Part 3: Notch-sparing γ-secretase inhibitors: SAR studies of 2-substituted aminopyridopyrimidinones
[Display omitted] In search for novel lead compounds as γ-secretase inhibitors, analogs of aminopyrido[2,3-d]pyrimidin-7-ones (I) were synthesized and evaluated for inhibitory effects on amyloid-β-peptide production and cleavage of the Notch1 receptor mediated by γ-secretase. Selected pyridopyrimidi...
Gespeichert in:
Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2016-05, Vol.26 (9), p.2138-2141 |
---|---|
Hauptverfasser: | , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 2141 |
---|---|
container_issue | 9 |
container_start_page | 2138 |
container_title | Bioorganic & medicinal chemistry letters |
container_volume | 26 |
creator | Zhang, Jing Lu, Dai Wei, Han-Xun Gu, Yongli Selkoe, Dennis J. Wolfe, Michael S. Augelli-Szafran, Corinne E. |
description | [Display omitted]
In search for novel lead compounds as γ-secretase inhibitors, analogs of aminopyrido[2,3-d]pyrimidin-7-ones (I) were synthesized and evaluated for inhibitory effects on amyloid-β-peptide production and cleavage of the Notch1 receptor mediated by γ-secretase. Selected pyridopyrimidines, such as 1, 8, 9, 10, 11 and 16 are γ-secretase inhibitors that did not have an effect on Notch1 receptor processing. |
doi_str_mv | 10.1016/j.bmcl.2016.03.077 |
format | Article |
fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8314044</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0960894X16303092</els_id><sourcerecordid>1790966433</sourcerecordid><originalsourceid>FETCH-LOGICAL-c488t-8b591df4a989457c568f6289e6a9e1985a1572ceccea65366caada9141fdcb883</originalsourceid><addsrcrecordid>eNqNUd1qFTEYDKLYY_UFvJBcerNrsslmkyJCKf4UShV_wLuQTb7tyWF3c5pkC30u38NnMqenLXpTvMmX8M0MkxmEXlJSU0LFm03dT3asm3KvCatJ1z1CK8oFrxgn7WO0IkqQSir-8wA9S2lDCOWE86fooOkIk1yJFXJfTMyYHeHzkO26SlsT_XyBf_-qEtgI2STAfl773ucQ0xH-dvwVp7w4DwmHATdVWvqUfV4yOGwmP4ftdfTu5py8K-8Z0nP0ZDBjghe38xD9-PD--8mn6uzzx9OT47PKcilzJftWUTdwo4rntrOtkINopAJhFFAlW0PbrrFgLRjRMiGsMc4oyungbC8lO0Tv9rrbpZ_AWZhzNKPeFismXutgvP53M_u1vghXWrKbZIrA61uBGC4XSFlPPlkYRzNDWJKmnSqZCs7Yf0AlbVlbGAXa7KE2hpQiDPeOKNG7JvVG75rUuyY1Ybo0WUiv_v7LPeWuugJ4uwdASfTKQ9TJepgtOB_BZu2Cf0j_D4MTsoc</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1781535179</pqid></control><display><type>article</type><title>Part 3: Notch-sparing γ-secretase inhibitors: SAR studies of 2-substituted aminopyridopyrimidinones</title><source>MEDLINE</source><source>Access via ScienceDirect (Elsevier)</source><creator>Zhang, Jing ; Lu, Dai ; Wei, Han-Xun ; Gu, Yongli ; Selkoe, Dennis J. ; Wolfe, Michael S. ; Augelli-Szafran, Corinne E.</creator><creatorcontrib>Zhang, Jing ; Lu, Dai ; Wei, Han-Xun ; Gu, Yongli ; Selkoe, Dennis J. ; Wolfe, Michael S. ; Augelli-Szafran, Corinne E.</creatorcontrib><description>[Display omitted]
In search for novel lead compounds as γ-secretase inhibitors, analogs of aminopyrido[2,3-d]pyrimidin-7-ones (I) were synthesized and evaluated for inhibitory effects on amyloid-β-peptide production and cleavage of the Notch1 receptor mediated by γ-secretase. Selected pyridopyrimidines, such as 1, 8, 9, 10, 11 and 16 are γ-secretase inhibitors that did not have an effect on Notch1 receptor processing.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2016.03.077</identifier><identifier>PMID: 27038496</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Alzheimer’s disease ; Aminopyridopyrimidines ; Amyloid beta-Peptides - antagonists & inhibitors ; Amyloid Precursor Protein Secretases - antagonists & inhibitors ; Animals ; Aβ production ; Humans ; Microsomes, Liver - metabolism ; Notch-processing ; Peptide Fragments - antagonists & inhibitors ; Protease Inhibitors - chemical synthesis ; Protease Inhibitors - pharmacology ; Pyridones - chemical synthesis ; Pyridones - pharmacology ; Pyrimidines - chemical synthesis ; Pyrimidines - pharmacology ; Rats ; Receptor, Notch1 - metabolism ; Structure-Activity Relationship ; γ-Secretase