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Discovery and optimization of pyrrolopyrimidines as highly potent, selective and brain-penetrant LRRK2 inhibitors.

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Title: Discovery and optimization of pyrrolopyrimidines as highly potent, selective and brain-penetrant LRRK2 inhibitors.
Authors: Axten JM; GSK Research and Development 1250 S. Collegeville Road Collegeville Pennsylvania 19426 USA jeffrey.m.axten@gsk.com., Ding X; GSK Research and Development 898 Halei Road, Zhangjiang Hi-Tech Park Pudong Shanghai 201203 PR China., Stasi LP; GSK Research and Development 898 Halei Road, Zhangjiang Hi-Tech Park Pudong Shanghai 201203 PR China., Zhao B; GSK Research and Development 898 Halei Road, Zhangjiang Hi-Tech Park Pudong Shanghai 201203 PR China., Sang Y; GSK Research and Development 898 Halei Road, Zhangjiang Hi-Tech Park Pudong Shanghai 201203 PR China., Ho MH; GSK Research and Development 1250 S. Collegeville Road Collegeville Pennsylvania 19426 USA jeffrey.m.axten@gsk.com., Wang L; GSK Research and Development 898 Halei Road, Zhangjiang Hi-Tech Park Pudong Shanghai 201203 PR China., Zhang M; GSK Research and Development 898 Halei Road, Zhangjiang Hi-Tech Park Pudong Shanghai 201203 PR China., Guo X; GSK Research and Development 898 Halei Road, Zhangjiang Hi-Tech Park Pudong Shanghai 201203 PR China., Tan C; GSK Research and Development 898 Halei Road, Zhangjiang Hi-Tech Park Pudong Shanghai 201203 PR China., Feng X; GSK Research and Development 898 Halei Road, Zhangjiang Hi-Tech Park Pudong Shanghai 201203 PR China., Edge C; GSK Research and Development Medicines Research Centre Gunnels Wood Road Stevenage SG1 2NY UK., Valko K; GSK Research and Development Medicines Research Centre Gunnels Wood Road Stevenage SG1 2NY UK., Li Y; GSK Research and Development 898 Halei Road, Zhangjiang Hi-Tech Park Pudong Shanghai 201203 PR China., Dong K; GSK Research and Development 898 Halei Road, Zhangjiang Hi-Tech Park Pudong Shanghai 201203 PR China., Guan X; GSK Research and Development 898 Halei Road, Zhangjiang Hi-Tech Park Pudong Shanghai 201203 PR China., Zinn N; Omics Technologies, Cellzome a GSK Company Meyerhofstrasse 1 D-69117 Heidelberg Germany., David Tattersall F; GSK Research and Development 1250 S. Collegeville Road Collegeville Pennsylvania 19426 USA jeffrey.m.axten@gsk.com., Ren F; GSK Research and Development 898 Halei Road, Zhangjiang Hi-Tech Park Pudong Shanghai 201203 PR China., Su DS; GSK Research and Development 1250 S. Collegeville Road Collegeville Pennsylvania 19426 USA jeffrey.m.axten@gsk.com., Reith AD; GSK Research and Development Medicines Research Centre Gunnels Wood Road Stevenage SG1 2NY UK.
Source: RSC medicinal chemistry [RSC Med Chem] 2025 Nov 17. Date of Electronic Publication: 2025 Nov 17.
Publication Type: Journal Article
Journal Info: Publisher: Royal Society of Chemistry Country of Publication: England NLM ID: 101759460 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2632-8682 (Electronic) Linking ISSN: 26328682 NLM ISO Abbreviation: RSC Med Chem
Database: MEDLINE Ultimate
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PubType: Academic Journal
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  Data: Discovery and optimization of pyrrolopyrimidines as highly potent, selective and brain-penetrant LRRK2 inhibitors.
