Novel sulfonylurea derivatives as H3 receptor antagonists. Preliminary SAR studies
The combination of antagonism at histamine H3 receptor and the stimulation of insulin secretion have been proposed as an approach to new dual therapeutic agents for the treatment of type 2 diabetes mellitus associated with obesity. We have designed and synthesized a new series of non-imidazole deriv...
| Main Authors: | , , , , , |
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| Format: | info:eu-repo/semantics/article |
| Language: | eng |
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Elsevier
2012
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| Subjects: | |
| Online Access: | https://hdl.handle.net/10171/23595 |
| _version_ | 1793400188384051200 |
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| author | Ceras, J. (Javier) Cirauqui, N. (Nuria) Pérez-Silanes, S. (Silvia) Aldana, I. (Ignacio) Monge, A. (Antonio) Galiano, S. (Silvia) |
| author_facet | Ceras, J. (Javier) Cirauqui, N. (Nuria) Pérez-Silanes, S. (Silvia) Aldana, I. (Ignacio) Monge, A. (Antonio) Galiano, S. (Silvia) |
| author_sort | Ceras, J. (Javier) |
| collection | DSpace |
| description | The combination of antagonism at histamine H3 receptor and the stimulation of insulin secretion have been proposed as an approach to new dual therapeutic agents for the treatment of type 2 diabetes mellitus associated with obesity. We have designed and synthesized a new series of non-imidazole derivatives, based on a basic amine ring connected through an alkyl spacer of variable length to a phenoxysulfonylurea moiety. These compounds were initially evaluated for histamine H3 receptor binding affinities, suggesting that a propoxy chain linker between the amine and the core ring could be essential for optimal binding affinity. Compound 56, 1-(naphthalen-1-yl)-3-[(p-(3-pyrrolidin-1-ylpropoxy)benzene)]sulfonylurea exhibited the best H3 antagonism affinity. However, since all these derivatives failed to block KATP channels, the link of these two related moieties should not be considered a good pharmacophore for obtaining new dual H3 antagonists with insulinotropic activity, suggesting the necessity to propose a new chemical hybrid prototype. |
| format | info:eu-repo/semantics/article |
| id | oai:dadun.unav.edu:10171-23595 |
| institution | Universidad de Navarra |
| language | eng |
| publishDate | 2012 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oai:dadun.unav.edu:10171-235952020-03-03T20:25:26Z Novel sulfonylurea derivatives as H3 receptor antagonists. Preliminary SAR studies Ceras, J. (Javier) Cirauqui, N. (Nuria) Pérez-Silanes, S. (Silvia) Aldana, I. (Ignacio) Monge, A. (Antonio) Galiano, S. (Silvia) Histamine H3 receptor Obesity Sulfonylurea Type 2 diabetes mellitus The combination of antagonism at histamine H3 receptor and the stimulation of insulin secretion have been proposed as an approach to new dual therapeutic agents for the treatment of type 2 diabetes mellitus associated with obesity. We have designed and synthesized a new series of non-imidazole derivatives, based on a basic amine ring connected through an alkyl spacer of variable length to a phenoxysulfonylurea moiety. These compounds were initially evaluated for histamine H3 receptor binding affinities, suggesting that a propoxy chain linker between the amine and the core ring could be essential for optimal binding affinity. Compound 56, 1-(naphthalen-1-yl)-3-[(p-(3-pyrrolidin-1-ylpropoxy)benzene)]sulfonylurea exhibited the best H3 antagonism affinity. However, since all these derivatives failed to block KATP channels, the link of these two related moieties should not be considered a good pharmacophore for obtaining new dual H3 antagonists with insulinotropic activity, suggesting the necessity to propose a new chemical hybrid prototype. 2012-10-31T16:12:47Z 2012-10-31T16:12:47Z 2012 info:eu-repo/semantics/article https://hdl.handle.net/10171/23595 eng info:eu-repo/semantics/openAccess application/pdf Elsevier |
| spellingShingle | Histamine H3 receptor Obesity Sulfonylurea Type 2 diabetes mellitus Ceras, J. (Javier) Cirauqui, N. (Nuria) Pérez-Silanes, S. (Silvia) Aldana, I. (Ignacio) Monge, A. (Antonio) Galiano, S. (Silvia) Novel sulfonylurea derivatives as H3 receptor antagonists. Preliminary SAR studies |
| title | Novel sulfonylurea derivatives as H3 receptor antagonists. Preliminary SAR studies |
| title_full | Novel sulfonylurea derivatives as H3 receptor antagonists. Preliminary SAR studies |
| title_fullStr | Novel sulfonylurea derivatives as H3 receptor antagonists. Preliminary SAR studies |
| title_full_unstemmed | Novel sulfonylurea derivatives as H3 receptor antagonists. Preliminary SAR studies |
| title_short | Novel sulfonylurea derivatives as H3 receptor antagonists. Preliminary SAR studies |
| title_sort | novel sulfonylurea derivatives as h3 receptor antagonists. preliminary sar studies |
| topic | Histamine H3 receptor Obesity Sulfonylurea Type 2 diabetes mellitus |
| url | https://hdl.handle.net/10171/23595 |
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