Jiangsu Simcere Pharmaceutical Co.

Wuxuan, China

Jiangsu Simcere Pharmaceutical Co.

Wuxuan, China

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Huang W.,Central China Normal University | Huang W.,Jiangsu Simcere Pharmaceutical Co. | Chen Q.,Central China Normal University | Yang W.-C.,Central China Normal University | Yang G.-F.,Central China Normal University
European Journal of Medicinal Chemistry | Year: 2013

As widely occurring natural products, flavonoids are an important source for drug discovery, due to their structural diversity and broad-spectrum biological activity. In this work, a library of novel, thioethersubstituted flavonoids with diverse heterocyclic groups was synthesized via a microwave-assisted procedure with the advantages of good yields, short times, mild conditions and ready isolation of the products. Their antiproliferative activities were evaluated against six cancer cell lines, HCCLM-7, Hela, MDA-MB-435S, SW-480, Hep-2, and MCF-7 by the MTT-based assay. Compared with the positive control 5-fluorouracil, three compounds, 6a, 6b and 6j were successfully identified as the most promising candidates, due to their higher potency and broad-spectrum bioactivity with IC50 values in the range of 0.43 μM-6.7 μM. © 2013 Elsevier Masson SAS. All rights reserved.


PubMed | Jiangsu Simcere Pharmaceutical Co., Xi'an Jiaotong University, Central China Normal University and China Pharmaceutical University
Type: Journal Article | Journal: Bioorganic & medicinal chemistry | Year: 2015

A series of novel 7-substituted 3-(4-phenoxyphenyl)thieno[3,2-c]pyridin-4-amines as potent BTK inhibitors were designed, synthesized and evaluated. These thieno[3,2-c]pyridin-4-amine derivatives displayed variant inhibitory activities against BTK in vitro. Among these, 7-pyrazol-4-yl substituted 3-(4-phenoxyphenyl)thieno[3,2-c]pyridin-4-amine subseries showed high BTK inhibition and several compounds displayed superior BTK inhibitory activity. Comprehensive SAR was disclosed and compound 13b showed excellent potency (IC=11.8 nM), outstanding hydrophilicity (AlogP=3.53), and relatively good kinase selectivity, being a promising lead for further evaluation.


PubMed | Jiangsu Simcere Pharmaceutical Co., Xi'an Jiaotong University, Central China Normal University and China Pharmaceutical University
Type: Journal Article | Journal: Bioorganic & medicinal chemistry | Year: 2015

A novel series of BTK inhibitors bearing thieno[3,2-c]pyridin-4-amine framework as the core scaffold were designed, synthesized and well characterized. In this paper, twenty one compounds displayed variant inhibitory activities against BTK in vitro, and compound 14 g showed the most potent inhibitory activity against BTK enzyme, with the IC50 value of 12.8 nM. Moreover, compounds 14 g displayed relatively good kinase selectivity and was subsequently evaluated in vivo for profiling its PK properties. This work identified the thieno[3,2-c]pyridin-4-amine derivatives as novel BTK inhibitors and verified the value of thieno[3,2-c]pyridin-4-amine scaffold in drug design.


PubMed | Jiangsu Simcere Pharmaceutical Co., Xi'an Jiaotong University, Central China Normal University and China Pharmaceutical University
Type: Journal Article | Journal: Bioorganic & medicinal chemistry | Year: 2015

A series of novel reversible Btk inhibitors has been designed based on the structure of the recently reported preclinical drug RN486. The synthesis and SAR of these compounds are described. Among these derivatives, compound 16b was identified to be a potent and orally available reversible agent with satisfactory Btk enzymatic and cellular inhibition in vitro, as well as favorable PK properties and inhibition of arthritis in vivo.


