Pictilisib

Base Information

• Chemical Name: Pictilisib
• CAS No.: 957054-30-7
• Molecular Formula: C23H27N7O3S2
• Molecular Weight: 513.644
• Hs Code.: 29350090
• UNII: ICY00EMP8P
• ChEMBL ID: CHEMBL521851
• DSSTox Substance ID: DTXSID40241930
• Metabolomics Workbench ID: 63787
• NCI Thesaurus Code: C165479
• Nikkaji Number: J2.731.432E
• Pharos Ligand ID: NWV29BXUZHUK
• Wikidata: Q27088388
• Mol file: 957054-30-7.mol

Synonyms:2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine;GDC 0941;GDC-0941;GDC0941;pictilisib

Chemical Property of Pictilisib

Chemical Property:

• Refractive Index: 1.753
• PKA: 12.22±0.40(Predicted)
• PSA: 144.17000
• Density: 1.53 g/cm³
• LogP: 3.17000
• Storage Temp.: -20°C
• Solubility.: Soluble in DMSO (>25 mg/ml)
• XLogP3: 1.6
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 10
• Rotatable Bond Count: 5
• Exact Mass: 513.16168010
• Heavy Atom Count: 35
• Complexity: 832

Purity/Quality:

99.9% ^*data from raw suppliers

2-(1H-Indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine 95+% ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CS(=O)(=O)N1CCN(CC1)CC2=CC3=C(S2)C(=NC(=N3)C4=C5C=NNC5=CC=C4)N6CCOCC6
• Recent ClinicalTrials: GDC-0941 and Cisplatin in Treating Patients With Androgen Receptor-Negative Triple Negative Metastatic Breast Cancer
• Recent EU Clinical Trials: A PHASE II, RANDOMIZED STUDY OF PACLITAXEL WITH GDC-0941 VERSUS PACLITAXEL WITH PLACEBO IN PATIENTS WITH LOCALLY RECURRENT OR METASTATIC BREAST CANCER
• Recent NIPH Clinical Trials: Phase I Study of GDC-0941
• Description: GDC-0941/Pictilisib (957054-30-7) is a potent and selective inhibitor of class I phosphatidylinositol-3-kinases (PI3K) with significant antitumor activity – IC50’s: PI3Kα = 3nM, PI3Kβ = 33 nM, PI3Kδ = 3 nM, PI3Kγ = 75 nM.1,2?? GDC-0941 is the chemical probe of choice for the pan-inhibition of class I PI3K’s.3?Currently in clinical trials.4
• Uses: GDC-0941 is a potent and selective oral inhibitor of the class I PI3K. GDC-0941 demonstrated broad spectrum of activity in breast, ovarian, lung, and prostate cancer models. Studies has also shown GDC -0941 may enhance anti-tumor activity of Docetaxel (D494420) in human breast cancer models. GDC-0941 is a potent and selective oral inhibitor of the class I PI3K. GDC-0941 demonstrated broad spectrum of activity in breast, ovarian, lung, and prostate cancer models. Studies has also shown GDC-0941 may enhance anti-tumor activity of Docetaxel (D494420) in human breast cancer models. Potent PI3K inhibitor.

Technology Process of Pictilisib

There total 2 articles about Pictilisib 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:

4-(2-chloro-6-((4-(methylsulfonyl)piperazin-1-yl)methyl)thieno[3,2-d]-pyrimidin-4-yl)morpholine (885675-66-1) + bis(pinacol)diborane (73183-34-3) + 4-bromoindazole (186407-74-9) → pictilisib (957054-30-7)

Guidance literature:

bis(pinacol)diborane; 4-bromoindazole; With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In dimethyl sulfoxide; at 80 ℃; for 40h; Inert atmosphere;

4-(2-chloro-6-((4-(methylsulfonyl)piperazin-1-yl)methyl)thieno[3,2-d]-pyrimidin-4-yl)morpholine; With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In ethanol; toluene; at 130 ℃; for 1.5h; Microwave irradiation;

DOI:10.1021/jm800295d

Reference yield:

4-bromoindazole (186407-74-9) → pictilisib (957054-30-7)

Guidance literature:

Multi-step reaction with 2 steps

1: potassium acetate / (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / dimethyl sulfoxide / 40 h / 80 °C / Inert atmosphere

2: sodium hydrogencarbonate / bis-triphenylphosphine-palladium(II) chloride / toluene; ethanol; water / 1 h / 120 °C / Inert atmosphere; Microwave irradiation

With potassium acetate; sodium hydrogencarbonate; bis-triphenylphosphine-palladium(II) chloride; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In ethanol; water; dimethyl sulfoxide; toluene;

Reference yield: 53.91%

pictilisib (957054-30-7) + triethylene glycol di-(p-toluenesulfonate) (19249-03-7) → 2-(2-(2-(4-(6-((4-(methylsulfonyl)piperazin-1-yl)methyl)-4-morpholinothieno[3,2-d]pyrimidin-2-yl)-1H-indazol-1-yl)ethoxy)ethoxy)ethyl 4-methylbenzenesulfonate

Guidance literature:

With potassium carbonate; In acetonitrile; at 70 ℃;

DOI:10.1021/acs.molpharmaceut.9b00690

upstream raw materials:

4-(2-chloro-6-((4-(methylsulfonyl)piperazin-1-yl)methyl)thieno[3,2-d]-pyrimidin-4-yl)morpholine

bis(pinacol)diborane

4-bromoindazole

Downstream raw materials:

4-(2-(1H-indazol-4-yl)-6-((4-(methylsulfonyl)-piperazin-1-yl)methyl)thieno[3,2-d]pyrimidin-4-yl)-morpholine bis-methanesulfonate

Refernces

• 1、 -. "TREATMENT OF CANCERS HAVING K-RAS MUTATIONS". . . Retrieved 2013/05/08.
• 2、 Folkes, Adrian J.,Ahmadi, Khatereh,Alderton, Wendy K.,Alix, Sonia,Baker, Stewart J.,Box, Gary,Chuckowree, Irina S.,Clarke, Paul A.,Depledge, Paul,Eccles, Suzanne A.,Friedman, Lori S.,Hayes, Angela,Hancox, Timothy C.,Kugendradas, Arumugam,Lensun, Letitia,Moore, Pauline,Olivero, Alan G.,Pang, Jodie,Patel, Sonal,Pergl-Wilson, Giles H.,Raynaud, Florence I.,Robson, Anthony,Saghir, Nahid,Salphati, Laurent,Sohal, Sukhjit,Ultsch, Mark H.,Valenti, Melanie,Wallweber, Heidi J. A.,Nan, Chi Wan,Wiesmann, Christian,Workman, Paul,Zhyvoloup, Alexander,Zvelebil, Marketa J.,Shuttleworth, Stephen J.. "The identification of 2-(1H-indazol-4-yl)-6-(4-methanesulfonyl-piperazin-1- ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine (GDC-0941) as a potent, selective, orally bioavailable inhibitor of class I PI3 kinase for the treatment of cancer". experimental part. p. 5522 - 5532. Retrieved 2009/09/06.