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Your search keyword '"Shripad S. Bhagwat"' showing total 5 results
Start Over Author "Shripad S. Bhagwat" Journal bioorganicmedicinal chemistry letters
5 results on '"Shripad S. Bhagwat"'

1. Aminopurine based JNK inhibitors for the prevention of ischemia reperfusion injury

Author

Elise Sudbeck, Jason Katz, Adam Kois, Brydon L. Bennett, Steven S. Clareen, Michael A. Shirley, Rachel Fan, Shripad S. Bhagwat, Jonathan Wright, Ronald Albers, Brian E. Cathers, Maria Celeridad, Lisa Nadolny, Yang Tang, Sogole Bahmanyar, Heather Raymon, Sutapa Ghosh, David Giegel, Henderson Ian, Philip P Chamberlain, Mehran F. Moghaddam, Kevin S. Hughes, Brent Benish, Kate Blease, Sema Pai, Veronique Plantevin Krenitsky, Jacek Nowakowski, Robert Hilgraf, Mercedes Delgado, Paul Omholt, Yoshitaka Satoh, Jeff Muir, Kiran Sahasrabudhe, Leticia Ayala, Andrew G. Cole, Oleg Khatsenko, and Li Xu

Subjects
Models, Molecular, Clinical Biochemistry, Ischemia, Pharmaceutical Science, 2-Aminopurine, Pharmacology, Biochemistry, Enzyme activator, chemistry.chemical_compound, Inhibitory Concentration 50, Structure-Activity Relationship, Dogs, Catalytic Domain, Drug Discovery, medicine, Potency, Structure–activity relationship, Animals, Enzyme Inhibitors, Molecular Biology, Molecular Structure, Chemistry, Kinase, Organic Chemistry, JNK Mitogen-Activated Protein Kinases, Haplorhini, medicine.disease, Rats, Enzyme Activation, Purines, Reperfusion Injury, Molecular Medicine, Reperfusion injury, Aminopurine
Abstract

In this Letter we describe the optimization of an aminopurine lead (1) with modest potency and poor overall kinase selectivity which led to the identification of a series of potent, selective JNK inhibitors. Improvement in kinase selectivity was enabled by introduction of an aliphatic side chain at the C-2 position. CC-359 (2) was selected as a potential clinical candidate for diseases manifested by ischemia reperfusion injury.

Published
2011

2. Synthesis and biological evaluation of pteridine and pyrazolopyrimidine based adenosine kinase inhibitors

Author

Shripad S. Bhagwat, Michael F. Jarvis, Arthur Gomtsyan, Chih-Hung Lee, Andrew O. Stewart, Elizabeth A. Kowaluk, and Stanley Didomenico

Subjects
Stereochemistry, Clinical Biochemistry, Pharmaceutical Science, Adenosine kinase, Biochemistry, Chemical synthesis, Pyrazolopyrimidine, chemistry.chemical_compound, Structure-Activity Relationship, Drug Discovery, medicine, Enzyme Inhibitors, Molecular Biology, IC50, Adenosine Kinase, chemistry.chemical_classification, biology, Bicyclic molecule, Chemistry, Pteridines, Organic Chemistry, Enzyme, Pyrimidines, Enzyme inhibitor, biology.protein, Molecular Medicine, Pyrazoles, Pteridine, medicine.drug
Abstract

Three new approaches have been tested to modify existing pyridopyrimidine and alkynylpyrimidine classes of nonnucleoside adenosine kinase inhibitors 2 and 3. 4-Amino-substituted pteridines 8a–e were generally less active than corresponding 5- and 6-substituted pyridopyrimidines 2. Pyrazolopyrimidine 13c with IC50=7.5 nM was superior to its open chain alkynylpyrimidine analog 13g (IC50=22 nM) while pyrrolopyrimidines such as 17a were inactive.

