Discovery and structural analyses of S-adenosyl-l-homocysteine hydrolase inhibitors based on non-adenosine analogs

Nakao, Akira; Suzuki, Hiroko; Ueno, Hiroaki; Iwasaki, Hiroshi; Setsuta, Tomofumi; Kashima, Akiko; Sunada, Shinji

doi:10.1016/j.bmc.2015.05.018

Cited by 5 publications

(2 citation statements)

References 48 publications

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“…For the preparation of 44, deprotection was unnecessary. Treating the Boc-protected intermediate 32 with an excess of LiAlH 4 (5 equiv) in anhydrous tetrahydrofuran (THF), 31 the monomethylated 2,4-diaminopyrimidine 45 was obtained in moderate yield (43%) after refluxing for 7 h (Scheme 1). Target compounds 33−35 were methylated under Eschweiler−Clarke conditions using formaldehyde and formic acid to give the mono-or dimethylated 2,4- diaminopyrimidines 46−48 (Scheme 1).…”

Section: ■ Results and Discussionmentioning

confidence: 99%

[³H]UR-DEBa176: A 2,4-Diaminopyrimidine-Type Radioligand Enabling Binding Studies at the Human, Mouse, and Rat Histamine H₄ Receptors

et al. 2019

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Differences in sequence homology between human (h), mouse (m), and rat (r) histamine H4 receptors (H4R) cause discrepancies regarding affinities, potencies, and/or efficacies of ligands and therefore compromise translational animal models and the applicability of radioligands. Aiming at a radioligand enabling robust and comparative binding studies at the h/m/rH4Rs, 2,4-diaminopyrimidines were synthesized and pharmacologically investigated. The most notable compounds identified were two (partial) agonists with comparable potencies at the h/m/rH4Rs: UR-DEBa148 (N-neopentyl-4-(1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)pyrimidin-2-amine bis(2,2,2-trifluoroacetate), 43), the most potent [pEC50 (reporter gene assay) = 9.9/9.6/10.3] compound in the series being slightly G-protein biased and UR-DEBa176 [(R)-4-[3-(dimethylamino)pyrrolidin-1-yl]-N-neopentylpyrimidin-2-amine bis(2,2,2-trifluoroacetate), 46, pEC50 (reporter gene assay) = 8.7/9.0/9.2], a potential “cold” form of a tritiated H4R ligand. After radiolabeling, binding studies with [3H]UR-DEBa176 ([3H]46) at the h/m/rH4Rs revealed comparable K d values (41/17/22 nM), low nonspecific binding (11–17%, ∼K d), and fast associations/dissociations (25–30 min) and disclosed [3H]UR-DEBa176 as useful molecular tool to determine h/m/rH4R binding affinities for H4R ligands.

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Section: ■ Results and Discussionmentioning

confidence: 99%

[³H]UR-DEBa176: A 2,4-Diaminopyrimidine-Type Radioligand Enabling Binding Studies at the Human, Mouse, and Rat Histamine H₄ Receptors

et al. 2019

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“…As demonstrated in the previous example, partial reduction of a nitrosamine to a hydrazine is a viable reaction pathway. A number of reducing agents have been reported to perform this transformation, including lithium aluminum hydride, − zinc, , Pd/C with hydrogen, and stannous chloride . Additionally, some of these reagents will directly cleave the nitroso group.…”

Section: Reductive Nitrosamine Chemistrymentioning

confidence: 99%

Nitrosamine Reactivity: A Survey of Reactions and Purge Processes

Borths

Burns

Curran

et al. 2021

Org. Process Res. Dev.

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Drug recalls have led to increased regulatory scrutiny into the formation and presence of nitrosamine (Nnitrosoamine) impurities in medicines. This review aims to assist the development of risk mitigation strategies by summarizing known reactions of nitrosamines, with a focus on reactions useful within the context of complex molecule synthesis. This review should serve as a useful reference and help lead to the development of chemical processes which effectively control nitrosamines.

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Brief Introduction of Measles Virus and Its Therapeutic Strategies

Nascimento

Santos-Júnior

Silva-Júnior

2021

Human Viruses: Diseases, Treatments and Vaccines

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Discovery and structural analyses of S-adenosyl-l-homocysteine hydrolase inhibitors based on non-adenosine analogs

Cited by 5 publications

References 48 publications

[³H]UR-DEBa176: A 2,4-Diaminopyrimidine-Type Radioligand Enabling Binding Studies at the Human, Mouse, and Rat Histamine H₄ Receptors

[³H]UR-DEBa176: A 2,4-Diaminopyrimidine-Type Radioligand Enabling Binding Studies at the Human, Mouse, and Rat Histamine H₄ Receptors

Nitrosamine Reactivity: A Survey of Reactions and Purge Processes

Brief Introduction of Measles Virus and Its Therapeutic Strategies

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Discovery and structural analyses of S-adenosyl-l-homocysteine hydrolase inhibitors based on non-adenosine analogs

Cited by 5 publications

References 48 publications

[3H]UR-DEBa176: A 2,4-Diaminopyrimidine-Type Radioligand Enabling Binding Studies at the Human, Mouse, and Rat Histamine H4 Receptors

[3H]UR-DEBa176: A 2,4-Diaminopyrimidine-Type Radioligand Enabling Binding Studies at the Human, Mouse, and Rat Histamine H4 Receptors

Nitrosamine Reactivity: A Survey of Reactions and Purge Processes

Brief Introduction of Measles Virus and Its Therapeutic Strategies

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Product

Resources

About

[³H]UR-DEBa176: A 2,4-Diaminopyrimidine-Type Radioligand Enabling Binding Studies at the Human, Mouse, and Rat Histamine H₄ Receptors

[³H]UR-DEBa176: A 2,4-Diaminopyrimidine-Type Radioligand Enabling Binding Studies at the Human, Mouse, and Rat Histamine H₄ Receptors