Synthesis of Imidazo[2, 1-a]phthalazines, Potential Inhibitors of p38 MAP Kinase. Prediction of Binding Affinities of Protein Ligands

Abstract

Based upon molecular modeling, the pharmacophore of potential inhibitors of p38 MAPK (mitogen‐activated protein kinases) is discussed and the predictive binding affinities are calculated. Syntheses of original diarylimidazo[2, 1‐a]phthalazines obtained by Suzuki coupling are described.

Cancer Exosomes Perform Cell-Independent MicroRNA Biogenesis and Promote Tumorigenesis

“…Similar to results previously published, MCF10A cells did not form tumors in nude mice (Mavel et al, 2002; Thery et al, 2002) (Figure 6I). MCF10A cells co-injected with cancer exosomes formed tumors, whereas MCF10A cells co-injected with cancer exosomes containing Dicer antibody (but not control anti-actin antibodies) showed a significant reduction in tumor growth (Figure 6I; Figure S6H).…”

Sonogashira Reaction: Synthesis of Novel Derivatives of 3‐Aryl‐Substituted 6‐Chloroimidazo[2, 1‐a]phthalazines Catalyzed by Pd‐Cu in Water

“…Surprisingly, we found that water was an efficient solvent for the reaction in the presence of potassium carbonate and sodium dodecyl sulfate (Table 1, entry 13). Also several catalytic palladium sources such as PdCl 2 , Pd/C, Pd(OAc) 2 , and PdCl 2 /PPh 3 were screened in water (Table 1, entries [14][15][16][17]. It is obvious that the use of Pd(PPh 3 ) 2 Cl 2 is the best reaction condition (Table 1, entry, 13).…”

“…The imidazophthalazine derivatives are of wide interest due to their diverse biological activities and clinical applications. Their core ring system is present in numerous compounds that possess properties such as inhibitors of p38 MAP kinase, [15] potential cytotoxic activity against several human tumor cells, [16] and benzodiazepine receptor binding activity. [17] Although several procedures have been developed for the synthesis of imidazo[2, 1-a]phthalazines, [18] no example involving arylation of imidazo-phthalazines through Sonogashira reactions has yet been reported in the literature.…”

Ceric Ammonium Nitrate (CAN)–Catalyzed Multicomponent Reactions: An Efficient Catalyst for Green Organic Synthesis

“…Phthalazine derivatives, that have two bridgehead nitrogen atoms in a fused ring system, have attracted considerable attention because of their pharmacological and biological properties, potential clinical application [75][76][77][78][79][80][81][82][83] and promising luminescent and fluorescent probes. [84] The synthesis of 1H-indazolo[1,2-b]phthalazine-1,6,11-trione derivatives have been achieved by Kidwai and colleagues via a convenient one-pot protocol using phthalhydrazide, cyclic-β-diketone and aldehydes catalyzed by CAN (5 mol%) in polyethylene glycol (PEG) at ambient temperature (Scheme 19).…”