Design and synthesis of benzodiazepines as brain penetrating PARP-1 inhibitors
The poly (ADP-ribose) polymerase (PARP) inhibitors play a crucial role in cancer therapy. However, most approved PARP inhibitors cannot cross the blood-brain barrier, thus limiting their application in the central nervous system. Here, 55 benzodiazepines were designed and synthesised to screen brain...
Gespeichert in:
| Veröffentlicht in: | Journal of enzyme inhibition and medicinal chemistry 2022-12, Vol.37 (1), p.952-972 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 972 |
|---|---|
| container_issue | 1 |
| container_start_page | 952 |
| container_title | Journal of enzyme inhibition and medicinal chemistry |
| container_volume | 37 |
| creator | Yu, Jiang Gou, Wenfeng Shang, Haihua Cui, Yating Sun, Xiao Luo, Lingling Hou, Wenbin Sun, Tiemin Li, Yiliang |
| description | The poly (ADP-ribose) polymerase (PARP) inhibitors play a crucial role in cancer therapy. However, most approved PARP inhibitors cannot cross the blood-brain barrier, thus limiting their application in the central nervous system. Here, 55 benzodiazepines were designed and synthesised to screen brain penetrating PARP-1 inhibitors. All target compounds were evaluated for their PARP-1 inhibition activity, and compounds with better activity were selected for further assays in vitro. Among them, compounds H34, H42, H48, and H52 displayed acceptable inhibition effects on breast cancer cells. Also, computational prediction together with the permeability assays in vitro and in vivo proved that the benzodiazepine PARP-1 inhibitors we synthesised were brain permeable. Compound H52 exhibited a B/P ratio of 40 times higher than that of Rucaparib and would be selected to develop its potential use in neurodegenerative diseases. Our study provided potential lead compounds and design strategies for the development of brain penetrating PARP-1 inhibitors.
HIGHLIGHTS
Structural fusion was used to screen brain penetrating PARP-1 inhibitors.
55 benzodiazepines were evaluated for their PARP-1 inhibition activity.
Four compounds displayed acceptable inhibition effects on breast cancer cells.
The benzodiazepine PARP-1 inhibitors were proved to be brain permeable. |
| doi_str_mv | 10.1080/14756366.2022.2053524 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmed_primary_35317687</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><doaj_id>oai_doaj_org_article_b263a5cf0d02430aa54e1d1ed749ebc1</doaj_id><sourcerecordid>2727916026</sourcerecordid><originalsourceid>FETCH-LOGICAL-c492t-2fc99844c8628ecc08bb9f487713a0c6ca2d77af3209a4b782e97b2f8832e7483</originalsourceid><addsrcrecordid>eNp9kcFuEzEQhi0Eom3gEUArceGyxR57be8FUZUClSqoEJytWa83cbSxg70BpU-PQ9KIcuBie8b_fJ7xT8gLRs8Z1fQNE6qRXMpzoABlaXgD4hE53eVryZV4fDxLeULOcl5SCgyYeEpOeMOZklqdks_vXfbzUGHoq7wN06KEuYpD1blwF3uPd27tg8sV5qpL6EO1dsFNCScf5tXtxdfbmlU-LHznp5jyM_JkwDG754d9Rr5_uPp2-am--fLx-vLipraihamGwbatFsJqCdpZS3XXtYPQSjGO1EqL0CuFAwfaouiUBteqDgatOTglNJ-R6z23j7g06-RXmLYmojd_EjHNDabJ29GZDiTHxg60pyA4RWyEYz1zvRKt6ywrrLd71nrTrVxvXSjjjQ-gD2-CX5h5_Gl0K6ARogBeHwAp_ti4PJmVz9aNIwYXN9mAFMA5L80X6at_pMu4SaF8lQEFqmWSlnZnpNmrbIo5Jzccm2HU7Nw39-6bnfvm4H6pe_n3JMeqe7uL4N1e4MMQ0wp_xTT2ZsLtGNOQMFifDf__G78Bum--LQ</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2727916026</pqid></control><display><type>article</type><title>Design and synthesis of benzodiazepines as brain penetrating PARP-1 inhibitors</title><source>Taylor & Francis Open Access</source><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><creator>Yu, Jiang ; Gou, Wenfeng ; Shang, Haihua ; Cui, Yating ; Sun, Xiao ; Luo, Lingling ; Hou, Wenbin ; Sun, Tiemin ; Li, Yiliang</creator><creatorcontrib>Yu, Jiang ; Gou, Wenfeng ; Shang, Haihua ; Cui, Yating ; Sun, Xiao ; Luo, Lingling ; Hou, Wenbin ; Sun, Tiemin ; Li, Yiliang</creatorcontrib><description>The poly (ADP-ribose) polymerase (PARP) inhibitors play a crucial role in cancer therapy. However, most approved PARP inhibitors cannot cross the blood-brain barrier, thus limiting their application in the central nervous system. Here, 55 benzodiazepines were designed and synthesised to screen brain penetrating PARP-1 inhibitors. All target compounds were evaluated for their PARP-1 inhibition activity, and compounds with better activity were selected for further assays in vitro. Among them, compounds H34, H42, H48, and H52 displayed acceptable inhibition effects on breast cancer cells. Also, computational prediction together with the permeability assays in vitro and in vivo proved that the benzodiazepine PARP-1 inhibitors we synthesised were brain permeable. Compound H52 exhibited a B/P ratio of 40 times higher than that of Rucaparib and would be selected to develop its potential use in neurodegenerative diseases. Our study provided potential lead compounds and design strategies for the development of brain penetrating PARP-1 inhibitors.
HIGHLIGHTS
Structural fusion was used to screen brain penetrating PARP-1 inhibitors.
55 benzodiazepines were evaluated for their PARP-1 inhibition activity.
Four compounds displayed acceptable inhibition effects on breast cancer cells.
The benzodiazepine PARP-1 inhibitors were proved to be brain permeable.</description><identifier>ISSN: 1475-6366</identifier><identifier>EISSN: 1475-6374</identifier><identifier>DOI: 10.1080/14756366.2022.2053524</identifier><identifier>PMID: 35317687</identifier><language>eng</language><publisher>England: Taylor & Francis</publisher><subject>benzodiazepine ; Benzodiazepines ; Benzodiazepines - chemical synthesis ; Benzodiazepines - chemistry ; Benzodiazepines - pharmacology ; Blood-brain barrier ; Breast cancer ; cancer ; Central nervous system ; CNS ; Computational neuroscience ; Dose-Response Relationship, Drug ; Drug Design ; Humans ; Kinases ; Molecular Structure ; Neurodegenerative diseases ; PARP-1 inhibitor ; Permeability ; Poly (ADP-Ribose) Polymerase-1 - antagonists & inhibitors ; Poly (ADP-Ribose) Polymerase-1 - metabolism ; Poly(ADP-ribose) polymerase ; Poly(ADP-ribose) Polymerase Inhibitors - chemical synthesis ; Poly(ADP-ribose) Polymerase Inhibitors - chemistry ; Poly(ADP-ribose) Polymerase Inhibitors - pharmacology ; Research Paper ; Ribose ; Rucaparib ; Structure-Activity Relationship</subject><ispartof>Journal of enzyme inhibition and medicinal chemistry, 2022-12, Vol.37 (1), p.952-972</ispartof><rights>2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. 2022</rights><rights>2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This work is licensed under the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. 2022 The Author(s)</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c492t-2fc99844c8628ecc08bb9f487713a0c6ca2d77af3209a4b782e97b2f8832e7483</citedby><cites>FETCH-LOGICAL-c492t-2fc99844c8628ecc08bb9f487713a0c6ca2d77af3209a4b782e97b2f8832e7483</cites><orcidid>0000-0001-5726-8807</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8942544/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8942544/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,27479,27901,27902,53766,53768,59116,59117</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35317687$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yu, Jiang</creatorcontrib><creatorcontrib>Gou, Wenfeng</creatorcontrib><creatorcontrib>Shang, Haihua</creatorcontrib><creatorcontrib>Cui, Yating</creatorcontrib><creatorcontrib>Sun, Xiao</creatorcontrib><creatorcontrib>Luo, Lingling</creatorcontrib><creatorcontrib>Hou, Wenbin</creatorcontrib><creatorcontrib>Sun, Tiemin</creatorcontrib><creatorcontrib>Li, Yiliang</creatorcontrib><title>Design