PubMed | Jiangsu Simcere Pharmaceutical Co., Xi'an Jiaotong University and Central China Normal University
Type: Journal Article | Journal: Bioorganic & medicinal chemistry | Year: 2016

Janus kinases inhibitor is considered to have therapeutic potential for the treatment of oncology and immune-inflammatory diseases. Two series of 4-(2-benzofuranyl)pyrimidin-2-amine and 4-(4,5,6,7-tetrahydrofuro[3,2-c]pyridin-2-yl)pyrimidin-2-amine derivatives have been designed and synthesized. Primary SAR studies resulted in the discovery of a novel class of 4,5,6,7-tetrahydrofuro[3,2-c]pyridine based JAK2 inhibitors with higher potency (IC


Xin M.,Xi'an Jiaotong University | Xin M.,Jiangsu Simcere Pharmaceutical Co. | Wen J.,Jiangsu Simcere Pharmaceutical Co. | Tang F.,Jiangsu Simcere Pharmaceutical Co. | And 7 more authors.
Bioorganic and Medicinal Chemistry Letters | Year: 2014

A novel series of hedgehog signaling pathway inhibitors has been designed based on the 4-(2-pyrimidinylamino) benzamides scaffold. The synthesis and SAR of these compounds are described. Optimization leads to the identification of compound 3c, a potent and orally available agent with improved physicochemical and pharmacokinetic properties. © 2014 Elsevier Ltd. All rights reserved.


PubMed | Jiangsu Simcere Pharmaceutical Co. and Xi'an Jiaotong University
Type: | Journal: European journal of medicinal chemistry | Year: 2016

A series of novel hedgehog signaling pathway inhibitors have been designed by structural modification based on the former reported scaffold of 4-(2-pyrimidinylamino)benzamide. The SAR for this series was described and many derivatives showed potent inhibitory activity. Among these compounds, compounds 12af and 12bf were identified to have high potency and optimal PK profiles. Although both of compounds 12af and 12bf did not show strong antitumor efficacy in LS-174T nude mice model, they were promising candidates as Hh signaling inhibitors due to great potency against Hh signaling pathway and outstanding PK properties, deserving further evaluation in other Hh signaling operative tumor models.


PubMed | Jiangsu Simcere Pharmaceutical Co. and Xi'an Jiaotong University
Type: Journal Article | Journal: Bioorganic & medicinal chemistry | Year: 2016

In present study, a series of novel containing trifluoromethyl 4-(2-pyrimidinylamino)benzamide derivatives were designed by the fluorine scan strategy. Their Hh signaling inhibitory activities were evaluated by Gli-luciferase reporter method. The comprehensive SAR was discussed and several derivatives were found to display more potent Hh signaling inhibitory activity than positive drug vismodegib. Compound 13d was the most potent compound with IC50 of 1.44nM against Hh signaling pathway and also exhibited optimal PK properties in the in vivo PK properties study, deserved as an ideal lead compound for further study in future.


Xin M.,Jiangsu Simcere Pharmaceutical Co. | Wen J.,Jiangsu Simcere Pharmaceutical Co. | Tang F.,Jiangsu Simcere Pharmaceutical Co. | Tu C.,Jiangsu Simcere Pharmaceutical Co. | And 2 more authors.
Bioorganic and Medicinal Chemistry Letters | Year: 2013

Hedgehog signaling pathway inhibitors are emerging as new therapeutic intervention against cancer. A novel series of N-(2-pyrimidinylamino) benzamide derivatives as hedgehog signaling pathway inhibitors were designed and synthesized. Most compounds presented significant inhibitory effect on hedgehog signaling pathway, among which 21 compounds exhibited more potent than vismodegib. Furthermore, compound 6a showed moderate pharmacokinetic properties in vivo, representing a promising lead compound for further exploration. © 2013 Elsevier Ltd. All rights reserved.


PubMed | Jiangsu Simcere Pharmaceutical Co. and China Pharmaceutical University
Type: | Journal: Journal of pharmaceutical and biomedical analysis | Year: 2016

Stress testing was carried out under acidic, alkaline, oxidative, thermal and photolytic conditions to evaluate the intrinsic stability of posaconazole injection. A total of four degradation products were detected and the drug was found to be susceptible to oxidative and thermal degradations. Three unknown degradants formed under oxidative stress condition were isolated by preparative HPLC and unambiguously elucidated by LC-TOF/MS, LC-MS/MS, (1)H NMR, (13)C NMR and 2D NMR techniques. Based on the spectrometric and spectroscopic information, these novel degradation products were unequivocally assigned as the N-oxides of posaconazole. Probable mechanisms for the formation of the degradants were proposed. A new and selective HPLC method was developed and validated to separate, detect and quantify all the degradants in posaconazole injection.

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