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Your search keyword '"Xing, Charles"' showing total 3 results
Start Over Author "Xing, Charles" Journal bioorganic medicinal chemistry letters
3 results on '"Xing, Charles"'

1. Fused tricyclic indoles as S1P₁ agonists with robust efficacy in animal models of autoimmune disease.

Author

Buzard DJ, Han S, Lopez L, Kawasaki A, Moody J, Thoresen L, Ullman B, Lehmann J, Calderon I, Zhu X, Gharbaoui T, Sengupta D, Krishnan A, Gao Y, Edwards J, Barden J, Morgan M, Usmani K, Chen C, Sadeque A, Thatte J, Solomon M, Fu L, Whelan K, Liu L, Al-Shamma H, Gatlin J, Le M, Xing C, Espinola S, and Jones RM

Subjects
Animals, Autoimmune Diseases drug therapy, Disease Models, Animal, Female, Humans, Immunologic Factors pharmacokinetics, Immunologic Factors therapeutic use, Indoles pharmacokinetics, Indoles therapeutic use, Lymphocytes immunology, Male, Mice, Mice, Inbred C57BL, Microsomes metabolism, Rats, Rats, Sprague-Dawley, Receptors, Lysosphingolipid metabolism, Structure-Activity Relationship, Immunologic Factors chemistry, Indoles chemistry, Receptors, Lysosphingolipid agonists
Abstract

Two series of fused tricyclic indoles were identified as potent and selective S1P(1) agonists. In vivo these agonists produced a significant reduction in circulating lymphocytes which translated into robust efficacy in several rodent models of autoimmune disease. Importantly, these agonists were devoid of any activity at the S1P(3) receptor in vitro, and correspondingly did not produce S1P(3) mediated bradycardia in telemeterized rat., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Published
2012
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2. Discovery and characterization of potent and selective 4-oxo-4-(5-(5-phenyl-1,2,4-oxadiazol-3-yl)indolin-1-yl)butanoic acids as S1P₁ agonists.

Author

Buzard D, Han S, Thoresen L, Moody J, Lopez L, Kawasaki A, Schrader T, Sage C, Gao Y, Edwards J, Barden J, Thatte J, Fu L, Solomon M, Liu L, Al-Shamma H, Gatlin J, Le M, Xing C, Espinola S, and Jones RM

Subjects
Animals, Butyrates pharmacokinetics, Disease Models, Animal, Dogs, Dose-Response Relationship, Drug, Drug Discovery, Drug Evaluation, Preclinical, Haplorhini, High-Throughput Screening Assays, Humans, Immunosuppressive Agents pharmacokinetics, Indoles pharmacokinetics, Male, Mice, Mice, Inbred BALB C, Nerve Tissue Proteins chemistry, Oxadiazoles pharmacokinetics, RNA-Binding Proteins chemistry, Rats, Rats, Sprague-Dawley, Structure-Activity Relationship, Substrate Specificity, Autoimmune Diseases drug therapy, Butyrates chemical synthesis, Butyrates pharmacology, Immunosuppressive Agents chemical synthesis, Immunosuppressive Agents pharmacology, Indoles chemical synthesis, Indoles pharmacology, Lymphocytes metabolism, Nerve Tissue Proteins agonists, Oxadiazoles chemical synthesis, Oxadiazoles pharmacology, RNA-Binding Proteins agonists
Abstract

S1P(1) receptor driven lymphopenia has proven utility in the treatment of an array of autoimmune disease states. As a part of our efforts to develop potent and selective S1P(1) receptor agonists, we have identified a novel chemical series of 4-oxo-4-(5-(5-phenyl-1,2,4-oxadiazol-3-yl)indolin-1-yl)butanoic acid S1P(1) receptor agonists., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Published
2011
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3. Discovery of fused bicyclic agonists of the orphan G-protein coupled receptor GPR119 with in vivo activity in rodent models of glucose control.

Author

Semple G, Ren A, Fioravanti B, Pereira G, Calderon I, Choi K, Xiong Y, Shin YJ, Gharbaoui T, Sage CR, Morgan M, Xing C, Chu ZL, Leonard JN, Grottick AJ, Al-Shamma H, Liang Y, Demarest KT, and Jones RM

Subjects
Animals, Bridged Bicyclo Compounds, Heterocyclic chemical synthesis, Bridged Bicyclo Compounds, Heterocyclic chemistry, Bridged Bicyclo Compounds, Heterocyclic pharmacology, Disease Models, Animal, Glucose metabolism, Hypoglycemic Agents chemical synthesis, Hypoglycemic Agents chemistry, Molecular Structure, Oxadiazoles chemistry, Oxadiazoles pharmacology, Pyrazoles chemistry, Pyrazoles pharmacology, Pyrimidines chemistry, Pyrimidines pharmacology, Rats, Rats, Zucker, Blood Glucose drug effects, Drug Discovery, Hypoglycemic Agents pharmacology, Receptors, G-Protein-Coupled agonists
Abstract

We herein outline the design of a new series of agonists of the pancreatic and GI-expressed orphan G-protein coupled receptor GPR119, a target that has been of significant recent interest in the field of metabolism, starting from our prototypical agonist AR231453. A number of key parameters were improved first by incorporation of a pyrazolopyrimidine core to create a new structural series and secondly by the introduction of a piperidine ether group capped with a carbamate. Chronic treatment with one compound from the series, 3k, showed for the first time that blood glucose and glycated hemoglobin (HbA1c) levels could be significantly reduced in Zucker Diabetic Fatty (ZDF) rats over several weeks of dosing. As a result of these and other data described here, 3k (APD668, JNJ-28630368) was the first compound with this mechanism of action to be progressed into clinical development for the treatment of diabetes., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Published
2011
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