Synthesis and evaluation of (E)-2-(5-phenylpent-2-en-4-ynamido)cyclohex-1-ene-1-carboxylate derivatives as HCA2 receptor agonists
Copyright © 2017 Elsevier Ltd. All rights reserved..
Novel series of compounds consisting of 2-amidocyclohex-1-ene carboxylate and phenyl parts which are connected by enyne (compounds 2a-f), but-1-yne (compounds 4a-j), and phenylethylene (compounds 5a-f) linkers as HCA2 full agonists were designed and their functional activity using cAMP assay and binding affinity using radioligand (3H-niacin) binding assay were evaluated. In general, compounds of all three series exhibit similar HCA2 binding and activation profile. However, the activity is strongly dependent on the substituent at the aromatic part of the structure. Among the structures evaluated, the highest affinity and potency in all series were exhibited by compounds containing 4-hydroxy and/or 2-chloro or 2-fluoro substituents. The most active compounds in the enyne and but-1-yne series in the cAMP assay are 2-fluoro,4-hydroxy and 2-chloro,4-hydroxy phenyl derivatives 2f, 4f, and 4g showing potency similar to the previously described 4-hydroxy-biphenyl analogue 5c.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2017 |
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| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:25 |
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| Enthalten in: |
Bioorganic & medicinal chemistry - 25(2017), 16 vom: 15. Aug., Seite 4314-4329 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Bobileva, Olga [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 14.08.2017 Date Revised 08.12.2017 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bmc.2017.06.028 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM273455702 |
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| 245 | 1 | 0 | |a Synthesis and evaluation of (E)-2-(5-phenylpent-2-en-4-ynamido)cyclohex-1-ene-1-carboxylate derivatives as HCA2 receptor agonists |
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| 500 | |a Date Revised 08.12.2017 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2017 Elsevier Ltd. All rights reserved. | ||
| 520 | |a Novel series of compounds consisting of 2-amidocyclohex-1-ene carboxylate and phenyl parts which are connected by enyne (compounds 2a-f), but-1-yne (compounds 4a-j), and phenylethylene (compounds 5a-f) linkers as HCA2 full agonists were designed and their functional activity using cAMP assay and binding affinity using radioligand (3H-niacin) binding assay were evaluated. In general, compounds of all three series exhibit similar HCA2 binding and activation profile. However, the activity is strongly dependent on the substituent at the aromatic part of the structure. Among the structures evaluated, the highest affinity and potency in all series were exhibited by compounds containing 4-hydroxy and/or 2-chloro or 2-fluoro substituents. The most active compounds in the enyne and but-1-yne series in the cAMP assay are 2-fluoro,4-hydroxy and 2-chloro,4-hydroxy phenyl derivatives 2f, 4f, and 4g showing potency similar to the previously described 4-hydroxy-biphenyl analogue 5c | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a 2-Amidocyclohex-1-ene carboxylate | |
| 650 | 4 | |a Agonist | |
| 650 | 4 | |a CAMP | |
| 650 | 4 | |a HCA2 | |
| 650 | 4 | |a Niacin receptor | |
| 650 | 4 | |a Radioligand binding | |
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| 650 | 7 | |a Cyclohexenes |2 NLM | |
| 650 | 7 | |a HCAR2 protein, human |2 NLM | |
| 650 | 7 | |a Receptors, G-Protein-Coupled |2 NLM | |
| 650 | 7 | |a Receptors, Nicotinic |2 NLM | |
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| 700 | 1 | |a Duburs, Gunars |e verfasserin |4 aut | |
| 700 | 1 | |a Mandrika, Ilona |e verfasserin |4 aut | |
| 700 | 1 | |a Petrovska, Ramona |e verfasserin |4 aut | |
| 700 | 1 | |a Klovins, Janis |e verfasserin |4 aut | |
| 700 | 1 | |a Loza, Einars |e verfasserin |4 aut | |
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