at low doses than the equimolecular quantity of cysteamine they release in vivo.

Effect of aromatic additives on the radiation resistance of ethylene-propylene-dieneterpolymer studied by optical emission spectroscopy of both steady-state and picosecond pulse radiolysis

To clarify the effect of aromatic additives (acenaphthene and acenaphthylene) on the radiation resistance of ethylene-propylene-diene-terpolymer (EPDM), pathways of transfer of radiation- induced excitation energy from polymer matrix to aromatic molecules have been studied by picosecond pulse radiolysis and steady-state electron beam irradiation. The energy absorbed by polymer matrix is transfered to the aromatic molecules very fast within 1 ns. The fluorescence of acenaphtene with peaks at 337 and 350 nm (named At emission band) was observed in EPDM containing acenaphthene. When dicumyl peroxide (DCP) was used as a crosslinking agent instead of di-t-butyl peroxide (DBP), another emission band (named Xn band) was observed at 400 nm. Xn band is considered to be due to the reaction species between DCP and naphthalene ring of the aromatic additives. It is found that the Xn band plays an important role in the energy transfer process in polymer matrix. When acenaphthylene was added instead of acenaphthene, excimer fluorescence (named Ex band) was observed at 450 nm. The energy level of the excimer is lower than that of the excited state of the oxidized portion of polymer with the emission peak at 420 nm (named P = O band); the intensity of the P = O emission is considered to be a measure of radiation induced degradation of EPDM. Acenaphthylene is more effective as an antiradiation agent than acenaphthene. It is considered to be due to the fact that deeper trapping sites of excitation energy are produced in polymer chains of grafted acenaphthylenes onto EPDM.

Synthesis of 4‐piperidazinethiols as potential antiradiation agents

AbstractThe free radical addition of thioacetic acid to 1,2‐dicarbethoxy‐1,2,3,6‐tetrahydropyridazines gave high yields of 1,2‐dicarbethoxy‐4‐S‐thiolacetoxypiperidazines. The latter compounds served as the key intermediates in the preparation of 4‐piperidazinethiols. The thiolacetoxy derivatives were partially hydrolyzed to afford the related 1,2‐dicarbethoxy‐4‐piperidazinethiols. Complete hydrolysis of the thiolacetates gave rise to 4‐piperidazinethiols. Finally, lithium aluminum hydride reduction of the thiolacetoxy esters produced a series of 1,2‐dimethyl‐4‐piperidazinethiols. Only 4‐piperidazinethiol hydrochloride showed appreciable anti‐radiation activity.

1,2-Dialkyl-4-Pyrazolidinethiols as Potential Antiradiation Agents

The reaction between 3-chloropropylene sulfide and the 1,2-dialkylhydrazines was employed to prepare a series of 1,2-dialkyl-4-pyrazolidinethiols. Evidence is presented to support the structure proposed for the product. These mercaptoheterocycles are related to the β-mercaptoethylamines and were prepared as potential radiation protective agents. No significant activity was observed.

S-2,.omega.-Diaminoalkyl dihydrogen phosphorothioates as antiradiation agents

To enable further structure-activity comparisons among radioprotective phosphorothioates, S-2,omega-diaminoalkyl dihydrogen phosphorothioates were synthesized from L-2,4-diaminobutyric acid, L-ornithine, L-lysine, and DL-2,7-diaminoheptanoic acid as homologues of S-2,3-diaminopropyl dihydrogen phosphorothioate (4) and as isomeric analogues of S-2-[(omega-aminoalkyl)amino]ethyl dihydrogen phosphorothioates (e.g., 1). The preferred route that evolved from exploratory trials retained optical activity and involved the reduction of methyl 2,omega-bis(benzoylamino)alkanoates with lithium borohydride, debenzoylation-bromodehydroxylation, and reaction of the resulting 1-(bromomethyl)-1,omega-alkanediamine dihydrobromides with trisodium phosphorothioate. The products of an alternative route that involved the reduction of phthaloylated intermediates with sodium borohydride were racemic. Exploratory conversions of N-(omega-alkenyl)phthalimides failed to provide suitable precursors of the target compounds. In terms of a protective index, these homologues were significantly more radioprotective than the parent phosphorothioate 4 when administered intraperitoneally to mice prior to whole-body gamma irradiation. The homologues derived from L-lysine also showed good peroral activity. No apparent difference was observed in the protection afforded by optically active homologues and the corresponding racemates.

Conformational Studies of Antiradiation Agents by NMR: Cysteamine and Its Derivatives

The conformations of cysteamine, thiazolidine, and thiazolidine-4-carboxylic acid were determined in aqueous solutions using NMR spectroscopy. At physiological pH, the population ratio of gauche- and trans-conformers was 3:1. The gauche-rotamer is probably responsible for the antiradiation activity and acts through metal chelation involving sulfur and nitrogen atoms. The puckering of the thiazolidine ring was calculated using NMR coupling constants. The observed results were compared with those obtained in the solid state using X-ray diffraction.

Hydroxy derivates of S-2-(3-aminopropylamino)ethyl dihydrogen phosphorothioate and related compounds as antiradiation agents.

