Exploration of 1-(3-chloro-4-(4-oxo-4H-chromen-2-yl)phenyl)-3-phenylurea derivatives as selective dual inhibitors of Raf1 and JNK1 kinases for anti-tumor treatment

Ortho-Substituent Effects on Diphenylurea Packing Motifs

“…N , N ′-Phenylurea (PU) is an interesting core unit that appears in a wide range of chemical compounds with diverse applications. It is found in pharmaceuticals developed to treat diseases ranging from African sleeping sickness to psoriasis and cancer. , PUs have also attracted negative attention for their persistence in the environment due to their use as herbicides − and as antibacterial ingredients in personal care products (e.g., triclocarban). − The persistence of hydrogen bonding between urea groups has also enabled the assembly of urea-based supramolecular materials such as gels, tubes, and capsules. − In the crystalline state, PUs have served as model systems for crystal polymorphism studies − and been explored as possible nonlinear optical materials. − …”

A review on pharmacophoric designs of antiproliferative agents

“…In addition, docking studies performed revealed their binding sites at Raf1 and JNK 1. The synthesized compounds were also found to be less toxic against normal liver cell-lines QSG7701 and HL7702 (Jin et al, 2013).…”

“…The multitargeting approach also involves merging of different inhibitors that target a single specific target which could offer a successful means to treat certain diseases such as cancer, type 2 diabetes mellitus, and viral as well bacterial infections (Melisi et al, 2013). Cai et al presented the synthesis of series of novel CUDC-101 (Jin et al, 2013;Zhang et al, 2014) compound (Fig. 21) and in the process identified multi-targeted hybrid 7-(4-(3-ethynylphenylamino)-7-methoxy quinazolin-6-yloxy)-N-hydroxyheptan-amide as a potential drug candidate.…”

Unraveling the Design and Discovery of c-Jun N-Terminal Kinase Inhibitors and Their Therapeutic Potential in Human Diseases

“…For example, Compounds 38 and 39 have simultaneously targeted both JNK3 and p38α kinases, resulting in dual inhibitors with nanomolar activity . In addition, the formation of multitarget inhibitors with kinases such as Raf1 and LRRK2 may also be considered, , and multitarget inhibitors offer the promise of eliminating drug–drug interactions and optimizing the dosage of individual inhibitors. Small-molecule drugs are still the main priority of new drug research and development because of their advantages of relatively low research and development costs and relatively skilled technology.…”

“…Studies have confirmed that it can effectively inhibit the proliferation of the human liver cancer cell lines HepG2 and HCT116, with IC 50 values of 2.8 and 28.7 μM, respectively. 84 In addition, Feng et al obtained dual inhibitors of JNK3 and LRRK2 (leucine rich repeat kinase 2) using a bidentate-binding strategy (Compound 42), and it simultaneously targeted the ATP hinge binding region and unique protein surface sites outside the ATP pocket. The IC 50 values were 12 and 99 nM, respectively (Figure 9).…”