Synthesis and structure-activity relationships of novel indazolyl glucocorticoid receptor partial agonists

John L. Gilmore; James E. Sheppeck; Jim Wang; T. G.Murali Dhar; Cullen Cavallaro; Arthur M. Doweyko; Lorraine McKay; Mark D. Cunningham; Sium F. Habte; Steven G. Nadler; John H. Dodd; John E. Somerville; Joel C. Barrish

doi:10.1016/j.bmcl.2013.06.085

Synthesis and structure-activity relationships of novel indazolyl glucocorticoid receptor partial agonists

John L. Gilmore, James E. Sheppeck, Jim Wang, T. G.Murali Dhar, Cullen Cavallaro, Arthur M. Doweyko, Lorraine McKay, Mark D. Cunningham, Sium F. Habte, Steven G. Nadler, John H. Dodd, John E. Somerville, Joel C. Barrish

Chemistry

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Abstract

SAR was used to further develop an indazole class of non-steroidal glucocorticoid receptor agonists aided by a GR LBD (ligand-binding domain)-agonist co-crystal structure described in the accompanying paper. Progress towards discovering a dissociated GR agonist guided by human in vitro assays biased the optimization of this compound series towards partial agonists that possessed excellent selectivity against other nuclear hormone receptors.

Original language	English (US)
Pages (from-to)	5448-5451
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	23
Issue number	19
DOIs	https://doi.org/10.1016/j.bmcl.2013.06.085
State	Published - Oct 1 2013

All Science Journal Classification (ASJC) codes

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

Access to Document

10.1016/j.bmcl.2013.06.085

Cite this

Gilmore, J. L., Sheppeck, J. E., Wang, J., Dhar, T. G. M., Cavallaro, C., Doweyko, A. M., McKay, L., Cunningham, M. D., Habte, S. F., Nadler, S. G., Dodd, J. H., Somerville, J. E., & Barrish, J. C. (2013). Synthesis and structure-activity relationships of novel indazolyl glucocorticoid receptor partial agonists. Bioorganic and Medicinal Chemistry Letters, 23(19), 5448-5451. https://doi.org/10.1016/j.bmcl.2013.06.085

@article{7b8c5665c3694dbc8f8dbd40a6726d03,

title = "Synthesis and structure-activity relationships of novel indazolyl glucocorticoid receptor partial agonists",

abstract = "SAR was used to further develop an indazole class of non-steroidal glucocorticoid receptor agonists aided by a GR LBD (ligand-binding domain)-agonist co-crystal structure described in the accompanying paper. Progress towards discovering a dissociated GR agonist guided by human in vitro assays biased the optimization of this compound series towards partial agonists that possessed excellent selectivity against other nuclear hormone receptors.",

author = "Gilmore, {John L.} and Sheppeck, {James E.} and Jim Wang and Dhar, {T. G.Murali} and Cullen Cavallaro and Doweyko, {Arthur M.} and Lorraine McKay and Cunningham, {Mark D.} and Habte, {Sium F.} and Nadler, {Steven G.} and Dodd, {John H.} and Somerville, {John E.} and Barrish, {Joel C.}",

year = "2013",

month = oct,

day = "1",

doi = "10.1016/j.bmcl.2013.06.085",

language = "English (US)",

volume = "23",

pages = "5448--5451",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Ltd",

number = "19",

}

Gilmore, JL, Sheppeck, JE, Wang, J, Dhar, TGM, Cavallaro, C, Doweyko, AM, McKay, L, Cunningham, MD, Habte, SF, Nadler, SG, Dodd, JH, Somerville, JE & Barrish, JC 2013, 'Synthesis and structure-activity relationships of novel indazolyl glucocorticoid receptor partial agonists', Bioorganic and Medicinal Chemistry Letters, vol. 23, no. 19, pp. 5448-5451. https://doi.org/10.1016/j.bmcl.2013.06.085

TY - JOUR

T1 - Synthesis and structure-activity relationships of novel indazolyl glucocorticoid receptor partial agonists

AU - Gilmore, John L.

AU - Sheppeck, James E.

AU - Wang, Jim

AU - Dhar, T. G.Murali

AU - Cavallaro, Cullen

AU - Doweyko, Arthur M.

AU - McKay, Lorraine

AU - Cunningham, Mark D.

AU - Habte, Sium F.

AU - Nadler, Steven G.

AU - Dodd, John H.

AU - Somerville, John E.

AU - Barrish, Joel C.

PY - 2013/10/1

Y1 - 2013/10/1

N2 - SAR was used to further develop an indazole class of non-steroidal glucocorticoid receptor agonists aided by a GR LBD (ligand-binding domain)-agonist co-crystal structure described in the accompanying paper. Progress towards discovering a dissociated GR agonist guided by human in vitro assays biased the optimization of this compound series towards partial agonists that possessed excellent selectivity against other nuclear hormone receptors.

AB - SAR was used to further develop an indazole class of non-steroidal glucocorticoid receptor agonists aided by a GR LBD (ligand-binding domain)-agonist co-crystal structure described in the accompanying paper. Progress towards discovering a dissociated GR agonist guided by human in vitro assays biased the optimization of this compound series towards partial agonists that possessed excellent selectivity against other nuclear hormone receptors.

UR - http://www.scopus.com/inward/record.url?scp=84883487208&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84883487208&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2013.06.085

DO - 10.1016/j.bmcl.2013.06.085

M3 - Article

C2 - 23916594

AN - SCOPUS:84883487208

SN - 0960-894X

VL - 23

SP - 5448

EP - 5451

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 19

ER -

Synthesis and structure-activity relationships of novel indazolyl glucocorticoid receptor partial agonists

Abstract

All Science Journal Classification (ASJC) codes

Access to Document

Other files and links

Fingerprint

Cite this