and synthesis of benzodiazepines as brain penetrating PARP-1 inhibitors</title><title>Journal of enzyme inhibition and medicinal chemistry</title><addtitle>J Enzyme Inhib Med Chem</addtitle><description>The poly (ADP-ribose) polymerase (PARP) inhibitors play a crucial role in cancer therapy. However, most approved PARP inhibitors cannot cross the blood-brain barrier, thus limiting their application in the central nervous system. Here, 55 benzodiazepines were designed and synthesised to screen brain penetrating PARP-1 inhibitors. All target compounds were evaluated for their PARP-1 inhibition activity, and compounds with better activity were selected for further assays in vitro. Among them, compounds H34, H42, H48, and H52 displayed acceptable inhibition effects on breast cancer cells. Also, computational prediction together with the permeability assays in vitro and in vivo proved that the benzodiazepine PARP-1 inhibitors we synthesised were brain permeable. Compound H52 exhibited a B/P ratio of 40 times higher than that of Rucaparib and would be selected to develop its potential use in neurodegenerative diseases. Our study provided potential lead compounds and design strategies for the development of brain penetrating PARP-1 inhibitors.
HIGHLIGHTS
Structural fusion was used to screen brain penetrating PARP-1 inhibitors.
55 benzodiazepines were evaluated for their PARP-1 inhibition activity.
Four compounds displayed acceptable inhibition effects on breast cancer cells.
The benzodiazepine PARP-1 inhibitors were proved to be brain permeable.</description><subject>benzodiazepine</subject><subject>Benzodiazepines</subject><subject>Benzodiazepines - chemical synthesis</subject><subject>Benzodiazepines - chemistry</subject><subject>Benzodiazepines - pharmacology</subject><subject>Blood-brain barrier</subject><subject>Breast cancer</subject><subject>cancer</subject><subject>Central nervous system</subject><subject>CNS</subject><subject>Computational neuroscience</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Design</subject><subject>Humans</subject><subject>Kinases</subject><subject>Molecular Structure</subject><subject>Neurodegenerative diseases</subject><subject>PARP-1 inhibitor</subject><subject>Permeability</subject><subject>Poly (ADP-Ribose) Polymerase-1 - antagonists & inhibitors</subject><subject>Poly (ADP-Ribose) Polymerase-1 - metabolism</subject><subject>Poly(ADP-ribose) polymerase</subject><subject>Poly(ADP-ribose) Polymerase Inhibitors - chemical synthesis</subject><subject>Poly(ADP-ribose) Polymerase Inhibitors - chemistry</subject><subject>Poly(ADP-ribose) Polymerase Inhibitors - pharmacology</subject><subject>Research Paper</subject><subject>Ribose</subject><subject>Rucaparib</subject><subject>Structure-Activity