103906-34-9

Upstream product

• 1455-77-2 guanazole 
• 68-12-2 N,N-dimethyl-formamide 
• 98-86-2 acetophenone 
• 13788-90-4 3,3-dimethoxy-1-phenylpropan-1-one 
• 1201-93-0 1-phenyl-3-dimethylaminoprop-2-enone 
• 1455-77-2 guanazole 
• 100-52-7 benzaldehyde 
• 121-44-8 triethylamine 
• 1131-80-2 (E)-3-(N,N-dimethylamino)-1-phenyl-2-propen-1-one 

Relevant academic research and scientific papers

Vinylation of α-Aminoazoles with Triethylamine: A General Strategy to Construct Azolo[1,5-a]pyrimidines with a Nonsubstituted Ethylidene Fragment

A new general synthesis of pharmaceutically important azolo[1,5-a]pyrimidines starting from widely available 3(5)-aminoazoles, aldehydes, and triethylamine is developed. The key is to enable the vinylation reaction that allows the in situ generation of elusive acyclic enamines and the subsequent annulation reaction to occur. This direct and practical strategy is capable of constructing a range of 5,6-unsubstituted pyrazolo[1,5-a]pyrimidines and [1,2,4]triazolo[1,5-a]pyrimidines. More importantly, this protocol provides a concise synthetic route to prepare the clinically used zaleplon.

Synthesis method of [1, 2, 4] triazolo [1, 5-a] pyrimidine compound

The invention discloses a synthesis method of a [1, 2, 4] triazolo [1, 5-a] pyrimidine compound, and belongs to the technical field of organic synthesis. According to the technical scheme, the preparation method is characterized by comprising the following steps: dissolving an aldehyde compound, a 3-amino-1, 2, 4-triazole compound and triethylamine in a solvent toluene, then adding ammonium iodide and di-tert-butyl peroxide, and then reacting at 130 DEG C to prepare the target product [1, 2, 4] triazole [1, 5-a] pyrimidine compound. The synthesis process is simple and efficient, the [1, 2, 4] triazolo [1, 5-a] pyrimidine compound is directly prepared in one step through the one-pot cascade reaction without transition metal catalysis, the synthesis process is convenient to operate, the raw materials are simple, the reaction conditions are mild, the yield is high, the method has a very good application prospect, and meanwhile, the production cost is greatly reduced by taking triethylamine as the raw material.

1,2,4-Triazolo[1,5-a]pyrimidines: Efficient one-step synthesis and functionalization as influenza polymerase PA-PB1 interaction disruptors

In the search for new anti-influenza virus (IV) compounds, we have identified the 1,2,4-triazolo[1,5-a]pyrimidine (TZP) as a very suitable scaffold to obtain compounds able to disrupt IV RNA-dependent RNA polymerase (RdRP) PA-PB1 subunits heterodimerization. In this work, in order to acquire further SAR insights for this class of compounds and identify more potent derivatives, we designed and synthesized additional series of analogues to investigate the role of the substituents around the TZP core. To this aim, we developed four facile and efficient one-step procedures for the synthesis of 5-phenyl-, 6-phenyl- and 7-phenyl-2-amino-[1,2,4]triazolo[1,5-a]pyrimidines, and 2-amino-5-phenyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-ol. Two analogues having the ethyl carboxylate moiety at the C-2 position of the TZP were also prepared in good yields. Then, the scaffolds herein synthesized and two previous scaffolds were functionalized and evaluated for their anti-IAV activity, leading to the identification of compound 22 that showed both anti-PA-PB1 (IC50 = 19.5 μM) and anti-IAV activity (EC50 = 16 μM) at non-toxic concentrations, thus resulting among the most active TZP derivatives reported to date by us. A selection of the synthesized compounds, along with a set of in-house available analogues, was also tested against SARS-CoV-2. The most promising compound 49 from this series displayed an EC50 value of 34.47 μM, highlighting the potential of the TPZ scaffold in the search for anti-CoV agents.

Triazolopyrimidine and triazolopyridine scaffolds as TDP2 inhibitors

Tyrosyl-DNA phosphodiesterase 2 (TDP2) repairs topoisomerase II (TOP2) mediated DNA damages and causes cellular resistance to clinically used TOP2 poisons. Inhibiting TDP2 can potentially sensitize cancer cells toward TOP2 poisons. Commercial compound P10A10, to which the structure was assigned as 7-phenyl triazolopyrimidine analogue 6a, was previously identified as a TDP2 inhibitor hit in our virtual and fluorescence-based biochemical screening campaign. We report herein that the hit validation through resynthesis and structure elucidation revealed the correct structure of P10A10 (Chembridge ID 7236827) to be the 5-phenyl triazolopyrimidine regioisomer 7a. Subsequent structure–activity relationship (SAR) via the synthesis of a total of 47 analogues of both the 5-phenyl triazolopyrimidine scaffold (7) and its bioisosteric triazolopyridine scaffold (17) identified four derivatives (7a, 17a, 17e, and 17z) with significant TDP2 inhibition (IC50 50 μM), with 17z showing excellent cell permeability and no cytotoxicity.

Triazolopyridines as selective JAK1 inhibitors: From hit identification to GLPG0634

Janus kinases (JAK1, JAK2, JAK3, and TYK2) are involved in the signaling of multiple cytokines important in cellular function. Blockade of the JAK-STAT pathway with a small molecule has been shown to provide therapeutic immunomodulation. Having identified

[1,2,4 ]TRIAZOLO [1,5-A]PYRIMIDIN-2-YLUREA DERIVATIVE AND USE THEREOF

Novel [1,2,4]triazolo[1,5-a]pyrimidine derivative of the general formula (1): (1) its prodrug or a pharmaceutically acceptable salt thereof, which exhibits an antigen presentation inhibiting activity and is useful as a preventive and/or therapeutic agent for immunological rejection and/or graft versus host reaction in organ/bone marrow transplant, autoimmune disease, allergic disease and/or inflammatory disease and also useful as an anticancer drug or as an immunological tolerance inducer for transplanted organ/transplanted bone marrow.

SUBSTITUTED 2-AMINO- 1,2,4 TRIAZOLO 1,5-a PYRIMIDINE DERIVATIVE AND USE THEREOF

Disclosed is a [1,2,4]triazolo[1,5-a]pyrimidine derivative represented by the general formula (I) below or a pharmaceutically acceptable salt thereof. Also disclosed is a medicine containing such a derivative or a salt thereof as an active constituent. In