Synthesis and Evaluation of (1,4-Disubstituted)-1,2,3-triazoles as Estrogen Receptor Beta Agonists
Abstract
1. Introduction
2. Materials and Methods
2.1. Chemistry
2.1.1. General Experimental Outline
2.1.2. General Procedure for the Preparation of Azidophenols
2.1.3. General Procedure for Triazole Synthesis
2.2. ERβ Assays
2.2.1. TR-FRET Assay
2.2.2. Cell-Based Functional Assay
2.3. Computational
3. Results
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Compound | Yield | ERβ EC50 (μM) | Volume (calc. Å3) 1 | O–O Distance 2 | Docking Score 3 | |
---|---|---|---|---|---|---|
5 | 70% | 5.53 | 212 | – | −7.6 | |
6 | 68% | ND | 212 | – | −7.9 | |
7 | 62% | 9.04 | 229 | – | −7.9 | |
8 | 48% | 25.8 | 229 | – | −8.0 | |
9 | 90% | 44.6 | 165 | 10.1 Å | −6.6 | |
10 | 78% | 4.28 | 165 | 9.1 Å | −7.9 | |
11 | 67% | 9.69 | 170 | 10.2 Å | −7.4 | |
12 | 74% | >50 | 198 | 9.3 Å | −6.6 | |
13 | 69% | 9.15 | 198 | 9.2 Å | −7.3 | |
14 | 80% | 48.1 | 215 | 9.3 Å | −6.6 | |
15 | 81% | ND | 215 | 9.4 Å | −7.0 | |
16 | 55% | 18.2 | 203 | 9.3 Å | −7.2 | |
17 | 76% | >50 | 212 | 9.4 Å | −6.8 | |
18 | 78% | 18.2 | 182 | 10.8 Å | −7.2 | |
19 | 82% | >50 | 179 | 10.6 Å | −7.0 | |
(±)-20 | 62% | 13.6 | 199 | 11.1 Å | −7.7 | |
(±)-21 | 69% | 1.59 | 254 | 9.2–10.9 Å | −9.3 (R) −9.3 (S) |
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Wetzel, E.A.; Corriero, G.C.; Brown-Ford, S.; Sem, D.S.; Donaldson, W.A. Synthesis and Evaluation of (1,4-Disubstituted)-1,2,3-triazoles as Estrogen Receptor Beta Agonists. Sci. Pharm. 2022, 90, 46. https://doi.org/10.3390/scipharm90030046
Wetzel EA, Corriero GC, Brown-Ford S, Sem DS, Donaldson WA. Synthesis and Evaluation of (1,4-Disubstituted)-1,2,3-triazoles as Estrogen Receptor Beta Agonists. Scientia Pharmaceutica. 2022; 90(3):46. https://doi.org/10.3390/scipharm90030046
Chicago/Turabian StyleWetzel, Edward A., Grace C. Corriero, Sandra Brown-Ford, Daniel S. Sem, and William A. Donaldson. 2022. "Synthesis and Evaluation of (1,4-Disubstituted)-1,2,3-triazoles as Estrogen Receptor Beta Agonists" Scientia Pharmaceutica 90, no. 3: 46. https://doi.org/10.3390/scipharm90030046
APA StyleWetzel, E. A., Corriero, G. C., Brown-Ford, S., Sem, D. S., & Donaldson, W. A. (2022). Synthesis and Evaluation of (1,4-Disubstituted)-1,2,3-triazoles as Estrogen Receptor Beta Agonists. Scientia Pharmaceutica, 90(3), 46. https://doi.org/10.3390/scipharm90030046