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Your search keyword '"Bass JY"' showing total 4 results
Start Over Author "Bass JY" Topic receptors, cytoplasmic and nuclear
4 results on '"Bass JY"'

1. Conformationally constrained farnesoid X receptor (FXR) agonists: heteroaryl replacements of the naphthalene.

Author

Bass JY, Caravella JA, Chen L, Creech KL, Deaton DN, Madauss KP, Marr HB, McFadyen RB, Miller AB, Mills WY, Navas F 3rd, Parks DJ, Smalley TL Jr, Spearing PK, Todd D, Williams SP, and Wisely GB

Subjects
Animals, Binding Sites, Blood Glucose metabolism, Crystallography, X-Ray, Diabetes Mellitus, Experimental metabolism, Dogs, Fluorescence Resonance Energy Transfer, Humans, Isoxazoles chemical synthesis, Isoxazoles pharmacokinetics, Ligands, Mice, Molecular Conformation, Protein Structure, Tertiary, Quinolines chemical synthesis, Quinolines pharmacokinetics, Rats, Receptors, Cytoplasmic and Nuclear metabolism, Weight Gain drug effects, Isoxazoles chemistry, Naphthalenes chemistry, Quinolines chemistry, Receptors, Cytoplasmic and Nuclear agonists
Abstract

To improve on the drug properties of GSK8062 1b, a series of heteroaryl bicyclic naphthalene replacements were prepared. The quinoline 1c was an equipotent FXR agonist with improved drug developability parameters relative to 1b. In addition, analog 1c lowered body weight gain and serum glucose in a DIO mouse model of diabetes., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Published
2011
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2. FXR agonist activity of conformationally constrained analogs of GW 4064.

Author

Akwabi-Ameyaw A, Bass JY, Caldwell RD, Caravella JA, Chen L, Creech KL, Deaton DN, Madauss KP, Marr HB, McFadyen RB, Miller AB, Navas F 3rd, Parks DJ, Spearing PK, Todd D, Williams SP, and Bruce Wisely G

Subjects
Animals, Binding Sites, Computer Simulation, Crystallography, X-Ray, Humans, Isoxazoles pharmacology, Naphthalenes pharmacokinetics, Rats, Receptors, Cytoplasmic and Nuclear metabolism, Structure-Activity Relationship, Thiophenes pharmacokinetics, Isoxazoles chemistry, Naphthalenes chemistry, Receptors, Cytoplasmic and Nuclear agonists, Thiophenes chemistry
Abstract

Two series of conformationally constrained analogs of the FXR agonist GW 4064 1 were prepared. Replacement of the metabolically labile stilbene with either benzothiophene or naphthalene rings led to the identification of potent full agonists 2a and 2g.

Published
2009
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3. Substituted isoxazole analogs of farnesoid X receptor (FXR) agonist GW4064.

Author

Bass JY, Caldwell RD, Caravella JA, Chen L, Creech KL, Deaton DN, Madauss KP, Marr HB, McFadyen RB, Miller AB, Parks DJ, Todd D, Williams SP, and Wisely GB

Subjects
Animals, Crystallography, X-Ray, Fluorescence Resonance Energy Transfer, Isoxazoles chemistry, Isoxazoles pharmacology, Rats, Receptors, Cytoplasmic and Nuclear metabolism, Structure-Activity Relationship, Isoxazoles chemical synthesis, Receptors, Cytoplasmic and Nuclear agonists
Abstract

Starting from the known FXR agonist GW 4064 1a, a series of alternately 3,5-substituted isoxazoles was prepared. Several of these analogs were potent full FXR agonists. A subset of this series, with a tether between the isoxazole ring and the 3-position aryl substituent, were equipotent FXR agonists to GW 4064 1a, with the 2,6-dimethyl phenol analog 1t having greater FRET FXR potency than GW 4064 1a.

Published
2009
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4. Conformationally constrained farnesoid X receptor (FXR) agonists: Naphthoic acid-based analogs of GW 4064.

Author

Akwabi-Ameyaw A, Bass JY, Caldwell RD, Caravella JA, Chen L, Creech KL, Deaton DN, Jones SA, Kaldor I, Liu Y, Madauss KP, Marr HB, McFadyen RB, Miller AB, Navas F III, Parks DJ, Spearing PK, Todd D, Williams SP, and Wisely GB

Subjects
Administration, Oral, Animals, Carboxylic Acids chemistry, Cholestasis metabolism, Cholestasis pathology, Crystallography, X-Ray, DNA-Binding Proteins chemistry, Disease Models, Animal, Dogs, Gastric Mucosa metabolism, Haplorhini, Isoxazoles chemistry, Mice, Molecular Conformation, Molecular Structure, Naphthalenes chemistry, Rats, Receptors, Cytoplasmic and Nuclear chemistry, Stomach drug effects, Structure-Activity Relationship, Transcription Factors chemistry, Carboxylic Acids chemical synthesis, Carboxylic Acids pharmacology, Cholestasis drug therapy, DNA-Binding Proteins agonists, Isoxazoles chemical synthesis, Isoxazoles pharmacology, Naphthalenes chemical synthesis, Naphthalenes pharmacology, Receptors, Cytoplasmic and Nuclear agonists, Transcription Factors agonists
Abstract

Starting from the known FXR agonist GW 4064 1a, a series of stilbene replacements were prepared. The 6-substituted 1-naphthoic acid 1b was an equipotent FXR agonist with improved developability parameters relative to 1a. Analog 1b also reduced the severity of cholestasis in the ANIT acute cholestatic rat model.

Published
2008
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