OSI-906

Base Information

• Chemical Name: OSI-906
• CAS No.: 867160-71-2
• Molecular Formula: C26H23N5O
• Molecular Weight: 421.502
• Mol file: 867160-71-2.mol

Synonyms:OSI 906;cis-3-[8-Amino-1-(2-phenyl-7-quinolinyl)imidazo[1,5-a]pyrazin-3-yl]-1-methylcyclobutanol;OSI-906AA;OSI906;

Chemical Property of OSI-906

Chemical Property:

• PKA: 14.84±0.40(Predicted)
• PSA: 89.33000
• Density: 1.39 g/cm³
• LogP: 5.40330
• Storage Temp.: -20°C
• Solubility.: Soluble in DMSO (up to 30 mg/ml)

Purity/Quality:

99%, ^*data from raw suppliers

Linsitinib ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Description: Linsitinib (OSI-906) is a selective inhibitor of IGF-1R with IC50 of 35 nM in cell-free assays; modestly potent to InsR with IC50 of 75 nM, and no activity towards Abl, ALK, BTK, EGFR, FGFR1/2, PKA etc. Phase 3. The binding of insulin-like growth factor 1 (IGF-1) to the IGF-1 receptor (IGF-1R) promotes cell growth while inhibiting apoptotic pathways. Overexpression of IGF-1R is found in certain solid tumors and hematologic neoplasias. However, insulin receptor (InsR) signaling can compensate for IGF-1R inhibition. Linsitinib is a dual inhibitor of IGF-1R and InsR kinases (IC50s = 35 and 75 nM, respectively). It also inhibits InsR-related receptor (IC50 = 75 nM) but is without effect (IC50 > 10 μM) against a large panel of other kinases. Linsitinib inhibits proliferation of a variety of tumor cell lines in vitro and has antitumor efficacy in an IGF-1R-driven xenograft mouse model when administered orally. A rapid, non-invasive method to predict the pharmacodynamic response to linsitinib has been reported.
• Uses: Linsitinib is a small-molecule dual insulin-like growth factor-1 receptor (IGF-IR) and insulin receptor (IR) kinase inhibitor. IGF-I receptor (IGF-IR) has been implicated in the promotion of tumorigenesis, metastasis and resistance to cancer therapies and thus Linsitinib may be a useful anticancer agent. Linsitinib is a small-molecule dual insulin-like growth factor-1 receptor (IGF-IR) and insulin receptor (IR) kinase inhibitor. IGF-I receptor (IGF-IR) has been implicated in the promotion of tumorigenesis, metastasis and resistance to cancer therapies and thus Linsitinib may be a useful anticancer agent. Potent IGF-1R inhibitor.

Technology Process of OSI-906

There total 2 articles about OSI-906 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: 65.0%

2-phenyl-7-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-quinoline (867164-54-3) + cis-3-(8-amino-1-bromo-imidazo[1,5-a]pyrazin-3-yl)-1-methylcyclobutanol (936901-75-6) → linsitinib (867160-71-2)

Guidance literature:

2-phenyl-7-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-quinoline; cis-3-(8-amino-1-bromo-imidazo[1,5-a]pyrazin-3-yl)-1-methylcyclobutanol; With caesium carbonate; triphenylphosphine; In water; N,N-dimethyl-formamide; at 95 - 105 ℃; Industry scale; Inert atmosphere;

palladium diacetate; In N,N-dimethyl-formamide; Industry scale; Inert atmosphere;

Reference yield:

3-(1-bromo-8-chloroimidazo[1,5-a]pyrazin-3-yl)cyclobutanone (936901-73-4) → linsitinib (867160-71-2)

Guidance literature:

Multi-step reaction with 3 steps

1.1: tetrahydrofuran / -65 - -45 °C / Industry scale

1.2: 10 °C / Industry scale; Inert atmosphere

2.1: ammonia / isopropyl alcohol; water / 18 h / 75 - 85 °C / Sealed vessel; Industry scale

3.1: caesium carbonate / triphenylphosphine / N,N-dimethyl-formamide; water / 95 - 105 °C / Industry scale; Inert atmosphere

3.2: Industry scale; Inert atmosphere

With ammonia; caesium carbonate; triphenylphosphine; In tetrahydrofuran; water; N,N-dimethyl-formamide; isopropyl alcohol;

Reference yield:

linsitinib (867160-71-2) → cis-8-amino-3-(3-hydroxy-3-methyl-cyclobutyl)-1-(2-phenyl-quinolin-7-yl)-imidazo[1,5-a]pyrazin-7-ium chloride (1356958-77-4)

Guidance literature:

With hydrogenchloride; In water;

upstream raw materials:

2-phenyl-7-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-quinoline

cis-3-(8-amino-1-bromo-imidazo[1,5-a]pyrazin-3-yl)-1-methylcyclobutanol

3-(1-bromo-8-chloroimidazo[1,5-a]pyrazin-3-yl)cyclobutanone

Downstream raw materials:

cis-8-amino-3-(3-hydroxy-3-methyl-cyclobutyl)-1-(2-phenyl-quinolin-7-yl)-imidazo[1,5-a]pyrazin-7-ium methanesulfonate

cis-8-amino-3-(3-hydroxy-3-methyl-cyclobutyl)-1-(2-phenyl-quinolin-7-yl)-imidazo[1,5-a]pyrazin-7-ium chloride

Refernces