38353-02-5

Upstream product

• 59-97-2 tolazoline hydrochloride 
• 65-85-0 benzoic acid 
• 98-88-4 benzoyl chloride 
• 76100-32-8 2-Benzylimidazol-4,5-dicarbonsaeure 
• 288-32-4 1H-imidazole 
• 14700-62-0 2-benzyl-1H-imidazole 

Downstream Products

• 49822-56-2 (4-chloro-phenyl)-(1H-imidazol-2-yl)-phenyl-methanol 
• 1214718-72-5 ethyl 8-phenylimidazo[1,2-a]pyridine-7-carboxylate 
• 1214718-73-6 ethyl 6-methyl-8-phenylimidazo[1,2-a]pyridine-7-carboxylate 
• 1071449-91-6 C₃₁H₂₇N₃O₃ 
• 122430-51-7 (4,5-dibromo-1H-imidazol-2-yl)-phenyl ketone 
• 179332-87-7 2-(benzoyl)-4⁽⁵⁾-[(4-(2-pyrimidinyl)-piperazin-1-yl)-methyl]-imidazole 

Relevant academic research and scientific papers

Copper-Catalyzed Synthesis of Fused Imidazopyrazine N-Oxide Skeletons

N-Propargyl-2-aroylimidazoles synthesized and converted into the corresponding ketoximes. Under various conditions, several mono- and diketoxime imidazole derivatives were formed by converting the carbonyl or carbonyl and propargyl groups into oxime groups. N -Propargyl monooxime imidazole derivatives were cyclized by treatment with CuI to give various imidazopyrazine N -oxides. Several copper salts, such as CuOAc, CuSO 4, and CuOTf, formed the same cyclization product. This cyclization reaction occurred only in the presence of Cu(I) or Cu(II) salts; other transition metals such as Au, Ag, In, and Fe did not yield cyclic products. The nucleus-independent chemical shift method was used to calculate the aromaticity of the bicyclic rings.

Design, synthesis, structure-activity relationships study and X-ray crystallography of 3-substituted-indolin-2-one-5-carboxamide derivatives as PAK4 inhibitors

We have previously described the identification of indolin-2-one-5-carboxamides as potent PAK4 inhibitors. This study expands the structure-activity relationships on our original series by presenting several modifications in the lead compounds, 2 and 3. A series of novel derivatives was designed, synthesized, and evaluated in biochemical and cellular assay. Most of this series displayed nanomolar biochemical activity and potent antiproliferative activity against A549 and HCT116 cells. The representative compound 10a exhibited excellent enzyme inhibition (PAK4 IC50 = 25 nM) and cellular potency (A549 IC50 = 0.58 μM, HCT116 IC50 = 0.095 μM). An X-ray structure of compound 10a bound to PAK4 was obtained. Crystallographic analysis confirmed predictions from molecular modeling and helped refine SAR results. In addition, Compound 10a displayed focused multi-targeted kinase inhibition, good calculated drug-likeness properties. Further profiling of compound 10a revealed it showed weak inhibitory activity against various isoforms of human cytochrome P450.

The design, synthesis, and biological evaluation of potent receptor tyrosine kinase inhibitors

Variously substituted indolin-2-ones were synthesized and evaluated for activity against KDR, Flt-1, FGFR-1 and PDGFR. Extension at the 5-position of the oxindole ring with ethyl piperidine (compound 7i) proved to be the most beneficial for attaining both biochemical and cellular potencies. Further optimization of 7i to balance biochemical and cellular potencies with favorable ADME/ PK properties led to the identification of 8h, a compound with a clean CYP profile, acceptable pharmacokinetic and toxicity profiles, and robust efficacy in multiple xenograft tumor models.

Facile synthesis of imidazo[1,2-a]pyridines via tandem reaction

An efficient method for the synthesis of 5,6,7-trisubstituted imidazo[1,2-a]pyridines was developed. The products were obtained in good yields under mild conditions.

Imidazotriazinone inhibitors of the Ca2+-calmodulin sensitive phosphodiesterase (PDE I)

Hybrid structural analogs 1 of the PDE V and PDE III inhibitors, zaprinast, milrinone, and CI-930 were prepared to identify dual PDE inhibitors. The SAR study led unexpectedly to the identification of WIN 61691 (8d), a potent inhibitor of PDE I (IC50 = 85 nM). A potent and selective inhibitor of PDE I would be a useful tool to elucidate the physiologic function of PDE I and other PDE isozymes in biological systems.

1H-IMIDAZOLE PREPARATION VIA PERMANGANATE DEHYDROGENATION OF 2-IMIDAZOLINES

Permanganate and manganate ions were evaluated as dehydrogenating agents in the conversion of 2-substituted 2-imidazolines into the corresponding 2-substituted imidazoles.It was found that permanganate ion in dry dioxane efficiently performs this transformation rendering this method competitive with related procedures.