March 8, 2016Journal of Medicinal ChemistryOpen Access

Discovery of 5-Chloro-1-(5-chloro-2-(methylsulfonyl)benzyl)-2-imino-1,2-dihydropyridine-3-carboxamide (TAK-259) as a Novel, Selective, and Orally Active α1DAdrenoceptor Antagonist with Antiurinary Frequency Effects: Reducing Human Ether-a-go-go-Related Gene (hERG) Liabilities

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Structured PICO

Population

In vitro models (hERG K+ channel, α1-AR subtypes) and in vivo rat models (rats with bladder outlet obstruction and cystitis-induced urinary frequency)

Intervention

Iminopyridine derivatives, specifically (R)-9s and 9u (TAK-259)

Outcome

Antagonistic activity in bladder strip test, amelioration of cystitis-induced urinary frequency, and reduced hERG K(+) channel inhibitionsurrogate

The discovery of TAK-259 (9u) provides a novel, selective, and orally active α1D-AR antagonist with reduced hERG liability for treating urinary frequency.

Discussion

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Implication

Supports progression of TAK-259 to human trials for urinary frequency; leaves open translation of rodent efficacy and safety.

Cite This Study

Sakauchi et al. (2016) studied this question.

synapsesocial.com/papers/6a87d78f4f54442d182633bb https://doi.org/10.1021/acs.jmedchem.5b01528

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Discovery of 5-Chloro-1-(5-chloro-2-(methylsulfonyl)benzyl)-2-imino-1,2-dihydropyridine-3-carboxamide (TAK-259) as a Novel, Selective, and Orally Active α1DAdrenoceptor Antagonist with Antiurinary Frequency Effects: Reducing Human Ether-a-go-go-Related Gene (hERG) Liabilities

Structured PICO

Discussion

Implication

Cite This Study

Discovery of 5-Chloro-1-(5-chloro-2-(methylsulfonyl)benzyl)-2-imino-1,2-dihydropyridine-3-carboxamide (TAK-259) as a Novel, Selective, and Orally Active α1DAdrenoceptor Antagonist with Antiurinary Frequency Effects: Reducing Human Ether-a-go-go-Related Gene (hERG) Liabilities

Structured PICO

Discussion

Implication

Cite This Study

Also Consider

Also Consider