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Your search keyword '"Ma, Xiaosu"' showing total 3 results
Start Over Author "Ma, Xiaosu" Journal journal of medicinal chemistry
3 results on '"Ma, Xiaosu"'

1. Discovery of LY3104607: A Potent and Selective G Protein-Coupled Receptor 40 (GPR40) Agonist with Optimized Pharmacokinetic Properties to Support Once Daily Oral Treatment in Patients with Type 2 Diabetes Mellitus

Author

Hamdouchi, Chafiq, primary, Maiti, Pranab, additional, Warshawsky, Alan M., additional, DeBaillie, Amy C., additional, Otto, Keith A., additional, Wilbur, Kelly L., additional, Kahl, Steven D., additional, Patel Lewis, Anjana, additional, Cardona, Guemalli R., additional, Zink, Richard W., additional, Chen, Keyue, additional, CR, Siddaramaiah, additional, Lineswala, Jayana P., additional, Neathery, Grace L., additional, Bouaichi, Cecilia, additional, Diseroad, Benjamin A., additional, Campbell, Alison N., additional, Sweetana, Stephanie A., additional, Adams, Lisa A., additional, Cabrera, Over, additional, Ma, Xiaosu, additional, Yumibe, Nathan P., additional, Montrose-Rafizadeh, Chahrzad, additional, Chen, Yanyun, additional, and Miller, Anne Reifel, additional

Published
2018
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2. The Discovery, Preclinical, and Early Clinical Development of Potent and Selective GPR40 Agonists for the Treatment of Type 2 Diabetes Mellitus (LY2881835, LY2922083, and LY2922470)

Author

Hamdouchi, Chafiq, primary, Kahl, Steven D., additional, Patel Lewis, Anjana, additional, Cardona, Guemalli R., additional, Zink, Richard W., additional, Chen, Keyue, additional, Eessalu, Thomas E., additional, Ficorilli, James V., additional, Marcelo, Marialuisa C., additional, Otto, Keith A., additional, Wilbur, Kelly L., additional, Lineswala, Jayana P., additional, Piper, Jared L., additional, Coffey, D. Scott, additional, Sweetana, Stephanie A., additional, Haas, Joseph V., additional, Brooks, Dawn A., additional, Pratt, Edward J., additional, Belin, Ruth M., additional, Deeg, Mark A., additional, Ma, Xiaosu, additional, Cannady, Ellen A., additional, Johnson, Jason T., additional, Yumibe, Nathan P., additional, Chen, Qi, additional, Maiti, Pranab, additional, Montrose-Rafizadeh, Chahrzad, additional, Chen, Yanyun, additional, and Reifel Miller, Anne, additional

Published
2016
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3. Discovery of LY3104607: A Potent and Selective G Protein-Coupled Receptor 40 (GPR40) Agonist with Optimized Pharmacokinetic Properties to Support Once Daily Oral Treatment in Patients with Type 2 Diabetes Mellitus

Author

Hamdouchi, Chafiq, Maiti, Pranab, Warshawsky, Alan M., DeBaillie, Amy C., Otto, Keith A., Wilbur, Kelly L., Kahl, Steven D., Patel Lewis, Anjana, Cardona, Guemalli R., Zink, Richard W., Chen, Keyue, CR, Siddaramaiah, Lineswala, Jayana P., Neathery, Grace L., Bouaichi, Cecilia, Diseroad, Benjamin A., Campbell, Alison N., Sweetana, Stephanie A., Adams, Lisa A., Cabrera, Over, Ma, Xiaosu, Yumibe, Nathan P., Montrose-Rafizadeh, Chahrzad, Chen, Yanyun, and Miller, Anne Reifel

Abstract

As a part of our program to identify potent GPR40 agonists capable of being dosed orally once daily in humans, we incorporated fused heterocycles into our recently disclosed spiropiperidine and tetrahydroquinoline acid derivatives 1, 2, and 3with the intention of lowering clearance and improving the maximum absorbable dose (Dabs). Hypothesis-driven structural modifications focused on moving away from the zwitterion-like structure. and mitigating the N-dealkylation and O-dealkylation issues led to triazolopyridine acid derivatives with unique pharmacology and superior pharmacokinetic properties. Compound 4(LY3104607) demonstrated functional potency and glucose-dependent insulin secretion (GDIS) in primary islets from rats. Potent, efficacious, and durable dose-dependent reductions in glucose levels were seen during glucose tolerance test (GTT) studies. Low clearance, volume of distribution, and high oral bioavailability were observed in all species. The combination of enhanced pharmacology and pharmacokinetic properties supported further development of this compound as a potential glucose-lowering drug candidate.

Published
2024
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