Synthesis and Biological Evaluation of Urea Derivatives as Highly Potent and Selective Rho Kinase Inhibitors

Yin, Yan; Lin, Li; Ruiz, Claudia; Khan, S. A.; Cameron, Michael D.; Grant, Wayne; Pocas, Jennifer; Eid, Nibal; Park, HaJeung; Schröter, Thomas; LoGrasso, Philip V.; Feng, Yangbo

doi:10.1021/jm400062r

Cited by 35 publications

(37 citation statements)

References 33 publications

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“…[24] Thus, the study of MAP2 in schizophrenia could potentially take advantage of the substantially greater knowledge of tau biology, including the rapidly emerging field of tau therapeutics. [90]…”

Section: Discussionmentioning

confidence: 99%

Dendritic spine alterations in schizophrenia

Moyer

Shelton

Sweet

2015

Neuroscience Letters

147

125

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Schizophrenia is a chronic illness affecting approximately 0.5–1% of the world’s population. The etiology of schizophrenia is complex, including multiple genes and contributing environmental effects that adversely impact neurodevelopment. Nevertheless, a final common result, present in many subjects with schizophrenia, is impairment of pyramidal neuron dendritic morphology in multiple regions of the cerebral cortex. In this review we summarize the evidence of reduced dendritic spine density and other dendritic abnormalities in schizophrenia, evaluate current data that informs the neurodevelopment timing of these impairments, and discuss what is known about possible upstream sources of dendritic spine loss in this illness.

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Section: Discussionmentioning

confidence: 99%

Dendritic spine alterations in schizophrenia

Moyer

Shelton

Sweet

2015

Neuroscience Letters

147

125

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“…Moreover, newly developed urea based compounds are potent inhibitors of enzymatic activity. Additionally, biological evaluation of the urea derivatives in rats demonstrated significant IOP lowering effect [75]. Similarly, Pireddu group designed and reported a library of pridylaminothiazole based derivatives by incorporating urea into the parent structure [76].…”

Section: Glaucoma Inhibitorsmentioning

confidence: 99%

Discovery of novel inhibitors for the treatment of glaucoma

Cholkar

Trinh

Pal

et al. 2015

Expert Opinion on Drug Discovery

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Introduction Glaucoma is a neurodegenerative disease with heterogeneous causes that result in retinal ganglionic cell death (RGC). The discovery of ocular anti-hypertensives has shifted glaucoma therapy, largely, from surgery to medical intervention. Indeed, several intraocular pressure (IOP) lowering drugs, with different mechanisms of action and RGC protective property, have been developed. Areas covered In this review, the authors discuss the main new class of kinase inhibitors used as glaucoma treatments, which lower IOP by enhancing drainage and/or lowering production of aqueous humor. The authors include novel inhibitors under preclinical evaluation and investigation for their anti-glaucoma treatment. Additionally, the authors look at treatments that are in clinics now and which may be available in the near future. Expert opinion Treatment of glaucoma remains challenging because the exact cause is yet to be delineated. Neuroprotection to the optic nerve head is undisputable. The novel ROCK inhibitors have the capacity to lower IOP and provide optic nerve and RGC protection. In particular, the S-isomer of roscovitine has the capacity to lower IOP and provide neuroprotection. Combinations of selected drugs, which can provide maximal and sustained IOP lowering effects as well as neuroprotection, are paramount to the prevention of glaucoma progression. In the near future, microRNA intervention may be considered as a potential therapeutic target.

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“…Aryl substituted urea derivatives have been discovered as potent inhibitors of various kinases [44][45][46][47] and sorafenib is a wellknown example of a drug used for treatment of some cancers 48 . We decided to pursue CDK inhibition because of the similarity of our compounds and those described in the literature taking urea moiety into account 21,49,50 .…”

Section: Cdk Inhibitionmentioning

confidence: 99%

Discovery of nitroaryl urea derivatives with antiproliferative properties

Wróbel¹,

Kiełbus

Kaczor

et al. 2015

Journal of Enzyme Inhibition and Medicinal Chemistry

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A series of urea derivatives bearing nitroaryl moiety has been synthesized and assayed for their potential antiproliferative activities. Some of the tested compounds displayed activity in RK33 laryngeal cancer cells and TE671 rhabdomyosarcoma cells while being generally less toxic to healthy HSF human fibroblasts cells. One compound was demonstrated to be a moderate CDK2 inhibitor with IC 50 ¼ 14.3 mM. Its structure was solved by an X-ray crystallography and molecular modelling was performed to determine structure-activity relationship. Obtained compounds constitute novel structures and generally demonstrated greater cytotoxicity in comparison to cisplatin. This study offers new structural motifs with potential for further development.

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Synthesis and Biological Evaluation of Urea Derivatives as Highly Potent and Selective Rho Kinase Inhibitors

Cited by 35 publications

References 33 publications

Dendritic spine alterations in schizophrenia

Dendritic spine alterations in schizophrenia

Discovery of novel inhibitors for the treatment of glaucoma

Discovery of nitroaryl urea derivatives with antiproliferative properties

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