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Your search keyword '"Lavoie Rico"' showing total 15 results
Start Over Author "Lavoie Rico" Publication Type Academic Journals
15 results on '"Lavoie Rico"'

4. N, N-Diethyl-4-[(3-hydroxyphenyl)(piperidin-4-yl)amino] benzamide derivatives: The development of diaryl amino piperidines as potent δ opioid receptor agonists with in vivo anti-nociceptive activity in rodent models

Author

Jones, Paul, Griffin, Andrew M., Gawell, Lars, Lavoie, Rico, Delorme, Daniel, Roberts, Edward, Brown, William, Walpole, Christopher, Xiao, Wenhau, Boulet, Jamie, Labarre, Maryse, Coupal, Martin, Butterworth, Joanne, St-Onge, Stephane, Hodzic, Lejla, and Salois, Dominic

Published
2009
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5. Indanylacetic acids as PPAR-δ activator insulin sensitizers

Author

Wickens, Philip, Zhang, Chengzhi, Ma, Xin, Zhao, Qian, Amatruda, John, Bullock, William, Burns, Michael, Cantin, Louis-David, Chuang, Chih-Yuan, Claus, Thomas, Dai, Miao, Dela Cruz, Fernando, Dickson, David, Ehrgott, Frederick J., Fan, Dongping, Heald, Sarah, Hentemann, Martin, Iwuagwu, Christiana I., Johnson, Jeffrey S., Kumarasinghe, Ellalahewage, Ladner, David, Lavoie, Rico, Liang, Sidney, Livingston, James N., Lowe, Derek, Magnuson, Steve, Mannelly, Gretchen, Mugge, Ingo, Ogutu, Herbert, Pleasic-Williams, Susan, Schoenleber, Robert W., Shapiro, Jeff, Shelekhin, Tatiana, Sweet, Laurel, Town, Christopher, and Tsutsumi, Manami

Published
2007
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6. Optimization of imidazole amide derivatives as cannabinoid-1 receptor antagonists for the treatment of obesity

Author

Smith, Roger A., Fathi, Zahra, Achebe, Furahi, Akuche, Christiana, Brown, Su-Ellen, Choi, Soongyu, Fan, Jianmei, Jenkins, Susan, Kluender, Harold C.E., Konkar, Anish, Lavoie, Rico, Mays, Ronald, Natoli, Jennifer, O’Connor, Stephen J., Ortiz, Astrid A., Su, Ning, Taing, Christy, Tomlinson, Susan, Tritto, Theresa, Wang, Gan, Wirtz, Stephan-Nicholas, Wong, Wai, Yang, Xiao-Fan, Ying, Shihong, and Zhang, Zhonghua

Published
2007
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13. Derivatives of Mesoxalic Acid Block Translocation of HIV-1 Reverse Transcriptase.

Author

Bernatchez, Jean A., Paul, Rakesh, Tchesnokov, Egor P., Ngure, Marianne, Beilhartz, Greg L., Berghuis, Albert M., Lavoie, Rico, Lianhai Li, Auger, Anick, Melnyk, Roman A., Grobler, Jay A., Miller, Michael D., Hazuda, Daria J., Hecht, Sidney M., and Götte, Matthias

Subjects
*PYROPHOSPHATES, *METAL ions, *HIV, *REVERSE transcriptase, *CHROMOSOMAL translocation
Abstract

The pyrophosphate mimic and broad spectrum antiviral phosphonoformic acid (PFA, foscarnet) was shown to freeze the pre-translocational state of the reverse transcriptase (RT) complex of the human immunodeficiency virus type 1 (HIV-1). However, PFA lacks a specificity domain, which is seen as a major reason for toxic side effects associated with the clinical use of this drug. Here, we studied the mechanism of inhibition of HIV-1 RT by the 4-chlorophenylhydrazone of mesoxalic acid (CPHM) and demonstrate that this compound also blocks RT translocation. Hot spots for inhibition with PFA or CPHM occur at template positions with a bias toward pre-translocation. Mutations at active site residue Asp-185 compromise binding of both compounds. Moreover, divalent metal ions are required for the formation of ternary complexes with either of the two compounds. However, CPHM contains both an anchor domain that likely interacts with the catalytic metal ions and a specificity domain. Thus, although the inhibitor binding sites may partly overlap, they are not identical. The K65R mutation in HIV-1 RT, which reduces affinity to PFA, increases affinity to CPHM. Details with respect to the binding sites of the two inhibitors are provided on the basis of mutagenesis studies, structure-activity relationship analyses with newly designed CPHM derivatives, and in silico docking experiments. Together, these findings validate the pre-translocated complex of HIV-1 RT as a specific target for the development of novel classes of RT inhibitors. [ABSTRACT FROM AUTHOR]

Published
2015
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14. Hepatitis C virus NS5A replication complex inhibitors: the discovery of daclatasvir.

