Sökning: L773:1860 7179
> Ma Y. >
Discovery of an Ora...
Discovery of an Orally Active and Long-Acting DPP-IV Inhibitor through Property-Based Optimization with an in Silico Biotransformation Prediction Tool
-
Zeng, S. (författare)
-
Dou, W. (författare)
-
Li, M. (författare)
-
visa fler...
-
- Zhou, Yang, 1989- (författare)
- KTH,Teoretisk kemi och biologi
-
Guo, J. (författare)
-
Zhao, N. (författare)
-
Huang, H. (författare)
-
Zhou, Q. (författare)
-
Hu, W. (författare)
-
Ma, Y. (författare)
-
Zhao, X. (författare)
-
Xie, H. (författare)
-
visa färre...
-
(creator_code:org_t)
- 2020-07-02
- 2020
- Engelska.
-
Ingår i: ChemMedChem. - : John Wiley and Sons Ltd. - 1860-7179 .- 1860-7187. ; 15:16, s. 1608-1617
- Relaterad länk:
-
https://doi.org/10.1...
-
visa fler...
-
https://urn.kb.se/re...
-
https://doi.org/10.1...
-
visa färre...
Abstract
Ämnesord
Stäng
- 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
- NATURVETENSKAP -- Kemi -- Organisk kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences -- Organic Chemistry (hsv//eng)
Nyckelord
- 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
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
-
Zeng, S.
-
Dou, W.
-
Li, M.
-
Zhou, Yang, 1989 ...
-
Guo, J.
-
Zhao, N.
-
visa fler...
-
Huang, H.
-
Zhou, Q.
-
Hu, W.
-
Ma, Y.
-
Zhao, X.
-
Xie, H.
-
visa färre...
- Om ämnet
-
- NATURVETENSKAP
-
NATURVETENSKAP
-
och Kemi
-
och Organisk kemi
- Artiklar i publikationen
-
ChemMedChem
- Av lärosätet
-
Kungliga Tekniska Högskolan