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Your search keyword '"Hsieh G"' showing total 6 results
Start Over Author "Hsieh G" Journal bioorganic medicinal chemistry letters
6 results on '"Hsieh G"'

1. Development of indole/indazole-aminopyrimidines as inhibitors of c-Jun N-terminal kinase (JNK): optimization for JNK potency and physicochemical properties.

Author

Gong L, Han X, Silva T, Tan YC, Goyal B, Tivitmahaisoon P, Trejo A, Palmer W, Hogg H, Jahagir A, Alam M, Wagner P, Stein K, Filonova L, Loe B, Makra F, Rotstein D, Rapatova L, Dunn J, Zuo F, Dal Porto J, Wong B, Jin S, Chang A, Tran P, Hsieh G, Niu L, Shao A, Reuter D, Hermann J, Kuglstatter A, and Goldstein D

Subjects
Crystallography, X-Ray, Indazoles chemistry, Indazoles pharmacology, JNK Mitogen-Activated Protein Kinases chemistry, Phosphorylation, Structure-Activity Relationship, Indoles chemistry, Indoles pharmacology, JNK Mitogen-Activated Protein Kinases antagonists & inhibitors, Protein Kinase Inhibitors chemistry, Protein Kinase Inhibitors pharmacology, Pyrimidines chemistry, Pyrimidines pharmacology
Abstract

A novel series of indole/indazole-aminopyrimidines was designed and synthesized with an aim to achieve optimal potency and selectivity for the c-Jun kinase family or JNKs. Structure guided design was used to optimize the series resulting in a significant potency improvement. The best compound (17) has IC50 of 3 nM for JNK1 and 20 nM for JNK2, with greater than 40-fold selectivity against other kinases with good physicochemical and pharmacokinetic properties., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Published
2013
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2. Development of amino-pyrimidine inhibitors of c-Jun N-terminal kinase (JNK): kinase profiling guided optimization of a 1,2,3-benzotriazole lead.

Author

Palmer WS, Alam M, Arzeno HB, Chang KC, Dunn JP, Goldstein DM, Gong L, Goyal B, Hermann JC, Hogg JH, Hsieh G, Jahangir A, Janson C, Jin S, Ursula Kammlott R, Kuglstatter A, Lukacs C, Michoud C, Niu L, Reuter DC, Shao A, Silva T, Trejo-Martin TA, Stein K, Tan YC, Tivitmahaisoon P, Tran P, Wagner P, Weller P, and Wu SY

Subjects
Animals, Crystallography, X-Ray, Drug Design, Humans, JNK Mitogen-Activated Protein Kinases metabolism, Models, Molecular, Protein Kinase Inhibitors chemical synthesis, Pyrimidines chemical synthesis, Rats, Structure-Activity Relationship, Triazoles chemical synthesis, JNK Mitogen-Activated Protein Kinases antagonists & inhibitors, Protein Kinase Inhibitors chemistry, Protein Kinase Inhibitors pharmacology, Pyrimidines chemistry, Pyrimidines pharmacology, Triazoles chemistry, Triazoles pharmacology
Abstract

A series of amino-pyrimidines was developed based upon an initial kinase cross-screening hit from a CDK2 program. Kinase profiling and structure-based drug design guided the optimization from the initial 1,2,3-benzotriazole hit to a potent and selective JNK inhibitor, compound 24f (JNK1 and 2 IC(50)=16 and 66 nM, respectively), with bioavailability in rats and suitable for further in vivo pharmacological evaluation., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Published
2013
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3. Discovery of a novel series of 4-quinolone JNK inhibitors.

Author

Gong L, Tan YC, Boice G, Abbot S, McCaleb K, Iyer P, Zuo F, Dal Porto J, Wong B, Jin S, Chang A, Tran P, Hsieh G, Niu L, Shao A, Reuter D, Lukacs CM, Ursula Kammlott R, Kuglstatter A, and Goldstein D

Subjects
4-Quinolones chemical synthesis, 4-Quinolones chemistry, Crystallography, X-Ray, Dose-Response Relationship, Drug, Humans, JNK Mitogen-Activated Protein Kinases metabolism, Models, Molecular, Molecular Structure, Protein Kinase Inhibitors chemical synthesis, Protein Kinase Inhibitors chemistry, Structure-Activity Relationship, 4-Quinolones pharmacology, Drug Discovery, JNK Mitogen-Activated Protein Kinases antagonists & inhibitors, Protein Kinase Inhibitors pharmacology
Abstract

