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Synthesis of novel and functionally selective non‐competitive muscarinic antagonists as chemical probes
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Zeitschriftentitel: | Chemical Biology & Drug Design |
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Personen und Körperschaften: | , , , , |
In: | Chemical Biology & Drug Design, 91, 2018, 1, S. 93-104 |
Medientyp: | E-Article |
Sprache: | Englisch |
veröffentlicht: |
Wiley
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Schlagwörter: |
author_facet |
Boulos, John F. Jakubik, Jan Boulos, John M. Randakova, Alena Momirov, Jelena Boulos, John F. Jakubik, Jan Boulos, John M. Randakova, Alena Momirov, Jelena |
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author |
Boulos, John F. Jakubik, Jan Boulos, John M. Randakova, Alena Momirov, Jelena |
spellingShingle |
Boulos, John F. Jakubik, Jan Boulos, John M. Randakova, Alena Momirov, Jelena Chemical Biology & Drug Design Synthesis of novel and functionally selective non‐competitive muscarinic antagonists as chemical probes Molecular Medicine Biochemistry Drug Discovery Pharmacology Organic Chemistry |
author_sort |
boulos, john f. |
spelling |
Boulos, John F. Jakubik, Jan Boulos, John M. Randakova, Alena Momirov, Jelena 1747-0277 1747-0285 Wiley Molecular Medicine Biochemistry Drug Discovery Pharmacology Organic Chemistry http://dx.doi.org/10.1111/cbdd.13059 <jats:p>Muscarinic receptors are known to play important biological roles and are drug targets for several human diseases. In a pilot study, novel muscarinic antagonists were synthesized and used as chemical probes to obtain additional information of the muscarinic pharmacophore. The design of these ligands made use of current orthosteric and allosteric models of drug–receptor interactions together with chemical motifs known to achieve muscarinic receptor selectivity. This approach has led to the discovery of several non‐competitive muscarinic ligands that strongly bind at a secondary receptor site. These compounds were found to be non‐competitive antagonists that completely abolished carbachol activation in functional assays. Several of these compounds antagonized functional response to carbachol with great potency at M<jats:sub>1</jats:sub> and M<jats:sub>4</jats:sub> than at the rest of receptor subtypes.</jats:p> Synthesis of novel and functionally selective non‐competitive muscarinic antagonists as chemical probes Chemical Biology & Drug Design |
doi_str_mv |
10.1111/cbdd.13059 |
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Wiley |
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Chemical Biology & Drug Design |
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title |
Synthesis of novel and functionally selective non‐competitive muscarinic antagonists as chemical probes |
title_unstemmed |
Synthesis of novel and functionally selective non‐competitive muscarinic antagonists as chemical probes |
title_full |
Synthesis of novel and functionally selective non‐competitive muscarinic antagonists as chemical probes |
title_fullStr |
Synthesis of novel and functionally selective non‐competitive muscarinic antagonists as chemical probes |
title_full_unstemmed |
Synthesis of novel and functionally selective non‐competitive muscarinic antagonists as chemical probes |
title_short |
Synthesis of novel and functionally selective non‐competitive muscarinic antagonists as chemical probes |
title_sort |
synthesis of novel and functionally selective non‐competitive muscarinic antagonists as chemical probes |
topic |
Molecular Medicine Biochemistry Drug Discovery Pharmacology Organic Chemistry |
url |
http://dx.doi.org/10.1111/cbdd.13059 |
publishDate |
2018 |
physical |
93-104 |
description |
<jats:p>Muscarinic receptors are known to play important biological roles and are drug targets for several human diseases. In a pilot study, novel muscarinic antagonists were synthesized and used as chemical probes to obtain additional information of the muscarinic pharmacophore. The design of these ligands made use of current orthosteric and allosteric models of drug–receptor interactions together with chemical motifs known to achieve muscarinic receptor selectivity. This approach has led to the discovery of several non‐competitive muscarinic ligands that strongly bind at a secondary receptor site. These compounds were found to be non‐competitive antagonists that completely abolished carbachol activation in functional assays. Several of these compounds antagonized functional response to carbachol with great potency at M<jats:sub>1</jats:sub> and M<jats:sub>4</jats:sub> than at the rest of receptor subtypes.</jats:p> |
