Tirabrutinib
- Product Name
- Tirabrutinib
- CAS No.
- 1351636-18-4
- Chemical Name
- Tirabrutinib
- Synonyms
- ONO-BKT;ONO BTK;Tirabrutinib;TIRABRUTINIB;GS-4059;Btk Kinase inhibitor;ONO-4059(Tirabrutinib);Tirabrutinib free base;Isoleucine Impurity 18;Tirabrutinib (ONO-4059);ONO-4059;ONO 4059;ONO4059
- CBNumber
- CB02716154
- Molecular Formula
- C25H22N6O3
- Formula Weight
- 454.48
- MOL File
- 1351636-18-4.mol
Tirabrutinib Property
- Boiling point:
- 672.0±65.0 °C(Predicted)
- Density
- 1.412±0.06 g/cm3(Predicted)
- storage temp.
- Store at -20°C
- solubility
- DMSO:65.0(Max Conc. mg/mL);143.02(Max Conc. mM)
DMSO:PBS (pH 7.2) (1:2):0.3(Max Conc. mg/mL);0.66(Max Conc. mM)
DMF:30.0(Max Conc. mg/mL);66.01(Max Conc. mM)
Ethanol:1.0(Max Conc. mg/mL);2.2(Max Conc. mM) - form
- A crystalline solid
- pka
- 3.16±0.20(Predicted)
- color
- White to yellow
- InChIKey
- SEJLPXCPMNSRAM-GOSISDBHSA-N
- SMILES
- N1(C2=CC=C(OC3=CC=CC=C3)C=C2)C2C(=NC=NC=2N)N([C@@H]2CCN(C(=O)C#CC)C2)C1=O
Hazard and Precautionary Statements (GHS)
- Symbol(GHS)
-
- Signal word
- Warning
- Hazard statements
-
H302Harmful if swallowed
H315Causes skin irritation
H319Causes serious eye irritation
H335May cause respiratory irritation
- Precautionary statements
-
P261Avoid breathing dust/fume/gas/mist/vapours/spray.
P264Wash hands thoroughly after handling.
P264Wash skin thouroughly after handling.
P270Do not eat, drink or smoke when using this product.
P271Use only outdoors or in a well-ventilated area.
P280Wear protective gloves/protective clothing/eye protection/face protection.
P301+P312IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P302+P352IF ON SKIN: wash with plenty of soap and water.
P304+P340IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.
P321Specific treatment (see … on this label).
P330Rinse mouth.
P332+P313IF SKIN irritation occurs: Get medical advice/attention.
P337+P313IF eye irritation persists: Get medical advice/attention.
P403+P233Store in a well-ventilated place. Keep container tightly closed.
P405Store locked up.
P501Dispose of contents/container to..…
N-Bromosuccinimide Price
- Product number
- CS-5676
- Product name
- Tirabrutinib
- Purity
- 99.31%
- Packaging
- 5mg
- Price
- $50
- Updated
- 2021/12/16
- Product number
- CS-5676
- Product name
- Tirabrutinib
- Purity
- 99.31%
- Packaging
- 10mg
- Price
- $90
- Updated
- 2021/12/16
- Product number
- AS117581
- Product name
- ONO-4059
- Purity
- 98+%
- Packaging
- 1mg
- Price
- $94
- Updated
- 2021/12/16
- Product number
- CS-5676
- Product name
- Tirabrutinib
- Purity
- 99.31%
- Packaging
- 50mg
- Price
- $250
- Updated
- 2021/12/16
- Product number
- 2840DM
- Product name
- Tirabrutinib
- Packaging
- 2mg
- Price
- $309
- Updated
- 2021/12/16
Tirabrutinib Chemical Properties,Usage,Production
Description
Btk Kinase inhibitor is highly potent and selective orally administered, small molecule, and also named tirabrutinib, Brutons tyrosine kinase (BTK) inhibitor being developed by Ono pharmaceutical and its licensee Gilead Sciences for the treatment of autoimmune disorders and haematological malignancies.
Uses
Tirabrutinib is a BTK inhibitor that was approved in Japan in March 2020 for the treatment of relapsed or refractory primary central nervous system lymphoma.
brand name
VelexbruTM
Biological Functions
In March 2020, tirabrutinib was approved in Japan to treat primary central nervous system lymphoma (PCNSL). Tirabrutinib shows excellent selectivity against all kinases with cysteines in the ATP-binding site corresponding to Cys481 in BTK with the exception of BMX, TXK, and TEC? However, it displays weaker BTK inhibition than ibrutinib (IC50 = 6.8 nM vs. 0.47 nM).
General Description
Class: non-receptor tyrosine kinase
Treatment: PCNSL
Elimination half-life = 6.5–8 h
Protein binding = 91%
Mechanism of action
The selective inhibition of cell growth by Btk Kinase inhibitor was due to blocking of BTK-mediated signaling through AKT and cellular protein kinase D. It can inhibit autophosphorylation of the BTK at the Tyr223 position through the ERK, AKT and PKD signaling pathways.
Side effects
Adverse effects of the Btk Kinase inhibitor that occurred in some patients were rash, vomiting, neutropenia, arthralgia, and malaise, and drug-related Grade 3–4 Adverse effects were neutropenia, leukopenia, anemia, hypophosphatemia, PT-INR increased, pneumonitis, and acute myeloid leukemia. in prior Japanese studies, rash, hematologic adverse effects, erythema multiforme, and constipation were frequent adverse effects in a Phase I/II study of some patients with PCNSL, and rash, hematologic adverse effects, and stomatitis were the most common adverse effects in a Phase II study of some patients with WM.
Synthesis
The synthesis started from 4-phenoxyaniline (384), which was reacted with diethyl chloromalonate (385) in water in the presence of a phase transfer catalyst (TBAB) to give diethyl aminomalonate (386). Condensation with ethyl foraminate gave the pyrimidine derivative 387 in 87% yield. Subsequently, the pyridine diol 387 was converted to the corresponding dichloroaryl system 388 by treatment with phosphorus oxychloride in DMF, with simultaneous N-formylation of the aniline nitrogen, probably via a Vilsmeier-Haack mechanism. Substitution reactions with compound 389 required precise control of the stoichiometry to achieve adequate conversion. Treatment with sodium hydroxide to remove the formyl group gave the diamine intermediate 390. Subsequently, the azabenzimidazolone structure was established by a CDI-mediated reaction, followed by a second SNAr reaction with benzylamine (392) to afford diamine 393 as the dihydrochloride salt after acidic deprotection. Finally, pyrroline 393 was reacted with butyric acid (394) via a T3P-mediated amidation reaction, which subsequently gave tilarabrutinib hydrochloride.
target
BTK
Tirabrutinib Preparation Products And Raw materials
Raw materials
Preparation Products
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View Lastest Price from Tirabrutinib manufacturers
- Product
- ONO-4059 1351636-18-4
- Price
- US $3.00/KG
- Min. Order
- 1KG
- Purity
- 99%
- Supply Ability
- 10kg
- Release date
- 2021-09-24
- Product
- ONO-4059 1351636-18-4
- Price
- US $3.00/KG
- Min. Order
- 1KG
- Purity
- 98%
- Supply Ability
- 100KG
- Release date
- 2022-08-05
- Product
- Tirabrutinib 1351636-18-4
- Price
- US $1.20/g
- Min. Order
- 1KG
- Purity
- 99%
- Supply Ability
- 500ton/Month
- Release date
- 2021-11-08