Published
2004

3. Lead identification of a potent benzopyranone selective estrogen receptor modulator

Author

Adam Kois, Normand Richard, Khammungkhune Sak, Graziella I. Shevlin, Shripad S. Bhagwat, John Sapienza, Helen Brady, Mathew Hickman, Jalluri Ravi Kumar, Deborah Mortensen, Gayo Leah M, Jeffrey A. Mckie, Mary Doubleday, May S Kung Sutherland, and Bernd Stein

Subjects
Clinical Biochemistry, Cell, Pharmaceutical Science, Pharmacology, Biochemistry, chemistry.chemical_compound, Estrogen Receptor Modulators, Piperidines, Coumarins, Drug Discovery, medicine, Tumor Cells, Cultured, Animals, Raloxifene, Molecular Biology, Binding Sites, Estradiol, Molecular Structure, Chemistry, Interleukin-6, Organic Chemistry, Estrogen Antagonists, Estrogen Receptor alpha, Ligand (biochemistry), In vitro, Tamoxifen, medicine.anatomical_structure, Selective estrogen receptor modulator, Raloxifene Hydrochloride, Molecular Medicine, Female, Estrogen receptor alpha, Lead compound, hormones, hormone substitutes, and hormone antagonists, medicine.drug
Abstract

Starting from a phenol screening hit (6), three series of benzopyranone selective estrogen receptor modulators (SERMs) have been designed, synthesized, and analyzed for both estrogen receptor alpha binding affinity and in vitro activity in two cell assays. The lead compound identified, SP500263 (13), was more potent than raloxifene and tamoxifen in a cell-based assay measuring inhibition of interleukin-6 release.

Published
2002

4. Pyridopyrimidine analogues as novel adenosine kinase inhibitors

Author

John R. Koenig, Elizabeth A. Kowaluk, Karen M. Alexander, Andrew O. Stewart, Guo Zhu Zheng, Carol T. Wismer, Michael F. Jarvis, Yui Mao, Katharine L. Chu, Mark A. Matulenko, Richard J. Perner, Steve Muchmore, Ki H. Kim, Mei Qun Jiang, Kennan C. Marsh, Chih-Hung Lee, Haixia Yu, Shripad S. Bhagwat, Joseph P. Mikusa, John K. Pratt, Kathy L. Kohlhaas, Steve McGaraughty, and Arthur Gomtsyan

Subjects
Models, Molecular, Stereochemistry, Morpholines, Clinical Biochemistry, Molecular Conformation, Pharmaceutical Science, Adenosine kinase, Biochemistry, Chemical synthesis, Structure-Activity Relationship, In vivo, Drug Discovery, Moiety, Enzyme Inhibitors, Molecular Biology, Adenosine Kinase, chemistry.chemical_classification, biology, Bicyclic molecule, Organic Chemistry, In vitro, Enzyme, Pyrimidines, chemistry, Enzyme inhibitor, biology.protein, Molecular Medicine
Abstract

A novel series of pyridopyrimidine analogues 9 was identified as potent adenosine kinase inhibitors based on the SAR and computational studies. Substitution of the C7 position of the pyridopyrimidino core with C2' substituted pyridino moiety increased the in vivo potency and enhanced oral bioavailability of these adenosine kinase inhibitors.

Published
2001

5. Structure-activity studies of 5-substituted pyridopyrimidines as adenosine kinase inhibitors

Author

Haixia Yu, Karen M. Alexander, Erol K. Bayburt, Chih-Hung Lee, Elizabeth A. Kowaluk, Gregory A. Gfesser, Carol T. Wismer, Andrew O. Stewart, Kathy L. Kohlhaas, Steve McGaraughty, Joseph P. Mikusa, Shripad S. Bhagwat, Chang Zhu, Marlon D. Cowart, and Michael F. Jarvis

Subjects
Cell Membrane Permeability, Tertiary amine, Clinical Biochemistry, Pharmaceutical Science, Administration, Oral, Pain, Adenosine kinase, Biochemistry, Inhibitory Concentration 50, Structure-Activity Relationship, Drug Discovery, medicine, Structure–activity relationship, Animals, Enzyme Inhibitors, Molecular Biology, Adenosine Kinase, Pain Measurement, chemistry.chemical_classification, biology, Molecular Structure, Chemistry, Organic Chemistry, Adenosine, Rats, Enzyme, Pyrimidines, Enzyme inhibitor, Hyperalgesia, biology.protein, Molecular Medicine, Phosphorylation, medicine.symptom, medicine.drug
Abstract

The synthesis and SAR of a novel series of non-nucleoside pyridopyrimidine inhibitors of the enzyme adenosine kinase (AK) are described. It was found that pyridopyrimidines with a broad range of medium and large non-polar substituents at the 5-position potently inhibited AK activity. A narrower range of analogues was capable of potently inhibiting adenosine phosphorylation in intact cells indicating an enhanced ability of these analogues to penetrate cell membranes. Potent AK inhibitors were found to effectively reduce nociception in animal models of thermal hyperalgesia and persistent pain.

Published
2001

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