Ruxolitinib

Base Information

• Chemical Name: Ruxolitinib
• CAS No.: 941678-49-5
• Molecular Formula: C17H18N6
• Molecular Weight: 306.37
• Hs Code.: 29335990
• Mol file: 941678-49-5.mol

Synonyms:Ruxolitinib;

Chemical Property of Ruxolitinib

Chemical Property:

• PKA: 11.63±0.50(Predicted)
• PSA: 83.18000
• Density: 1.40g/cm3
• LogP: 3.46638
• Storage Temp.: -20°
• Solubility.: Soluble in DMSO (up to 28 mg/ml) or in Ethanol (up to 15 mg/ml with warming).

Purity/Quality:

98% ^*data from raw suppliers

(R)-Ruxolitinib(>90%) ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Indications: Ruxolitinib is a kind of kinase inhibitor which is suitable for the treatment of intermediate or high-risk myelofibrosis, including primary myelofibrosis, post-polycythemia Vera myelofibrosis and post essential thrombocythemia myelofibrosis.
• Description: In November 2011, the U.S. FDA approved ruxolitinib (INCB018424) for the treatment of patients with intermediate or high-risk myelofibrosis. Ruxolitinib is an ATP-competitive inhibitor of JAK1 and JAK2 (IC50's of 3.3±1.2 nM and 2.8±1.2 nM, respectively) and inhibition occurs regardless of the JAK2V617F mutational status. Ruxolitinib is a moderately potent inhibitor of the related JAK, TYK2 (IC50=19±3.2 nM) but is selective versus JAK3 (IC50=428±243 nM). It was also selective versus a panel of 26 other kinases at concentrations approximately 100-fold the IC50 of JAK1 and JAK2. Inhibition of JAK1 and JAK2 downregulates the JAK-signal transducer and activator of transcription (STAT) pathway, inhibiting myeloproliferation, inducing apoptosis, and reducing numerous cytokine plasma levels.
• Uses: Janus-associated kinases (JAKs) are cytoplasmic tyrosine kinases that are required for activating the signaling of certain cytokines and growth factor receptors. A JAK2 gene fusion mutation, JAK2V617F, that causes unchecked activation of various growth factors and cytokines, has been linked to myeloproliferative neoplasms (MPNs), including polycythemia vera, essential thrombocythemia, and primary myelofibrosis. Ruxolitinib is a potent ATP mimetic that inhibits both JAK1 and JAK2 with IC50 values of 2.7 and 4.5 nM, respectively and is relatively less selective for JAK3 (IC50 = 322 nM). It can block interleukin-6 (IL-6) signaling (IC50 = 281 nM) and proliferation of JAK2V617F+ Ba/F3 cells (IC50 = 127 nM). In primary cultures, ruxolitinib preferentially suppresses erythroid progenitor colony formation from JAK2V617F+ polycythemia vera patients (IC50 = 67 nM) versus healthy donors (IC50 > 400 nM). In a mouse model of JAK2V617F+ MPN, 90 mg/kg ruxolitinib reduced splenomegaly, decreased circulating levels of IL-6 and TNF-α, eliminated neoplastic cells, and prolonged survival of the treated animals.[Cayman Chemical] A JAK family kinase inhibitor of JAK1, JAK2 and JAK3 with IC50s of 2.7 nM, 4.5 nM and 322 nM, respectively Ruxolitinib is a selective Janus tyrosine kinase (JAK1 and JAK2) inhibitor used in the treatment of myeloproliferative neoplasms and psoriasis. INCB018424 is the first potent, selective, JAK1/2 inhibitor to enter the clinic with IC50 of 3.3 nM/2.8 nM, >130-fold selectivity for JAK1/2 versus JAK3. Phase 3
• Clinical Use: Tyrosine kinase inhibitor: Treatment of disease related splenomegaly or symptoms in patients with primary myelofibrosis (MF), post polycythaemia vera (PV) myelofibrosis or post-essential thrombocythemia myelofibrosis
• Drug interactions: Potentially hazardous interactions with other drugs Antibacterials: concentration increased by clarithromycin and telithromycin, reduced dose of ruxolitinib; concentration reduced by rifampicin. Antifungals: reduce dose of ruxolitinib with fluconazole, itraconazole, ketoconazole, posaconazole and voriconazole. Antipsychotics: avoid with clozapine, risk of agranulocytosis. Antivirals: reduce dose of ruxolitinib with boceprevir, indinavir, lopinavir, ritonavir, saquinavir and telaprevir.

Technology Process of Ruxolitinib

There total 75 articles about Ruxolitinib which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 100.0%

(R)-(4-(1-(2-cyano-1-cyclopentylethyl)-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl pivalate (1146629-80-2) → ruxolitinib (941678-49-5,941685-37-6)

Guidance literature:

With water; sodium hydroxide; In methanol; at 20 ℃; Product distribution / selectivity;

Reference yield: 92.1%

(3R)-3-cyclopentyl-3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]-pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile (941685-40-1) → ruxolitinib (941678-49-5,941685-37-6)

Guidance literature:

(3R)-3-cyclopentyl-3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]-pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile; With boron trifluoride diethyl etherate; In acetonitrile; at 60 - 70 ℃; for 5h;

With ammonium hydroxide; water; In acetonitrile; at 20 ℃; for 12h;

Reference yield: 77.3%

(R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropionamide → ruxolitinib (941678-49-5,941685-37-6)

Guidance literature:

With trichlorophosphate; In 1-methyl-pyrrolidin-2-one; dichloromethane; at 20 - 30 ℃; for 3h;

upstream raw materials:

(3R)-3-cyclopentyl-3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]-pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile

(R)-(4-(1-(2-cyano-1-cyclopentylethyl)-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl pivalate

(3R)-3-cyclopentyl-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]propanenitrile

4-chloro-1H-pyrrolo[2,3-d]pyrimidine

Downstream raw materials:

(3R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile sulfuric acid

(3R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile maleic acid

Refernces

• 1、 -. "PROCESS FOR PREPARING ENANTIOMERICALLY ENRICHED JAK INHIBITORS". Paragraph 248; 259. . Retrieved 2020/08/22.
• 2、 -. "Intermediate of JAK inhibitor, and preparation method thereof". . . Retrieved 2018/03/24.