Next-Generation Analogues of AC265347 as Positive Allosteric Modulators of the Calcium-Sensing Receptor: Pharmacological Investigation of Structural Modifications at the Stereogenic Centre
Abstract
1. Introduction
2. Results and Discussion
2.1. Chemistry
2.2. Pharmacology
Entry | Structure | pKB ± SEM (KB, μM) | Logαβ ± SEM (αβ) | LogτB ± SEM (τB) | n |
---|---|---|---|---|---|
AC265347 (1) a | 5.47 ± 0.11 (3.4) | 1.63 ± 0.16 (43) | 0.12 ± 0.08 (1.3) | 5 | |
5 a | 5.30 ± 0.23 (5.0) | 0.94 ± 0.27 (8.7) | 0.53 ± 0.18 (3.4) | 5 | |
6 | 4.54 ± 0.49 (29) | 1.45± 0.41 (28) | ND b | 3–7 | |
7 | 3.91 ± 0.66 (123) | 1.95 ± 0.61 (89) | −0.29 ± 0.54 (0.5) | 3–7 | |
7b | 5.09 ± 0.27 (8.1) | 2.24 ± 0.37 (174) | 0.58 ± 0.20 (3.8) | 4 | |
8 c | ND b | ND b | ND b | 3 | |
9 | 4.98 ± 0.41 (10) | 1.59 ± 0.37 (39) | −0.43 ± 0.26 (0.4) | 4 |
2.3. Molecular Docking Study
3. Materials and Methods
3.1. Materials
3.1.1. General Chemistry
3.1.2. Cell Culture
3.2. Chemical Synthesis of Compounds
- General procedure A [34] (lithiation)
- General procedure B [17] (O-cyclisation)
- Synthesis of 1-(Benzo[d]thiazol-2-yl)-1-(2,4-dimethylphenyl)ethan-1-ol (1) [4]
- Synthesis of 2-(2-(2,4-Dimethylphenyl)oxiran-2-yl)benzo[d]thiazole (6)
- Synthesis of 2-(2-(2,4-Dimethylphenyl)oxetan-2-yl)benzo[d]thiazole (7)
- 1-(Benzo[d]thiazol-2-yl)-1-(2,4-dimethylphenyl)prop-2-en-1-ol (7b)
- Synthesis of 2-(1-(2,4-Dimethylphenyl)-1-methoxyethyl)benzo[d]thiazole (8)
- Synthesis of 2-(1-(2,4-Dimethylphenyl)-1-fluoroethyl)benzo[d]thiazole (9)
3.3. Pharmacological Evaluation of Compounds
3.3.1. Functional Assay—Ca2+i Mobilisation
3.3.2. Data Statistical Analysis
3.4. Computational Modelling of Compounds
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Dinh, L.V.; Dangerfield, J.; DeBono, A.; Keller, A.N.; Josephs, T.M.; Gregory, K.J.; Leach, K.; Capuano, B. Next-Generation Analogues of AC265347 as Positive Allosteric Modulators of the Calcium-Sensing Receptor: Pharmacological Investigation of Structural Modifications at the Stereogenic Centre. Int. J. Mol. Sci. 2025, 26, 2580. https://doi.org/10.3390/ijms26062580
Dinh LV, Dangerfield J, DeBono A, Keller AN, Josephs TM, Gregory KJ, Leach K, Capuano B. Next-Generation Analogues of AC265347 as Positive Allosteric Modulators of the Calcium-Sensing Receptor: Pharmacological Investigation of Structural Modifications at the Stereogenic Centre. International Journal of Molecular Sciences. 2025; 26(6):2580. https://doi.org/10.3390/ijms26062580
Chicago/Turabian StyleDinh, Le Vi, Jesse Dangerfield, Aaron DeBono, Andrew N. Keller, Tracy M. Josephs, Karen J. Gregory, Katie Leach, and Ben Capuano. 2025. "Next-Generation Analogues of AC265347 as Positive Allosteric Modulators of the Calcium-Sensing Receptor: Pharmacological Investigation of Structural Modifications at the Stereogenic Centre" International Journal of Molecular Sciences 26, no. 6: 2580. https://doi.org/10.3390/ijms26062580
APA StyleDinh, L. V., Dangerfield, J., DeBono, A., Keller, A. N., Josephs, T. M., Gregory, K. J., Leach, K., & Capuano, B. (2025). Next-Generation Analogues of AC265347 as Positive Allosteric Modulators of the Calcium-Sensing Receptor: Pharmacological Investigation of Structural Modifications at the Stereogenic Centre. International Journal of Molecular Sciences, 26(6), 2580. https://doi.org/10.3390/ijms26062580