| Identification | Back Directory | [Name]
BIIB-021 | [CAS]
848695-25-0 | [Synonyms]
CS-479
CNF2024
BIIB-021
CNF-2024EC102
BIIB021/CNF2024
BIIB-021 USP/EP/BP
CNF 2024 - BIIB 021
BIIB021(CNF2024)BIIB021
BIIB021;BIIB-021; BIIB 021
CNF2024; BIIB-021; BIIB 021; CNF 2024; CNF-2024
BIIB 021 (This product is only available in Japan.)
6-CHLORO-9-[(4-METHOXY-3,5-DIMETHYLPYRIDIN-2-YL)METHYL]PURIN-2-AMINE
6-Chloro-9-[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]-9H-purin-2-amine
6-chloro-9-((4-Methoxy-3,5-diMethylpyridin-2-yl)Methyl)-9H-purin-2-aMine
9H-Purin-2-aMine, 6-chloro-9-[(4-Methoxy-3,5-diMethyl-2-pyridinyl)Methyl]-
9-[2-(2,2-diMethyl-propylaMino)ethyl]-8-(2-iodo-5-Methoxy-phenylsulfanyl)-9H-purin-6-ylaMine
6-Chloro-9-[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]-9H-purin-2-amine BIIB 021
BIIB 021 6-Chloro-9-[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]-9H-purin-2-amine | [EINECS(EC#)]
812-781-2 | [Molecular Formula]
C14H15ClN6O | [MDL Number]
MFCD15528939 | [MOL File]
848695-25-0.mol | [Molecular Weight]
318.76 |
| Chemical Properties | Back Directory | [Melting point ]
192-193℃ | [Boiling point ]
588.5±60.0 °C(Predicted) | [density ]
1.50 | [storage temp. ]
-20°C | [solubility ]
Soluble in DMSO (>25 mg/ml) | [form ]
solid | [pka]
6.07±0.40(Predicted) | [color ]
White | [Stability:]
Stable for 1 year as supplied. Solutions in DMSO may be stored at -20°C for up to 3 montha. | [InChI]
InChI=1S/C14H15ClN6O/c1-7-4-17-9(8(2)11(7)22-3)5-21-6-18-10-12(15)19-14(16)20-13(10)21/h4,6H,5H2,1-3H3,(H2,16,19,20) | [InChIKey]
QULDDKSCVCJTPV-UHFFFAOYSA-N | [SMILES]
N1C2C(=NC(N)=NC=2Cl)N(CC2=NC=C(C)C(OC)=C2C)C=1 |
| Hazard Information | Back Directory | [Description]
BIIB021 is a potent HSP90 inhibitor (IC50 = 30 nM HER-2 degradation).1 It inhibited the proliferation of MCF7 and BT474 breast cancer cell lines (IC50 = 100 nM for each).? BIIB021 has shown efficacy as a therapeutic in multiple cancer models.2-5 | [Uses]
BIIB 021 an orally available, fully synthetic small-molecule inhibitor of the heat shock protein Hsp90. Studies show that BIIB 021 adminisitration led to degradation of Hsp90 client proteins measured in tumor tissue and resulted in the inhibition of tumor growth in several human tumor xenograft models. | [Definition]
ChEBI: A member of the class of 2-aminopurines that is 2-aminopurine which is substituted by a chlorine at position 6 and by a (4-methoxy-3,5-dimethylpyridin-2-yl)methyl group at position 9. | [Synthesis]
The general procedure for the synthesis of 6-chloro-9-[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]-9H-purin-2-amine (BIIB021) from 2-chloromethyl-3,5-dimethyl-4-methoxypyridine hydrochloride and 2-amino-6-chloropurine was as follows:
1. 2-Amino-6-chloropurine (10 mmol) and anhydrous potassium carbonate (12 mmol) were weighed separately and added to 25 mL of DMSO in a 50 mL round bottom flask.
2. The reaction mixture was heated to 48°C in an oil bath with continuous stirring for 30 minutes.
3. 2-chloromethyl-3,5-dimethyl-4-methoxypyridine hydrochloride (11 mmol) was weighed and added to the above reaction solution in 3 portions at 30 minute intervals.
4. After continuing the reaction at 48°C for 10 hours, the reaction temperature was adjusted to 22°C and stirred for 2 hours.
5. Upon completion of the reaction, the reaction mixture was filtered and the filtrate was retained.
6. A mixture of water and isopropanol (1:1 by volume) was added slowly and dropwise to the filtrate until the solution became turbid.
7. Place the turbid solution in a refrigerator overnight.
8. Collect the precipitate by filtration to obtain the target product BIIB021.
The product 6-chloro-9-[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]-9H-purin-2-amine (BIIB021) was a pale yellow solid with 77% yield. | [in vivo]
Oral administration of BIIB021 leads to tumor growth inhibition in many tumor xenograft models including N87, BT474, CWR22, U87, SKOV3 and Panc-1[1]. BIIB021 effectively inhibits growth of L540cy tumor at a dose of 120 mg/kg[2]. BIIB021 significantly enhances antitumor growth effect of radiation in JHU12 xenograft[3]. | [IC 50]
HSP90: 1.7 nM (Ki); HSP90: 38 nM (EC50) | [References]
Kasibhatla et al. (2007), Rationally designed high-affinity 2-amino-6-halopurine heat shock protein 90 inhibitors that exhibit potent antitumor activity; J. Med. Chem. 50 2767
Lundgren et al. (2009), BIIB021, an orally available, fully synthetic small-molecule inhibitor of the heat shock protein Hsp90; Mol. Cancer Ther. 8 921
Boll et al. (2009), Heat shock protein 90 inhibitor BIIB021 (CNF2024) depletes NF-kappaB and sensitizes Hodgkin’s lymphoma cells for natural killer cell-mediated cytotoxicity; Clin. Cancer Res. 15 5108
Zhang et al. (2010), BIIB021, a synthetic Hsp90 inhibitor, has broad application against tumors with acquired multidrug resistance; Int. J. Cancer 126 1226
Wang et al. (2014), BIIB021, a novel Hsp90 inhibitor, sensitizes esophageal squamous cell carcinoma to radiation; Biochem. Biophys. Res. Commun. 452 945 |
|
|