Highly tractable, sub-nanomolar non-steroidal glucocorticoid receptor agonists
The discovery of 38E1 as a highly potent non-steroidal glucocorticoid agonist is described. Starting from a non-steroidal glucocorticoid agonist aryl pyrazole derivative, the NFκB agonist activity was optimised in an iterative process from pIC 50 7.5 (for 7), to pIC 50 10.1 (for 38E1). An explanatio...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2009-08, Vol.19 (16), p.4846-4850 |
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| container_issue | 16 |
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| container_title | Bioorganic & medicinal chemistry letters |
| container_volume | 19 |
| creator | Biggadike, Keith Caivano, Matilde Clackers, Margaret Coe, Diane M. Hardy, George W. Humphreys, Davina Jones, Haydn T. House, David Miles-Williams, Annette Skone, Philip A. Uings, Iain Weller, Vicki McLay, Iain M. Macdonald, Simon J.F. |
| description | The discovery of
38E1 as a highly potent non-steroidal glucocorticoid agonist is described.
Starting from a non-steroidal glucocorticoid agonist aryl pyrazole derivative, the NFκB agonist activity was optimised in an iterative process from pIC
50 7.5 (for
7), to pIC
50 10.1 (for
38E1). An explanation for the SAR observed based is presented along with a proposed docking of
38E1 into the active site of the glucocorticoid receptor. |
| doi_str_mv | 10.1016/j.bmcl.2009.06.020 |
| format | Article |
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38E1 as a highly potent non-steroidal glucocorticoid agonist is described.
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50 7.5 (for
7), to pIC
50 10.1 (for
38E1). An explanation for the SAR observed based is presented along with a proposed docking of
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38E1 as a highly potent non-steroidal glucocorticoid agonist is described.
Starting from a non-steroidal glucocorticoid agonist aryl pyrazole derivative, the NFκB agonist activity was optimised in an iterative process from pIC
50 7.5 (for
7), to pIC
50 10.1 (for
38E1). An explanation for the SAR observed based is presented along with a proposed docking of
38E1 into the active site of the glucocorticoid receptor.</description><subject>Agonist</subject><subject>Biological and medical sciences</subject><subject>Bones, joints and connective tissue. Antiinflammatory agents</subject><subject>Catalytic Domain</subject><subject>Cell Line</subject><subject>Computer Simulation</subject><subject>Glucocorticoid</subject><subject>Hormones. Endocrine system</subject><subject>Humans</subject><subject>Indazoles - chemistry</subject><subject>Medical sciences</subject><subject>NF-kappa B - metabolism</subject><subject>Non-steroidal</subject><subject>Pharmacology. 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38E1 as a highly potent non-steroidal glucocorticoid agonist is described.
Starting from a non-steroidal glucocorticoid agonist aryl pyrazole derivative, the NFκB agonist activity was optimised in an iterative process from pIC
50 7.5 (for
7), to pIC
50 10.1 (for
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| ispartof | Bioorganic & medicinal chemistry letters, 2009-08, Vol.19 (16), p.4846-4850 |
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| subjects | Agonist Biological and medical sciences Bones, joints and connective tissue. Antiinflammatory agents Catalytic Domain Cell Line Computer Simulation Glucocorticoid Hormones. Endocrine system Humans Indazoles - chemistry Medical sciences NF-kappa B - metabolism Non-steroidal Pharmacology. Drug treatments Pyrazoles - chemistry Receptors, Glucocorticoid - agonists Receptors, Glucocorticoid - metabolism Structure-Activity Relationship Tractable |
| title | Highly tractable, sub-nanomolar non-steroidal glucocorticoid receptor agonists |
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