Adagrasib
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- CAS-Nr.
- 2326521-71-3
- Englisch Name:
- Adagrasib
- Synonyma:
- Adagrasib;2-((S)-4-(7-(8-chloronaphthalen-1-yl)-2-(((S)-1-methylpyrrolidin-2-yl)methoxy)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yl)-1-(2-fluoroacryloyl)piperazin-2-yl)acetonitrile;Adarese;MRTX-849;MTRX-849;Agdarcy step;Adagrasib/MRTX-849;MRTX849(Adagrasib);Azvudine Impurity 23;Adagrasib, 10 mM in DMSO
- CBNumber:
- CB94918285
- Summenformel:
- C32H35ClFN7O2
- Molgewicht:
- 604.12
- MOL-Datei:
- 2326521-71-3.mol
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Adagrasib Eigenschaften
- Siedepunkt:
- 860.2±75.0 °C(Predicted)
- Dichte
- 1.295±0.06 g/cm3(Predicted)
- storage temp.
- Store at -20°C
- L?slichkeit
- Soluble in DMSO:1.0(Max Conc. mg/mL);1.7(Max Conc. mM)
- Aggregatzustand
- A crystalline solid
- pka
- 9.31±0.40(Predicted)
- Farbe
- White to yellow
- InChIKey
- PEMUGDMSUDYLHU-ZEQRLZLVSA-N
- SMILES
- N1(C(=O)C(F)=C)CCN(C2N=C(OC[C@@H]3CCCN3C)N=C3CN(C4=C5C(C=CC=C5Cl)=CC=C4)CCC3=2)C[C@@H]1CC#N
Sicherheit
- Risiko- und Sicherheitserkl?rung
- Gefahreninformationscode (GHS)
| Bildanzeige (GHS) |
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| Alarmwort |
Warnung |
| Gefahrenhinweise |
| Code |
Gefahrenhinweise |
Gefahrenklasse |
Abteilung |
Alarmwort |
Symbol |
P-Code |
| H302 |
Gesundheitssch?dlich bei Verschlucken. |
Akute Toxizit?t oral |
Kategorie 4 |
Warnung |
![GHS hazard pictograms]() src="/GHS07.jpg" width="20" height="20" /> |
P264, P270, P301+P312, P330, P501 |
| H315 |
Verursacht Hautreizungen. |
Hautreizung |
Kategorie 2 |
Warnung |
![GHS hazard pictograms]() src="/GHS07.jpg" width="20" height="20" /> |
P264, P280, P302+P352, P321,P332+P313, P362 |
| H319 |
Verursacht schwere Augenreizung. |
Schwere Augenreizung |
Kategorie 2 |
Warnung |
![GHS hazard pictograms]() src="/GHS07.jpg" width="20" height="20" /> |
P264, P280, P305+P351+P338,P337+P313P |
| H335 |
Kann die Atemwege reizen. |
Spezifische Zielorgan-Toxizit?t (einmalige Exposition) |
Kategorie 3 (Atemwegsreizung) |
Warnung |
![GHS hazard pictograms]() src="/GHS07.jpg" width="20" height="20" /> |
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| Sicherheit |
| P261 |
Einatmen von Staub vermeiden. |
| P280 |
Schutzhandschuhe/Schutzkleidung/Augenschutz tragen. |
| P301+P312 |
BEI VERSCHLUCKEN: Bei Unwohlsein GIFTINFORMATIONSZENTRUM/Arzt/... (geeignete Stelle für medizinische Notfallversorgung vom Hersteller/Lieferanten anzugeben) anrufen. |
| P302+P352 |
BEI BERüHRUNG MIT DER HAUT: Mit viel Wasser/... (Hersteller kann, falls zweckm??ig, ein Reinigungsmittel angeben oder, wenn Wasser eindeutig ungeeignet ist, ein alternatives Mittel empfehlen) waschen. |
| P305+P351+P338 |
BEI KONTAKT MIT DEN AUGEN: Einige Minuten lang behutsam mit Wasser spülen. Eventuell vorhandene Kontaktlinsen nach M?glichkeit entfernen. Weiter spülen. |
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Adagrasib Chemische Eigenschaften,Einsatz,Produktion Methoden
Beschreibung
MRTX-849 was identified as a potent, selective, and covalent KRASG12C inhibitor that exhibits favourable drug-like properties, modifies mutant cysteine 12 in GDP-bound KRASG12C, and inhibits KRAS-dependent signalling. MRTX-849 demonstrated pronounced tumour regression in 17 of 26 (65%) KRASG12C-positive cell line- and patient-derived xenograft models from multiple tumour types, and objective responses have been observed in patients with KRASG12C-positive lung and colon adenocarcinomas[1].
