9-Amino-5,7-dibromo-1,2,3,4-tetrahydroacridine hemihydrate

Çeli̇k, İsmail; Akkurt, Mehmet; Ekiz, Makbule; Ökten, Salih; Tutar, Ahmet; Ersanlı, Cem Cüneyt

doi:10.1107/s2414314617010112

Cited by 3 publications

(6 citation statements)

References 17 publications

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“…The synthesis of dibromo (1-5) tacrines via Friedländer reactions and disubstituted (7)(8)(9)(10)(11)(12)(13)(14) tacrine derivatives via metal assisted electrophilic and nucleophilic substituted reactions and MeI salt form (6) of unsubstituted tacrine were reported recently by our previous publications. 18,21 The isolated compounds (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) were fully characterized with melting point, HRMS analysis, infrared, 1 H, 13 C, HMBC and HETCOR spectroscopy in this paper. 18 This study was carried out with disubstituted tacrine derivatives (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) according to our previous paper.…”

Section: Chemistrymentioning

confidence: 99%

“…18 This study was carried out with disubstituted tacrine derivatives (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) according to our previous paper. 18,21,22…”

Section: Chemistrymentioning

confidence: 99%

“…In our previous papers, 18,[21][22] one-pot synthesis was described for bromo tacrine derivatives (1-5) ( Figure 1) using Friedländer reactions of several cyclic ketones and brominated 2-amino-3,5-dibromobenzonitrile (17) in the presence of some Lewis acids. To achieve the direct bromination, tacrine was treated to methyl iodine to protect of the N atom in the cycle.…”

Section: Chemistrymentioning

confidence: 99%

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SAR Evaluation of Disubstituted Tacrine Analogues as Promising Cholinesterase and Carbonic Anhydrase Inhibitors

Ökten¹,

Ekiz²,

Tutar³

et al. 2019

IJPER

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Background: The inhibition of both hydrolysis products of acetylcholine (ACh), Acetylcholinesterase (AChE) and Butyrylcholinesterase (BChE), is essential for successful treatment of Alzhemier patients. Objectives: This study was investigated inhibition potentials of recently synthesized disubstituted tacrines derivatives on going our research against AChE, BChE and carbonic anhydrase cyctosolic (hCA I and II) enzymes to explore the Structure activity relationship (SAR). Methods: Inhibitory activities of tested compounds against AChE and BChE were measured by spectrophotometric method, developed by Ellman et al. Furthermore, the disubstituted tacrines were determined as inhibitors of two physiologically relevant CA isoforms, the cytosolic hCA I and II by an esterase assay method. Results: The silyl, thiomethyl and cyano substituted seven membered hydrocycle tacrines (9, 11 and 14) significantly inhibited AChE, compared with starting compound 3 (6,8-dibromo-2,3,4,5-teytrahydro-1H-cyclohepta[1,2-b] quinoline) and reference compounds, galantamine and tacrine, while methoxy substituted seven membered hydrocycle tacrine derivative 10 showed selective inhibition against BChE (IC 50 = 563 nM). Interestingly, disubstituted tacrines displayed higher or parallel inhibition to galantamine. Additionally, all these tacrine analogues were recorded to be powerful inhibitor compounds of the cytosolic isoenzyme hCA I with K i in the range of 43.81-471.67 nM, as well as a moderate selectivity toward hCA II isoenzyme with K i in the range from 87.14 to 614.68 nM compared with AZA, as standard. Conclusion: The disubstituted seven membered hydrocycle tacrine analogues 9-12 and 14 may have promising anti Alzhemier drug candidate and dibromo six membered hydrocycle 2 and dibromo seven membered hydrocycle 3 derivatives may be novel hCA I and II enzyme inhibitors.

