id:"swepub:oai:DiVA.org:kth-286487"
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- Zeng, S. (författare)
Discovery of an Orally Active and Long-Acting DPP-IV Inhibitor through Property-Based Optimization with an in Silico Biotransformation Prediction Tool
- Artikel/kapitelEngelska2020
Förlag, utgivningsår, omfång ...
- 2020-07-02
- John Wiley and Sons Ltd,2020
- printrdacarrier
Nummerbeteckningar
- LIBRIS-ID:oai:DiVA.org:kth-286487
- https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-286487URI
- https://doi.org/10.1002/cmdc.202000175DOI
Kompletterande språkuppgifter
- Språk:engelska
- Sammanfattning på:engelska
Ingår i deldatabas
- SwePubSwePub
Klassifikation
Anmärkningar
- QC 20201217
- Long-acting dipeptidyl peptidase IV inhibitors have emerged as promising molecules for interventions for type 2 diabetes. Once weekly dosing brings greater patient compliance and more stable glycemic control. Starting from our previous highly potent compound with a thienoprimidine scaffold, which is unfortunately severely hit by hepatic biotransformation, a lead compound was rapidly generated by drawing on the experience of our previously discovered long-acting compounds with pyrrolopyrimidine scaffold. With the aid of an in silico biotransformation prediction tool, (R)-2-((2-(3-aminopiperidin-1-yl)-4-oxo-6-(pyridin-3-yl)thieno[3,2-d]pyrimidin-3(4H)-yl)methyl)-4-fluorobenzonitrile was eventually generated and determined to have high potency, a fine pharmacokinetic profile, and a long-acting in vivo efficacy.
Ämnesord och genrebeteckningar
- NATURVETENSKAP Kemi Organisk kemi hsv//swe
- NATURAL SCIENCES Chemical Sciences Organic Chemistry hsv//eng
- biostability
- DPP-IV
- in silico testing
- inhibitors
- metabolism
- 2 [[2 (3 aminopiperidin 1 yl) 4 oxo 6 (1h pyrazol 4 yl)thieno[3
- 2 d]pyrimidin 3(4h) yl]methyl] 4 fluorobenzonitrile
- 2 [[2 (3 aminopiperidin 1 yl) 4 oxo 6 (pyridin 3 yl)thieno[3
- 2 d]pyrimidin 3(4h) yl]methyl] 4 fluorobenzonitrile
- 2 [[2 (3 aminopiperidin 1 yl) 4 oxo 6 (pyridin 4 yl)thieno[3
- 2 d]pyrimidin 3(4h) yl]methyl] 4 fluorobenzonitrile
- 2 [[2 (3 aminopiperidin 1 yl) 4 oxo 6 [3 (trifluoromethyl)phenyl]thieno[3
- 2 d]pyrimidin 3(4h) yl]methyl] 4 fluorobenzonitrile
- 2 [[2 (3 aminopiperidin 1 yl) 4 oxo 7 (pyridin 3 yl)thieno[3
- 2 d]pyrimidin 3(4h) yl]methyl] 4 fluorobenzonitrile
- 2 [[2 (3 aminopiperidin 1 yl) 4 oxothieno[3
- 2 d]pyrimidin 3(4h) yl]methyl] 4 fluorobenzonitrile
- 2 [[2 (3 aminopiperidin 1 yl) 6 (2 methoxypyridin 4 yl) 4 oxothieno[3
- 2 d]pyrimidin 3(4h) yl]methyl] 4 fluorobenzonitrile
- 2 [[2 (3 aminopiperidin 1 yl) 6 (2 methylpyridin 4 yl) 4 oxothieno[3
- 2 d]pyrimidin 3(4h) yl]methyl] 4 fluorobenzonitrile
- 2 [[2 (3 aminopiperidin 1 yl) 6 (3 fluorophenyl) 4 oxothieno[3
- 2 d]pyrimidin 3(4h) yl]methyl] 4 fluorobenzonitrile
- 2 [[2 (3 aminopiperidin 1 yl) 6 (3
- 5 dimethylisoxazol 4 yl) 4 oxothieno[3
- 2 d]pyrimidin 3(4h) yl]methyl] 4 fluorobenzonitrile
- 2 [[2 (3 aminopiperidin 1 yl) 6 (4 fluorophenyl) 4 oxothieno[3
- 2 d]pyrimidin 3(4h) yl]methyl] 4 fluorobenzonitrile
- 2 [[2 (3 aminopiperidin 1 yl) 6 bromo 4 oxothieno[3
- 2 d]pyrimidin 3(4h) yl]methyl] 4 fluorobenzonitrile
- 2 [[2 (3 aminopiperidin 1 yl) 6 [3 (methylsulfonyl)phenyl] 4 oxothieno[3
- 2 d]pyrimidin 3(4h) yl]methyl] 4 fluorobenzonitrile
- 2 [[2 (3 aminopiperidin 1 yl) 7 bromo 4 oxothieno[3
- 2 d]pyrimidin 3(4h) yl]methyl] 4 fluorobenzonitrile
- 2 [[2 (3 aminopiperidin 1 yl) 7 fluoro 4 oxothieno[3
- 2 d]pyrimidin 3(4h) yl]methyl] 4 fluorobenzonitrile
- 2 [[2 (3 aminopiperidin 1 yl) 7 methyl 4 oxo 6 (pyridin 3 yl)thieno[3
- 2 d]pyrimidin 3(4h) yl]methyl] 4 fluorobenzonitrile
- 2 [[2 (3 aminopiperidin 1 yl) 7 methyl 4 oxothieno[3
- 2 d]pyrimidin 3(4h) yl]methyl] 4 fluorobenzonitrile
- antidiabetic agent
- cytochrome P450
- dipeptidyl peptidase IV inhibitor
- long acting drug
- pyrimidine derivative
- trelagliptin
- unclassified drug
- xanthine derivative
- animal experiment
- area under the curve
- Article
- computer model
- controlled study
- drug bioavailability
- drug design
- drug efficacy
- drug half life
- drug potency
- drug transformation
- glycemic control
- IC50
- in vitro study
- in vivo study
- infant
- male
- maximum plasma concentration
- mean residence time
- metabolic stability
- nonhuman
- priority journal
- rat
- time to maximum plasma concentration
Biuppslag (personer, institutioner, konferenser, titlar ...)
- Dou, W. (författare)
- Li, M. (författare)
- Zhou, Yang,1989-KTH,Teoretisk kemi och biologi(Swepub:kth)u1qoay2o (författare)
- Guo, J. (författare)
- Zhao, N. (författare)
- Huang, H. (författare)
- Zhou, Q. (författare)
- Hu, W. (författare)
- Ma, Y. (författare)
- Zhao, X. (författare)
- Xie, H. (författare)
- KTHTeoretisk kemi och biologi (creator_code:org_t)
Sammanhörande titlar
- Ingår i:ChemMedChem: John Wiley and Sons Ltd15:16, s. 1608-16171860-71791860-7187
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