58066-85-6 Usage
Description
Miltefosin, representing the prototype of a new phospholipid structure, was introduced
for the palliative treatment of skin metastases in patients with breast cancer. It is highly
active against the human leukemia tumor cells xenograft in nude mice, leading to growth
inhibition and regression of large established tumors. Its mode of antitumor activity is not
mediated by the host immune system but by its pharmacological effects at the level of the
cancer cell membrane, distinctly different from that of the classical cytostatic drugs which
interact with cell proliferation at the level of DNA replication. Protein kinase C inhibition has
been suggested as a possible mechanism.
Uses
A phospholipid drug with antineoplastic and antiprotozoal/antifungal properties, also acts as an Akt inhibitor, and under investigation as a potential therapy against HIV infection.
Definition
ChEBI: A phospholipid that is the hexadecyl monoester of phosphocholine.
Brand name
Miltex
Antimicrobial activity
Concentrations of 1–5 μm inhibit the promastigotes and amastigotes
of Leishmania spp. and the epimastigotes and amastigotes
of T. cruzi. Inhibitory concentrations against T. brucei spp.
and E. histolytica are closer to 50 μm. Acanthamoeba spp. are variably
susceptible, depending on the experimental conditions.
Acquired resistance
There are no reports of clinical resistance in Leishmania
so far. Experimental resistance has been induced in vitro
against the promastigote stage of Leishmania and two
plasma membrane proteins, LdMT and Ld Ros3, are necessary
for miltefosine uptake. There is evidence that reduced
sensitivity of promastigotes is passed on to intracellular
amastigotes.
Pharmaceutical Applications
An alkylphospholipid, originally investigated as an anticancer
compound, formulated for oral administration.
Biochem/physiol Actions
Inhibitor of protein kinase C and of phosphatidylcholine synthesis. Used for the treatment of visceral and cutaneous leishmaniasis. Active against metronidazole-resistant and -susceptible strains of Trichomonas vaginalis
Pharmacokinetics
In rodent models the drug is almost completely absorbed after
oral administration. About 90% is bound to plasma proteins. It
is widely distributed in the body; studies in rats showed highest
uptake in kidney, liver and spleen. In rats and dogs bioavailability
was 82% and 94%, with maximum values reached after 4–48 h.
In adult human trials repeated oral dosing with 100 mg per
day achieved a peak plasma concentration of 70 mg/L after
8–24 h (day 23). The half-life is 6–8 days.
Clinical Use
Visceral leishmaniasis
Cutaneous leishmaniasis
Side effects
Mild to moderate gastrointestinal side effects are reported
in 40–60% of patients. Moderate to severe nephrotoxicity
was seen in 2% and 1% of patients, respectively; increases
in creatinine
levels were reversible. Miltefosine is contraindicated
in pregnancy, based on findings of teratogenicity in
rats. It causes hemolysis and cannot be given intravenously.
Check Digit Verification of cas no
The CAS Registry Mumber 58066-85-6 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 5,8,0,6 and 6 respectively; the second part has 2 digits, 8 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 58066-85:
(7*5)+(6*8)+(5*0)+(4*6)+(3*6)+(2*8)+(1*5)=146
146 % 10 = 6
So 58066-85-6 is a valid CAS Registry Number.
InChI:InChI=1/C21H46NO4P/c1-5-6-7-8-9-10-11-12-13-14-15-16-17-18-20-25-27(23,24)26-21-19-22(2,3)4/h5-21H2,1-4H3
58066-85-6Relevant articles and documents
Efficient synthesis of the cholinephosphate phospholipid headgroup
Hendrickson, Elizabeth K.,Hendrickson, H.Stewart
, p. 203 - 207 (2001)
In search of an efficient method to prepare cholinephosphate headgroups in phospholipids under mild conditions (where the diacylglycerol moiety is not subject to oxidation), a method was developed for phosphorylation using a trialkyl phosphite and I2. The active intermediate is a phosphoryl iodide formed by oxidation of the phosphite with I2. 2-Bromoethanol, dimethyl chlorophosphite, and an alcohol (diglyceride) are converted to a phosphate triester in a one-pot reaction with high yield. In the second reaction, the phosphate triester is demethylated, and the ethyl bromide group is converted to choline by treatment with aqueous trimethylamine. This procedure is applied to the synthesis of hexadecylphosphocholine, and 1,2-didecanoyl-1-deoxy-1-thio-sn-glyceryo-3-phosphocholine.
An effective reagent to functionalize alcohols with phosphocholine
Xu, Lianyan L.,Berg, Lawrence J.,Jamin Keith,Townsend, Steven D.
supporting information, p. 767 - 770 (2020/02/11)
Phosphocholine is a small haptenic molecule that is both a precursor and degradation product of choline. Phosphocholine decorates a number of biologics such as lipids and oligosaccharides. In this study, an air and bench stable phosphocholine donor has been developed and evaluated with a number of alcohol acceptors. Using a one-pot, three-step sequence, (phosphitylation, oxidation, and phosphate deprotection) phosphocholine derivatives are synthesized in high yields. Of particular interest is the synthesis of miltefosine, the lone oral drug approved to treat leishmaniasis. Due to its prohibitive expense ($1500 per g), miltefosine is not accesable for the majority of the world's patients. Based on the described reaction sequence, this drug can be produced for $25 per g.
BODP - A versatile reagent for phospholipid synthesis
Zaffalon, Pierre-Leonard,Zumbuehl, Andreas
, p. 778 - 782 (2011/04/22)
Benzyloxydichlorophosphine (BODP) has been found to be a convenient reagent for the synthesis of phospholipids. A series of artificial ether and ester phospholipids have been prepared in good to high yields. Georg Thieme Verlag Stuttgart New York.