inhibitors</subject><ispartof>Bioorganic & medicinal chemistry letters, 2016-05, Vol.26 (9), p.2138-2141</ispartof><rights>2016 Elsevier Ltd</rights><rights>Copyright © 2016 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c488t-8b591df4a989457c568f6289e6a9e1985a1572ceccea65366caada9141fdcb883</citedby><cites>FETCH-LOGICAL-c488t-8b591df4a989457c568f6289e6a9e1985a1572ceccea65366caada9141fdcb883</cites><orcidid>0000-0002-7676-6120</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bmcl.2016.03.077$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27038496$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Jing</creatorcontrib><creatorcontrib>Lu, Dai</creatorcontrib><creatorcontrib>Wei, Han-Xun</creatorcontrib><creatorcontrib>Gu, Yongli</creatorcontrib><creatorcontrib>Selkoe, Dennis J.</creatorcontrib><creatorcontrib>Wolfe, Michael S.</creatorcontrib><creatorcontrib>Augelli-Szafran, Corinne E.</creatorcontrib><title>Part 3: Notch-sparing γ-secretase inhibitors: SAR studies of 2-substituted aminopyridopyrimidinones</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>[Display omitted]
In search for novel lead compounds as γ-secretase inhibitors, analogs of aminopyrido[2,3-d]pyrimidin-7-ones (I) were synthesized and evaluated for inhibitory effects on amyloid-β-peptide production and cleavage of the Notch1 receptor mediated by γ-secretase. Selected pyridopyrimidines, such as 1, 8, 9, 10, 11 and 16 are γ-secretase inhibitors that did not have an effect on Notch1 receptor processing.</description><subject>Alzheimer’s disease</subject><subject>Aminopyridopyrimidines</subject><subject>Amyloid beta-Peptides - antagonists & inhibitors</subject><subject>Amyloid Precursor Protein Secretases - antagonists & inhibitors</subject><subject>Animals</subject><subject>Aβ production</subject><subject>Humans</subject><subject>Microsomes, Liver - metabolism</subject><subject>Notch-processing</subject><subject>Peptide Fragments - antagonists & inhibitors</subject><subject>Protease Inhibitors - chemical synthesis</subject><subject>Protease Inhibitors - pharmacology</subject><subject>Pyridones - chemical synthesis</subject><subject>Pyridones - pharmacology</subject><subject>Pyrimidines - chemical synthesis</subject><subject>Pyrimidines - pharmacology</subject><subject>Rats</subject><subject>Receptor, Notch1 - metabolism</subject><subject>Structure-Activity Relationship</subject><subject>γ-Secretase inhibitors</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNUd1qFTEYDKLYY_UFvJBcerNrsslmkyJCKf4UShV_wLuQTb7tyWF3c5pkC30u38NnMqenLXpTvMmX8M0MkxmEXlJSU0LFm03dT3asm3KvCatJ1z1CK8oFrxgn7WO0IkqQSir-8wA9S2lDCOWE86fooOkIk1yJFXJfTMyYHeHzkO26SlsT_XyBf_-qEtgI2STAfl773ucQ0xH-dvwVp7w4DwmHATdVWvqUfV4yOGwmP4ftdfTu5py8K-8Z0nP0ZDBjghe38xD9-PD--8mn6uzzx9OT47PKcilzJftWUTdwo4rntrOtkINopAJhFFAlW0PbrrFgLRjRMiGsMc4oyungbC8lO0Tv9rrbpZ_AWZhzNKPeFismXutgvP53M_u1vghXWrKbZIrA61uBGC4XSFlPPlkYRzNDWJKmnSqZCs7Yf0AlbVlbGAXa7KE2hpQiDPeOKNG7JvVG75rUuyY1Ybo0WUiv_v7LPeWuugJ4uwdASfTKQ9TJepgtOB_BZu2Cf0j_D4MTsoc</recordid><startdate>20160501</startdate><enddate>20160501</enddate><creator>Zhang, Jing</creator><creator>Lu, Dai</creator><creator>Wei, Han-Xun</creator><creator>Gu, Yongli</creator><creator>Selkoe, Dennis J.</creator><creator>Wolfe, Michael S.</creator><creator>Augelli-Szafran, Corinne E.</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-7676-6120</orcidid></search><sort><creationdate>20160501</creationdate><title>Part 3: Notch-sparing γ-secretase inhibitors: SAR studies of 2-substituted aminopyridopyrimidinones</title><author>Zhang, Jing ; Lu, Dai ; Wei, Han-Xun ; Gu, Yongli ; Selkoe, Dennis J. ; Wolfe, Michael S. ; Augelli-Szafran, Corinne E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c488t-8b591df4a989457c568f6289e6a9e1985a1572ceccea65366caada9141fdcb883</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Alzheimer’s disease</topic><topic>Aminopyridopyrimidines</topic><topic>Amyloid beta-Peptides - antagonists & inhibitors</topic><topic>Amyloid Precursor