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Your search keyword '"Tagat, Jayaram R."' showing total 22 results
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22 results on '"Tagat, Jayaram R."'

1. SCH-C (SCH 351125), An Orally Bioavailable, Small Molecule Antagonist of the Chemokine Receptor CCR5, is a Potent Inhibitor of HIV-1 Infection in vitro and in vivo

Author

Strizki, Julie M., Xu, Serena, Wagner, Nicole E., Wojcik, Lisa, Liu, Jia, Hou, Yan, Endres, Michael, Palani, Anandan, Shapiro, Sherry, Clader, John W., Greenlee, William J., Tagat, Jayaram R., McCombie, Stuart, Cox, Kathleen, Fawzi, Ahmad B., Chou, Chuan-Chu, Pugliese-Sivo, Catherine, Davies, Liza, Moreno, Mary E., Ho, David D., Trkola, Alexandra, Stoddart, Cheryl A., Moore, John P., Reyes, Gregory R., and Baroudy, Bahige M.

Published
2001

5. Piperazine-based CCR5 antagonists as HIV-1 inhibitors. III: synthesis, antiviral and pharmacokinetic profiles of symmetrical heteroaryl carboxamides

Author

McCombie, Stuart W., Tagat, Jayaram R., Vice, Susan F., Lin, Sue-Ing, Steensma, Ruo, Palani, Anandan, Neustadt, Bernard R., Baroudy, Bahige M., Strizki, Julie M., Endres, Michael, Cox, Kathleen, Dan, Niya, and Chou, Chuan-Chu

Subjects
*NICOTINAMIDE, *PIPERAZINE
Abstract

The unsymmetrical nicotinamide-N-oxide moiety in compound 1 was replaced with symmetrical isonicotinamides as well as 4,6-dimethyl pyrimidine-5-carboxamides. Compound 16 from the latter set reduced the number of rotamers, improved potency of inhibiting UIV entry, slightly diminished the affinity for the muscarine receptors and showed very good oral absorption. [Copyright &y& Elsevier]

Published
2003
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6. Synthesis of Mono- and Difluoronaphthoic Acids.

Author

Tagat, Jayaram R., McCombie, Stuart W., Nazareno, Dennis V., Boyle, Craig D., Kozlowski, Joseph A., Chackalamannil, Samuel, Josien, Hubert, Yuguang Wang, and Guowei Zhou

Subjects
*SPECTRAL synthesis (Mathematics), *DECARBOXYLASES
Abstract

Examines the synthesis of difluoronaphthoic acids. Use of aryl carboxamides on biologically active compounds; Elaboration of commercial fluorinated phenylacetic acids to glutaric acids with different esters group; Effects of hydrolysis to mono acids.

Published
2002
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18. <atl>Synthesis and structure–Activity relationships of M2-Selective muscarinic receptor ligands in the 1-[4-(4-Arylsulfonyl)-phenylmethyl]-4-(4-piperidinyl)-piperazine family

Author

McCombie, Stuart W., Lin, Sue-Ing, Tagat, Jayaram R., Nazareno, Dennis, Vice, Susan, Ford, Jennifer, Asberom, Theodros, Leone, Daria, Kozlowski, Joseph A., Zhou, Guowei, Ruperto, Vilma B., Duffy, Ruth A., and Lachowicz, Jean E.

Subjects
*MUSCARINIC receptors, *PIPERAZINE, *METHYL groups
Abstract

The synthesis and muscarinic binding properties of compounds based on the 1-[4-(4-arylsulfonyl)phenylmethyl]-4-(1-aroyl-4-piperidinyl)-piperazine skeleton are described. For compounds, substituted with appropriately configured methyl groups at the benzylic center and at the piperazine 2-position, high levels of selective, M2 subtype affinity could be obtained, particularly when the terminal N-aroyl residue was ortho-substituted. [Copyright &y& Elsevier]

Published
2002
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19. <atl>Substituted 2-(R)-Methyl piperazines as muscarinic M2 selective ligands

Author

Kozlowski, Joseph A., Zhou, Guowei, Tagat, Jayaram R., Lin, Sue-Ing, McCombie, Stuart W., Ruperto, Vilma B., Duffy, Ruth A., McQuade, Robert A., Crosby Jr., Gordon, Taylor, Lisa A., Billard, William, Binch III, Herbert, and Lachowicz, Jean E.

