Pamiparib
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- CAS-Nr.
- 1446261-44-4
- Englisch Name:
- Pamiparib
- Synonyma:
- Pamiparib;bgb-290;EOS-61090;Pamiparib(BGB290);BGB-290,Pamiparib;Alflutinib Impurity 17;Pamiparib, 10 mM in DMSO;PAMIPARIB; BGB-290; BGB 290; BGB290.;inhibit,Pamiparib,PARP,Inhibitor,poly ADP ribose polymerase,BGB 290,BGB290;(R)-2-fluoro-10a-methyl-5,8,9,10,10a,11-hexahydro-5,6,7a,11-tetraazacyclohepta[def]cyclopenta[a]fluoren-4(7H)-one
- CBNumber:
- CB13137483
- Summenformel:
- C16H15FN4O
- Molgewicht:
- 298.31
- MOL-Datei:
- 1446261-44-4.mol
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Pamiparib Eigenschaften
- Dichte
- 1.68±0.1 g/cm3(Predicted)
- storage temp.
- Store at -20°C
- L?slichkeit
- DMF:20.0(Max Conc. mg/mL);67.04(Max Conc. mM)
DMF:PBS (pH 7.2) (1:10):0.09(Max Conc. mg/mL);0.3(Max Conc. mM)
DMSO:40.83(Max Conc. mg/mL);136.88(Max Conc. mM)
Ethanol:45.0(Max Conc. mg/mL);150.84(Max Conc. mM)
- Aggregatzustand
- A solid
- pka
- 11.56±0.40(Predicted)
- Farbe
- Light yellow to yellow
- InChI
- InChI=1S/C16H15FN4O/c1-16-3-2-4-21(16)7-11-13-12-9(15(22)20-19-11)5-8(17)6-10(12)18-14(13)16/h5-6,18H,2-4,7H2,1H3,(H,20,22)/t16-/m1/s1
- InChIKey
- DENYZIUJOTUUNY-MRXNPFEDSA-N
- SMILES
- N1C2=C3C(C(=O)NN=C4C3=C1[C@@]1(C)CCCN1C4)=CC(F)=C2
Sicherheit
- Risiko- und Sicherheitserkl?rung
- Gefahreninformationscode (GHS)
| Bildanzeige (GHS) |
  
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| Alarmwort |
Achtung
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| Gefahrenhinweise |
| Code |
Gefahrenhinweise |
Gefahrenklasse |
Abteilung |
Alarmwort |
Symbol |
P-Code |
| H226 |
Flüssigkeit und Dampf entzündbar. |
Entzündbare Flüssigkeiten |
Kategorie 3 |
Warnung |
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| H314 |
Verursacht schwere Ver?tzungen der Haut und schwere Augensch?den. |
?tzwirkung auf die Haut |
Kategorie 1B |
Achtung |
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P260,P264, P280, P301+P330+ P331,P303+P361+P353, P363, P304+P340,P310, P321, P305+ P351+P338, P405,P501 |
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| Sicherheit |
| P210 |
Von Hitze, hei?en Oberfl?chen, Funken, offenen Flammen und anderen Zündquellenarten fernhalten. Nicht rauchen. |
| P233 |
Beh?lter dicht verschlossen halten. |
| P240 |
Beh?lter und zu befüllende Anlage erden. |
| P241 |
Explosionsgeschützte [elektrische/Lüftungs-/ Beleuchtungs-/...] Ger?te verwenden. |
| P242 |
Nur funkenfreies Werkzeug verwenden. |
| P243 |
Ma?nahmen gegen elektrostatische Entladungen treffen. |
| P260 |
Dampf/Aerosol/Nebel nicht einatmen. |
| P262 |
Nicht in die Augen, auf die Haut oder auf die Kleidung gelangen lassen. |
| P264 |
Nach Gebrauch gründlich waschen. |
| P264 |
Nach Gebrauch gründlich waschen. |
| P270 |
Bei Gebrauch nicht essen, trinken oder rauchen. |
| P271 |
Nur im Freien oder in gut belüfteten R?umen verwenden. |
| P280 |
Schutzhandschuhe/Schutzkleidung/Augenschutz tragen. |
| P284 |
Atemschutz tragen. |
| P370+P378 |
Bei Brand: zum L?schen verwenden. |
| P501 |
Inhalt/Beh?lter ... (Entsorgungsvorschriften vom Hersteller anzugeben) zuführen. |
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Pamiparib Chemische Eigenschaften,Einsatz,Produktion Methoden
Beschreibung
Pamiparib (BGB-290) is an investigational small molecule inhibitor of PARP1 and PARP2. Pamiparib is being evaluated as a monotherapy in pivotal clinical trials in China in recurrent platinum-sensitive and BRCA1/2 mutated ovarian cancers.