Author

Belema M, Nguyen VN, Bachand C, Deon DH, Goodrich JT, James CA, Lavoie R, Lopez OD, Martel A, Romine JL, Ruediger EH, Snyder LB, St Laurent DR, Yang F, Zhu J, Wong HS, Langley DR, Adams SP, Cantor GH, Chimalakonda A, Fura A, Johnson BM, Knipe JO, Parker DD, Santone KS, Fridell RA, Lemm JA, O'Boyle DR 2nd, Colonno RJ, Gao M, Meanwell NA, and Hamann LG

Subjects
Animals, Antiviral Agents chemistry, Antiviral Agents pharmacokinetics, Area Under Curve, Carbamates, Dogs, Drug Discovery, Enzyme Inhibitors chemistry, Enzyme Inhibitors pharmacokinetics, Hepacivirus enzymology, Hepacivirus physiology, Imidazoles chemistry, Imidazoles pharmacokinetics, Magnetic Resonance Spectroscopy, Pyrrolidines, Rats, Spectrometry, Mass, Electrospray Ionization, Structure-Activity Relationship, Valine analogs & derivatives, Antiviral Agents pharmacology, Enzyme Inhibitors pharmacology, Hepacivirus drug effects, Imidazoles pharmacology, Viral Nonstructural Proteins antagonists & inhibitors, Virus Replication drug effects
Abstract

The biphenyl derivatives 2 and 3 are prototypes of a novel class of NS5A replication complex inhibitors that demonstrate high inhibitory potency toward a panel of clinically relevant HCV strains encompassing genotypes 1-6. However, these compounds exhibit poor systemic exposure in rat pharmacokinetic studies after oral dosing. The structure-activity relationship investigations that improved the exposure properties of the parent bis-phenylimidazole chemotype, culminating in the identification of the highly potent NS5A replication complex inhibitor daclatasvir (33) are described. An element critical to success was the realization that the arylglycine cap of 2 could be replaced with an alkylglycine derivative and still maintain the high inhibitory potency of the series if accompanied with a stereoinversion, a finding that enabled a rapid optimization of exposure properties. Compound 33 had EC50 values of 50 and 9 pM toward genotype-1a and -1b replicons, respectively, and oral bioavailabilities of 38-108% in preclinical species. Compound 33 provided clinical proof-of-concept for the NS5A replication complex inhibitor class, and regulatory approval to market it with the NS3/4A protease inhibitor asunaprevir for the treatment of HCV genotype-1b infection has recently been sought in Japan.

Published
2014
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15. Development of potential antitumor agents. Synthesis and biological evaluation of a new set of sulfonamide derivatives as histone deacetylase inhibitors.

Author

Bouchain G, Leit S, Frechette S, Khalil EA, Lavoie R, Moradei O, Woo SH, Fournel M, Yan PT, Kalita A, Trachy-Bourget MC, Beaulieu C, Li Z, Robert MF, MacLeod AR, Besterman JM, and Delorme D

Subjects
Animals, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Cell Cycle drug effects, Cell Line, Drug Screening Assays, Antitumor, Enzyme Inhibitors chemistry, Enzyme Inhibitors pharmacology, Humans, Hydroxamic Acids chemistry, Hydroxamic Acids pharmacology, Mice, Mice, Nude, Neoplasm Transplantation, Structure-Activity Relationship, Sulfonamides chemistry, Sulfonamides pharmacology, Transplantation, Heterologous, Antineoplastic Agents chemical synthesis, Enzyme Inhibitors chemical synthesis, Histone Deacetylase Inhibitors, Hydroxamic Acids chemical synthesis, Sulfonamides chemical synthesis
Abstract

A series of sulfonamide hydroxamic acids and anilides have been synthesized and studied as histone deacetylase (HDAC) inhibitors that can induce hyperacetylation of histones in human cancer cells. The inhibition of HDAC activity represents a novel approach for intervening in cell cycle regulation. The lead candidates were screened in a panel of human tumor and normal cell lines. They selectively inhibit proliferation, cause cell cycle blocks, and induce apoptosis in human cancer cells but not in normal cells. The structure-activity relationships, the antiproliferative activity, and the in vivo efficacy are described.

Published
2003
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