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Section: Chemistrymentioning

confidence: 99%

“…18 This study was carried out with disubstituted tacrine derivatives (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) according to our previous paper. 18,21,22…”

Section: Chemistrymentioning

confidence: 99%

Section: Chemistrymentioning

confidence: 99%

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SAR Evaluation of Disubstituted Tacrine Analogues as Promising Cholinesterase and Carbonic Anhydrase Inhibitors

Ökten¹,

Ekiz²,

Tutar³

et al. 2019

IJPER

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“…Then, tacrine bromides ( 2 and 3 ) were converted corresponding disubstituted tacrine derivatives via metal‐halogen and copper‐assisted substitution reactions . Furthermore, the evaluation of their anti‐Alzheimer and anticarbonic anhydrase potentials indicated that methoxy ( 10 ), cyano ( 7 ), silyl ( 6 and 9 ), and thiomethyl ( 8 ) tacrine derivatives had selective AChE and BChE inhibitory activities and showed significant inhibition against hCA I and hCA II enzymes …”

Section: Resultsmentioning

confidence: 99%

“…In continuation of our research on bioactive molecules, we designed and synthesized a new series of bromo‐ and phenyl‐substituted indenoquinoline amine. Due to having the AChE, hCA I and hCA II inhibition potentials of the tricyclic structure of the 1,2,3,4‐tetrahydroacridine nucleus, we expanded to tetracyclic ones. Thus, this work was to explore the synthesis of novel bromoindenoquinoline amines via Friedlander reaction between 2‐amino‐3,5‐dibromobenzonitrile ( 7 ) and 2‐amino‐5‐bromobenzonitrile ( 11 ) and bromoindan‐1‐ones ( 12 and 13 ) in the presence of some Lewis acids.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, characterization, and SAR of arylated indenoquinoline‐based cholinesterase and carbonic anhydrase inhibitors

Ekiz

Tutar

Ökten

et al. 2018

Archiv der Pharmazie

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We report the synthesis of bromoindenoquinolines (15a-f) by Friedlander reactions in low yields (13-50%) and the conversion of the corresponding phenyl-substituted indenoquinoline derivatives 16-21 in high yields (80-96%) by Suzuki coupling reactions. To explore the structure-activity relationship (SAR), their inhibition potentials to inhibit acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and human carbonic anhydrase cyctosolic (hCA I and II) enzymes were determined. Monophenyl (16-18) indenoquinolines significantly inhibited the AChE and BChE enzymes in ranges of IC 37-57 nM and 84-93 nM, respectively, compared with their starting materials 15a-c and reference compounds (galanthamine and tacrine). On the other hand, these novel arylated indenoquinoline-based derivatives were effective inhibitors of the BChE, hCA I and II, BChE and AChE enzymes with K values in the range of 37 ± 2.04 to 88640 ± 1990 nM for AChE, 120.94 ± 37.06 to 1150.95 ± 304.48 nM for hCA I, 267.58 ± 98.05 to 1568.16 ± 438.67 nM for hCA II, and 84 ± 3.86 to 144120 ± 2910 nM for BChE. As a result, monophenyl indenoquinolines 16-18 may have promising anti-Alzheimer drug potential and 3,8-dibromoindenoquinoline amine (15f) can be novel hCA I and hCA II enzyme inhibitors.

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Synthesis, characterization, crystal structures, theoretical calculations and biological evaluations of novel substituted tacrine derivatives as cholinesterase and carbonic anhydrase enzymes inhibitors

Ökten

Ekiz

Koçyiğit

et al. 2019

Journal of Molecular Structure

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9-Amino-5,7-dibromo-1,2,3,4-tetrahydroacridine hemihydrate

Cited by 3 publications

References 17 publications

SAR Evaluation of Disubstituted Tacrine Analogues as Promising Cholinesterase and Carbonic Anhydrase Inhibitors

SAR Evaluation of Disubstituted Tacrine Analogues as Promising Cholinesterase and Carbonic Anhydrase Inhibitors

Synthesis, characterization, and SAR of arylated indenoquinoline‐based cholinesterase and carbonic anhydrase inhibitors

Synthesis, characterization, crystal structures, theoretical calculations and biological evaluations of novel substituted tacrine derivatives as cholinesterase and carbonic anhydrase enzymes inhibitors

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