Ze-mei Ge

Find an error

Name:

Organization: Peking University

Department: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences

Title:

TOPICS

Organic Chemistry

allene

Chemicals
References

Urea-containing peptide boronic acids as potent proteasome inhibitors

Co-reporter:Li-Qiang Han, Xia Yuan, Xing-Yu Wu, Ri-Dong Li, Bo Xu, Qing Cheng, Zhen-Ming Liu, Tian-Yan Zhou, Hao-Yun An, Xin Wang, Tie-Ming Cheng, Ze-Mei Ge, Jing-Rong Cui, Run-Tao Li

European Journal of Medicinal Chemistry 2017 Volume 125() pp:925-939

Publication Date(Web):5 January 2017

DOI:10.1016/j.ejmech.2016.10.023

•Two series of novel urea-containing peptide boronic acids were designed and synthesized as proteasome inhibitors.•The SAR was investigated and one of the two series showed impressive anti-proteasome and anti-tumor activities.•More human tumor cell lines were tested and compound I-14 was selected to evaluate its anticancer activity in vivo.•Compound I-14 showed obvious in vivo anticancer activity with much lower toxicity comparing to Bortezomib.A novel class of urea-containing peptide boronic acids as proteasome inhibitors was designed by introducing a urea scaffold to replace an amido bond. Compounds were synthesized and their antitumor activities were evaluated. After two rounds of optimizations, the compound I-14 was found to be a potent proteasome inhibitor. Compared with Bortezomib, I-14 showed higher potency against the chymotrypsin-like activity of human 20S proteasome (IC50 < 1 pM), similar potency against four different cancer cell lines (IC50 < 10 nM), and better pharmacokinetic profile. Furthermore, I-14 significantly inhibited tumor growth in Bel7404 mouse xenograft model. The excellent proteasome inhibition by I-14 was rationalized through docking and molecular dynamics studies.

Discovery of novel heteroarylmethylcarbamodithioates as potent anticancer agents: Synthesis, structure-activity relationship analysis and biological evaluation

Co-reporter:Ying-Bo Li, Xu Yan, Ri-Dong Li, Peng Liu, Shao-Qian Sun, Xin Wang, Jing-Rong Cui, De-Min Zhou, Ze-Mei Ge, Run-Tao Li

European Journal of Medicinal Chemistry 2016 Volume 112() pp:217-230

Publication Date(Web):13 April 2016

DOI:10.1016/j.ejmech.2016.02.015

•A series of novel dithiocarbamates were synthesized as potential anti-cancer agents.•The structure-activity relationship was investigated.•Most compounds showed significant antiproliferative activity.•Compound 17o showed obvious selectivity against human tumour cells and non-tumor cells.A series of new analogs based on the structure of lead compound 10 were designed, synthesized and evaluated for their in vitro anti-cancer activities against four selected human cancer cell lines (HL-60, Bel-7402, SK-BR-3 and MDA-MB-468). Several synthesized compounds exhibited improved anti-cancer activities comparing with lead compound 10. Among them, 1,3,4-oxadiazole analogs 17o showed highest bioactivity with IC50 values of 1.23, 0.58 and 4.29 μM against Bel-7402, SK-BR-3 and MDA-MB-468 cells, respectively. It is noteworthy that 17o has potent anti-proliferation activity toward a panel of cancer cells with relatively less cytotoxicity to nonmalignant cells. The further mechanistic study showed that it induced apoptosis and cell cycle arrest through disrupting spindle assembly in mitotic progression, indicating these synthesized dithiocarbamates represented a novel series of anti-cancer compounds targeting mitosis.

An efficient synthesis of 2-thio-5-amino substituted benzoquinones via KI catalyzed cascade oxidation/Michael addition/oxidation starting from hydroquinone

Co-reporter:Yihuan Lu, Yuqiong Zhao, Shucheng Wang, Xin Wang, Zemei Ge and Runtao Li

RSC Advances 2016 vol. 6(Issue 14) pp:11378-11381

Publication Date(Web):22 Jan 2016

DOI:10.1039/C5RA26524J

A simple and efficient synthesis of 2-thio-5-amino substituted benzoquinones via KI catalyzed cascade oxidation/S-Michael addition/oxidation/N-Michael addition/oxidation starting from hydroquinone, amines and S-alkylisothiouronium salts was described. Various 2-thio-5-amino substituted benzoquinones were obtained by this method in moderate to good yields. The use of S-alkylisothiouronium salts as thiol equivalents is more convenient and environmental friendly.

Efficient synthesis of organic sulfonic acid derivatives containing dithiocarbamate side chains

Co-reporter:Bowen Li, Shuo Zhou, Shucheng Wang, Xingyi Sun, Zemei Ge, Runtao Li

Tetrahedron 2016 Volume 72(27–28) pp:3885-3889

Publication Date(Web):7 July 2016

DOI:10.1016/j.tet.2016.05.011

An efficient method for the synthesis of organic sulfonic acid potassiums containing dithiocarbamate side chains was developed through the reaction of amines, carbon disulfide and sultones in the presence of K3PO4 in water at room temperature. The organic sulfonic acid potassium derivatives are easily transformed into the corresponding organic sulfonic acids, which were further reacted with amines to afford the important organic sulfonamides containing dithiocarbamate side chains.

Efficient and regioselective one-pot synthesis of S-vinyl dithiocarbamates from electron-deficient allenes, amines and CS2

Co-reporter:Ridong Li, Penglin Leng, Bin Liu, Xin Wang, Zemei Ge, Runtao Li

Tetrahedron 2016 Volume 72(Issue 37) pp:5707-5712

Publication Date(Web):15 September 2016

DOI:10.1016/j.tet.2016.07.075

A novel and efficient one-pot procedure for the synthesis of S-vinyl dithiocarbamates from electron-deficient allenes, amines and CS2 was presented. The reactions proceed at room temperature for 10–30 min without any catalyst to afford the products in high yields, excellent regioselectivity and stereoselectivity.

Discovery and optimization of novel dual dithiocarbamates as potent anticancer agents

Co-reporter:Ri-Dong Li, Hui-Ling Wang, Ying-Bo Li, Zhong-Qing Wang, Xin Wang, Yi-Tao Wang, Ze-Mei Ge, Run-Tao Li

European Journal of Medicinal Chemistry 2015 Volume 93() pp:381-391

Publication Date(Web):26 March 2015

DOI:10.1016/j.ejmech.2015.02.030

•A series of dual dithiocarbamates were synthesized.•Most compounds showed significant antiproliferative activities against H460.•Compound 14m exhibited potent activity against nine types of tumor cells.•Compound 14m showed excellent antitumor potency in vitro against HepG2 and MCF-7.A series of dual dithiocarbamates were synthesized and evaluated for their in-vitro anticancer activities on human non-small cell lung cancer cell line H460. Nine compounds exhibited significant antiproliferative activities with IC50 less than 1 μM. Among them, compound 14m showed the highest inhibitory activity against H460 cell and inhibited the growth of nine types of tumor cells with IC50 values less than 1 μM. It also achieved IC50 of 54 nM and 23 nM against HepG2 and MCF-7 cell lines, respectively. Preliminary structure–activity relationship study indicated that: a) when the methyl group (region A) is substituted with benzene rings, ortho substitution on the benzene ring is favored for activity; b) substitution with heterocyclic structures at region A exhibited greater impact on the anti-tumor activity of compounds, in which pyridine ring, thiazole ring, coumarin and benzo[b]thiophene are favored and quinoline ring is the most favored; c) substitution with different amines (region B) also showed marked effect on the activity of compounds and dimethylamine and morpholine are preferred to other tested amines.

Iodine–triphenylphosphine mediated sulfenylation of imidazoheterocycles with sodium sulfinates

Co-reporter:Xuhu Huang, Shucheng Wang, Bowen Li, Xin Wang, Zemei Ge and Runtao Li

RSC Advances 2015 vol. 5(Issue 29) pp:22654-22657

Publication Date(Web):23 Feb 2015

DOI:10.1039/C4RA17237J

An efficient approach to sulfenyl imidazoheterocycles has been developed via iodine–triphenylphosphine mediated direct sulfenylation of imidazoheterocycles with sodium sulfinates. The reactions proceed smoothly under transition-metal-free conditions with a broad range of substrate scope, giving the desired products in moderate to excellent yields.

A convenient four-component one-pot synthesis of 2-amino-1,3,4-thiadiazoles in water

Co-reporter:Peng Liu;Ao-Ze Su;Yuan-Qiang Wang;Tie-Ming Cheng

Molecular Diversity 2014 Volume 18( Issue 4) pp:737-743

Publication Date(Web):2014 November

DOI:10.1007/s11030-014-9526-6

A novel four-component one-pot approach for the synthesis of 2-amino-1,3,4-thiadiazoles from primary amines, carbon disulfide, hydrazine, and acyl chlorides has been developed. A series of 5-substituted-2-amino-1,3,4-thiadiazoles were synthesized in medium-to-good yields utilizing this newly developed method.

Novel atom-economic reaction: comprehensive utilization of S-alkylisothiouronium salt in the synthesis of thioethers and guanidinium salts

Co-reporter:Pengchao Gao, Penglin Leng, Qi Sun, Xin Wang, Zemei Ge and Runtao Li

RSC Advances 2013 vol. 3(Issue 38) pp:17150-17155

Publication Date(Web):17 Jul 2013

DOI:10.1039/C3RA42503G

A novel atom-economic three-component one-pot reaction of a primary amine, an S-alkylisothiouronium salt and a Michael receptor is reported, which affords a guanidinium salt and thioether simultaneously. The guanidine moiety is involved in catalyzing the conjugated Michael addition of the mercaptan. The reaction proceeds under ambient conditions using a non-toxic EtOH–H2O mixture as the solvent, and the two products can be very easily purified. Complete atom economy is achieved by fully utilizing the S-alkylisothiouronium salt and converting the previously wasted mercaptan by-product into the valuable thioether.

Novel Dithiocarbamic Acid Esters Derived from 6-Aminomethyl-4-anilinoquinazolines and 6-Aminomethyl-4-anilino-3-cyanoquinolines as Potent EGFR Inhibitors

Co-reporter:Xin Zhang;Ridong Li;Kang Qiao;Zemei Ge;Liangren Zhang;Tieming Cheng;Runtao Li

Archiv der Pharmazie 2013 Volume 346( Issue 1) pp:44-52

Publication Date(Web):

DOI:10.1002/ardp.201200267

Abstract

Two series of dithiocarbamic acid esters, 4-anilinoquinazoline-6-ylmethylcarbamodithioic acid esters and 3-cyano-4-anilinoquinolin-6-ylmethylcarbamodithioic acid esters, were designed and synthesized. The effect of the synthesized compounds on cell proliferation was evaluated by MTT assay against three human cancer cell lines: MDA-MB-468, SK-BR-3 and HCT-116. Most of the compounds are equally or more potent than the positive control lapatinib. Three compounds (14d, 14h and 14i) were identified as dual inhibitors of the EGFR and ErbB-2 kinases and two compounds (14b and 14c) were identified as multi-target kinase inhibitors, and they are very worthy of further study. Installation of the dithiocarbamic acid ester group at the 6-position of 4-anilinoquinazoline or 3-cyano-4-anilinoquinoline could improve the inhibitory activity. Different dithiocarbamic acid ester groups significantly affect the activities.

Efficient direct asymmetric vinylogous Michael addition reactions of γ-butenolides to chalcones catalyzed by vicinal primary-diamine salts

Co-reporter:Junfeng Wang, Chao Qi, Zemei Ge, Tieming Cheng and Runtao Li

Chemical Communications 2010 vol. 46(Issue 12) pp:2124-2126

Publication Date(Web):19 Feb 2010

DOI:10.1039/B923925A

The first direct organocatalytic asymmetric vinylogous Michael addition reactions of γ-butenolides to chalcones have been developed by using chiral 1,2-diaminocyclohexane as a novel organocatalyst via a di-iminium transition state to provide syn-Michael products with good yields, high diastereoselectivities and enantioselectivities (up to 78% yield, >99:1 dr and 96% ee).

Highly enantioselective Michael addition of cyclopentanone with chalcones via novel di-iminium mechanism

Co-reporter:Junfeng Wang, Xin Wang, Zemei Ge, Tieming Cheng and Runtao Li

Chemical Communications 2010 vol. 46(Issue 10) pp:1751-1753

Publication Date(Web):12 Jan 2010

DOI:10.1039/B915852A

The highly efficient asymmetric Michael addition reactions of cyclopentanone with chalcones were catalyzed by a simple and commercially available chiral 1,2-diaminocyclohexane-hexanedioic acid, and exhibited good yields (up to 92%) and excellent enantioselectivities (up to 99% ee). A new di-iminium mechanism for the reaction was proposed.

Primary 1,2-diamine catalysis III: an unexpected domino reaction for the synthesis of multisubstituted cyclohexa-1,3-dienamines

Co-reporter:Junfeng Wang, Qin Li, Chao Qi, Yi Liu, Zemei Ge and Runtao Li

Organic & Biomolecular Chemistry 2010 vol. 8(Issue 19) pp:4240-4242

Publication Date(Web):09 Aug 2010

DOI:10.1039/C0OB00089B

The first organocatalyzed multicomponent domino reactions of aryl ketones, aldehydes and malononitrile were carried out successfully to afford multisubstituted cyclohexa-1,3-dienamines in satisfactory yields.

An efficient dipeptide-catalyzed direct asymmetric aldol reaction of equimolar reactants in solid media

Co-reporter:Meng Lei;Shuai Xia;Junfeng Wang;Zemei Ge;Tieming Cheng ;Runtao Li

Chirality 2010 Volume 22( Issue 6) pp:580-586

Publication Date(Web):

DOI:10.1002/chir.20783

Abstract

The direct asymmetric aldol reactions of equivalent molar amounts of aldehydes and ketones were carried out at −20 °C over alkaline Al₂O₃ with 20 mol % of Pro-Trp as catalyst and 20 mol % of N-methylmorpholine or 1,4-diazabicyclo[2.2.2]octane as additive. After simple and environmentally friendly work-up, moderate to high isolated yields (up to 95%), good diastereoselectivities (>99:1), and enantioselectivities (up to 98% ee) have been achieved for the reactions of different kinds of ketones with various aldehydes. The catalytic system could be reused without decrease of activity by addition of 10 mol % catalyst and base in the catalytic system. Chirality 2010. © 2009 Wiley-Liss, Inc.

Synthesis of -Hydroxy Sulfides via Thiolysis of Epoxides Using S-Alkylisothiouronium Salts as Thiol Equivalents in Basic Aqueous Medium

Co-reporter:Jirang ZHU;Ridong LI;Zemei GE;Tieming CHENG ;Runtao LI

Chinese Journal of Chemistry 2009 Volume 27( Issue 4) pp:791-796

Publication Date(Web):

DOI:10.1002/cjoc.200990132

Abstract

S-Alkylisothiouronium salt as a nontoxic, odorless and simply operational alternative of thiol was reacted with different kinds of epoxides in basic aqueous medium at room temperature affording the β-hydroxy sulfides with high regioselectivity in excellent yields.

Novel class of cyclophosphamide prodrug: Cyclophosphamide spiropiperaziniums (CPSP)

Co-reporter:Qi Sun, Run-Tao Li, Wei Guo, Jing-Rong Cui, Tie-Ming Cheng, Ze-Mei Ge

Bioorganic & Medicinal Chemistry Letters 2006 Volume 16(Issue 14) pp:3727-3730

Publication Date(Web):15 July 2006

DOI:10.1016/j.bmcl.2006.04.049

A novel class of cyclophosphamide spiropiperaziniums was synthesized and evaluated for their in vivo anti-cancer activities against S180 and H22. Most of them exhibited definite activities. Especially, compounds 8b and 8k showed good anti-cancer activities, meanwhile, 8k also showed much lower toxicity than CP. Several interesting structure–activity relationships were revealed.

Highly enantioselective Michael addition of cyclopentanone with chalcones via novel di-iminium mechanism

Co-reporter:Junfeng Wang, Xin Wang, Zemei Ge, Tieming Cheng and Runtao Li

Chemical Communications 2010 - vol. 46(Issue 10) pp:NaN1753-1753

Publication Date(Web):2010/01/12

DOI:10.1039/B915852A

Primary 1,2-diamine catalysis III: an unexpected domino reaction for the synthesis of multisubstituted cyclohexa-1,3-dienamines

Co-reporter:Junfeng Wang, Qin Li, Chao Qi, Yi Liu, Zemei Ge and Runtao Li

Organic & Biomolecular Chemistry 2010 - vol. 8(Issue 19) pp:NaN4242-4242

Publication Date(Web):2010/08/09

DOI:10.1039/C0OB00089B

Efficient direct asymmetric vinylogous Michael addition reactions of γ-butenolides to chalcones catalyzed by vicinal primary-diamine salts

Co-reporter:Junfeng Wang, Chao Qi, Zemei Ge, Tieming Cheng and Runtao Li