943320-53-4

Usage

Uses

3-Ethynylimidazo[1,2-a]pyridine can be prepared to use as antibacterial agents.

Upstream product

• 1148027-21-7 3-[2-(trimethylsilyl)ethynyl]imidazo[1,2-a]pyridine 
• 17175-39-2 N,N-dimethyl-N'-pyridin-2-yl-formamidine 
• 504-29-0 2-aminopyridine 
• 307503-19-1 3-iodo-imidazo[1,2-a]pyridine 
• 1066-54-2 trimethylsilylacetylene 
• 274-76-0 imidazo[1,2-a]pyridine 
• 4926-47-0 3-bromoimidazo[1,2-a]pyridine 

Downstream Products

• 1407999-86-3 C₃₀H₂₉F₃N₈O 
• 1428445-67-3 C₂₇H₂₇F₃N₈O 

Relevant academic research and scientific papers

NEW COMPOUNDS AND METHODS

The present invention relates to compounds of Formula (I) or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, optical isomer, N-oxide, and/or prodrug thereof. The present invention also relates to pharmaceutical compositions comprising the compounds of the invention, and to their use in the treatment or prevention of medical conditions in which inhibition of c-ABL is beneficial. (I)

Facile synthesis of 3-substituted imidazo[1,2-: A] pyridines through formimidamide chemistry

A facile entry to 3-aryl/alkenyl/alkynyl substituted imidazo[1,2-a]pyridines (3a-p, 6a-d & 9a-9e) has been developed from readily available benzyl/allyl/propargyl halides and 2-amino pyridines as substrates via formimidamide chemistry that is devoid of caustic or expensive reagents, such as transition metal complexes. Quantum chemical calculations performed to understand the underlying mechanism of the transformation revealed a preference for intramolecular Mannich-type addition over pericyclic 1,5-electrocyclization for the systems reported herein that enable a Baldwin allowed 5-exo-trig cyclization instead of a formally anti-Baldwin 5-endo-trig process.

Deuterated acetylene derivatives, its pharmaceutical composition and application

The invention discloses a deuterated acetylenic derivative, a pharmaceutical composition and application thereof. The deuterated acetylenic derivative comprises one or more of the deuterated acetylenic derivative (I) with curative effective dose, pharmace

Preparation method of novel fluorescent probe used for detecting diamine

The invention discloses a preparation method of a novel fluorescent probe used for detecting diamine. According to the preparation method, 2-aminopyridine is taken as an initial raw material, and a novel fluorescent probe compound 3-(imidazo[1,2-a]pyridine-3-yl)-1-phenyl-2-alkynyl-1-one is obtained via four steps of reaction. It is confirmed by study that a reaction product of the novel fluorescent probe compound with diamine possesses fluorescence performance, and the fluorescent intensity is increased with the increasing of concentration of diamine; and the fluorescence intensification factor is linearly dependent to the concentration of diamine; so that the novel fluorescent probe compound can be taken as a high sensitivity fluorescent probe used for detecting diamine.

Anti-tumor activity with acetylene derivatives

The present invention relates to an aromatic ring disubstituted acetylene derivative of formula I, a pharmaceutical composition comprising the compound, and a use of the compound and of the pharmaceutical composition in the treatment and/or prevention of tumors, where A, B, T, M, Ra, Rb, Rt, m, n, and p are as defined in the present document.

HYBRID NECROPTOSIS INHIBITORS

The present invention relates to heterocyclic compounds (e.g., compounds described by Formula (I)) and pharmaceutically acceptable salts thereof. The invention also features pharmaceutical compositions that include these compounds and their use in therapy for treating conditions in which necroptosis is likely to play a substantial role. The heterocyclic compounds described herein can also achieve improved activity and selectivity towards RIP1 and/or RIP3.

METHODS AND COMPOSITIONS FOR RAF KINASE MEDIATED DISEASES

The invention discloses methods and compositions for treating or preventing RAF kinase mediated diseases or conditions by administering a compound of Formula 1: or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the variables are defined as herein.

Rapid discovery of a novel series of Abl kinase inhibitors by application of an integrated microfluidic synthesis and screening platform

Drug discovery faces economic and scientific imperatives to deliver lead molecules rapidly and efficiently. Using traditional paradigms the molecular design, synthesis, and screening loops enforce a significant time delay leading to inefficient use of data in the iterative molecular design process. Here, we report the application of a flow technology platform integrating the key elements of structure-activity relationship (SAR) generation to the discovery of novel Abl kinase inhibitors. The platform utilizes flow chemistry for rapid in-line synthesis, automated purification, and analysis coupled with bioassay. The combination of activity prediction using Random-Forest regression with chemical space sampling algorithms allows the construction of an activity model that refines itself after every iteration of synthesis and biological result. Within just 21 compounds, the automated process identified a novel template and hinge binding motif with pIC50 > 8 against Abl kinase - both wild type and clinically relevant mutants. Integrated microfluidic synthesis and screening coupled with machine learning design have the potential to greatly reduce the time and cost of drug discovery within the hit-to-lead and lead optimization phases.

Design, synthesis, and biological evaluation of 3-(1H-1,2,3-triazol-1-yl) benzamide derivatives as potent pan Bcr-Abl inhibitors including the threonine315←isoleucine315 mutant

A series of 3-(1H-1,2,3-triazol-1-yl)benzamide derivatives were designed and synthesized as new Bcr-Abl inhibitors by using combinational strategies of bioisosteric replacement, scaffold hopping, and conformational constraint. The compounds displayed significant inhibition against a broad spectrum of Bcr-Abl mutants including the gatekeeper T315I and p-loop mutations, which are associated with disease progression in CML. The most potent compounds 6q and 6qo strongly inhibited the kinase activities of Bcr-AblWT and Bcr-AblT315I with IC50 values of 0.60, 0.36 and 1.12, 0.98 nM, respectively. They also potently suppressed the proliferation of K562, KU812 human CML cells, and a panel of murine Ba/F3 cells ectopically expressing either Bcr-AblWT or any of a panel of other Bcr-Abl mutants that have been shown to contribute to clinical acquired resistance, including Bcr-AblT315I, with IC50 values in low nanomolar ranges. These compounds may serve as lead compounds for further development of new Bcr-Abl inhibitors capable of overcoming clinical acquired resistance against imatinib.

Discovery of 3-[2-(imidazo[1,2- b ]pyridazin-3-yl)ethynyl]-4-methyl- N -{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide (AP24534), a potent, orally active pan-inhibitor of breakpoint cluster region-abelson (BCR-ABL) kinase including the T315I gatekeeper mutant

In the treatment of chronic myeloid leukemia (CML) with BCR-ABL kinase inhibitors, the T315I gatekeeper mutant has emerged as resistant to all currently approved agents. This report describes the structure-guided design of a novel series of potent pan-inhibitors of BCR-ABL, including the T315I mutation. A key structural feature is the carbon-carbon triple bond linker which skirts the increased bulk of Ile315 side chain. Extensive SAR studies led to the discovery of development candidate 20g (AP24534), which inhibited the kinase activity of both native BCR-ABL and the T315I mutant with low nM IC 50s, and potently inhibited proliferation of corresponding Ba/F3-derived cell lines. Daily oral administration of 20g significantly prolonged survival of mice injected intravenously with BCR-ABLT315I expressing Ba/F3 cells. These data, coupled with a favorable ADME profile, support the potential of 20g to be an effective treatment for CML, including patients refractory to all currently approved therapies.