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Your search keyword '"Tom Wisniewski"' showing total 3 results
Start Over Author "Tom Wisniewski" Topic internal medicine
3 results on '"Tom Wisniewski"'

1. Imidazopyridyl compounds as aldosterone synthase inhibitors

Author

Brent R. Whitehead, Michael M.-C. Lo, Amjad Ali, Min K. Park, Scott B. Hoyt, Yusheng Xiong, Jiaqiang Cai, Emma Carswell, Andrew Cooke, John MacLean, Paul Ratcliffe, John Robinson, D. Jonathan Bennett, Joseph A. Clemas, Tom Wisniewski, Mary Struthers, Doris Cully, and Douglas J. MacNeil

Subjects
Male, Aldosterone synthase, medicine.medical_specialty, Pyridines, Stereochemistry, Clinical Biochemistry, Pharmaceutical Science, 01 natural sciences, Biochemistry, Structure-Activity Relationship, Cricetulus, Internal medicine, Drug Discovery, medicine, Animals, Cytochrome P-450 CYP11B2, Humans, Rats, Wistar, Molecular Biology, biology, 010405 organic chemistry, Chemistry, Organic Chemistry, Imidazoles, Macaca mulatta, humanities, 0104 chemical sciences, 010404 medicinal & biomolecular chemistry, Endocrinology, Microsomes, Liver, biology.protein, Steroid 11-beta-Hydroxylase, Molecular Medicine
Abstract

This invention relates to triazolopyridyl compounds of the structural formula: [Formula should be inserted here] or their pharmaceutically acceptable salts, wherein the variable are defined herein. The inventive compounds selectively inhibit aldosterone synthase. This invention also provides for pharmaceutical compositions comprising the compounds of Formula I or their salts as well as potentially to methods for the treatment, amelioration or prevention of conditions that could be treated by inhibiting aldosterone synthase.

Published
2017

2. Discovery of Triazole CYP11B2 Inhibitors with in Vivo Activity in Rhesus Monkeys

Author

Chris J. van Koppen, Scott B. Hoyt, Gino Salituro, Elaine Tung, Jim Tata, Joe Clemas, Mark Rosenbach, Jack Gibson, Daphne Szeto, Wei Tang, Andreas Verras, Lee-Yuh Pai, Ning Ren, Carrie Ann Maxwell, Joe Metzger, Jose Castro-Perez, Qing Chen, Lina Yin, Daniel R. McMasters, Yusheng Xiong, Rolf W. Hartmann, Mary Struthers, Gui-Bai Liang, Charlene Bopp, Xiuying Ma, Gaochao Zhou, Richard Hajdu, Tom Wisniewski, Mike E. Lassman, Nicole Buist, Clare London, Andrea Sok, Gail Forrest, Sloan Stribling, Theresa McLaughlin, Qingzhong Hu, Tian-Quan Cai, and Whitney Lane Petrilli

Subjects
Aldosterone synthase, medicine.medical_specialty, Aldosterone, Organic Chemistry, Triazole, Hit to lead, Biology, Pharmacology, Biochemistry, chemistry.chemical_compound, Endocrinology, chemistry, Pharmacokinetics, In vivo, Pharmacodynamics, Internal medicine, Drug Discovery, medicine, biology.protein, Cortisol level
Abstract

Hit-to-lead efforts resulted in the discovery of compound 19, a potent CYP11B2 inhibitor that displays high selectivity vs related CYPs, good pharmacokinetic properties in rat and rhesus, and lead-like physical properties. In a rhesus pharmacodynamic model, compound 19 displays robust, dose-dependent aldosterone lowering efficacy, with no apparent effect on cortisol levels.

Published
2015

3. Discovery of Benzimidazole CYP11B2 Inhibitors with in Vivo Activity in Rhesus Monkeys

Author

Daphne Szeto, Doris F. Cully, Scott B. Hoyt, Ning Ren, Elaine Tung, Charlene Bopp, Jack Gibson, Gino Salituro, Clare London, Jiaqiang Cai, Amjad Ali, Qing Chen, Andrea Sok, Simone Belshaw, Carrie Ann Maxwell, Mark Rosenbach, Gaochao Zhou, Gail Forrest, Tian-Quan Cai, Daniel R. McMasters, Lee-Yuh Pai, Nelo R. Rivera, Sloan Stribling, Emma Carswell, Richard Hajdu, Robinson John E, Andrew J. Cooke, Jeff Kuethe, Tom Wisniewski, Joe Metzger, Thomas R. Clarkson, Gui-Bai Liang, Mary Struthers, Jim Tata, Mike E. Lassman, Lindsay Brown, Wei Tang, Theresa McLaughlin, Xiuying Ma, Nicole Buist, Kun Liu, Joe Clemas, D. Jonathan Bennett, Andreas Verras, Min K. Park, Yusheng Xiong, John Maclean, and Jose Castro-Perez

Subjects
Aldosterone synthase, Benzimidazole, medicine.medical_specialty, Aldosterone, Organic Chemistry, High selectivity, Biology, Pharmacology, Biochemistry, chemistry.chemical_compound, Endocrinology, chemistry, Pharmacokinetics, In vivo, Internal medicine, Pharmacodynamics, Drug Discovery, medicine, biology.protein, Cortisol level
Abstract

We report the discovery of a benzimidazole series of CYP11B2 inhibitors. Hit-to-lead and lead optimization studies identified compounds such as 32, which displays potent CYP11B2 inhibition, high selectivity versus related CYP targets, and good pharmacokinetic properties in rat and rhesus. In a rhesus pharmacodynamic model, 32 produces dose-dependent aldosterone lowering efficacy, with no apparent effect on cortisol levels.

Published
2015

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