(Pyrrolo-pyridin-5-yl)benzamides: BBB permeable monoamine oxidase B inhibitors with neuroprotective effect on cortical neurons

Tzvetkov NT, Stammler H-G, Hristova S, Atanasov AG, Antonov L (2019)
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 162: 793-809.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
 
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Autor*in
Tzvetkov, Nikolay T.; Stammler, Hans-GeorgUniBi; Hristova, Silvia; Atanasov, Atanas G.; Antonov, Liudmil
Abstract / Bemerkung
An extensive study was performed to develop a series of (pyrrolo-pyridin-5-yl)benzamides as reversible MAO-B inhibitors. Compounds 14 (NTZ-2020, hMAO-B IC50 = 1.11 nM, K-i = 0.56 nM, >9000-fold selective versus MAO-A) and 15 (NTZ-2027, hMAO-B IC50 = 3.27 nM, K-i=1.45 nM, SI > 3058) are identified as the most promising BBB permeable derivatives within the series of (1H-pyrrolo[3,2-b]pyridine-5-yl)benzamides, combining both high potency and selectivity with optimal physicochemical and drug-like properties required for CNS active drugs. Extended photophysical analysis, including single X-ray analysis, quantum-chemical calculations and spectroscopic experiments provided insights into their tautomerism and structural behavioral, which relates to their biologically active form. The reversible MAO-B inhibitor 14 (NTZ-2020) exhibits a neuroprotective effect on cortical neuron survival and induces neurite network outgrowth. These effects are associated with a good BBB penetration of 14 that was confirmed in a triple cell neurovascular unit (NVU) model. (C) 2018 Elsevier Masson SAS. All rights reserved.
Erscheinungsjahr
2019
Zeitschriftentitel
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Band
162
Seite(n)
793-809
ISSN
0223-5234
eISSN
1768-3254
Page URI
https://pub.uni-bielefeld.de/record/2933916

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Tzvetkov NT, Stammler H-G, Hristova S, Atanasov AG, Antonov L. (Pyrrolo-pyridin-5-yl)benzamides: BBB permeable monoamine oxidase B inhibitors with neuroprotective effect on cortical neurons. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. 2019;162:793-809.
Tzvetkov, N. T., Stammler, H. - G., Hristova, S., Atanasov, A. G., & Antonov, L. (2019). (Pyrrolo-pyridin-5-yl)benzamides: BBB permeable monoamine oxidase B inhibitors with neuroprotective effect on cortical neurons. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 162, 793-809. doi:10.1016/j.ejmech.2018.11.009
Tzvetkov, N. T., Stammler, H. - G., Hristova, S., Atanasov, A. G., and Antonov, L. (2019). (Pyrrolo-pyridin-5-yl)benzamides: BBB permeable monoamine oxidase B inhibitors with neuroprotective effect on cortical neurons. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 162, 793-809.
Tzvetkov, N.T., et al., 2019. (Pyrrolo-pyridin-5-yl)benzamides: BBB permeable monoamine oxidase B inhibitors with neuroprotective effect on cortical neurons. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 162, p 793-809.
N.T. Tzvetkov, et al., “(Pyrrolo-pyridin-5-yl)benzamides: BBB permeable monoamine oxidase B inhibitors with neuroprotective effect on cortical neurons”, EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, vol. 162, 2019, pp. 793-809.
Tzvetkov, N.T., Stammler, H.-G., Hristova, S., Atanasov, A.G., Antonov, L.: (Pyrrolo-pyridin-5-yl)benzamides: BBB permeable monoamine oxidase B inhibitors with neuroprotective effect on cortical neurons. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. 162, 793-809 (2019).
Tzvetkov, Nikolay T., Stammler, Hans-Georg, Hristova, Silvia, Atanasov, Atanas G., and Antonov, Liudmil. “(Pyrrolo-pyridin-5-yl)benzamides: BBB permeable monoamine oxidase B inhibitors with neuroprotective effect on cortical neurons”. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 162 (2019): 793-809.

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Monoamine Oxidases (MAOs) as Privileged Molecular Targets in Neuroscience: Research Literature Analysis.
Yeung AWK, Georgieva MG, Atanasov AG, Tzvetkov NT., Front Mol Neurosci 12(), 2019
PMID: 31191248

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