1282512-48-4

Usage

Uses

Used in Oncology:
GDC-0032 is used as an antitumor agent for the treatment of cancer. It targets the PI3K pathway, which is commonly dysregulated in various cancers, leading to uncontrolled cell growth and proliferation. By inhibiting the PI3K isoforms α, δ, and γ, GDC-0032 can effectively suppress tumor growth and has shown promising results in mouse xenograft models at low drug dose levels.
Used in Drug Development:
GDC-0032 is used as a lead compound in the development of new cancer therapies. Its high potency, selectivity, and in vivo antitumor activity make it a valuable candidate for further research and optimization to improve its pharmacokinetic properties and therapeutic potential.
Used in Cancer Research:
GDC-0032 is used as a research tool to study the role of the PI3K pathway in cancer. Its ability to selectively inhibit specific PI3K isoforms allows researchers to investigate the molecular mechanisms underlying the PI3K pathway's involvement in cancer development and progression, as well as to identify potential biomarkers and therapeutic targets for cancer treatment.
Used in Combination Therapy:
GDC-0032 is used in combination with other cancer therapies to enhance their efficacy and overcome drug resistance. Its ability to target the PI3K pathway, which is often implicated in resistance to conventional chemotherapy and targeted therapies, makes it a promising candidate for combination treatments to improve patient outcomes in various cancer types.

references

[1] ndubaku co1, heffron tp, staben st, baumgardner m, blaquiere n, bradley e, bull r, do s, dotson j, dudley d, edgar ka, friedman ls, goldsmith r, heald ra, kolesnikov a, lee l, lewis c, nannini m, nonomiya j, pang j, price s, prior ww, salphati l, sideris s, wallin jj, wang l, wei b, sampath d, olivero ag. discovery of 2-{3-[2-(1-isopropyl-3-methyl-1h-1,2-4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl]-1h-pyrazol-1-yl}-2-methylpropanamide (gdc-0032): a β-sparing phosphoinositide 3-kinase inhibitor with high unbound exposure and robust in vivo antitumor activity. j med chem. 2013 jun 13;56(11):4597-610.

Upstream product

• 1282514-64-0 ethyl 2-(4-(2-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl)-1H-pyrazol-1-yl)-2-methylpropanoate 
• 1282513-03-4 2-(4-(2-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl)-1H-pyrazol-1-yl)-2-methylpropanoic acid 
• 1282514-63-9 9-bromo-2-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f ]imidazo[1,2-d][1,4]oxazepine 
• 1282518-81-3 C₁₃H₂₂BN₃O₃ 
• 22532-62-3 4-bromosalicylaldehyde 
• 1282516-66-8 5-bromo-2-(1H-imidazol-2-yl)phenol 
• 1282516-67-9 9-bromo-5,6-dihydrobenzo[f ]imidazo[1,2-d][1,4]oxazepine 
• 1282516-68-0 9-bromo-2,3-diiodo-5,6-dihydrobenzo[f ]imidazo[1,2-d][1,4]oxazepine 
• 1282516-69-1 9-bromo-2-iodo-5,6-dihydrobenzo[f ]imidazo[1,2-d][1,4]oxazepine 
• 1282516-65-7 9-bromo-5,6-dihydrobenzo[f ]imidazo[1,2-d][1,4]oxazepine-2-carboxamide 
• 1201657-32-0 ethyl 2-methyl-2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)propanoate 
• 1401305-30-3 1-isopropyl-3-methyl-1H-1,2,4-triazole 
• 105942-08-3 4-bromo-6-fluorobenzonitrile 
• 1282516-76-0 5-(2-(4-bromo-2-fluorophenyl)-1H-imidazol-4-yl)-1-isopropyl-3-methyl-1H-1,2,4-triazole 

Downstream Products

• 1282514-64-0 ethyl 2-(4-(2-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl)-1H-pyrazol-1-yl)-2-methylpropanoate 

Relevant academic research and scientific papers

Manufacture of the PI3K β-Sparing Inhibitor Taselisib. Part 2: Development of a Highly Efficient and Regioselective Late-Stage Process

A highly efficient and regioselective manufacturing route for the phosphoinositide 3-kinase β-sparing inhibitor taselisib was developed. Highlights of the synthesis include: (1) magnesium-mediated formation of a challenging cyclic amidine; (2) regioselect

PROCESS FOR MAKING BENZOXAZEPIN COMPOUNDS

Processes are described for the preparation of PI3K inhibitor, GDC-0032, Formula (I), having the structure: Formula (I) (GDC-0032), and intermediates useful for the preparation of (I).

MUTANT SELECTIVITY AND COMBINATIONS OF A PHOSPHOINOSITIDE 3 KINASE INHIBITOR COMPOUND AND CHEMOTHERAPEUTIC AGENTS FOR THE TREATMENT OF CANCER

Methods and compositions are provided for treating hyperproliferative disorders in patients with a PI3K inhibitor, GDC-0032 as a single agent or in combination with chemotherapeutic agents.

Discovery of 2-{3-[2-(1-isopropyl-3-methyl-1H-1,2-4-triazol-5-yl)-5,6- dihydrobenzo[f]imidazo[1,2- d ][1,4]oxazepin-9-yl]-1H-pyrazol-1-yl}-2- methylpropanamide (GDC-0032): A β-sparing phosphoinositide 3-kinase inhibitor with high unbound exposure and robust in vivo antitumor activity

Dysfunctional signaling through the phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway leads to uncontrolled tumor proliferation. In the course of the discovery of novel benzoxepin PI3K inhibitors, we observed a strong dependency of in vivo antitumor activity on the free-drug exposure. By lowering the intrinsic clearance, we derived a set of imidazobenzoxazepin compounds that showed improved unbound drug exposure and effectively suppressed growth of tumors in a mouse xenograft model at low drug dose levels. One of these compounds, GDC-0032 (11l), was progressed to clinical trials and is currently under phase I evaluation as a potential treatment for human malignancies.

BENZOXAZEPIN PI3K INHIBITOR COMPOUNDS AND METHODS OF USE

Benzoxazepin compounds of Formula I, including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, wherein: Z1 is CR1 or N; Z2 is CR2 or N; Z3 is CR3 or N; Z4 is CR4 or N; and B is a pyrazolyl, imidazolyl, or triazolyl ring fused to the benzoxepin ring, are useful for inhibiting lipid kinases including p110 alpha and other isoforms of PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.