2-(2,6-Dioxo-3-piperidinyl)-1H-isoindol-1,3(2H)-dion Chemische Eigenschaften,Einsatz,Produktion Methoden
R-Sätze Betriebsanweisung:
R46:Kann vererbbare Schäden verursachen.
R61:Kann das Kind im Mutterleib schädigen.
R21:Gesundheitsschädlich bei Berührung mit der Haut.
R25:Giftig beim Verschlucken.
R62:Kann möglicherweise die Fortpflanzungsfähigkeit beeinträchtigen.
S-Sätze Betriebsanweisung:
S53:Exposition vermeiden - vor Gebrauch besondere Anweisungen einholen.
S22:Staub nicht einatmen.
S26:Bei Berührung mit den Augen sofort gründlich mit Wasser abspülen und Arzt konsultieren.
S36/37/39:Bei der Arbeit geeignete Schutzkleidung,Schutzhandschuhe und Schutzbrille/Gesichtsschutz tragen.
S45:Bei Unfall oder Unwohlsein sofort Arzt zuziehen (wenn möglich, dieses Etikett vorzeigen).
Chemische Eigenschaften
White Powder
Verwenden
Inhibits FGF-induced angiogenesis. Inhibits replication of human immunodeficiency virus type 1. Teratogenic sedative. There is now a growing clinical interest in Thalidomide, and it is introduced as
an immunomodulatory agent used primarily in combination with dexamethasone to treat multiple myeloma.
Indications
Thalidomide (Thalomid) is a derivative of glutamic acid
that is chemically related to glutethimide. It exerts a
number of biological effects as an immunosuppressive,
antiinflammatory, and antiangiogenic agent, yet its
mechanisms of action have not been fully elucidated.
Thalidomide potently inhibits production of tumor
necrosis factor (TNF) and interleukin (IL) 12, and its
effect on these and other cytokines may account for
some of its clinical effects.
Definition
ChEBI: A dicarboximide that is isoindole-1,3(2H)-dione in which the hydrogen attached to the nitrogen is substituted by a 2,6-dioxopiperidin-3-yl group.
Weltgesundheitsorganisation (WHO)
Notwithstanding the highly potent teratogenic action of
thalidomide, this drug retains a place in the treatment of reactional lepromatous
leprosy and several serious dermatological conditions refractory to other
treatment. In many countries, the competent authorities have granted exemption
from licensing requirements to enable doctors to obtain limited supplies of
thalidomide under strictly controlled circumstances for use in named patients.
Arrangements have also been made by some national drug regulatory authorities
for thalidomide to be used in institutions concerned with the treatment of leprosy.
Allgemeine Beschreibung
Needles or white powder.
Air & Water Reaktionen
Insoluble in water.
Reaktivität anzeigen
Organic amides/imides, such as Thalidomide, react with azo and diazo compounds to generate toxic gases. Flammable gases are formed by the reaction of organic amides/imides with strong reducing agents. Amides are very weak bases (weaker than water). Imides are less basic yet and in fact react with strong bases to form salts. That is, they can react as acids. Mixing amides with dehydrating agents such as P2O5 or SOCl2 generates the corresponding nitrile. The combustion of these compounds generates mixed oxides of nitrogen (NOx).
Health Hazard
Thalidomide is a strong teratogen. Exposureto this compound during the first trimesterof pregnancy resulted in deformities inbabies. Infants born suffered from ameliaor phocomelia, the absence or severe shortening of limbs. Administration of thalidomide in experimental animals caused fetaldeaths, postimplantation mortality, and specific developmental abnormalities in theeyes, ear, central nervous system, musculoskeletal system, and cardiovascular system. Several thousand children were affected.The drug has been withdrawn from themarket.Thalidomide is usually administeredorally. Its toxicity is dose dependent. Someother effects are drowsiness, constipation andrash and nerve damage in the arms and legs.Interest in thalidomide resurged in recentyears because of its antitumor activity in thetreatment of multiple myeloma (Oxberry andJohnson 2006). The compound is an inhibitorof angiogenesis, that is, it prevents formationof new blood vessels in tumors. Also, it hasbeen found to be effective in treating AIDS-related Kaposis sarcoma.
Brandgefahr
Flash point data for Thalidomide are not available; however, Thalidomide is probably combustible.
Biologische Aktivität
Teratogen, sedative-hypnotic with inherent anti-inflammatory properties. A selective inhibitor of tumor necrosis factor α (TNF- α ) synthesis.
Mechanism of action
Its absorption from the gastrointestinal tract is slow,
with peak plasma levels being reached after 3 to 6
hours. It appears to undergo nonenzymatic hydrolysis in
the plasma to a large number of metabolites.The elimination
half-life is approximately 9 hours.
Clinical Use
Thalidomide is approved for use in the United
States for the treatment of cutaneous manifestations
of erythema nodosum leprosum, a potentially lifethreatening
systemic vasculitis that occurs in some patients
with leprosy.Although not approved for other indications,
thalidomide has also been shown to be very
effective in the management of Beh?et’s disease, HIVrelated
mucosal ulceration (aphthosis), and select cases
of lupus erythematosus.
Nebenwirkungen
Thalidomide is a highly teratogenic drug, characteristically
causing phocomelia (aplasia of the midportions of
the limbs). Even a single dose may cause fetal malformation.
Thalidomide should be prescribed to women of
childbearing potential only when no acceptable alternative
exists. Because it is not known whether thalidomide
is present in the ejaculate of males receiving the drug,
male patients must use a latex condom when engaging in
sexual activity with women of childbearing potential.
Other side effects of thalidomide may include sedation
(in fact, thalidomide was originally marketed in
Europe as a sleeping aid), constipation, and peripheral
neuropathy, which may be permanent.
Sicherheitsprofil
Poison by ingestion. Moderately toxic by skin contact and intraperitoneal routes. Human teratogenic effects by ingestion: developmental abnormalities of the musculoskeletal and cardiovascular systems. Experimental reproductive effects. Questionable carcinogen with experimental tumorigenic and teratogenic data. Human mutation data reported. It was commonly used as a prescription drug in Europe in the late 1950s and early 1960s. Its use was dscontinued because it was lscovered to cause serious congenital abnormalities in the fetus, notably amelia and phocomelia (absence or deformity of the limbs, including hands and feet) when taken by a woman during early pregnancy. When heated to decomposition it emits toxic fumes of NOx. Used as a sedative and hypnotic.
2-(2,6-Dioxo-3-piperidinyl)-1H-isoindol-1,3(2H)-dion Upstream-Materialien And Downstream Produkte
Upstream-Materialien
Downstream Produkte