Relationship</subject><issn>1475-6366</issn><issn>1475-6374</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>0YH</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNp9kcFuEzEQhi0Eom3gEUArceGyxR57be8FUZUClSqoEJytWa83cbSxg70BpU-PQ9KIcuBie8b_fJ7xT8gLRs8Z1fQNE6qRXMpzoABlaXgD4hE53eVryZV4fDxLeULOcl5SCgyYeEpOeMOZklqdks_vXfbzUGHoq7wN06KEuYpD1blwF3uPd27tg8sV5qpL6EO1dsFNCScf5tXtxdfbmlU-LHznp5jyM_JkwDG754d9Rr5_uPp2-am--fLx-vLipraihamGwbatFsJqCdpZS3XXtYPQSjGO1EqL0CuFAwfaouiUBteqDgatOTglNJ-R6z23j7g06-RXmLYmojd_EjHNDabJ29GZDiTHxg60pyA4RWyEYz1zvRKt6ywrrLd71nrTrVxvXSjjjQ-gD2-CX5h5_Gl0K6ARogBeHwAp_ti4PJmVz9aNIwYXN9mAFMA5L80X6at_pMu4SaF8lQEFqmWSlnZnpNmrbIo5Jzccm2HU7Nw39-6bnfvm4H6pe_n3JMeqe7uL4N1e4MMQ0wp_xTT2ZsLtGNOQMFifDf__G78Bum--LQ</recordid><startdate>202212</startdate><enddate>202212</enddate><creator>Yu, Jiang</creator><creator>Gou, Wenfeng</creator><creator>Shang, Haihua</creator><creator>Cui, Yating</creator><creator>Sun, Xiao</creator><creator>Luo, Lingling</creator><creator>Hou, Wenbin</creator><creator>Sun, Tiemin</creator><creator>Li, Yiliang</creator><general>Taylor & Francis</general><general>Taylor & Francis Ltd</general><general>Taylor & Francis Group</general><scope>0YH</scope><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>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0001-5726-8807</orcidid></search><sort><creationdate>202212</creationdate><title>Design and synthesis of benzodiazepines as brain penetrating PARP-1 inhibitors</title><author>Yu, Jiang ; Gou, Wenfeng ; Shang, Haihua ; Cui, Yating ; Sun, Xiao ; Luo, Lingling ; Hou, Wenbin ; Sun, Tiemin ; Li, Yiliang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c492t-2fc99844c8628ecc08bb9f487713a0c6ca2d77af3209a4b782e97b2f8832e7483</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>benzodiazepine</topic><topic>Benzodiazepines</topic><topic>Benzodiazepines - chemical synthesis</topic><topic>Benzodiazepines - chemistry</topic><topic>Benzodiazepines - pharmacology</topic><topic>Blood-brain barrier</topic><topic>Breast cancer</topic><topic>cancer</topic><topic>Central nervous system</topic><topic>CNS</topic><topic>Computational neuroscience</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Design</topic><topic>Humans</topic><topic>Kinases</topic><topic>Molecular Structure</topic><topic>Neurodegenerative diseases</topic><topic>PARP-1 inhibitor</topic><topic>Permeability</topic><topic>Poly (ADP-Ribose) Polymerase-1 - antagonists & inhibitors</topic><topic>Poly (ADP-Ribose) Polymerase-1 - metabolism</topic><topic>Poly(ADP-ribose) polymerase</topic><topic>Poly(ADP-ribose) Polymerase Inhibitors - chemical synthesis</topic><topic>Poly(ADP-ribose) Polymerase Inhibitors - chemistry</topic><topic>Poly(ADP-ribose) Polymerase Inhibitors - pharmacology</topic><topic>Research Paper</topic><topic>Ribose</topic><topic>Rucaparib</topic><topic>Structure-Activity Relationship</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yu, Jiang</creatorcontrib><creatorcontrib>Gou, Wenfeng</creatorcontrib><creatorcontrib>Shang, Haihua</creatorcontrib><creatorcontrib>Cui, Yating</creatorcontrib><creatorcontrib>Sun, Xiao</creatorcontrib><creatorcontrib>Luo, Lingling</creatorcontrib><creatorcontrib>Hou, Wenbin</creatorcontrib><creatorcontrib>Sun, Tiemin</creatorcontrib><creatorcontrib>Li, Yiliang</creatorcontrib><collection>Taylor & Francis Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Journal of enzyme inhibition and medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yu, Jiang</au><au>Gou, Wenfeng</au><au>Shang, Haihua</au><au>Cui, Yating</au><au>Sun, Xiao</au><au>Luo, Lingling</au><au>Hou, Wenbin</au><au>Sun, Tiemin</au><au>Li, Yiliang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Design and synthesis of benzodiazepines as brain penetrating PARP-1 inhibitors</atitle><jtitle>Journal of enzyme inhibition and medicinal chemistry</jtitle><addtitle>J Enzyme Inhib Med