Abstract
A series of benzamide derivatives were assembled by using the privileged-fragment-merging (PFM) strategy and their SAR studies as glucokinase activators were described. Compounds 5 and 16b were identified having a suitable balance of potency and activation profile. They showed EC 50 values of 28.3 and 44.8 nM, and activation folds of 2.4 and 2.2, respectively. However, both compounds displayed a minor reduction in plasma glucose levels on imprinting control region (ICR) mice. Unfavorable pharmacokinetic profiles (PK) were also observed on these two compounds.
Original language | English (US) |
---|---|
Pages (from-to) | 2982-2991 |
Number of pages | 10 |
Journal | Bioorganic and Medicinal Chemistry |
Volume | 20 |
Issue number | 9 |
DOIs | |
State | Published - May 1 2012 |
Externally published | Yes |
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Keywords
- Aminothiazole
- Benzamide derivatives
- Glucokinase activator
- Privileged-fragment-merging
- Type 2 diabetes (T2D)
ASJC Scopus subject areas
- Pharmaceutical Science
- Drug Discovery
- Organic Chemistry
- Molecular Medicine
- Molecular Biology
- Clinical Biochemistry
- Biochemistry
Cite this
Design, synthesis, and pharmacological evaluation of benzamide derivatives as glucokinase activators. / Mao, Weiwei; Ning, Mengmeng; Liu, Zhiqing; Zhu, Qingzhang; Leng, Ying; Zhang, Ao.
In: Bioorganic and Medicinal Chemistry, Vol. 20, No. 9, 01.05.2012, p. 2982-2991.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Design, synthesis, and pharmacological evaluation of benzamide derivatives as glucokinase activators
AU - Mao, Weiwei
AU - Ning, Mengmeng
AU - Liu, Zhiqing
AU - Zhu, Qingzhang
AU - Leng, Ying
AU - Zhang, Ao
PY - 2012/5/1
Y1 - 2012/5/1
N2 - A series of benzamide derivatives were assembled by using the privileged-fragment-merging (PFM) strategy and their SAR studies as glucokinase activators were described. Compounds 5 and 16b were identified having a suitable balance of potency and activation profile. They showed EC 50 values of 28.3 and 44.8 nM, and activation folds of 2.4 and 2.2, respectively. However, both compounds displayed a minor reduction in plasma glucose levels on imprinting control region (ICR) mice. Unfavorable pharmacokinetic profiles (PK) were also observed on these two compounds.
AB - A series of benzamide derivatives were assembled by using the privileged-fragment-merging (PFM) strategy and their SAR studies as glucokinase activators were described. Compounds 5 and 16b were identified having a suitable balance of potency and activation profile. They showed EC 50 values of 28.3 and 44.8 nM, and activation folds of 2.4 and 2.2, respectively. However, both compounds displayed a minor reduction in plasma glucose levels on imprinting control region (ICR) mice. Unfavorable pharmacokinetic profiles (PK) were also observed on these two compounds.
KW - Aminothiazole
KW - Benzamide derivatives
KW - Glucokinase activator
KW - Privileged-fragment-merging
KW - Type 2 diabetes (T2D)
UR - http://www.scopus.com/inward/record.url?scp=84862819984&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84862819984&partnerID=8YFLogxK
U2 - 10.1016/j.bmc.2012.03.008
DO - 10.1016/j.bmc.2012.03.008
M3 - Article
C2 - 22459213
AN - SCOPUS:84862819984
VL - 20
SP - 2982
EP - 2991
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
SN - 0968-0896
IS - 9
ER -