JNJ-42756493 anti-proliferative activity against cancer cells lines from multiple origins.. Detailed data supporting Figure 2.

Efficacy of JNJ-42756493 against human tumor xenograft models from different origins and FGFR alteration status. Mice bearing xenograft tumors (100-200mm3) were treated with 25mg/kg of JNJ-42756493 QD for indicated time and percent tumor growth inhibition (%TGI) compared to vehicle treated animal calculated at end of treatment.

A) Structure of JNJ-42541707, a structurally related compound to JNJ-42756493. B) 72h growth inhibition (IC50) of JNJ-42541707 against 236 cancer cell lines from multiple origins color coded based on FGFR1,2,4 mRNA overexpression and FGFR WT.

Supplementary Data from JNJ-26481585, a Novel Second-Generation Oral Histone Deacetylase Inhibitor, Shows Broad-Spectrum Preclinical Antitumoral Activity

In vitro kinase inhibition by DiscoverX KinomeScan assay. For details see (19)

Inhibitory activity of Brivanib and JNJ-42756943 in kinase (top) and BaF3 kinase dependent proliferation (bottom) assays and ratio of FGFRs/VEGFR2 activities.

The palladium-catalyzed arylation and alkenylation of N-substituted methyl imidazole-4-carboxylates are described through inter- and intramolecular pathways. Both direct C2–H and C5–H arylation and alkenylation proceed under Pd(0)/Cu(I) cooperative catalysis and Pd(0) catalysis, respectively, in low-polarity 1,4-dioxane solvent. The methodology gives access to C2 (hetero)aryl or alkenyl imidazoles as well as innovative C2- and C5-arylated fused imidazoles tricycles with a five- to seven-membered middle ring.

A Frustrated Lewis Pair Solution to a Frustrating Problem: Mono-Selec

The winners of the Malcolm Campbell Memorial Prize for 2019 discuss the discovery of erdafitinib.

Developing new access to original silylated heterocycles is an emerging challenge in medicinal chemistry. In this paper, we describe a synthesis of silylated and germylated Motesanib analogues relying on a peptide coupling between a nicotinic acid derivative and silylated or germylated heterocycles, prepared according to our previous reports.

The transition metal-catalyzed direct CH bond arylation of heterocycles is considered to be one of the key methods for the construction of valuable bis-(hetero)aromatic systems, frequent in both natural products and pharmaceuticals. Over the past ten years, efforts have been made to develop methodologies to improve the chemoselectivity of CH arylation reactions of heterocycles, functionalized with various functions such as halogen, amine, nitro, ester, cyano...

trans-2,3-Diaryl(heteroaryl)-dihydropyrans were synthesized by an allylboration/ring-closing-metathesis sequence, using allylboranes formed in situ from the corresponding allylic alcohols. Aryl(heteroaryl) substituents were thus installed diastereoselectively onto dihydropyran rings in a trans fashion. These disubstituted dihydropyrans were further transformed into monosaccharide-like tetrahydropyrans.

Abstract Fibroblast growth factor (FGF) signaling plays critical roles in key biological processes ranging from embryogenesis to wound healing and has strong links to several hallmarks of cancer. Genetic alterations in FGF receptor (FGFR) family members are associated with increased tumor growth, metastasis, angiogenesis, and decreased survival. JNJ-42756493, erdafitinib, is an orally active small molecule with potent tyrosine kinase inhibitory activity against all four FGFR family members and selectivity versus other highly related kinases. JNJ-42756493 shows rapid uptake into the lysosomal compartment of cells in culture, which is associated with prolonged inhibition of FGFR signaling, possibly due to sustained release of the inhibitor. In xenografts from human tumor cell lines or patient-derived tumor tissue with activating FGFR alterations, JNJ-42756493 administration results in potent and dose-dependent antitumor activity accompanied by pharmacodynamic modulation of phospho-FGFR and phospho-ERK in tumors. The results of the current study provide a strong rationale for the clinical investigation of JNJ-42756493 in patients with tumors harboring FGFR pathway alterations. Mol Cancer Ther; 16(6); 1010–20. ©2017 AACR.

An extensive study of the chemoselective Pd-catalyzed inter- and intramolecular direct C–H arylation of N-benzylated 5-carboxyimidazoles with halides with and without CuI assistance in 1,4-dioxane as a low-polarity solvent was explored. The method was suitable for the synthesis of fused imidazole-based tricyclic systems incorporating medium-sized rings, including, for the first time, eight-membered rings, which are valuable in modern drug design.