A novel series of highly selective JNK inhibitors based on the 4-quinolone scaffold was designed and synthesized. Structure based drug design was utilized to guide the compound design as well as improvements in the physicochemical properties of the series. Compound (13c) has an IC(50) of 62/170 nM for JNK1/2, excellent kinase selectivity and impressive efficacy in a rodent asthma model., (Published by Elsevier Ltd.)

Published
2012
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4. Rapamycin analogs with reduced systemic exposure.

Author

Wagner R, Mollison KW, Liu L, Henry CL, Rosenberg TA, Bamaung N, Tu N, Wiedeman PE, Or Y, Luly JR, Lane BC, Trevillyan J, Chen YW, Fey T, Hsieh G, Marsh K, Nuss M, Jacobson PB, Wilcox D, Carlson RP, Carter GW, and Djuric SW

Subjects
Animals, Antirheumatic Agents toxicity, Arthritis, Rheumatoid diagnostic imaging, Arthritis, Rheumatoid drug therapy, Male, Radiography, Rats, Rats, Inbred Lew, Rats, Sprague-Dawley, Antirheumatic Agents chemistry, Antirheumatic Agents pharmacokinetics, Arthritis, Rheumatoid metabolism, Sirolimus analogs & derivatives
Abstract

The synthesis and biological activities of rapamycin (I) analogs modified at the C-40 position are reported. Emphasis placed on compounds that potentially have an improved safety profile on account of their shorter in vivo half-life when compared with rapamycin.

Published
2005
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5. Synthesis and immunosuppressant activity of pyrazole carboxamides.

Author

Wang AX, Xie Q, Lane B, Mollison KW, Hsieh GC, Marsh K, Sheets MP, Luly JR, and Coghlan MJ

Subjects
Animals, Biological Availability, Humans, Immunosuppressive Agents pharmacokinetics, Isoxazoles pharmacology, Leflunomide, Lymphocyte Activation drug effects, Lymphocyte Culture Test, Mixed, Pyrazoles pharmacokinetics, Rats, Structure-Activity Relationship, T-Lymphocytes drug effects, T-Lymphocytes immunology, Immunosuppressive Agents chemical synthesis, Immunosuppressive Agents pharmacology, Pyrazoles chemical synthesis, Pyrazoles pharmacology
Abstract

A series of novel pyrazole carboxamides is disclosed that demonstrate strong immunosuppressant activity in rodent and human mixed leukocyte response (MLR) assays (IC50 < 1 microM). The synthesis, biological activity, mode of action, and pharmacokinetic properties of this new lead series are discussed.

Published
1998
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6. Studies on an immunosuppressive macrolactam, ascomycin: synthesis of a C-33 hydroxyl derivative.

Author

Kawai M, Gunawardana IW, Mollison KW, Hsieh GC, Lane BC, and Luly JR

Subjects
Animals, Humans, Hydrogen-Ion Concentration, Hyperplasia, Immunosuppressive Agents chemistry, Immunosuppressive Agents pharmacology, Indicators and Reagents, Lymph Nodes drug effects, Lymph Nodes pathology, Lymphocyte Culture Test, Mixed, Molecular Conformation, Molecular Structure, Rats, Solubility, Structure-Activity Relationship, Tacrolimus chemical synthesis, Tacrolimus chemistry, Tacrolimus pharmacology, Immunosuppressive Agents chemical synthesis, Lymphocyte Activation drug effects, Tacrolimus analogs & derivatives
Abstract

Ascomycin 2, a close analogue of the immunosuppressant FK506 1, was modified to incorporate a hydroxyl group at the C-33 position. This increased the aqueous solubility of ascomycin by a hundred-fold at pH 7.4 and by approximately 300-fold at pH 6.5. Ascomycin 3 also exhibited an excellent immunosuppressive activity in vitro, as tested in a human mixed lymphocyte proliferation (HuMLR) assay, and in vivo using a rat popliteal lymph node (rPLN) hyperplasia assay.

Published
1998
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