Subjects
*PIPERAZINE, *ACETYLCHOLINE
Abstract

A novel series of 2-(R)-methyl-substituted piperazines (e.g., 2) is described. They are potent M2 selective ligands that have >100-fold selectivity versus the M1 receptor. In the rat microdialysis assay, compound 14 showed significantly enchanced levels of acetylcholine after oral administration. [Copyright &y& Elsevier]

Published
2002
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20. Discovery of a highly potent orally bioavailable imidazo-[1, 2-a]pyrazine Aurora inhibitor.

Author

Yu, Tao, Zhang, Yonglian, Kerekes, Angela D., Tagat, Jayaram R., Doll, Ronald J., Xiao, Yushi, Esposite, Sara, Hruza, Alan, Belanger, David B., Voss, Matthew, Rainka, Matthew P., Basso, Andrea, Liu, Ming, Liang, Lianzhu, Sui, Ning, Prelusky, Daniel, Rindgen, Diane, and Zhang, Likang

Subjects
*PYRAZINES, *AURORA kinases, *ORAL drug administration, *ENZYME inhibitors, *LABORATORY mice
Abstract

Imidazo-[1, 2- a ]pyrazine 1 is a potent inhibitor of Aurora A and B kinase in vitro and is effective in in vivo tumor models, but has poor oral bioavailbility and is unsuitable for oral dosing. We describe herein our effort to improve oral exposure in this class, resulting ultimately in the identification of a potent Aurora inhibitor 16 , which exhibited good drug exposure levels across species upon oral dosing, and showed excellent in vivo efficacy in a mouse xenograft tumor model when dosed orally. [ABSTRACT FROM AUTHOR]

Published
2018
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21. Himbacine derived thrombin receptor antagonists: Discovery of a new tricyclic core

Author

Clasby, Martin C., Chackalamannil, Samuel, Czarniecki, Michael, Doller, Darío, Eagen, Keith, Greenlee, William J., Lin, Yan, Tagat, Jayaram R., Tsai, Hsingan, Xia, Yan, Ahn, Ho-Sam, Agans-Fantuzzi, Jacqueline, Boykow, George, Chintala, Madhu, Hsieh, Yunsheng, and McPhail, Andrew T.

Subjects
*THROMBIN, *KRA, *BLOOD platelet aggregation, *ANIMAL models in research
Abstract

Abstract: The synthesis and biological activity of a novel series of thrombin receptor antagonists is described. This series of compounds showed excellent in vitro and in vivo potency. The most potent compound 40 had an IC50 of 7.6nM and showed robust inhibition of platelet aggregation in a cynomolgus monkey model after oral administration. [Copyright &y& Elsevier]

Published
2007
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22. Analysis of the Mechanism by Which the Small-Molecule CCR5 Antagonists SCH-351125 and SCH-350581 Inhibit Human Immunodeficiency Virus Type 1 Entry.

Author

Tsamis, Fotini, Gavrilov, Svetlana, Kajumo, Francis, Seibert, Christoph, Kuhmann, Shawn, Ketas, Tom, Trkola, Alexandra, Palani, Anadan, Clader, John W., Tagat, Jayaram R., McCombie, Stuart, Baroudy, Bahige, Moore, John P., Sakmar, Thomas P., and Dragic, Tatjana

Subjects
*HIV, *GLYCOPROTEINS
Abstract

Human immunodeficiency virus type 1 (HIV-1) entry is mediated by the consecutive interaction of the envelope glycoprotein gp120 with CD4 and a coreceptor such as CCR5 or CXCR4. The CCR5 coreceptor is used by the most commonly transmitted HIV-1 strains that often persist throughout the course of infection. Compounds targeting CCR5-mediated entry are a novel class of drugs being developed to treat HIV-1 infection. In this study, we have identified the mechanism of action of two inhibitors of CCR5 function, SCH-350581 (AD101) and SCH-351125 (SCH-C). AD101 is more potent than SCH-C at inhibiting HIV-1 replication in primary lymphocytes, as well as viral entry and gp120 binding to cell lines. Both molecules also block the binding of several anti-CCR5 monoclonal antibodies that recognize epitopes in the second extracellular loop of CCR5. Alanine mutagenesis of the transmembrane domain of CCR5 suggests that AD101 and SCH-C bind to overlapping but nonidentical sites within a putative ligand-binding cavity formed by transmembrane helices 1, 2, 3, and 7. We propose that the binding of small molecules to the transmembrane domain of CCR5 may disrupt the conformation of its extracellular domain, thereby inhibiting ligand binding to CCR5. [ABSTRACT FROM AUTHOR]

Published
2003
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