Mechanism of action
Pamiparib inhibits the activity of PARP enzymes, interfering with the DNA damage repair mechanism of tumor cells, especially in those cancer cells with BRCA gene mutations, which have become dependent on the PARP-mediated repair pathway to maintain the stability of their genome. Therefore, pamiparib can increase DNA damage in these tumor cells, leading to tumor cell death.
Synthese
Using 2-bromo-5-fluorobenzoic acid (27.1) as the raw material, a series of reactions were performed to obtain methyl benzoate 27.2, which was then reduced and protected to obtain the key aromatic bromide fragment 27.3. Using pyrrolene 27.4 as the raw material, alkane 27.8 was obtained by reaction with tert-butyl bromoacetate 27.5, addition of acetylene group, removal of silicon group, etc., and then enantiomer separation was performed to obtain the desired (R)-enantiomer 27.10. The alkynyl group 27.10 and the bromide group 27.3 were subjected to Larock heterocyclization reaction to generate indole 27.11, which was then treated with trifluoromethanesulfonic acid and hydrazine hydrate reaction to finally obtain Pamiparib (27) as a semihydrate crystalline solid with a yield of 50%.
in vivo
Oral administration of Pamiparib results in time-dependent and dose-dependent inhibition of PARylation in MDA-MB-436 (BRCA1 mutant) breast cancer xenograft, correlating well with the tumor drug concentrations. It has also demonstrated good combination activity with chemotherapeutics in patient biopsy derived SCLC models. Also Pamiparib has significant brain penetration in C57 mice. The drug exposure in brain vs. that in plasma was close to 20% after oral administration of BGB-290.
Pamiparib Upstream-Materialien And Downstream Produkte
Upstream-Materialien
Downstream Produkte
Pamiparib Anbieter Lieferant Produzent Hersteller Vertrieb H?ndler.
Global( 102)Lieferanten
- (R)-2-fluoro-10a-methyl-7,8,9,10,10a,11-hexahydro-5,6,7a,11-tetraazacyclohepta[def]cyclopenta[a]fluoren-4(5H)-one
- (R)-2-fluoro-10a-methyl-5,8,9,10,10a,11-hexahydro-5,6,7a,11-tetraazacyclohepta[def]cyclopenta[a]fluoren-4(7H)-one
- 5,6,7a,11-Tetraazacyclohepta[def]cyclopenta[a]fluoren-4(7H)-one, 2-fluoro-5,8,9,10,10a,11-hexahydro-10a-methyl-, (10aR)-
- PAMIPARIB; BGB-290; BGB 290; BGB290.
- BGB-290,Pamiparib
- Pamiparib(BGB290)
- EOS-61090
- bgb-290
- Pamiparib
- inhibit,Pamiparib,PARP,Inhibitor,poly ADP ribose polymerase,BGB 290,BGB290
- (2R)-14-fluoro-2-methyl-6,9,10,19-tetraazapentacyclo[14.2.1.02,?.0?,1?.012,1?]nonadeca-1(18),8,12(17),13,15-pentaen-11-one
- Alflutinib Impurity 17
- Pamiparib, 10 mM in DMSO
- 1446261-44-4
- 1446261-44-1
- APIS
