Entospletinib (GS-9973)

Base Information

• Chemical Name: Entospletinib (GS-9973)
• CAS No.: 1229208-44-9
• Molecular Formula: C23H21N7O
• Molecular Weight: 411.466
• Mol file: 1229208-44-9.mol

Synonyms:GS-9973;Entospletinib;6-(1H-Indazol-6-yl)-N-[4-(4-morpholinyl)phenyl]imidazo[1,2-a]pyrazin-8-amine;6-(1H-indazol-6-yl)-N-(4-morpholinophenyl)imidazo[1,2-a]pyrazin-8-amine;Entospletinib (GS-9973);GS-9973, Entospletinib;Entospletinib Dimesylate

Chemical Property of Entospletinib (GS-9973)

Chemical Property:

• PKA: 12.54±0.40(Predicted)
• PSA: 86.60000
• Density: 1.45±0.1 g/cm3(Predicted)
• LogP: 3.33970
• Solubility.: insoluble in EtOH; insoluble in H2O; ≥20.55 mg/mL in DMSO

Purity/Quality:

98% min ^*data from raw suppliers

GS 9973 ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Description: Entospletinib (GS-9973) is an orally bioavailable, selective Syk inhibitor with IC50 of 7.7 nM in a cell-free assay and showed 13-to >1000-fold cellular selectivity for Syk over other kinases(including Jak2, ckit, Flt3, Ret, KDR) as assessed by target protein phosphorylation or functional response. Spleen tyrosine kinase (Syk) is a non-receptor tyrosine kinase that upon phosphorylation binds to immunoreceptor tyrosine-based activation motifs of FcRγ chains and mediates downstream signaling related to platelet function and inflammation. GS-9973 is a potent Syk inhibitor (IC50 = 7.7 nM) that demonstrates 10-35-fold selectivity for Syk over a panel of 359 nonmutant kinases. In conjunction with the PI3Kδ inhibitor CAL-101 , it has been used to reduce chronic lymphocytic leukemia cell survival and to disrupt chemokine signaling at nanomolar concentrations.
• Uses: GS 9973 is a selective and orally bioavailable inhibitor of spleen tyrosine kinase (Syk).

Technology Process of Entospletinib (GS-9973)

There total 2 articles about Entospletinib (GS-9973) 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:

6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole (937049-58-6) + 6-bromo-N-(4-morpholinophenyl)imidazo[1,2-a]pyrazine-8-amine (445263-72-9) → 6-(1H-indazol-6-yl)-N-[4-(4-morpholinyl)phenyl]imidazo[1,2-a]pyrazin-8-amine (1229208-44-9)

Guidance literature:

With tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate; In 1,4-dioxane; water; at 135 ℃; for 0.583333h; Inert atmosphere; Microwave irradiation;

DOI:10.1021/jm500228a

Reference yield:

→ 6-(1H-indazol-6-yl)-N-[4-(4-morpholinyl)phenyl]imidazo[1,2-a]pyrazin-8-amine (1229208-44-9)

Guidance literature:

Reference yield: 88.0%

6-(1H-indazol-6-yl)-N-[4-(4-morpholinyl)phenyl]imidazo[1,2-a]pyrazin-8-amine (1229208-44-9) + isoprene (78-79-5,9003-31-0) → 6-(1-(3-methylbut-3-en-2-yl)-1H-indazol-6-yl)-N-(4-morpholinophenyl)imidazo[1,2-a]pyrazin-8-amine

Guidance literature:

With bis(tri-t-butylphosphine)palladium⁽⁰⁾; triethyl borane; 1,2-bis[di(t-butyl)phosphinomethyl]benzene; In isopropyl alcohol; at 80 ℃; for 18h; Inert atmosphere; Sealed tube;

DOI:10.1002/anie.202100137

upstream raw materials:

6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole

6-bromo-N-(4-morpholinophenyl)imidazo[1,2-a]pyrazine-8-amine

Refernces

• 1、 -. "IMIDAZOPYRAZINE SYK INHIBITORS". Page/Page column 142. . Retrieved 2010/07/02.