Amine-free melanin-concentrating hormone receptor 1 antagonists: Novel non-basic 1-(2H-indazole-5-yl)pyridin-2(1H)-one derivatives and mitigation of mutagenicity in Ames test

Igawa, Hideyuki; Takahashi, Masashi; Ikoma, Minoru; Kaku, Hiromi; Kakegawa, Keiko; Kina, Asato; Aida, Jumpei; Okuda, Suguru; Kawata, Y.; Noguchi, Toshihiro; Hotta, Natsu; Yamamoto, Satoshi; Nakayama, Masaharu; Nagisa, Yasutaka; Kasai, Shizuo; Maekawa, Taira

doi:10.1016/j.bmc.2016.04.013

Cited by 13 publications

(4 citation statements)

References 32 publications

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“…Igawa et al [ 112 ] reported the synthesis of a novel series 1-(2 H -indazole-5-yl)pyridin-2(1 H )-one hybrids and investigated the potencies of the melanin-concentrating hormone receptor 1 (MCHR1). During the optimization, compound 186 showed binding affinity with MCHR1 (hMCHR1: IC 50 = 35 nM) in the Ames test ( Figure 63 ).…”

Section: Biological Applications Of Indazole Derivativesmentioning

confidence: 99%

Recent Advances in Indazole-Containing Derivatives: Synthesis and Biological Perspectives

2018

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Indazole-containing derivatives represent one of the most important heterocycles in drug molecules. Diversely substituted indazole derivatives bear a variety of functional groups and display versatile biological activities; hence, they have gained considerable attention in the field of medicinal chemistry. This review aims to summarize the recent advances in various methods for the synthesis of indazole derivatives. The current developments in the biological activities of indazole-based compounds are also presented.

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Section: Biological Applications Of Indazole Derivativesmentioning

confidence: 99%

Recent Advances in Indazole-Containing Derivatives: Synthesis and Biological Perspectives

2018

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“…Some examples of compounds that have been evaluated using the Ames test are: nitrofuranylamides as anti-tuberculosis agents ( Hurdle et al., 2008 ), non-basic melanin-concentrating hormone receptor 1 (MCHR1) antagonists such as 1-(2-cyclopropyl-3-methyl-2H-indazol-5-yl)-4-{[5-(trifluoromethyl)thiophen-3-yl]methoxy}pyridin-2(1H)-one ( Igawa et al., 2016 ), derivatives of 5-fluorouracil which is one of the first line drugs for the systemic therapy of solid tumors such as breast, colorectal, esophageal, gastric, pancreatic, head and neck tumors, such as 5-fluorouracil derivative 1-[{1’-(2″,3″,4″,6″-tetra-O-acetyl-β-d-glycopyronosyl)-1’H-1’,2’,3’-triazole-4’-yl} methyl]5-fluorouracil ( Köksal Karayildirim et al., 2018 ), novel multipotent compounds modulating endocannabinoid and dopaminergic systems ( Grillo et al., 2019 ), novel selenocompounds ( Marć et al., 2022 ), alkyl-nitrosamines- N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA), and N- nitrosamines ( Trejo-Martin et al., 2022 ; Thomas et al., 2023 ) etc.…”

Section: Evaluating Safety Of Novel Compoundsmentioning

confidence: 99%

Evaluation of novel compounds as anti-bacterial or anti-virulence agents

Filipić,

Ušjak,

Rambaher

et al. 2024

Front. Cell. Infect. Microbiol.

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Antimicrobial resistance is a global threat, leading to an alarming increase in the prevalence of bacterial infections that can no longer be treated with available antibiotics. The World Health Organization estimates that by 2050 up to 10 million deaths per year could be associated with antimicrobial resistance, which would equal the annual number of cancer deaths worldwide. To overcome this emerging crisis, novel anti-bacterial compounds are urgently needed. There are two possible approaches in the fight against bacterial infections: a) targeting structures within bacterial cells, similar to existing antibiotics; and/or b) targeting virulence factors rather than bacterial growth. Here, for the first time, we provide a comprehensive overview of the key steps in the evaluation of potential new anti-bacterial and/or anti-virulence compounds. The methods described in this review include: a) in silico methods for the evaluation of novel compounds; b) anti-bacterial assays (MIC, MBC, Time-kill); b) anti-virulence assays (anti-biofilm, anti-quorum sensing, anti-adhesion); and c) evaluation of safety aspects (cytotoxicity assay and Ames test). Overall, we provide a detailed description of the methods that are an essential tool for chemists, computational chemists, microbiologists, and toxicologists in the evaluation of potential novel antimicrobial compounds. These methods are cost-effective and have high predictive value. They are widely used in preclinical studies to identify new molecular candidates, for further investigation in animal and human trials.

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“…35 ) as melanin-concentrating hormone receptor 1 (MCHR1) antagonists. 142 The structure–activity relationship (SAR) studies revealed that the 2,4-disubstituted thiophene derivatives (78c and d) were more potent than the 2,5-disubstituted thiophene (78b) and thiazole derivatives (78e and f). Interestingly, the 2-cyclopropylindazole derivatives (78j–l) possessed better activity than the methyl analogs (78a, 78g and 78d).…”

Section: Mono-kinase Inhibitorsmentioning

confidence: 99%

Current progress, challenges and future prospects of indazoles as protein kinase inhibitors for the treatment of cancer

et al. 2021

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Amine-free melanin-concentrating hormone receptor 1 antagonists: Novel non-basic 1-(2H-indazole-5-yl)pyridin-2(1H)-one derivatives and mitigation of mutagenicity in Ames test

Cited by 13 publications

References 32 publications

Recent Advances in Indazole-Containing Derivatives: Synthesis and Biological Perspectives

Recent Advances in Indazole-Containing Derivatives: Synthesis and Biological Perspectives

Evaluation of novel compounds as anti-bacterial or anti-virulence agents

Current progress, challenges and future prospects of indazoles as protein kinase inhibitors for the treatment of cancer

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