Verwenden
MRTX 849 is used as combination therapy for treatment of cancer.
Definition
Adagrasib is an orally available, potent, irreversible, small molecule inhibitor of KRAS G12C mutant isoform being developed by Mirati Therapeutics for the treatment of solid tumours harbouring KRAS G12C oncogenic driver mutation, including non-small cell lung cancer (NSCLC) and colorectal cancer (CRC).
Trademarks
Krazati
Synthese
Boc deprotection was achieved by treatment with hydrochloric acid, and the resulting deprotected amine (19.5) crystallized as the tartrate salt in 80% isolated yield. Compound 19.5 was then coupled with naphthyl bromide 19.6 as the free base via the Buchwald-Hartwig reaction, and product 19.7 crystallized as the p-toluenesulfonate salt and was isolated in 71% yield. To avoid the complications caused by the potential mutagenic impurities and retro-Michael products that may be generated by the conventional carboxybenzoyl deprotection protocol, the authors developed a novel nucleophilic deprotection reaction using 2-mercaptoethanol and potassium phosphate in DMA. This approach afforded the deprotected piperazine 19.8 with minimal racemization, affording the crystalline product in 86% isolated yield. Finally, the cysteine-active warhead was introduced by coupling sodium 2-fluoroacrylate 19.9 with piperazine 19.8 using T3P (propylphosphonic anhydride) in acetonitrile, and Adagrasib (19) was isolated in 70% yield after two consecutive recrystallizations.
Adagrasib Upstream-Materialien And Downstream Produkte
Upstream-Materialien
Downstream Produkte
Adagrasib Anbieter Lieferant Produzent Hersteller Vertrieb H?ndler.
Global( 180)Lieferanten
- MRTX849(Adagrasib)
- Adagrasib/MRTX-849
- 4-[7-(8-CHLORO-1-NAPHTHALENYL)-5,6,7,8-TETRAHYDRO-2-[[(2S)-1-METHYL-2-PYRR
- MRTX-849
- MRTX849;MRTX-849;MRTX 849
- 2-PIPERAZINEACETONITRILE, 4-[7-(8-CHLORO-1-NAPHTHALENYL)-5,6,7,8-TETRAHYDRO-2-[[(2S)-1-METHYL-2-PYRR
- 2-Piperazineacetonitrile, 4-[7-(8-chloro-1-naphthalenyl)-5,6,7,8-tetrahydro-2-[[(2S)-1-methyl-2-pyrrolidinyl]methoxy]pyrido[3,4-d]pyrimidin-4-yl]-1-(2-fluoro-1-oxo-2-propen-1-yl)-, (2S)-
- 2-[(2S)-4-[7-(8-chloronaphthalen-1-yl)-2-[[(2S)-1-methylpyrrolidin-2-yl]methoxy]-6,8-dihydro-5H-pyrido[3,4-d]pyrimidin-4-yl]-1-(2-fluoroprop-2-enoyl)piperazin-2-yl]acetonitrile
- Adagrasib
- 2-((S)-4-(7-(8-chloronaphthalen-1-yl)-2-(((S)-1-methylpyrrolidin-2-yl)methoxy)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yl)-1-(2-fluoroacryloyl)piperazin-2-yl)acetonitrile
- inhibit,GDP-bound,mutant,MIA PaCa-2,MRTX-849,Adagrasib,selective,Inhibitor,MRTX 849,inactive,state,G12C,H1373,covalent,anti-tumor,KRAS,Ras,cells
- 2-PIPERAZINEACETONITRILE,4-[7-(8-CHLORO-1-NAPHTHALENYL)-5,Chemicalbook6,7,8-TETRAHYDRO-2-[[(2S)-1-METHYL-2-PYRR
- 2-[(S)-4-[7-(8-chloro-1-naphthyl)-2-[[(S)-1-methyl-2-pyrrolidinyl]methoxy]-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yl]-1-(2-fluoroacryloyl)-2-piperazinyl]acetonitrile
- MTRX-849
- Azvudine Impurity 23
- Adarese
- Agdarcy step
- Adagrasib, 10 mM in DMSO
- 2326521-71-3
- api
- 2326521-71-3
