Altretamine Property

Melting point:

171-175 °C (lit.)

Boiling point:

339.81°C (rough estimate)

Density 

1.0441 (rough estimate)

refractive index 

1.6100 (estimate)

storage temp. 

Keep in dark place,Inert atmosphere,Room temperature

solubility 

Chloroform (Sparingly), Methanol (Slightly, Heated)

pka

pKa 10.3 (Uncertain)

form 

solid

color 

White to Off-White

Water Solubility 

Insoluble

Merck 

13,318

CAS DataBase Reference

645-05-6(CAS DataBase Reference)

NIST Chemistry Reference

Altretamine(645-05-6)

EPA Substance Registry System

Altretamine (645-05-6)

Safety

Hazard Codes 

Xn

Risk Statements 

22-36/37/38

Safety Statements 

26-36

WGK Germany 

3

RTECS 

OS1050000

HS Code 

2933690000

Hazardous Substances Data

645-05-6(Hazardous Substances Data)

Toxicity

LD50 in rats, guinea pigs (mg/kg): 350, 255 orally (Jasper)

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P270Do not eat, drink or smoke when using this product.

P301+P312IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.

P302+P352IF ON SKIN: wash with plenty of soap and water.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

Altretamine Chemical Properties,Usage,Production

Chemical Properties

White Solid

Originator

Hexastat,Roger Bellon,France,1979

Uses

An antitumor agent which also acts as a chemosterilant for male houseflies and other insects. Antineoplastic.

Uses

antimalarial

Uses

As experimental insect chemosterilant.

Indications

Although both DNA and RNA synthesis are inhibited in cells exposed to hexamethylmelamine (Hexalen), the molecular mechanisms of these effects are not known.

Definition

A hexamethyl-2,4,6- triamine derivative of 1,3,5-triazine.

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

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.

General Description

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.