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author | Boulos, John F., Jakubik, Jan, Boulos, John M., Randakova, Alena, Momirov, Jelena |
author_facet | Boulos, John F., Jakubik, Jan, Boulos, John M., Randakova, Alena, Momirov, Jelena, Boulos, John F., Jakubik, Jan, Boulos, John M., Randakova, Alena, Momirov, Jelena |
author_sort | boulos, john f. |
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container_title | Chemical Biology & Drug Design |
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description | <jats:p>Muscarinic receptors are known to play important biological roles and are drug targets for several human diseases. In a pilot study, novel muscarinic antagonists were synthesized and used as chemical probes to obtain additional information of the muscarinic pharmacophore. The design of these ligands made use of current orthosteric and allosteric models of drug–receptor interactions together with chemical motifs known to achieve muscarinic receptor selectivity. This approach has led to the discovery of several non‐competitive muscarinic ligands that strongly bind at a secondary receptor site. These compounds were found to be non‐competitive antagonists that completely abolished carbachol activation in functional assays. Several of these compounds antagonized functional response to carbachol with great potency at M<jats:sub>1</jats:sub> and M<jats:sub>4</jats:sub> than at the rest of receptor subtypes.</jats:p> |
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series | Chemical Biology & Drug Design |
source_id | 49 |
spelling | Boulos, John F. Jakubik, Jan Boulos, John M. Randakova, Alena Momirov, Jelena 1747-0277 1747-0285 Wiley Molecular Medicine Biochemistry Drug Discovery Pharmacology Organic Chemistry http://dx.doi.org/10.1111/cbdd.13059 <jats:p>Muscarinic receptors are known to play important biological roles and are drug targets for several human diseases. In a pilot study, novel muscarinic antagonists were synthesized and used as chemical probes to obtain additional information of the muscarinic pharmacophore. The design of these ligands made use of current orthosteric and allosteric models of drug–receptor interactions together with chemical motifs known to achieve muscarinic receptor selectivity. This approach has led to the discovery of several non‐competitive muscarinic ligands that strongly bind at a secondary receptor site. These compounds were found to be non‐competitive antagonists that completely abolished carbachol activation in functional assays. Several of these compounds antagonized functional response to carbachol with great potency at M<jats:sub>1</jats:sub> and M<jats:sub>4</jats:sub> than at the rest of receptor subtypes.</jats:p> Synthesis of novel and functionally selective non‐competitive muscarinic antagonists as chemical probes Chemical Biology & Drug Design |
spellingShingle | Boulos, John F., Jakubik, Jan, Boulos, John M., Randakova, Alena, Momirov, Jelena, Chemical Biology & Drug Design, Synthesis of novel and functionally selective non‐competitive muscarinic antagonists as chemical probes, Molecular Medicine, Biochemistry, Drug Discovery, Pharmacology, Organic Chemistry |
title | Synthesis of novel and functionally selective non‐competitive muscarinic antagonists as chemical probes |
title_full | Synthesis of novel and functionally selective non‐competitive muscarinic antagonists as chemical probes |
title_fullStr | Synthesis of novel and functionally selective non‐competitive muscarinic antagonists as chemical probes |
title_full_unstemmed | Synthesis of novel and functionally selective non‐competitive muscarinic antagonists as chemical probes |
title_short | Synthesis of novel and functionally selective non‐competitive muscarinic antagonists as chemical probes |
title_sort | synthesis of novel and functionally selective non‐competitive muscarinic antagonists as chemical probes |
title_unstemmed | Synthesis of novel and functionally selective non‐competitive muscarinic antagonists as chemical probes |
topic | Molecular Medicine, Biochemistry, Drug Discovery, Pharmacology, Organic Chemistry |
url | http://dx.doi.org/10.1111/cbdd.13059 |