180695-85-6Relevant academic research and scientific papers
The optimization of xanthine derivatives leading to HBK001 hydrochloride as a potent dual ligand targeting DPP-IV and GPR119
Li, Gang,Meng, Bingxu,Yuan, Baokun,Huan, Yi,Zhou, Tian,Jiang, Qian,Lei, Lei,Sheng, Li,Wang, Weiping,Gong, Ningbo,Lu, Yang,Ma, Chen,Li, Yan,Shen, Zhufang,Huang, Haihong
, (2020/01/09)
A series of xanthine compounds derived from the previous hit 20i with modification on the terminal side chain was discovered through ring formation strategy. Systematic optimization of the compounds with rigid heterocycles in the hydrophobic side chain led to the new lead compound HBK001 (21h) with the improved DPP-IV inhibition and moderate GPR119 agonism activity in vitro. As a continuing work to further study the PK and PD profiles, 21h and its hydrochloride (22) were synthesized on grams scale and evaluated on the ADME/T and oral glucose tolerance test (OGTT) in ICR mice. Compound 22 showed the improved bioavailability and blood glucose-lowering effect in vivo compared to its free base 21h probably attributed to its improved solubility and permeability. The preliminary toxicity studies on compound 22 exhibited that the result of mini-Ames was negative and the preliminary acute toxicity LD50 in mice was above 1.5 g/kg, while it showed moderate inhibition on hERG channel with IC50 4.9 μM maybe due to its high lipophilicity. These findings will be useful for the future drug design for more potent and safer dual ligand targeting DPP-IV and GPR119 for the treatment of diabetes.
4-Substituted 4-(1H-1,2,3-triazol-1-yl)piperidine: Novel C7 moieties of fluoroquinolones as antibacterial agents
Huang, Xiaoguang,Zhang, Aiqin,Chen, Dongliang,Jia, Zhenhua,Li, Xingshu
experimental part, p. 2859 - 2863 (2010/08/19)
A series of 4-substituted 4-(1H-1,2,3-triazol-1-yl)piperidine building blocks was synthesized and introduced to the C7 position of the quinolone core, 7-chloro-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid, to afford the cor
Regioselective synthesis of [1,2,3]-triazoles catalyzed by Cu(I) generated in situ from Cu(0) nanosize activated powder and amine hydrochloride salts
Orgueira, Hernán A.,Fokas, Demosthenes,Isome, Yuko,Chan, Philip C.-M.,Baldino, Carmen M.
, p. 2911 - 2914 (2007/10/03)
A straightforward and efficient method for the regioselective synthesis of functionalized 1,4-disubstituted [1,2,3]-triazoles, from terminal alkynes and azides, has been established utilizing Cu(0) as the source of the catalytic species. The presumed cata
4-N-linked-heterocyclic piperidine derivatives with high affinity and selectivity for human dopamine D4 receptors
Moore, Kevin W.,Bonner, Katrine,Jones, Elizabeth A.,Emms, Frances,Leeson, Paul D.,Marwood, Rosemary,Patel, Shil,Patel, Smita,Rowley, Michael,Thomas, Steven,Carling, Robert W.
, p. 1285 - 1290 (2007/10/03)
The syntheses of a number of different N-linked heterocyclic pyrazole replacements based on the structure 1 are described (compounds 3-12) as hD4 ligands. After further optimisation the best compound identified was 13 which has high affinity for hD4 (5.2 nM) and >300-fold selectivity for hD4 receptors over hD2 and hD3 receptors.
