HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

O-Phosphonatomethylcholine, its analogues, alkyl esters, and their biological activity.

Abstract
O-Phosphonatomethylcholine, an isopolar phosphocholine analogue with a phosphonomethyl ether group replacing a phosphomonoester residue, was prepared by reaction of diisopropyl 2-chloroethoxymethylphosphonate with dimethylamine followed by quaternization of the thus-obtained diisopropyl 2-dimethylaminoethoxymethylphosphonate with iodomethane; the ester groups in the quaternary intermediate were cleaved with bromotrimethylsilane. Replacement of dimethylamine in the reaction sequence by morpholine and/or pyrrolidine gave the N-methylmorpholinium or N-methylpyrrolidinium analogues of O-phosphonatomethylcholine. Reaction of O-phosphonomethylcholine monotetrabutylammonium salt with 1-bromoalkanes in acetonitrile afforded a series of the corresponding monoalkyl (C10-C16) esters. None of these compounds except for the hexadecyl ester exhibited any appreciable cytostatic activity against DU-145, H460, HT-29, or MES-SA cell lines in vitro (evaluated by 3H-Thd incorporation assay). The hexadecyl ester exhibited modest in vitro cytotoxic activity comparable to that of the anticancer drug miltefosine (hexadecyl O-phosphocholine). In vivo evaluation of hexadecyl O-phosphonomethylcholine [transplanted SD lymphoma in inbred SD/cub rats, 10 mg kg(-1) day(-1) intratumoral injection for 10 days] resulted in a 40% decrease in lymphoma mass.
AuthorsA Holý, B Otová, M Budesínský, D Emerson, M E Wiles
JournalJournal of medicinal chemistry (J Med Chem) Vol. 44 Issue 25 Pg. 4462-7 (Dec 06 2001) ISSN: 0022-2623 [Print] United States
PMID11728191 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents
  • Organophosphonates
  • hexadecyl O-phosphonomethylcholine
  • Phosphorylcholine
  • Choline
Topics
  • Animals
  • Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
  • Choline (analogs & derivatives, chemical synthesis, chemistry, pharmacology)
  • Drug Screening Assays, Antitumor
  • Humans
  • Male
  • Organophosphonates (chemical synthesis, chemistry, pharmacology)
  • Phosphorylcholine (analogs & derivatives, chemical synthesis, chemistry, pharmacology)
  • Rats
  • Structure-Activity Relationship
  • Transplantation, Heterologous
  • Tumor Cells, Cultured

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: