GnRH Research Publications

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2007
2006
2005
2004
2003

2008

Discovery of Sodium R-(+)-4-{2-[5-(2-Fluoro-3-methoxyphenyl)-3-(2-fluoro-6-[trifluoromethyl]benzyl)-4-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-1-phenylethylamino}butyrate (Elagolix), a Potent and Orally Available Nonpeptide Antagonist of the Human Gonadotropin-Releasing Hormone Receptor.
Chen C, Wu D, Guo Z, Xie Q, Reinhart GJ, Madan A, Wen J, Chen T, Huang CQ, Chen M, Chen Y, Tucci FC, Rowbottom M, Pontillo J, Zhu YF, Wade W, Saunders J, Bozigian H, Struthers RS. J Med Chem. 2008 Nov 12. [Epub ahead of print]

The use of ligand-based de novo design for scaffold hopping and sidechain optimization: two case studies
Feher M; Gao Y; Baber JC; Shirley WA; Saunders J, Bioorganic & Medicinal Chemistry [Bioorg Med Chem] 2008 Jan 1; Vol. 16 (1), pp. 422-7. Date of Electronic Publication: 2007 Sep 18

Zwitterionic uracil derivatives as potent GnRH receptor antagonists with improved pharmaceutical properties.
Regan CF, Guo Z, Chen Y, Huang CQ, Chen M, Jiang W, Rueter JK, Coon T, Chen C, Saunders J, Brown MS, Betz SF, Struthers RS, Yang C, Wen J, Madan A, Zhu YF. Bioorg Med Chem Lett. 2008 Aug 15;18(16):4503-7. Epub 2008 Jul 17.
See also Bioorganic & Medicinal Chemistry Letters

Non-peptide gonadotropin-releasing hormone receptor antagonists.
Betz SF, Zhu YF, Chen C, Struthers RS. J Med Chem. 2008 Jun 26;51(12):3331-48. Review. No abstract available.

Potent and orally bioavailable zwitterion GnRH antagonists with low CYP3A4 inhibitory activity.
Chen C, Chen Y, Pontillo J, Guo Z, Huang CQ, Wu D, Madan A, Chen T, Wen J, Xie Q, Tucci FC, Rowbottom M, Zhu YF, Wade W, Saunders J, Bozigian H, Struthers RS. Bioorg Med Chem Lett. 2008 Jun 1;18(11):3301-5. Epub 2008 Apr 26.
See also Bioorganic & Medicinal Chemistry Letters

5-Aryluracils as potent GnRH antagonists-Characterization of atropisomers.
Zhao L, Guo Z, Chen Y, Hu T, Wu D, Zhu YF, Rowbottom M, Gross TD, Tucci FC, Struthers RS, Xie Q, Chen C. Bioorg Med Chem Lett. 2008 Jun 1;18(11):3344-9. Epub 2008 Apr 15.
See also Bioorganic & Medicinal Chemistry Letters

Small molecule antagonists of the corticotropin releasing factor (CRF) receptor: recent medicinal chemistry developments.
Tellew JE, Luo Z. Curr Top Med Chem. 2008;8(6):506-20. Review.

2007

Identification of 2-(4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridine-3-yl)-ethylamine derivatives as novel GnRH receptor antagonists
Chen M, Guo Z, Lanier MC, et al. Bioorg Med Chem 2007, 17(14):3845-50

Scintillation Proximity Assay as a High-throughput method to identify slowly dissociating nonpeptide ligand binding to the GnRH Receptor
Heise CE, Sullivan SK, Crowe PD. J. Biomol Screen 12(2): 235-9

Human endometriosis is associated with plasma cells and overexpression of B lymphocyte stimulator
Hever A, Roth RB, Hevezi P, et al. Proc Natl Acad Sci USA, 104(30): 12451-6

Trapping of a Nonpeptide Ligand by the Extracellular Domains of the Gonadotropin-releasing Hormone Receptor Results in Insurmountable Antagonism
Kohout TA, Xie Q, Reijmer S, et al. Mol Pharmacol, 72(2): 238-47

Selection, synthesis, and structure-activity relationship of tetrahydropyrido[4,3-d]pyrimidine-2,4-diones as human GnRH receptor antagonists
Lanier MC, Feher M, Ashweek NJ, et al. Bioorg Med Chem 2007 15(16): 5590-603

Pharmacological Characterization of a novel nonpeptide antagonists of the human gonadotropin-releasing hormone receptor
Struthers RS., Xie Q, Sullivan, SK, et al. NBI-42902, Endoctrinology 148(2):857-67

2006

Overlapping, nonidentical binding sites of different classes of nonpeptide antagonists for the human gonadotropin-releasing hormone receptor.
Betz SF, Reinhart GJ, Lio FM, Chen C, Struthers RS. J Med Chem 2006, 49(2):637-47

Determination of the binding mode of thienopyrimidinedione antagonists to the human gonadotropin releasing hormone receptor using structure-activity relationships, site-directed mutagenesis, and homology modeling
Betz SF, Lio FM, et al. J Med Chem 49(21): 6170-6

Molecular characterization of human adenomyosis
Hever A, Roth RB, et al. Mol Hum Reprod 12(12): 737-48

Suppression of Serum Luteinizing Hormone in Postmenopausal Women by an Orally Administered Nonpeptide Antagonist of the Gonadotropin-Releasing Hormone Receptor (NBI-42902)
Struthers RS, Chen T, et al. J Clin Endocrinol Metab 91(10):3903-7

Allosteric and Orthosteric Binding Modes of Two Nonpeptide Hman Gonadotropin-Releasing Hormone Receptor Antagonists
Sullivan SK, Brown MS, et al. Biochemistry 45(51): 15327-37

Kinetics of nonpeptide antagonists binding to the human gonadotropin-releasing hormone receptor: Implications for structure-activity relationships and insurmountable antagonism
Sullivan SK, Hoare SR, et al. Biochem Pharmacol 72(7): 838-49

2005

Uracils as potent antagonists of the human gonadotropin-releasing hormone receptor without atropisomers.
Guo Z, Chen Y, Huang CQ, Gross TD, Pontillo J, Rowbottom MW, Saunders J, Struthers S, Tucci FC, Xie Q, et al. Bioorg Med Chem Lett 2005, 15:2519-2522

A convenient one-pot synthesis of asymmetric 1,3,5-triazine-2,4,6-triones and its application towards a novel class of gonadotropin-releasing hormone receptor antagonists.
Guo Z, Wu D, Zhu YF, Tucci FC, Pontillo J, Saunders J, Xie Q, Struthers RS, Chen C. Bioorg Med Chem Lett 2005, 15:693-698

Structure-activity relationships of 1,3,5-triazine-2,4,6-triones as human gonadotropin-releasing hormone receptor antagonists.
Guo Z, Wu D, Zhu YF, Tucci FC, Regan CF, Rowbottom MW, Struthers RS, Xie Q, Reijmers S, Sullivan SK, et al. Bioorg Med Chem Lett 2005, 15:3685-3690

Efficient synthesis of bicyclic oxazolino- and thiazolino[3,2-c]pyrimidine-5,7-diones and its application to the synthesis of GnRH antagonists.
Pontillo J, Chen C. Bioorg Med Chem Lett 2005, 15:1407-1411

Synthesis of aryl-1,2,4-triazine-3,5-diones as antagonists of the gonadotropin-releasing hormone receptor.
Pontillo J, Guo Z, Wu D, Struthers RS, Chen C. Bioorg Med Chem Lett 2005, 15:4363-4366

3-[(2R)-Amino-2-phenylethyl]-1-(2,6-difluorobenzyl)-5-(2-fluoro-3-methoxyp henyl)- 6-methylpyrimidin-2,4-dione (NBI 42902) as a potent and orally active antagonist of the human gonadotropin-releasing hormone receptor. Design, synthesis, and in vitro and in vivo characterization.
Tucci FC, Zhu YF, Struthers RS, Guo Z, Gross TD, Rowbottom MW, Acevedo O, Gao Y, Saunders J, Xie Q, et al. J Med Chem 2005, 48:1169-1178

2004

Synthesis and structure-activity relationships of uracil derived human GnRH receptor antagonists: (R)-3-[2-(2-amino)phenethyl]-1-(2,6-difluorobenzyl)-6-methyluracils containing a substituted thiophene or thiazole at C-5.
Rowbottom MW, Tucci FC, Connors PJ, Jr., Gross TD, Zhu YF, Guo Z, Moorjani M, Acevedo O, Carter L, Sullivan SK, et al. Bioorg Med Chem Lett 2004, 14:4967-4973

Synthesis and structure-activity relationships of (R)-1-alkyl-3-[2-(2-amino)phenethyl]-5-(2-fluorophenyl)-6-methyluracils as human GnRH receptor antagonists.
Rowbottom MW, Tucci FC, Zhu YF, Guo Z, Gross TD, Reinhart GJ, Xie Q, Struthers RS, Saunders J, Chen C. Bioorg Med Chem Lett 2004, 14:2269-2274

2003

Synthesis and structure-activity relationships of thieno[2,3-d]pyrimidine-2,4-dione derivatives as potent GnRH receptor antagonists.
Guo Z, Chen Y, Wu D, Zhu YF, Struthers RS, Saunders J, Xie Q, Chen C. Bioorg Med Chem Lett 2003, 13:3617-3622

Synthesis and structure-activity relationships of 1-arylmethyl-3-(2-aminopropyl)-5-aryl-6-methyluracils as potent GnRH receptor antagonists.
Guo Z, Zhu YF, Tucci FC, Gao Y, Struthers RS, Saunders J, Gross TD, Xie Q, Reinhart GJ, Chen C. Bioorg Med Chem Lett 2003, 13:3311-3315

Synthesis and structure-activity relationships of 1-arylmethyl-3-(1-methyl-2-amino)ethyl-5-aryl-6-methyluracils as antagonists of the human GnRH Receptor.
Tucci FC, Zhu YF, Guo Z, Gross TD, Connors PJ, Jr., Struthers RS, Reinhart GJ, Saunders J, Chen C. Bioorg Med Chem Lett 2003, 13:3317-3322

Design and structure-activity relationships of 2-alkyl-3-aminomethyl-6-(3-methoxyphenyl)-7-methyl-8-(2-fluorobenzyl)imida zolo[1,2-a]pyrimid-5-ones as potent GnRH receptor antagonists.
Zhu YF, Guo Z, Gross TD, Gao Y, Connors PJ, Jr., Struthers RS, Xie Q, Tucci FC, Reinhart GJ, Wu D, et al. J Med Chem 2003, 46:1769-1772