99451-55-5

Usage

Uses

Used in Pharmaceutical Industry:
8-Bromo-5-(methylthio)[1,2,4]triazolo[4,3-c]pyrimidine serves as a key intermediate in the synthesis of various bioactive molecules due to its ability to inhibit different enzymes. Its unique structure allows for the development of drugs targeting specific enzyme pathways, which is crucial for treating a range of diseases and conditions.
Used in Medicinal Chemistry:
As a building block in medicinal chemistry, 8-Bromo-5-(methylthio)[1,2,4]triazolo[4,3-c]pyrimidine is utilized for the creation of novel compounds with potential therapeutic applications. Its versatility in chemical modifications enables the design of molecules with enhanced potency, selectivity, and pharmacokinetic properties.
Used in Antifungal Applications:
8-Bromo-5-(methylthio)[1,2,4]triazolo[4,3-c]pyrimidine is considered for its antifungal properties, making it a candidate for the development of new antifungal agents. These agents are essential for combating fungal infections, which are a significant concern in both human medicine and agriculture.
Used in Antiparasitic Applications:
8-Bromo-5-(methylthio)[1,2,4]triazolo[4,3-c]pyrimidine has also demonstrated potential antiparasitic activities, positioning it as a candidate for the development of new treatments against parasitic diseases. This is particularly important in regions where parasitic infections are prevalent and can have severe health implications.

Upstream product

• 67-56-1 methanol 
• 875-96-7 5-bromo-4-hydrazineyl-2-(methylthio)pyrimidine 
• 149-73-5 trimethyl orthoformate 
• 122-51-0 orthoformic acid triethyl ester 
• 63810-78-6 4?chloro?5?bromo?2?(methylthio)pyrimidine 

Downstream Products

• 1951408-58-4 N-((5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl)-8-(2-methylpyridin-3-yl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine 

Relevant academic research and scientific papers

Degradation of Polycomb Repressive Complex 2 with an EED-Targeted Bivalent Chemical Degrader

Protein degradation via the use of bivalent chemical degraders provides an alternative strategy to block protein function and assess the biological roles of putative drug targets. This approach capitalizes on the advantages of small-molecule inhibitors while moving beyond the restrictions of traditional pharmacology. Here, we report a chemical degrader (UNC6852) that targets polycomb repressive complex 2 (PRC2). UNC6852 contains an EED226-derived ligand and a ligand for VHL which bind to the WD40 aromatic cage of EED and CRL2VHL, respectively, to induce proteasomal degradation of PRC2 components, EED, EZH2, and SUZ12. Degradation of PRC2 with UNC6852 blocks the histone methyltransferase activity of EZH2, decreasing H3K27me3 levels in HeLa cells and diffuse large B cell lymphoma (DLBCL) cells containing EZH2 gain-of-function mutations. UNC6852 degrades both wild-type and mutant EZH2, and additionally displays anti-proliferative effects in this cancer model system. Using an EED-targeted chemical degrader, Potjewyd et al. demonstrate successful degradation of the PRC2 complex. UNC6852 provides a unique tool to study PRC2 function and downregulation of PRC2 activity in cancer and demonstrates the feasibility of developing PRC2-targeted degraders as potential therapeutics.

Diverse, Potent, and Efficacious Inhibitors That Target the EED Subunit of the Polycomb Repressive Complex 2 Methyltransferase

Aberrant activity of the histone methyltransferase polycomb repressive complex 2 (PRC2) has been linked to several cancers, with small-molecule inhibitors of the catalytic subunit of the PRC2 enhancer of zeste homologue 2 (EZH2) being recently approved fo

Free energy perturbation in the design of EED ligands as inhibitors of polycomb repressive complex 2 (PRC2) methyltransferase

Free Energy Perturbation (FEP) calculations can provide high-confidence predictions of the interaction strength between a ligand and its protein target. We sought to explore a series of triazolopyrimidines which bind to the EED subunit of the PRC2 complex

IMIDAZOPYRIMIDINE DERIVATIVES

The present disclosure provides a compound of Formula (I): or a pharmaceutically acceptable salt thereof as described herein. The present disclosure also provides pharmaceutical compositions comprising a compound of Formula I, processes for preparing compounds of Formula I, therapeutic methods for treating cancers.

Discovery of First-in-Class, Potent, and Orally Bioavailable Embryonic Ectoderm Development (EED) Inhibitor with Robust Anticancer Efficacy

Overexpression and somatic heterozygous mutations of EZH2, the catalytic subunit of polycomb repressive complex 2 (PRC2), are associated with several tumor types. EZH2 inhibitor, EPZ-6438 (tazemetostat), demonstrated clinical efficacy in patients with acceptable safety profile as monotherapy. EED, another subunit of PRC2 complex, is essential for its histone methyltransferase activity through direct binding to trimethylated lysine 27 on histone 3 (H3K27Me3). Herein we disclose the discovery of a first-in-class potent, selective, and orally bioavailable EED inhibitor compound 43 (EED226). Guided by X-ray crystallography, compound 43 was discovered by fragmentation and regrowth of compound 7, a PRC2 HTS hit that directly binds EED. The ensuing scaffold hopping followed by multiparameter optimization led to the discovery of 43. Compound 43 induces robust and sustained tumor regression in EZH2MUT preclinical DLBCL model. For the first time we demonstrate that specific and direct inhibition of EED can be effective as an anticancer strategy.

CRYSTALLINE FORMS OF TRIAZOLOPYRIMIDINE COMPOUND

Provided herein are crystalline forms of a triazolopyrimidine compound, which is useful for treating a PRC2-mediated disease or disorder.

TRIAZOLOPYRIMIDINE COMPOUNDS AND USES THEREOF

A compound of Formula (I), or a pharmaceutically acceptable salt thereof, is provided that has been shown to be useful for treating a PRC2-mediated disease or disorder: wherein R1, R2, R3, R4, R5, and n are as defined herein.