Evofosfamide
Grundinformationen
- CAS
918633-87-1- Standard-SMILES
Cn1c(COP(=O)(NCCBr)NCCBr)cnc1[N+](=O)[O-]- InChIKey
UGJWRPJDTDGERK-UHFFFAOYSA-N- Summenformel
- C9H16Br2N5O4P
- Durchschnittliche Molmasse
- 449,04 g/mol
- Monoisotopische Masse
- 446,93067
Überblick
Evofosfamide is a member of the class of imidazoles that is 1H-imidazole substituted by methyl, nitro, and ({bis[(2-bromoethyl)amino]phosphoryl}oxy)methyl groups at positions 1, 2 and 5, respectively. It is a hypoxia-activated prodrug that targets hypoxic regions of tumors. The drug was being evaluated for first-line treatment of advanced pancreatic adenocarcinoma and advanced soft tissue sarcoma, in combination with chemotherapy (phase 3 trial now discontinued since the drug did not meet primary endpoints). It has a role as an alkylating agent, an antineoplastic agent and a prodrug. It is a member of imidazoles, a C-nitro compound, an organobromine compound, a tertiary amino compound and a phosphorodiamidate ester.
Namen und Bezeichner
- Bevorzugter Name
- Evofosfamide
- IUPAC
- 2-bromo-N-[(2-bromoethylamino)-[(3-methyl-2-nitroimidazol-4-yl)methoxy]phosphoryl]ethanamine
- Englischer Name
- N,N'-Bis(2-bromoethyl)phosphorodiamidic acid (1-methyl-2-nitro-1H-imidazol-5-yl)methyl ester
- Summenformel
- C9H16Br2N5O4P
- Molmasse
- 449.04
Namen und Synonyme
evofosfamide918633-87-1TH-302HAP-302TH 3022-bromo-N-[(2-bromoethylamino)-[(3-methyl-2-nitroimidazol-4-yl)methoxy]phosphoryl]ethanamineEvofosfamida8A9RZ3HN8WPhosphorodiamidic acid, N,N'-bis(2-bromoethyl)-, (1-methyl-2-nitro-1H-imidazol-5-yl)methyl esterDTXSID60238721(1-Methyl-2-nitro-1H-imidazol-5-yl)methyl N,N'-bis(2-bromoethyl)phosphorodiamidate(1-METHYL-2-NITRO-1H-IMIDAZOLE-5-YL)METHYL N,N'-BIS(2-BROMOETHYL) DIAMIDOPHOSPHATE
Weitere Namen anzeigen
CS-516EOS-61724EVOFOSFAMIDTH-302, >=98%TH302Evofosfamide(TH 302)TH-302 (Evofosfamide)
(1-METHYL-2-NITRO-1H-IMIDAZOL-5-YL)METHYL N,N'-BIS(2-BROMOETHYL)DIAMIDOPHOSPHATE(2-bromoethyl)({[(2-bromoethyl)amino][(1-methyl-2-nitro-1H-imidazol-5-yl)methoxy]phosphoryl})amineTH302 cpdevofosfamidum(2-bromoethyl)((((2-bromoethyl)amino)((1-methyl-2-nitro-1H-imidazol-5-yl)methoxy)phosphoryl))amine2-bromo-N-((2-bromoethylamino)-((3-methyl-2-nitroimidazol-4-yl)methoxy)phosphoryl)ethanamineRefChem:596969HAP TH-302
Eigenschaften
Berechnete Struktureigenschaften
- XLogP
- 0,6
- Polarare Oberfläche (TPSA)
- 114 Ų
- H-Brücken-Donoren
- 2
- H-Brücken-Akzeptoren
- 7
- Frei drehbare Bindungen
- 9
- Schwere Atome
- 21
- Formalladung
- 0
- Komplexität
- 374
Experimentelle und physikochemische Eigenschaften
DrugsPharmaceuticals -> Listed in ZINC15
Physikochemische Eigenschaften
- Schmelzpunkt
- 97 · 97-98°C
- Siedepunkt
- 565.4 · 565.4±60.0 °C(Predicted)
- Dichte
- 1.97 · 1.97
- storage temp.
- -20 °C · Hygroscopic, -20°C Freezer, Under inert atmosphere
- Löslichkeit
- DMSO (Slightly), Methanol (Slightly)
- pka
- 0.34 · 0.34±0.70(Predicted)
- Aggregatzustand
- Solid
- Farbe
- Off-White to Pale Yellow
- InChI
- InChI=1S/C9H16Br2N5O4P/c1-15-8(6-12-9(15)16(17)18)7-20-21(19,13-4-2-10)14-5-3-11/h6H,2-5,7H2,1H3,(H2,13,14,19)
- InChIKey
- UGJWRPJDTDGERK-UHFFFAOYSA-N
- SMILES
- P(NCCBr)(NCCBr)(OCC1N(C)C([N+]([O-])=O)=NC=1)=O
Sicherheit und Regulatorisches
Sicherheitsangaben dienen nur zur Orientierung und ersetzen weder das Sicherheitsdatenblatt (SDB) des Lieferanten noch geltende Vorschriften oder eine fachliche Bewertung.
Sicherheitsdaten
- Alarmwort
- Warnung
- Gefahrenhinweise
- Code Gefahrenhinweise Gefahrenklasse Abteilung Alarmwort Symbol P-Code H302
Chemie und Industrie
Pharmakologische Informationen
Mechanism of Action
TH-302 combines a 2-nitroimidazole oxygen-sensing trigger with a masked DNA crosslinker. Upon activation in oxygen deficient zones, TH-302 is converted selectively to the drug's active form, dibromo isophosphoramide mustard, a potent alkylator. TH-302 targets levels of severe hypoxia that are found in tumors but are rare in normal tissues - this is how selective targeting of the tumor occurs. After conversion to the active form of the drug, the hypoxic cells are exposed to high concentrations of released cytotoxic agent, which can also diffuse into the adjacent regions of the tumor.
Anwendungen
BeschreibungTH-302 is a hypoxia-activated prodrug and DNA alkylating agent with anticancer activity. It is selectively cytotoxic to H460 human non-small cell lung cancer (NSCLC) cells grown under hypoxic over normoxic conditions (IC50s = 0.019 and 5.1 μM, respectively). Under hypoxic conditions, TH-302 undergoes a one-electron reduction to form an active radical intermediate that is then further reduced to form a DNA-intercalating hydroxylamine. Under normoxic conditions, the radical intermediate is quenched and induces reformation of the inactive nitroazole prodrug. TH-302 reduces survival of H460 and HT-29 cells in a clonogenic assay (IC50s = 0.2 and 0.2 μM, respectively). In vivo, TH-302 (33 mg/kg per day) inhibits primary tumor growth by 41% in an MIA PaCa-2-RFP mouse orthotopic xenograft model. It inhibits tumor growth by greater than 40% in Calu-6 NSCLC, H82 small cell lung, A375 melanoma, PC-3 prostate, and BxPC-3 pancreatic cancer mouse xenograft models when administered at 50 mg/kg.
Zugehörige Reaktionen
0
Keine Reaktionsaufzeichnungen unter den aktuellen Filterkriterien.
Notizen zur Verbindung
Wird geladen…