id:"swepub:oai:DiVA.org:uu-100377"
Search: id:"swepub:oai:DiVA.org:uu-100377" > Design and Synthesi...
- 1 of 1
- Previous record
- Next record
- To hitlist
- Lagerlund, OlofUppsala universitet,Avdelningen för organisk farmaceutisk kemi (author)
Design and Synthesis of Novel Glutamine Synthetase Inhibitors and Development of Palladium(0)-Catalyzed Aminocarbonylation
- BookEnglish2009
Publisher, publication year, extent ...
- Uppsala :Acta Universitatis Upsaliensis,2009
- 55 s.
- electronicrdacarrier
Numbers
- LIBRIS-ID:oai:DiVA.org:uu-100377
- ISBN:9789155474928
- https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-100377URI
Supplementary language notes
- Language:English
- Summary in:English
Part of subdatabase
- SwePubSwePub
Classification
Series
- Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy,1651-6192 ;95
Notes
- Tuberculosis (TB) is a major infectious disease, killing about 2 million people annually throughout the world. Today's TB treatment is a lengthy procedure involving a combination of antibiotics. No new TB drug has been introduced onto the market in the past 40 years, and the emergence of multi- and extensively drug-resistant TB calls for new drugs. Finding new drug targets is important and one such target is the Mycobacterium tuberculosis enzyme glutamine synthetase (GS), which catalyses the formation of glutamine from glutamic acid. In this work, novel GS inhibitors and new Pd(0)-catalyzed methods have been developed. A microwave-enhanced Pd(0)-catalyzed α-arylation reaction was developed using water as solvent, and a phenylglycine scaffold was identified using structure-based design. A series of α-arylated phenylglycine derivates was produced at moderate to good yields. Some of these were biologically evaluated against GS. A novel scaffold, 3-amino-imidazo[1,2-a]pyridine, was identified by high-throughput screening directed towards GS. This type of compound could be easily produced via a Ugi-type, microwave-promoted multi-component reaction in 20 min. The scaffold was investigated by changing one substituent at a time, and in an experimental design where 8 factors were varied in the same design. Several potent inhibitors were identified; amongst them the most potent inhibitor to date (IC50 = 0.38 µM). Two discrete structure-activity relationships were established, and one of the inhibitors was co-crystallized. The first general aminocarbonylation of aryl chlorides and the first aminocarbonylation of alkenyl phosphates were developed. Alkenyl chlorides, bromides and triflates were investigated in the same transformation utilizing Mo(CO)6 as a solid carbon monoxide source. Two different Pd(0)-based catalytic systems were developed. A wide variety of aryl chlorides and amines could be transformed into the corresponding amides with good yields. The alkenyl substrates produced low to good yields.
Subject headings and genre
- MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Läkemedelskemi hsv//swe
- MEDICAL AND HEALTH SCIENCES Basic Medicine Medicinal Chemistry hsv//eng
- Pharmaceutical chemistry
- Farmaceutisk kemi
- Medicinal Chemistry
- läkemedelskemi
Added entries (persons, corporate bodies, meetings, titles ...)
- Larhed, Mats,ProfessorUppsala universitet,Avdelningen för organisk farmaceutisk kemi (thesis advisor)
- Karlén, Anders,ProfessorUppsala universitet,Avdelningen för organisk farmaceutisk kemi (thesis advisor)
- Hallberg, Anders,ProfessorUppsala universitet,Avdelningen för organisk farmaceutisk kemi (thesis advisor)
- Begtrup, Michael,ProfessorDanish University Pharmaceutical Sciences, Dept Med Chem, Copenhagen, Denmark (opponent)
- Uppsala universitetAvdelningen för organisk farmaceutisk kemi (creator_code:org_t)
Internet link
Find in a library
- Design and Synthesis of Novel Glutamine Synthetase Inhibitors and Development of... (Search the publication in LIBRIS)
To the university's database
- 1 of 1
- Previous record
- Next record
- To hitlist
Find more in SwePub
- By the author/editor
- Lagerlund, Olof
- Larhed, Mats, Pr ...
- Karlén, Anders, ...
- Hallberg, Anders ...
- Begtrup, Michael ...
- About the subject
-
- MEDICAL AND HEALTH SCIENCES
- MEDICAL AND HEAL ...
- and Basic Medicine
- and Medicinal Chemis ...
- Parts in the series
- Digital Comprehe ...
- By the university
- Uppsala University
Search outside SwePub
- Extend your search to:
- Google Book Search
- Google Scholar
Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.
- Copyright © LIBRIS - National Library Systems
- LIBRIS.kb.se