Chem</addtitle><date>2022-12</date><risdate>2022</risdate><volume>37</volume><issue>1</issue><spage>952</spage><epage>972</epage><pages>952-972</pages><issn>1475-6366</issn><eissn>1475-6374</eissn><abstract>The poly (ADP-ribose) polymerase (PARP) inhibitors play a crucial role in cancer therapy. However, most approved PARP inhibitors cannot cross the blood-brain barrier, thus limiting their application in the central nervous system. Here, 55 benzodiazepines were designed and synthesised to screen brain penetrating PARP-1 inhibitors. All target compounds were evaluated for their PARP-1 inhibition activity, and compounds with better activity were selected for further assays in vitro. Among them, compounds H34, H42, H48, and H52 displayed acceptable inhibition effects on breast cancer cells. Also, computational prediction together with the permeability assays in vitro and in vivo proved that the benzodiazepine PARP-1 inhibitors we synthesised were brain permeable. Compound H52 exhibited a B/P ratio of 40 times higher than that of Rucaparib and would be selected to develop its potential use in neurodegenerative diseases. Our study provided potential lead compounds and design strategies for the development of brain penetrating PARP-1 inhibitors.
HIGHLIGHTS
Structural fusion was used to screen brain penetrating PARP-1 inhibitors.
55 benzodiazepines were evaluated for their PARP-1 inhibition activity.
Four compounds displayed acceptable inhibition effects on breast cancer cells.
The benzodiazepine PARP-1 inhibitors were proved to be brain permeable.</abstract><cop>England</cop><pub>Taylor & Francis</pub><pmid>35317687</pmid><doi>10.1080/14756366.2022.2053524</doi><tpages>21</tpages><orcidid>https://orcid.org/0000-0001-5726-8807</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1475-6366 |
| ispartof | Journal of enzyme inhibition and medicinal chemistry, 2022-12, Vol.37 (1), p.952-972 |
| issn | 1475-6366 1475-6374 |
| language | eng |
| recordid | cdi_pubmed_primary_35317687 |
| source | Taylor & Francis Open Access; MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | benzodiazepine Benzodiazepines Benzodiazepines - chemical synthesis Benzodiazepines - chemistry Benzodiazepines - pharmacology Blood-brain barrier Breast cancer cancer Central nervous system CNS Computational neuroscience Dose-Response Relationship, Drug Drug Design Humans Kinases Molecular Structure Neurodegenerative diseases PARP-1 inhibitor Permeability Poly (ADP-Ribose) Polymerase-1 - antagonists & inhibitors Poly (ADP-Ribose) Polymerase-1 - metabolism Poly(ADP-ribose) polymerase Poly(ADP-ribose) Polymerase Inhibitors - chemical synthesis Poly(ADP-ribose) Polymerase Inhibitors - chemistry Poly(ADP-ribose) Polymerase Inhibitors - pharmacology Research Paper Ribose Rucaparib Structure-Activity Relationship |
| title | Design and synthesis of benzodiazepines as brain penetrating PARP-1 inhibitors |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-05T05%3A07%3A25IST&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=Design%20and%20synthesis%20of%20benzodiazepines%20as%20brain%20penetrating%20PARP-1%20inhibitors&rft.jtitle=Journal%20of%20enzyme%20inhibition%20and%20medicinal%20chemistry&rft.au=Yu,%20Jiang&rft.date=2022-12&rft.volume=37&rft.issue=1&rft.spage=952&rft.epage=972&rft.pages=952-972&rft.issn=1475-6366&rft.eissn=1475-6374&rft_id=info:doi/10.1080/14756366.2022.2053524&rft_dat=%3Cproquest_pubme%3E2727916026%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=2727916026&rft_id=info:pmid/35317687&rft_doaj_id=oai_doaj_org_article_b263a5cf0d02430aa54e1d1ed749ebc1&rfr_iscdi=true |