PI-103

Base Information

• Chemical Name: PI-103
• CAS No.: 371935-74-9
• Molecular Formula: C19H16N4O3
• Molecular Weight: 348.361
• UNII: YQX02F616F
• DSSTox Substance ID: DTXSID40190676
• Nikkaji Number: J2.482.104H
• Wikidata: Q27088379
• Pharos Ligand ID: DXQXNXSQXFP3
• ChEMBL ID: CHEMBL573339
• Mol file: 371935-74-9.mol

Synonyms:PI 103;PI-103;PI103

Chemical Property of PI-103

Chemical Property:

• Boiling Point: 520.25 °C at 760 mmHg
• PKA: 9.06±0.10(Predicted)
• Flash Point: 268.438 °C
• PSA: 84.51000
• Density: 1.409 g/cm³
• LogP: 3.84720
• Storage Temp.: Desiccate at +4°C
• Solubility.: Soluble in DMSO (up to 40 mg/ml)
• XLogP3: 2.7
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 2
• Exact Mass: 348.12224039
• Heavy Atom Count: 26
• Complexity: 489

Purity/Quality:

98%,99%, ^*data from raw suppliers

PI 103 hydrochloride ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: C1COCCN1C2=NC(=NC3=C2OC4=C3C=CC=N4)C5=CC(=CC=C5)O
• Description: PI-103 (371935-74-9) is a potent inhibitor of PI-3 kinase, mTOR and DNA-PK, IC50 = 8, 88, 150, 48,? 20, 83 and 2 nM for p110α, p110?, p110γ, p110δ, mTORC1, mTORC2 and DNA-PK respectively.1,2 Synergizes with arsenic disulfide to eradicate AML stem cells by induction of differentiation.3 Inhibits the growth of gefitinib-resistant non-small cell lung cancer cell lines.4 Induces autophagy in drug-resistant glioma.5 Protects against a-synuclein-induced toxicity in human neurons by induction of macroautophagy.6
• Uses: PI 103 is a dual inhbitor of Class IA phosphatidylinositol 3-kinase and mammalian target of rapaymycin complex 1 (mTORC1), both of which are involved in pathways often activated in myelogenous leukemia. PI 103 also functions to enhance tumour radiosensitivity.

Technology Process of PI-103

There total 12 articles about PI-103 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: 32.0%

morpholine (110-91-8,99108-56-2) + 3-(4-oxo-3,4-dihydropyrido[3′,2′:4,5]furo[3,2-d]pyrimidin-2-yl)phenyl acetate (371945-23-2) → 3-(4-(4-morpholinyl)pyrido[3',2':4,5]furo[3,2-d]pyrimidin-2-yl)phenol (371935-74-9)

Guidance literature:

3-(4-oxo-3,4-dihydropyrido[3′,2′:4,5]furo[3,2-d]pyrimidin-2-yl)phenyl acetate; With trichlorophosphate; for 3h; Reflux;

morpholine; In tetrahydrofuran; for 1.5h; Reflux;

DOI:10.1016/j.bmcl.2020.127258

Reference yield:

2-(3-methoxyphenyl)pyrido[3′,2′:4,5]furo[3,2-d]pyrimidin-4(3H)-one (371945-16-3) → 3-(4-(4-morpholinyl)pyrido[3',2':4,5]furo[3,2-d]pyrimidin-2-yl)phenol (371935-74-9)

Guidance literature:

Multi-step reaction with 4 steps

1: HBr / acetic acid / Heating

2: AcONa / Heating

3: phosphorus oxychloride / Heating

4: Heating

With hydrogen bromide; trichlorophosphate; sodium acetate; In acetic acid;

DOI:10.1016/j.bmcl.2007.02.032

Reference yield:

3-amino-furo[2,3-b]pyridine-2-carboxylic acid ethyl ester (371945-06-1) → 3-(4-(4-morpholinyl)pyrido[3',2':4,5]furo[3,2-d]pyrimidin-2-yl)phenol (371935-74-9)

Guidance literature:

Multi-step reaction with 9 steps

1: aq. NaOH / ethanol

2: SOCl₂ / Heating

3: aq. NH₃ / tetrahydrofuran

4: aq. NaOH / propan-2-ol / Heating

5: HBr / acetic acid / Heating

6: AcONa / Heating

7: phosphorus oxychloride / Heating

8: Heating

With ammonium hydroxide; sodium hydroxide; thionyl chloride; hydrogen bromide; trichlorophosphate; sodium acetate; In tetrahydrofuran; ethanol; acetic acid; isopropyl alcohol;

DOI:10.1016/j.bmcl.2007.02.032

upstream raw materials:

morpholine

2-(3-methoxyphenyl)pyrido[3′,2′:4,5]furo[3,2-d]pyrimidin-4(3H)-one

3-(4-oxo-3,4-dihydropyrido[3′,2′:4,5]furo[3,2-d]pyrimidin-2-yl)phenyl acetate

3-amino-furo[2,3-b]pyridine-2-carboxylic acid ethyl ester

Downstream raw materials:

C₂₃H₂₂N₄O₅

Refernces

• 1、 Hayakawa, Masahiko,Kaizawa, Hiroyuki,Moritomo, Hiroyuki,Koizumi, Tomonobu,Ohishi, Takahide,Yamano, Mayumi,Okada, Minoru,Ohta, Mitsuaki,Tsukamoto, Shin-ichi,Raynaud, Florence I.,Workman, Paul,Waterfield, Michael D.,Parker, Peter. "Synthesis and biological evaluation of pyrido[3′,2′:4,5]furo[3,2-d]pyrimidine derivatives as novel PI3 kinase p110α inhibitors". . p. 2438 - 2442. Retrieved 2008/02/05.