| S-2,omega-Diaminoalkyl dihydrogen phosphorothioates as antiradiation agents. | |
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MedLine Citation:
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PMID: 458819 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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J R Piper; L M Rose; T P Johnston; M M Grenan |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
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Title: Journal of medicinal chemistry Volume: 22 ISSN: 0022-2623 ISO Abbreviation: J. Med. Chem. Publication Date: 1979 Jun |
Date Detail:
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Created Date: 1979-09-17 Completed Date: 1979-09-17 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9716531 Medline TA: J Med Chem Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 631-9 Citation Subset: IM |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cesium Radioisotopes Dose-Response Relationship, Drug Gamma Rays Methods Mice Organothiophosphorus Compounds / chemical synthesis*, pharmacology Radiation-Protective Agents / chemical synthesis* Stereoisomerism Structure-Activity Relationship |
| Chemical | |
Reg. No./Substance:
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0/Cesium Radioisotopes; 0/Organothiophosphorus Compounds; 0/Radiation-Protective Agents |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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