New Histamine-Related Five-Membered N-Heterocycle Derivatives as Carbonic Anhydrase I Activators
Abstract
:1. Introduction
2. Results
2.1. Chemistry
2.2. CA Activating Properties
2.2.1. Activity on hCA I
2.2.2. Activity on hCA VA, VII and XIII and Selectivity
3. Discussion
4. Materials and Methods
4.1. Chemistry
4.1.1. General Considerations
4.1.2. Compounds Prepared According to Literature Procedures
4.1.3. 3-(1H-imidazol-4-yl)propan-1-amine (9)
4.1.4. N-benzyl-2-(1H-pyrrol-2-yl)ethan-1-amine (14)
4.1.5. 4-phenyl-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridine (15)
4.1.6. 4-(4-methoxyphenyl)-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridine (16)
4.1.7. General Procedure for the Synthesis of Schiff Bases (17–19)
4.1.8. General Procedure for the Reduction of Schiff Bases to Amines 20–22
4.2. CA Activation
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Sample Availability
References
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Cmp (Salt) a | Structure | KA (μM) b | ||||
---|---|---|---|---|---|---|
hCA I | hCA II | hCA VA | hCA VII | hCA XIII | ||
HST | 2.10 | 125 | 0.010 | 37.5 | 4.6 | |
1 (oxalate) | 2.16 | >150 | 29.8 | 44.6 | >100 | |
2 (oxalate) | 11.6 | >150 | 37.9 | 32.8 | >100 | |
3 | 28.4 | >150 | 51.0 | 23.7 | >100 | |
3a | 2.19 | >150 | 78.5 | 120 | >100 | |
4 | 13.5 | >150 | 42.7 | 25.4 | >100 | |
5 | 9.84 | >150 | 24.6 | 35.5 | >100 | |
6 (oxalate) | >150 | >150 | 21.7 | 23.0 | >100 | |
7 (HCl) | >150 | >150 | 28.6 | 12.1 | >100 | |
8.2HCl | 2.9 | >100 | 12.5 | 13.2 | 29.0 | |
9.2HCl | 2.4 | >100 | 12.5 | 10.8 | 28.2 | |
11.3HCl | 7.0 | >100 | 12.9 | 11.5 | 84.8 | |
12 | 11.6 | >100 | 34.9 | 13.8 | 96.4 | |
13 | 5.6 | >100 | 24.8 | 10.8 | >100 | |
14 | 3.0 | >100 | 14.0 | 12.5 | 91.1 | |
15 | 3.7 | >100 | 20.6 | 11.1 | >100 | |
16 | 5.7 | >100 | 19.1 | 14.3 | >100 | |
17 | 59.1 | >100 | 15.2 | 38.6 | 64.4 | |
18 | 56.1 | >100 | 16.0 | 22.1 | 33.0 | |
19 | 93.5 | >100 | 13.3 | 35.4 | 57.3 | |
20 | 5.8 | >100 | 27.2 | 9.7 | 46.0 | |
21 | 4.9 | >100 | 11.9 | 18.3 | 73.0 | |
22 | 0.9 | >100 | 11.2 | 13.2 | >100 | |
23 | 86.0 | >100 | 18.8 | 74.6 | >100 |
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Chiaramonte, N.; Gabellini, A.; Angeli, A.; Bartolucci, G.; Braconi, L.; Dei, S.; Teodori, E.; Supuran, C.T.; Romanelli, M.N. New Histamine-Related Five-Membered N-Heterocycle Derivatives as Carbonic Anhydrase I Activators. Molecules 2022, 27, 545. https://doi.org/10.3390/molecules27020545
Chiaramonte N, Gabellini A, Angeli A, Bartolucci G, Braconi L, Dei S, Teodori E, Supuran CT, Romanelli MN. New Histamine-Related Five-Membered N-Heterocycle Derivatives as Carbonic Anhydrase I Activators. Molecules. 2022; 27(2):545. https://doi.org/10.3390/molecules27020545
Chicago/Turabian StyleChiaramonte, Niccolò, Alessio Gabellini, Andrea Angeli, Gianluca Bartolucci, Laura Braconi, Silvia Dei, Elisabetta Teodori, Claudiu T. Supuran, and Maria Novella Romanelli. 2022. "New Histamine-Related Five-Membered N-Heterocycle Derivatives as Carbonic Anhydrase I Activators" Molecules 27, no. 2: 545. https://doi.org/10.3390/molecules27020545