Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

Glucose-6-phosphatase catalytic enzyme inhibitors: synthesis and in vitro evaluation of novel 4,5,6,7-tetrahydrothieno[3,2-c]- and -[2,3-c]pyridines

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Convergent (18)F-labeling and evaluation of N-benzyl-phenethylamines as 5-HT2A receptor PET ligands

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Synthesis and evaluation of [¹¹C]Cimbi-806 as a potential PET ligand for 5-HT₇ receptor imaging

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. The process of health behaviour change following participation in a randomised controlled trial targeting prediabetes

    Publikation: KonferencebidragKonferenceabstrakt til konferenceForskningpeer review

  2. Supporting positive parenting and promoting healthy living through family cooking classes

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Livsstilsguide i praksis - 3. udgave

    Publikation: Bog/antologi/afhandling/rapportRapport

  4. Determinants of glycaemic control among patients with type 2 diabetes: testing a process model based on self-determination theory

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Vis graf over relationer

The discovery of the first class of potent glucose-6-phosphatase catalytic site inhibitors, substituted 4,5,6,7-tetrahydrothieno[3,2-c]- and -[2,3-c]pyridines, is described. Optimisation of this series involved solution phase combinatorial synthesis and very potent compounds were prepared with IC50 values down to 140 nM. The structure activity relationship (SAR) of these compounds indicates that: a tetrahydrothieno[3,2-c]pyridine core ring system and the isomeric [2,3-c] system are equipotent and much better than the corresponding benzo analogue, 1,2,3,4-tetrahydro-isoquinoline. The 4-substituent of the tetrahydrothieno[3,2-c]pyridine ring has to be a phenyl group, optionally substituted with a lipophilic 4-substituent, such as trifluoromethoxy or chloro. The 5-substituent of the tetrahydrothieno[3,2-c]pyridine ring has to be a substituted benzoyl; anisoyl and (E)-3-furan-3-ylacryloyl are the best of the investigated groups. Substitution in the benzoyl ortho position seems to be forbidden, whereas substitution in the meta position is tolerated only if a methoxy para substituent is present. These SAR findings were parallel to those obtained in the 4,5,6,7-tetrahydrothieno[2,3-c]pyridine system. Enantioselectivity in enzyme recognition was observed and the activity resided in all cases only in one of the enantiomers.

OriginalsprogEngelsk
TidsskriftBioorganic and Medicinal Chemistry
Vol/bind8
Udgave nummer9
Sider (fra-til)2277-89
Antal sider13
ISSN0968-0896
StatusUdgivet - sep. 2000
Eksternt udgivetJa

ID: 53313292