دورية أكاديمية
Design, synthesis and evaluation of a series of potential prodrugs of a Bruton’s tyrosine kinase (BTK) inhibitor
| العنوان: | Design, synthesis and evaluation of a series of potential prodrugs of a Bruton’s tyrosine kinase (BTK) inhibitor |
|---|---|
| المؤلفون: | Zhou-Peng Xiao, Min Liao, Xue-Juan Huang, Yu-Tong Wang, Xiao-Cui Lan, Xue-Ying Wang, Xi-Tao Li |
| المصدر: | Frontiers in Pharmacology, Vol 14 (2023) |
| بيانات النشر: | Frontiers Media S.A., 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Therapeutics. Pharmacology |
| مصطلحات موضوعية: | prodrug, BTK-bruton’s tyrosine kinase, inhibitor, solubility, DFG-out, Therapeutics. Pharmacology, RM1-950 |
| الوصف: | BTK has become a particularly attractive therapeutic target in autoimmune diseases and B-cell malignancies, making BTK inhibitors a valuable and important therapeutic option. We present the design, synthesis, and evaluation of a series of prodrugs of a BTK inhibitor with an insoluble 2,5-diaminopyrimidine structure. Tails containing different solubilizing groups were added to the parent molecule via an ester linkage. Prodrug 5a showed good aqueous solubility and could be efficiently converted to the parent in a human plasma stability study. The rational prodrug design was supported by molecular studies and a dramatically reduced BTK kinase-inhibitory potential. Taken together, the chemical, biological, and molecular studies suggest that prodrug derivatization of the 2,5-diaminopyrimidine scaffold could be a potential strategy for advancing this series of BTK inhibitors into the therapeutic arena. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1663-9812 |
| العلاقة: | https://www.frontiersin.org/articles/10.3389/fphar.2023.1162216/fullTest; https://doaj.org/toc/1663-9812Test |
| DOI: | 10.3389/fphar.2023.1162216 |
| الوصول الحر: | https://doaj.org/article/d7b1a8fb14f848d282283c024b3012a3Test |
| رقم الانضمام: | edsdoj.7b1a8fb14f848d282283c024b3012a3 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | ResultId |
1 |
|---|---|
| Header |
edsdoj Directory of Open Access Journals edsdoj.7b1a8fb14f848d282283c024b3012a3 983 3 Academic Journal academicJournal 983.050231933594 |
| PLink |
https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&scope=site&db=edsdoj&AN=edsdoj.7b1a8fb14f848d282283c024b3012a3&custid=s6537998&authtype=sso |
| FullText |
Array
(
[Availability] => 0
)
Array ( [0] => Array ( [Url] => https://doaj.org/article/d7b1a8fb14f848d282283c024b3012a3 [Name] => EDS - DOAJ [Category] => fullText [Text] => View record in DOAJ [MouseOverText] => View record in DOAJ ) [1] => Array ( [Url] => https://resolver.ebscohost.com/openurl?custid=s6537998&groupid=main&authtype=ip,guest&sid=EBSCO:edsdoj&genre=article&issn=16639812&ISBN=&volume=14&issue=&date=20230301&spage=&pages=&title=Frontiers in Pharmacology&atitle=Design%2C%20synthesis%20and%20evaluation%20of%20a%20series%20of%20potential%20prodrugs%20of%20a%20Bruton%E2%80%99s%20tyrosine%20kinase%20%28BTK%29%20inhibitor&id=DOI:10.3389/fphar.2023.1162216 [Name] => Full Text Finder (s6537998api) [Category] => fullText [Text] => Full Text Finder [Icon] => https://imageserver.ebscohost.com/branding/images/FTF.gif [MouseOverText] => Full Text Finder ) ) |
| Items |
Array
(
[Name] => Title
[Label] => Title
[Group] => Ti
[Data] => Design, synthesis and evaluation of a series of potential prodrugs of a Bruton’s tyrosine kinase (BTK) inhibitor
)
Array ( [Name] => Author [Label] => Authors [Group] => Au [Data] => <searchLink fieldCode="AR" term="%22Zhou-Peng+Xiao%22">Zhou-Peng Xiao</searchLink><br /><searchLink fieldCode="AR" term="%22Min+Liao%22">Min Liao</searchLink><br /><searchLink fieldCode="AR" term="%22Xue-Juan+Huang%22">Xue-Juan Huang</searchLink><br /><searchLink fieldCode="AR" term="%22Yu-Tong+Wang%22">Yu-Tong Wang</searchLink><br /><searchLink fieldCode="AR" term="%22Xiao-Cui+Lan%22">Xiao-Cui Lan</searchLink><br /><searchLink fieldCode="AR" term="%22Xue-Ying+Wang%22">Xue-Ying Wang</searchLink><br /><searchLink fieldCode="AR" term="%22Xi-Tao+Li%22">Xi-Tao Li</searchLink> ) Array ( [Name] => TitleSource [Label] => Source [Group] => Src [Data] => Frontiers in Pharmacology, Vol 14 (2023) ) Array ( [Name] => Publisher [Label] => Publisher Information [Group] => PubInfo [Data] => Frontiers Media S.A., 2023. ) Array ( [Name] => DatePubCY [Label] => Publication Year [Group] => Date [Data] => 2023 ) Array ( [Name] => Subset [Label] => Collection [Group] => HoldingsInfo [Data] => LCC:Therapeutics. Pharmacology ) Array ( [Name] => Subject [Label] => Subject Terms [Group] => Su [Data] => <searchLink fieldCode="DE" term="%22prodrug%22">prodrug</searchLink><br /><searchLink fieldCode="DE" term="%22BTK-bruton%27s+tyrosine+kinase%22">BTK-bruton’s tyrosine kinase</searchLink><br /><searchLink fieldCode="DE" term="%22inhibitor%22">inhibitor</searchLink><br /><searchLink fieldCode="DE" term="%22solubility%22">solubility</searchLink><br /><searchLink fieldCode="DE" term="%22DFG-out%22">DFG-out</searchLink><br /><searchLink fieldCode="DE" term="%22Therapeutics%2E+Pharmacology%22">Therapeutics. Pharmacology</searchLink><br /><searchLink fieldCode="DE" term="%22RM1-950%22">RM1-950</searchLink> ) Array ( [Name] => Abstract [Label] => Description [Group] => Ab [Data] => BTK has become a particularly attractive therapeutic target in autoimmune diseases and B-cell malignancies, making BTK inhibitors a valuable and important therapeutic option. We present the design, synthesis, and evaluation of a series of prodrugs of a BTK inhibitor with an insoluble 2,5-diaminopyrimidine structure. Tails containing different solubilizing groups were added to the parent molecule via an ester linkage. Prodrug 5a showed good aqueous solubility and could be efficiently converted to the parent in a human plasma stability study. The rational prodrug design was supported by molecular studies and a dramatically reduced BTK kinase-inhibitory potential. Taken together, the chemical, biological, and molecular studies suggest that prodrug derivatization of the 2,5-diaminopyrimidine scaffold could be a potential strategy for advancing this series of BTK inhibitors into the therapeutic arena. ) Array ( [Name] => TypeDocument [Label] => Document Type [Group] => TypDoc [Data] => article ) Array ( [Name] => Format [Label] => File Description [Group] => SrcInfo [Data] => electronic resource ) Array ( [Name] => Language [Label] => Language [Group] => Lang [Data] => English ) Array ( [Name] => ISSN [Label] => ISSN [Group] => ISSN [Data] => 1663-9812 ) Array ( [Name] => NoteTitleSource [Label] => Relation [Group] => SrcInfo [Data] => https://www.frontiersin.org/articles/10.3389/fphar.2023.1162216/full; https://doaj.org/toc/1663-9812 ) Array ( [Name] => DOI [Label] => DOI [Group] => ID [Data] => 10.3389/fphar.2023.1162216 ) Array ( [Name] => URL [Label] => Access URL [Group] => URL [Data] => <link linkTarget="URL" linkTerm="https://doaj.org/article/d7b1a8fb14f848d282283c024b3012a3" linkWindow="_blank">https://doaj.org/article/d7b1a8fb14f848d282283c024b3012a3</link> ) Array ( [Name] => AN [Label] => Accession Number [Group] => ID [Data] => edsdoj.7b1a8fb14f848d282283c024b3012a3 ) |
| RecordInfo |
Array
(
[BibEntity] => Array
(
[Identifiers] => Array
(
[0] => Array
(
[Type] => doi
[Value] => 10.3389/fphar.2023.1162216
)
)
[Languages] => Array
(
[0] => Array
(
[Text] => English
)
)
[Subjects] => Array
(
[0] => Array
(
[SubjectFull] => prodrug
[Type] => general
)
[1] => Array
(
[SubjectFull] => BTK-bruton’s tyrosine kinase
[Type] => general
)
[2] => Array
(
[SubjectFull] => inhibitor
[Type] => general
)
[3] => Array
(
[SubjectFull] => solubility
[Type] => general
)
[4] => Array
(
[SubjectFull] => DFG-out
[Type] => general
)
[5] => Array
(
[SubjectFull] => Therapeutics. Pharmacology
[Type] => general
)
[6] => Array
(
[SubjectFull] => RM1-950
[Type] => general
)
)
[Titles] => Array
(
[0] => Array
(
[TitleFull] => Design, synthesis and evaluation of a series of potential prodrugs of a Bruton’s tyrosine kinase (BTK) inhibitor
[Type] => main
)
)
)
[BibRelationships] => Array
(
[HasContributorRelationships] => Array
(
[0] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Zhou-Peng Xiao
)
)
)
[1] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Min Liao
)
)
)
[2] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Xue-Juan Huang
)
)
)
[3] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Yu-Tong Wang
)
)
)
[4] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Xiao-Cui Lan
)
)
)
[5] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Xue-Ying Wang
)
)
)
[6] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Xi-Tao Li
)
)
)
)
[IsPartOfRelationships] => Array
(
[0] => Array
(
[BibEntity] => Array
(
[Dates] => Array
(
[0] => Array
(
[D] => 01
[M] => 03
[Type] => published
[Y] => 2023
)
)
[Identifiers] => Array
(
[0] => Array
(
[Type] => issn-print
[Value] => 16639812
)
)
[Numbering] => Array
(
[0] => Array
(
[Type] => volume
[Value] => 14
)
)
[Titles] => Array
(
[0] => Array
(
[TitleFull] => Frontiers in Pharmacology
[Type] => main
)
)
)
)
)
)
)
|
| IllustrationInfo |