Protein Secretases - antagonists & inhibitors</topic><topic>Animals</topic><topic>Aβ production</topic><topic>Humans</topic><topic>Microsomes, Liver - metabolism</topic><topic>Notch-processing</topic><topic>Peptide Fragments - antagonists & inhibitors</topic><topic>Protease Inhibitors - chemical synthesis</topic><topic>Protease Inhibitors - pharmacology</topic><topic>Pyridones - chemical synthesis</topic><topic>Pyridones - pharmacology</topic><topic>Pyrimidines - chemical synthesis</topic><topic>Pyrimidines - pharmacology</topic><topic>Rats</topic><topic>Receptor, Notch1 - metabolism</topic><topic>Structure-Activity Relationship</topic><topic>γ-Secretase inhibitors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Jing</creatorcontrib><creatorcontrib>Lu, Dai</creatorcontrib><creatorcontrib>Wei, Han-Xun</creatorcontrib><creatorcontrib>Gu, Yongli</creatorcontrib><creatorcontrib>Selkoe, Dennis J.</creatorcontrib><creatorcontrib>Wolfe, Michael S.</creatorcontrib><creatorcontrib>Augelli-Szafran, Corinne E.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Bioorganic & medicinal chemistry letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Jing</au><au>Lu, Dai</au><au>Wei, Han-Xun</au><au>Gu, Yongli</au><au>Selkoe, Dennis J.</au><au>Wolfe, Michael S.</au><au>Augelli-Szafran, Corinne E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Part 3: Notch-sparing γ-secretase inhibitors: SAR studies of 2-substituted aminopyridopyrimidinones</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2016-05-01</date><risdate>2016</risdate><volume>26</volume><issue>9</issue><spage>2138</spage><epage>2141</epage><pages>2138-2141</pages><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>[Display omitted]
In search for novel lead compounds as γ-secretase inhibitors, analogs of aminopyrido[2,3-d]pyrimidin-7-ones (I) were synthesized and evaluated for inhibitory effects on amyloid-β-peptide production and cleavage of the Notch1 receptor mediated by γ-secretase. Selected pyridopyrimidines, such as 1, 8, 9, 10, 11 and 16 are γ-secretase inhibitors that did not have an effect on Notch1 receptor processing.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>27038496</pmid><doi>10.1016/j.bmcl.2016.03.077</doi><tpages>4</tpages><orcidid>https://orcid.org/0000-0002-7676-6120</orcidid><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0960-894X |
ispartof | Bioorganic & medicinal chemistry letters, 2016-05, Vol.26 (9), p.2138-2141 |
issn | 0960-894X 1464-3405 |
language | eng |
recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8314044 |
source | MEDLINE; Access via ScienceDirect (Elsevier) |
subjects | Alzheimer’s disease Aminopyridopyrimidines Amyloid beta-Peptides - antagonists & inhibitors Amyloid Precursor Protein Secretases - antagonists & inhibitors Animals Aβ production Humans Microsomes, Liver - metabolism Notch-processing Peptide Fragments - antagonists & inhibitors Protease Inhibitors - chemical synthesis Protease Inhibitors - pharmacology Pyridones - chemical synthesis Pyridones - pharmacology Pyrimidines - chemical synthesis Pyrimidines - pharmacology Rats Receptor, Notch1 - metabolism Structure-Activity Relationship γ-Secretase inhibitors |
title | Part 3: Notch-sparing γ-secretase inhibitors: SAR studies of 2-substituted aminopyridopyrimidinones |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-30T18%3A18%3A11IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Part%203:%20Notch-sparing%20%CE%B3-secretase%20inhibitors:%20SAR%20studies%20of%202-substituted%20aminopyridopyrimidinones&rft.jtitle=Bioorganic%20&%20medicinal%20chemistry%20letters&rft.au=Zhang,%20Jing&rft.date=2016-05-01&rft.volume=26&rft.issue=9&rft.spage=2138&rft.epage=2141&rft.pages=2138-2141&rft.issn=0960-894X&rft.eissn=1464-3405&rft_id=info:doi/10.1016/j.bmcl.2016.03.077&rft_dat=%3Cproquest_pubme%3E1790966433%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1781535179&rft_id=info:pmid/27038496&rft_els_id=S0960894X16303092&rfr_iscdi=true |