The high antiradiation activity and low toxicity of sodium 3-amino-2-hydroxypropyl hydrogen phosphorothioate (1) suggested the introduction of hydroxyl groups into other types of radioprotective phosphorothioates. A number of such compounds were synthesized, including S-3-(3-aminopropylamino)-2-hydroxypropyl dihydrogen phosphorothioate (11, n equals 3), S-2-(3-amino-2-hydroxypropylamino)ethyl dihydrogen phosphorothioate (20) and its propyl homolog 26, N,N'-(2-hydroxytrimethylene)bis(S-2-aminoethyl dihydrogen phosphorothioate) (40), S-2-[3-(2-hydroxyethylamino)propylaminoi1ethyl dihydrogen phosphorothioate (44), and sodium S-2-amino-2-(hydroxymethyl)-3-hydroxypropyl hydrogen phosphorothioate (49). Compounds 11 (n equals 3), 20, 26, and 49 were highly protective when administered intraperitoneally but were generally ineffective when given perorally, as were the other hydroxylated phosphorothioates prepared. The introduction of hydroxyl groups significantly enhanced the radioprotective properties of nonhydroxylated parent compounds, however, only in the case of intraperitoneally administered.

Nomega-(2-mercaptoethyl) derivatives of ornithine and lysine as antiradiation agents.

Nomega-(2-mercaptoethyl) derivatives of ornithine and lysine as antiradiation agents.

Antiradiation agents. Substituted 2-pyridyloxy and 2-quinolyloxy derivatives of S-2-(ankylamino)ethyl hydrogen thiosulfates and 3-alkylthiazolidines and substituted 2-pyridyloxy derivatives of 2-(alkylamino)ethanethiols and corresponding disulfides.

Substituted 2-pyridyloxy and 2-quinolyloxy derivatives of S- 2(alkylannino)ethyl hydrogen thiosulfates, 3-alkylthiazolidines, and substituted 2-pyridyloxy derivatives of 2- (alkylamino)ethanethiols and corresponding disulfides were synthesized as antiradiation agents by the appropriate aziridine ring-opening reactions of substituted 2-{STA(1-aziridinyl)alkyl!oxy}pyridines and -quinolines. 5Substituted 2-chloropyridines and substituted 2-chloroquinolines were prepared for heterocyclic ether-forming reactions by treatment with the Na salts of 1-aziridinealkanols to give the aziridinylalkyloxy derivatives. 5-Halo- 2-pyridyl ethers resulted in the highest antiradiation activity regardless of route of administration or type of sulfur-coveringg group. S-2- ({5-STA(5-Chloro- 2-pyridyl)oxy!-pentyl}amino)ethyl hydrogen thiosulfate and S-2- ({5-STA (3,5dichloro-2-pyridyl)oxy! pentyl}amino)ethyl hydrogen thiosulfate afforded 87% survival of mice in the 30-day test at 19 (1/12 of LD/sub 50/ dose) and 12.5 mg/ kg ip (1/14 of LD/sub 50/ dose), respectively. In view of the dearth of agents effective perorally, remarkably good radioprotection was found on oral administration of thiazolidines substituted in the 3 position with 5-halo-2- {pyridyloxypentyl or -hexyl groups; 5-chloro- and 5-iodo-2-{STA6-(3- thiazolidinyl)hexyl! oxy}pyridine hydrochlorides resulted in survival rates of 73% at 150 mg/kg po (0.25 of LD/sub 50/ dose) and 93% at 300 mg/kg po (0.5 of LD/ sub 50/ dose), respectively. (auth)

2-Mercaptoacetamidine and derivatives as antiradiation agents.

2-Mercaptoacetamidine and derivatives as antiradiation agents.

N-Alicyclic-substituted derivatives of 2-aminoethanethiol and related compounds as antiradiation agents.

N-Alicyclic-substituted derivatives of 2-aminoethanethiol and related compounds as antiradiation agents.

Syntheses of 9‐β‐D‐Ribofuranosylpurine Derivatives as Effective Antiradiation Agents

Abstract6‐(2‐Hydroxyethyl‐1, 2‐14C) amino‐9‐β‐D‐ribofuranosylpurine (I) and 6‐(2‐mercaptoethyl‐35S) amino‐9‐β‐D‐ribofuranosylpurine (II) were synthesized for the investigation of their in vivo distribution in mice. All the reaction conditions were made by non‐radioactive runs and it was found that thiol compound II was easily oxidized to form the disulfide IV in the purification procedure.

Terminal dicarboximido analogs of S-2-.omega.-aminoalkylamino)ethyl dihydrogen phosphorothioates and related compounds as potential antiradiation agents. 2. Succinimides, glutarimides, and cis-1,2-cyclohexanedicarboximides

Terminal dicarboximido analogs of S-2-.omega.-aminoalkylamino)ethyl dihydrogen phosphorothioates and related compounds as potential antiradiation agents. 2. Succinimides, glutarimides, and cis-1,2-cyclohexanedicarboximides

Terminal dicarboximido analogs of S-2-(omega-aminoalkylamino)ethyl dihydrogen phosphorothioates and related compounds as potential antiradiation agents. 1. Phthalimides and saccharins.

Terminal dicarboximido analogs of S-2-(omega-aminoalkylamino)ethyl dihydrogen phosphorothioates and related compounds as potential antiradiation agents. 1. Phthalimides and saccharins.

Alpha-amidrazonium thiosulfates as potential antiradiation agents.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT.alpha.-Amidrazonium thiosulfates as potential antiradiation agentsTomas Lee Fridinger and Jerry Earl RobertsonCite this: J. Med. Chem. 1969, 12, 6, 1114–1115Publication Date (Print):November 1, 1969Publication History Published online1 May 2002Published inissue 1 November 1969https://doi.org/10.1021/jm00306a041RIGHTS & PERMISSIONSArticle Views33Altmetric-Citations3LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (265 KB) Get e-Alerts Get e-Alerts