Synthesis and Antiproliferative Activity of New Aminoisoquinolinylurea Derivatives against Melanoma Cell Line

Cho, Hye‐Kyung; El‐Gamal, Mohammed I.; Oh, Chang‐Hyun; Lee, So Ha; Kım, Garam; Hong, Jun Hee; Choi, Hong Seok; Yoo, Kyung Ho

doi:10.5012/bkcs.2012.33.11.3635

Cited by 16 publications

(7 citation statements)

References 18 publications

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“…Na2CO3 [60,61,65]; iii, H2, Pd/C, EtOH [60,61,65] or Zn, NH4Cl, water, THF, EtOH [67] ; iv, Ph2O, 230C [68,69] or Bu3N, Ph2O, 230C [70,71] or tetraglyme, 280C [69]; v, Br2, (PhCO2)2, CCl4, h, reflux [72]; vi, Et4N + -CN, MeCN [72]; vii, DiBAL-H, CH2Cl2, -78C [72]; viii, (MeO)2CHNMe2, reflux [65,67,[73][74][75]; ix, (a) HCl, MeOH reflux, (b) aq. Na2CO3 [75]; x, SiO2, hexane, EtOAc [67,73,74]; xi, NH3, EtOH, autoclave [67] or NH3, EtOH, ambient temperature [74] or NH3, MeOCH2CH2OH, reflux [73]; xii, HNO3, H2SO4, 0C-20C [76][77][78] or KNO3, H2SO4 [79,80]; xiv, AcOH, 100C [78] or aq. HCl, reflux [81]; xiii, HgSO4, H2SO4, acetone, reflux [82].…”

Section: Synthesis Of 5-aiqmentioning

confidence: 99%

“…The above sequence was the most efficient synthesis of 1 for some years until Sunderland et al disclosed a three-step process. Nitration of 1-chloroisoquinoline 32 occurs selectively at the 5-position [76][77][78][79][80], in contrast to nitrations of 2substituted isoquinolin-1-ones which tend to occur at the 4position [69]. Acetolysis of the 1-chloro of 33 and hydrolysis of the ester upon work-up forms 5-nitroisoquinolin-1-one 20, from which the target 1 can be obtained readily [77].…”

Section: Synthesis Of 5-aiqmentioning

confidence: 99%

“…= Ar, cyclopropyl, Me, (subst)Bn, BnO[83] 38: R = Ar, adamantyl, Bu t , cHex, thiophene[76] of the 3-unsubstituted analogue 31, as treatment with Hg 2+ gave only the acetyl compound 36, the product of hydration of the terminal alkyne of 34b, via a 5-exo-dig first step[82].…”

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5-Aminoisoquinolin-1-one (5-AIQ), a Water-Soluble Inhibitor of the Poly(ADP-Ribose)Polymerases (PARPs)

Threadgill

2015

CMC

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5-Aminoisoquinolin-1-one (5-AIQ) is a water-soluble inhibitor of the poly(ADPribose) polymerases (PARPs), lacking isoform-selectivity. Although of only moderate potency in vitro against PARP-1, it is highly active in many assays in cells and in models in vivo, indicating excellent uptake. Optimisation of the several synthetic sequences to 5-AIQ has led to development of a short and efficient route from 1-chloroisoquinoline. It has been used widely as a biochemical and pharmacological tool to study the effects of inhibition of the PARPs. It ameliorates the damage to cells and tissues following reperfusion of ischaemic tissue, showing significant protective activity in a rodent model of haemorrhagic shock at the remarkably low dose of 30 µg Kg(-1). Protection is also seen in models of myocardial infarction, ischaemic kidney and liver disorders, stroke and organ transplantation. Inhibition of PARP-1 by 5-AIQ causes down-regulation of the activity of NF-κB, which then down-regulates the expression of several gene products. Thus 5-AIQ has anti-inflammatory activity in vivo, through modulating the expression of cytokines and adhesion molecules. This indirect inhibition of expression is relevant in the activity of 5-AIQ in models of arthritis, Parkinson's disease, multiple sclerosis, spinal cord injury, periodontitis and inflammatory conditions of the lung. Inhibition of expression of matrix metalloproteinases and other factors gives rise to anti-angiogenic activity and to remarkable anti-metastatic activity in a mouse model. Thus, although it has been overtaken by other PARP-inhibiting drugs in the oncological clinic, 5-AIQ remains a valuable tool to study the roles of PARPs in health and in diverse diseases.

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Section: Synthesis Of 5-aiqmentioning

confidence: 99%

Section: Synthesis Of 5-aiqmentioning

confidence: 99%

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5-Aminoisoquinolin-1-one (5-AIQ), a Water-Soluble Inhibitor of the Poly(ADP-Ribose)Polymerases (PARPs)

Threadgill

2015

CMC

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“…Ureas are very important compounds in organic chemistry because of their extensive applications in medicine and agriculture. The substituted ureas exhibit diversified medicinal activities such as antimicrobial [ 1 ], antiviral [ 2 ], anti-HIV [ 3 ], anti-AIDS [ 4 ], anti-malaria [ 5 ], anti-proliferative [ 6 ], antitumor [ 7 ], anticancer [ 8 ], anti-inflammatory [ 9 ], anti-ulcerogenic [ 10 ], anticonvulsant [ 11 ], anti-nociceptive [ 12 ], antihypertensive [ 9 ], antidepressant [ 13 ], complement inhibition [ 14 ], HDL-elevating [ 15 ], and inhibition of nitric oxide [ 16 ]. Urea compounds also possess a broad spectrum of pesticidal activities, such as benzoylurea type insecticides (Diflubenzuron, Chlorbenzuron, etc.)…”

