645-05-6 Usage
Chemical Properties
White Solid
Originator
Hexastat,Roger Bellon,France,1979
Uses
Different sources of media describe the Uses of 645-05-6 differently. You can refer to the following data:
1. An antitumor agent which also acts as a chemosterilant for male houseflies and other insects. Antineoplastic.
2. antimalarial
3. As experimental insect chemosterilant.
Definition
A hexamethyl-2,4,6-
triamine derivative of 1,3,5-triazine.
Indications
Although both DNA and RNA synthesis are inhibited
in cells exposed to hexamethylmelamine (Hexalen), the
molecular mechanisms of these effects are not known.
Manufacturing Process
50 g of hexamethylolmelamine-hexamethyl ether in 950 cc methanol are
hydrogenated, at 90°C to 100°C, in the presence of 2 g Raney nickel with 100
atmospheres excess pressure of hydrogen in a steel autoclave holding 2 L
until the absorption of hydrogen is terminated. After the catalyst has been
filtered off with suction, the methanol is distilled off. As a result, 23.1 g (86%
of the theoretical) of crude hexamethylmelamine are formed having a melting
point of 158°C to 162°C. After recrystallization from methanol, the pure
product is obtained having a melting point of 168°C.
Brand name
Hexalen (Millot Laboratories,
France).
Therapeutic Function
Antitumor
General Description
Different sources of media describe the General Description of 645-05-6 differently. You can refer to the following data:
1. Altretamine is available in 50-mg capsules for oraladministration as a second-line treatment for ovarian cancer.The mechanism of action has not been firmly established, althoughthe spectrum of activity is similar to that for otheralkylating agents; however, cross-resistance is not seen.Cytotoxicity has been correlated with metabolism to give thecarbinolamines, which may form imines capable of crosslinking,or decompose to give formaldehyde, which may reactwith nucleophiles on DNA or proteins. The agent is well absorbedupon oral administration, well distributed, and highly(90%) plasma protein bound. The agent is extensively metabolizedin the liver by CYP to give demethylated metabolites via the previously mentioned carbinolamines. Elimination occursprimarily in the urine as mostly demethylated metaboliteswith a terminal elimination half-life of 4 to 10 hours.Myleosuppression and nausea/vomiting are dose-limitingtoxicities. Other adverse effects include lethargy, agitation,hallucinations, skin rash, and elevations in transaminase levels,flulike symptoms, abdominal cramps, and diarrhea.
2. Colorless crystalline solid. Insoluble in water.
Air & Water Reactions
Insoluble in water.
Reactivity Profile
Altretamine neutralizes acids in exothermic reactions to form salts plus water. May be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides. Flammable gaseous hydrogen may be generated in combination with strong reducing agents, such as hydrides.
Hazard
Toxic.
Mechanism of action
Hexamethylmelamine is readily absorbed after oral
administration, with peak plasma levels achieved after 1
hour.The drug is readily metabolized to form a number
of demethylated metabolites. Urinary elimination is the
primary route of drug excretion.
Clinical Use
Hexamethylmelamine is useful for the treatment of
ovarian adenocarcinoma and is frequently combined
with cyclophosphamide, cisplatin, and doxorubicin in
the treatment of this tumor. It also has some activity
against small cell lung cancer.
Side effects
Nausea and vomiting are the major toxicities associated
with hexamethylmelamine administration. Myelosuppression
and a peripheral neuropathy also may
occur.
Metabolism
This unique structure is believed to damage tumor cells through the production of the weakly alkylating species formaldehyde, a product of CYP450-mediated N-demethylation. Administered orally, altretamine is extensively metabolized on first pass, producing primarily mono- and didemethylated metabolites. Additional demethylation reactions occur in tumor cells, releasing formaldehyde in situ before the drug is excreted in the urine.
Check Digit Verification of cas no
The CAS Registry Mumber 645-05-6 includes 6 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 3 digits, 6,4 and 5 respectively; the second part has 2 digits, 0 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 645-05:
(5*6)+(4*4)+(3*5)+(2*0)+(1*5)=66
66 % 10 = 6
So 645-05-6 is a valid CAS Registry Number.
InChI:InChI=1/C9H24N6/c1-10(2)13-7-14(11(3)4)9-15(8-13)12(5)6/h7-9H2,1-6H3
645-05-6Relevant articles and documents
N-Methylmelamines: Synthesis, Characterization, and Physical Properties
List, Manuela,Puchinger, Helmut,Gabriel, Herbert,Monkowius, Uwe,Schwarzinger, Clemens
, p. 4066 - 4075 (2016/06/09)
N-Methylmelamines have recently gained importance as valuable compounds for manufacturing modified melamine formaldehyde resins and other polymer building blocks. A great advantage of these polymers is the reduction of the carcinogenic formaldehyde. Selecting the polymerization processes (e.g., substance polymerization, polymerization in solution) and controlling the polymerization reaction and properties of these novel materials requires knowledge of the properties of the individual melamine derivatives used as new building blocks. All possible permutations of N-methylmelamines were prepared, and reaction progress was monitored by GC/MS. 2,4,6-Tris(dimethylamino)-1,3,5-triazine was prepared to complete the series; this is, however, also a possible byproduct in various synthesis routes. The reaction conditions were optimized to obtain high yields of each derivative with the highest possible purity. The substances were characterized by NMR and IR spectroscopy, mass spectrometry, elemental analysis, and single-crystal X-ray diffraction. In addition, physical properties, such as solubility, melting points, and pKb values, were determined. The number of amino-, methylamino-, and dimethylamino groups has a significant effect on these properties. In summary, we found that by increasing the number of amino- and methylamino groups, solubility and pKb increase. With increasing number of amino groups, the compounds tend to form hydrogen bonds, and thus, the melting point shifts to higher temperature ranges where they start to decompose.
The umpolung of substituent effect in nucleophilic aromatic substitution. A new approach to the synthesis of N,N-disubstituted melamines (triazine triskelions) under mild reaction conditions
Kolesinska, Beata,Kaminski, Zbigniew J.
experimental part, p. 3573 - 3576 (2009/09/08)
By the umpolung of substituent effect 1,3,5-triazines substituted with three dialkylamino groups were prepared under mild reaction conditions by treatment of cyanuric chloride with tertiary amines. Quaternary N-triazinylammonium salts were identified as reactive intermediates activating the triazine ring and strongly promoting the persubstitution of all chlorine atoms. The final degradation of intermediate N-triazinylammonium chlorides proceeded at room temperature or in boiling dichloromethane spontaneously within irreversible evolution of appropriate chloroalkane.
Synthesis and cytotoxic activity of trisubstituted-1,3,5-triazines
Arya, Kapil,Dandia, Anshu
, p. 3298 - 3304 (2008/02/09)
1,3,5-Triazine derivatives were screened for phototoxicity as well as the cytotoxic activities against leukemia and adenocarcinoma derived cell lines in comparison to the normal human keratinocytes. A simple and environmentally friendly procedure has been developed for the synthesis of 1,3,5-triazine derivatives under microwave irradiation in the presence of a HY zeolite. The catalyst can be recovered and reused. Thus, the procedure provides a simple and green synthetic methodology under environmentally friendly conditions. Structure-activity relationships between the chemical structures and antimycobacterial and photosynthesis-inhibiting activity of the evaluated compounds are also discussed.