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  Data: <searchLink fieldCode="AU" term="%22Axten+JM%22">Axten JM</searchLink>; GSK Research and Development 1250 S. Collegeville Road Collegeville Pennsylvania 19426 USA jeffrey.m.axten@gsk.com.<br /><searchLink fieldCode="AU" term="%22Ding+X%22">Ding X</searchLink>; GSK Research and Development 898 Halei Road, Zhangjiang Hi-Tech Park Pudong Shanghai 201203 PR China.<br /><searchLink fieldCode="AU" term="%22Stasi+LP%22">Stasi LP</searchLink>; GSK Research and Development 898 Halei Road, Zhangjiang Hi-Tech Park Pudong Shanghai 201203 PR China.<br /><searchLink fieldCode="AU" term="%22Zhao+B%22">Zhao B</searchLink>; GSK Research and Development 898 Halei Road, Zhangjiang Hi-Tech Park Pudong Shanghai 201203 PR China.<br /><searchLink fieldCode="AU" term="%22Sang+Y%22">Sang Y</searchLink>; GSK Research and Development 898 Halei Road, Zhangjiang Hi-Tech Park Pudong Shanghai 201203 PR China.<br /><searchLink fieldCode="AU" term="%22Ho+MH%22">Ho MH</searchLink>; GSK Research and Development 1250 S. Collegeville Road Collegeville Pennsylvania 19426 USA jeffrey.m.axten@gsk.com.<br /><searchLink fieldCode="AU" term="%22Wang+L%22">Wang L</searchLink>; GSK Research and Development 898 Halei Road, Zhangjiang Hi-Tech Park Pudong Shanghai 201203 PR China.<br /><searchLink fieldCode="AU" term="%22Zhang+M%22">Zhang M</searchLink>; GSK Research and Development 898 Halei Road, Zhangjiang Hi-Tech Park Pudong Shanghai 201203 PR China.<br /><searchLink fieldCode="AU" term="%22Guo+X%22">Guo X</searchLink>; GSK Research and Development 898 Halei Road, Zhangjiang Hi-Tech Park Pudong Shanghai 201203 PR China.<br /><searchLink fieldCode="AU" term="%22Tan+C%22">Tan C</searchLink>; GSK Research and Development 898 Halei Road, Zhangjiang Hi-Tech Park Pudong Shanghai 201203 PR China.<br /><searchLink fieldCode="AU" term="%22Feng+X%22">Feng X</searchLink>; GSK Research and Development 898 Halei Road, Zhangjiang Hi-Tech Park Pudong Shanghai 201203 PR China.<br /><searchLink fieldCode="AU" term="%22Edge+C%22">Edge C</searchLink>; GSK Research and Development Medicines Research Centre Gunnels Wood Road Stevenage SG1 2NY UK.<br /><searchLink fieldCode="AU" term="%22Valko+K%22">Valko K</searchLink>; GSK Research and Development Medicines Research Centre Gunnels Wood Road Stevenage SG1 2NY UK.<br /><searchLink fieldCode="AU" term="%22Li+Y%22">Li Y</searchLink>; GSK Research and Development 898 Halei Road, Zhangjiang Hi-Tech Park Pudong Shanghai 201203 PR China.<br /><searchLink fieldCode="AU" term="%22Dong+K%22">Dong K</searchLink>; GSK Research and Development 898 Halei Road, Zhangjiang Hi-Tech Park Pudong Shanghai 201203 PR China.<br /><searchLink fieldCode="AU" term="%22Guan+X%22">Guan X</searchLink>; GSK Research and Development 898 Halei Road, Zhangjiang Hi-Tech Park Pudong Shanghai 201203 PR China.<br /><searchLink fieldCode="AU" term="%22Zinn+N%22">Zinn N</searchLink>; Omics Technologies, Cellzome a GSK Company Meyerhofstrasse 1 D-69117 Heidelberg Germany.<br /><searchLink fieldCode="AU" term="%22David+Tattersall+F%22">David Tattersall F</searchLink>; GSK Research and Development 1250 S. Collegeville Road Collegeville Pennsylvania 19426 USA jeffrey.m.axten@gsk.com.<br /><searchLink fieldCode="AU" term="%22Ren+F%22">Ren F</searchLink>; GSK Research and Development 898 Halei Road, Zhangjiang Hi-Tech Park Pudong Shanghai 201203 PR China.<br /><searchLink fieldCode="AU" term="%22Su+DS%22">Su DS</searchLink>; GSK Research and Development 1250 S. Collegeville Road Collegeville Pennsylvania 19426 USA jeffrey.m.axten@gsk.com.<br /><searchLink fieldCode="AU" term="%22Reith+AD%22">Reith AD</searchLink>; GSK Research and Development Medicines Research Centre Gunnels Wood Road Stevenage SG1 2NY UK.
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  Data: <searchLink fieldCode="JN" term="%22101759460%22">RSC medicinal chemistry</searchLink> [RSC Med Chem] 2025 Nov 17. <i>Date of Electronic Publication: </i>2025 Nov 17.
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  Data: <i>Publisher: </i><searchLink fieldCode="PB" term="%22Royal+Society+of+Chemistry%22">Royal Society of Chemistry </searchLink><i>Country of Publication: </i>England <i>NLM ID: </i>101759460 <i>Publication Model: </i>Print-Electronic <i>Cited Medium: </i>Internet <i>ISSN: </i>2632-8682 (Electronic) <i>Linking ISSN: </i><searchLink fieldCode="IS" term="%2226328682%22">26328682 </searchLink><i>NLM ISO Abbreviation: </i>RSC Med Chem
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=mdl&AN=41393202
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        Value: 10.1039/d5md00856e
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      – Code: eng
        Text: English
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            – D: 17
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              Text: 2025 Nov 17
              Type: published
              Y: 2025
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