Section: Introductionmentioning

confidence: 99%

Novel Trifluoromethylcoumarinyl Urea Derivatives: Synthesis, Characterization, Fluorescence, and Bioactivity

Qiao

Hao

2018

Molecules

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A series of novel trifluoromethylcoumarinyl urea derivatives were designed, synthesized, and characterized by 1H-NMR, 13C-NMR, and HR-ESI-MS. The fluorescence spectra of the target compounds were recorded. The spectra show that most of the title compounds glow green with λmaxem of 500–517 nm, while compounds 5r, 5s, 5u, and 5l (compounds named by authors) glow violet with λmaxem of 381–443 nm. Moreover, the herbicidal and antifungal activities of the synthesized compounds were evaluated for their potential use as pesticides. The results indicate that compound 5f against the caulis of Amaranthus retroflexus and compounds 5j and 5l against the taproot of Digitaria sanguinalis are equivalent to the commercial herbicide Acetochlor. Nine of the title compounds are more antifungal than commercial fungicide Carbendazim against Botrytis cinerea.

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“…8) Numerous compounds with structural similarity to Sorafenib have been recently reported as potential antiproliferative agents against melanoma. [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] In addition, amino-heterocycles as urea bioisosteres have been reported as RAF kinase inhibitors. The 2-aminoquinazoline and 2-aminoquinoline derivatives illustrated in Fig.…”

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confidence: 99%

Novel Quinolinylaminoisoquinoline Bioisosteres of Sorafenib as Selective RAF1 Kinase Inhibitors: Design, Synthesis, and Antiproliferative Activity against Melanoma Cell Line

Cho

El‐Gamal

et al. 2013

CHEMICAL & PHARMACEUTICAL BULLETIN

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Design and synthesis of a new series of quinolinylaminoisoquinoline derivatives as conformationally restricted bioisosteres of Sorafenib are described. Their in vitro antiproliferative activity against A375P melanoma cell line was tested. Compounds 1b, 1d, 1g, and 1j showed the highest potency against A375P cell line with IC 50 values in sub-micromolar scale. In addition, compound 1d exerted high selectivity towards RAF1 serine/threonine kinase with 96.47% inhibition at 10 µm, and IC 50 of 0.96 µm. This compound can possess antiproliferative activity against melanoma cells through inhibition of RAF1 kinase.Key words bioisostere; melanoma; quinolinylaminoisoquinoline; Sorafenib; antiproliferative activityThe RAS/RAF/MEK/extraccellular signal-regulated kinase (ERK) (ERK pathway) is a well-known cell signaling network essential for cell survival, growth, and proliferation. 1)The RAS proteins are membrane-bound small G-protein, whereas RAF, MEK, and ERK are cytosolic protein kinases which compose a sequential signaling cascade. Among these four kinases, RAF kinases have been the most studied drug targets since mutations of the RAF protein were found in approximately 7% of human cancers 2,3) with particularly high frequency in melanoma (50-70%), ovarian cancer (35%), thyroid cancer (30%), and colorectal cancer (10%). Due to high incidence of RAF overexpression in melanoma, it has been a potential drug target for treatment of melanoma.Melanoma is a malignant tumor of melanocytes. It is considered as the most aggressive form of skin cancer. The major risk factors for melanoma development include exposure to solar UV irradiation, fair skin, dysplastic nevi syndrome, and a family history of melanoma. Melanomas can metastasize either by the lymphatic or by the hematogenous route. 4) Early stage melanoma (stage I/II) can be cured surgically with more than 95% success rate. But melanoma metastasizing to major organs (stage IV) is virtually incurable. 5) Patients with advanced melanoma have a median survival time of less than one year, and the estimated 5-year survival rate is less than 15%.6,7) With the incidence of melanoma rapidly rising in the United States and other developed countries, there has been an urgent need to develop more effective drugs.Sorafenib (Nexavar ® , Fig. 1) targets ERK pathway. It inhibits basal phosphorylation of ERK (pERK) in numerous cancer cell lines in vitro, including melanoma cell lines, independent of their K-RAS and B-RAF mutational status.8) Numerous compounds with structural similarity to Sorafenib have been recently reported as potential antiproliferative agents against melanoma.9-23) In addition, amino-heterocycles as urea bioisosteres have been reported as RAF kinase inhibitors. The 2-aminoquinazoline and 2-aminoquinoline derivatives illustrated in Fig. 1 are bioisosteres of Sorafenib with RAF kinase inhibitory activity. 24) In the present investigation, the target compounds were designed as conformationally restricted bioisosteres of Sorafenib. The pyridine-2-carboxamide moiety of Sor...

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Synthesis and Antiproliferative Activity of New Aminoisoquinolinylurea Derivatives against Melanoma Cell Line

Cited by 16 publications

References 18 publications

5-Aminoisoquinolin-1-one (5-AIQ), a Water-Soluble Inhibitor of the Poly(ADP-Ribose)Polymerases (PARPs)

5-Aminoisoquinolin-1-one (5-AIQ), a Water-Soluble Inhibitor of the Poly(ADP-Ribose)Polymerases (PARPs)

Novel Trifluoromethylcoumarinyl Urea Derivatives: Synthesis, Characterization, Fluorescence, and Bioactivity

Novel Quinolinylaminoisoquinoline Bioisosteres of Sorafenib as Selective RAF1 Kinase Inhibitors: Design, Synthesis, and Antiproliferative Activity against Melanoma Cell Line

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