Synthesis and evaluation of thiomannosides, potent and orally active FimH inhibitors

被引：7

作者：

Sattigeri, Jitendra A. ^{[1
]}

Garg, Malvika ^{[1
]}

Bhateja, Pragya ^{[1
]}

Soni, Ajay ^{[1
]}

Rauf, Abdul Rehman Abdul ^{[1
]}

Gupta, Mahendrakumar ^{[1
]}

Deshmukh, Mahesh S. ^{[1
]}

Jain, Tarun ^{[1
]}

Alekar, Nidhi ^{[1
]}

Barman, Tarani Kanta ^{[1
]}

Jha, Paras ^{[1
]}

Chaira, Tridib ^{[1
]}

Bambal, Ramesh B. ^{[1
]}

Upadhyay, Dilip J. ^{[1
]}

Nishi, Takahide ^{[2
]}

机构：

[1] Dauchi Sankyo India Pharma Pvt Ltd, Udyog Vihar Ind Area, Sect 18, Gurugram 122015, Haryana, India

[2] Dauchi Sankyo RD Novare Co Ltd, Edogawa Ku, 1-16-13 Kitakasai, Tokyo 1348630, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2018年 / 28卷 / 17期

关键词：

Thiomannoside; FimH inhibitor; Urinary tract infection; URINARY-TRACT-INFECTIONS; BACTERIAL ADHESIN FIMH; DRUG DISCOVERY; IN-VITRO; ANTAGONISTS; OPTIMIZATION; MANNOSIDES; BINDING; DESIGN;

D O I：

10.1016/j.bmcl.2018.06.017

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

FimH is a type I fimbrial lectin located at the tip of type-1 pili of Gram-negative uropathogenic Escherichia coil (UPEC) guiding its ability to adhere and infect urothelial cells. Accordingly, blocking FimH with small molecule inhibitor is considered as a promising new therapeutic alternative to treat urinary tract infections caused by UPEC. Herein, we report that compounds having the S-glycosidic bond (thiomannosides) had improved metabolic stability and plasma exposures when dosed orally. Especially compound 5h showed the potential to inhibit biofilm formation and also to disrupt the preformed biofilm. And compound 5h showed prophylactic effect in UTI model in mice.

引用

页码：2993 / 2997

页数：5

共 20 条

[1] Non-Antibiotic Prophylaxis for Urinary Tract Infections [J].

Beerepoot, Marielle ;

Geerlings, Suzanne .

PATHOGENS, 2016, 5 (02)

[2] Thiazolylaminomannosides As Potent Antiadhesives of Type 1 Piliated Escherichia coli Isolated from Crohn's Disease Patients [J].

Brument, Sarni ;

Sivignon, Adeline ;

Dumych, Tetiana I. ;

Moreau, Nicolas ;

Roos, Goedele ;

Guerardel, Yann ;

Chalopin, Thibaut ;

Deniaud, David ;

Bilyy, Rostyslav O. ;

Darfeuille-Michaud, Arlette ;

Bouckaert, Julie ;

Gouin, Sebastien G. .

JOURNAL OF MEDICINAL CHEMISTRY, 2013, 56 (13) :5395-5406

[3] Effect of antibiotic prescribing in primary care on antimicrobial resistance in individual patients: systematic review and meta-analysis [J].

Costelloe, Ceire ;

Metcalfe, Chris ;

Lovering, Andrew ;

Mant, David ;

Hay, Alastair D. .

BMJ-BRITISH MEDICAL JOURNAL, 2010, 340 :1120

[4] Lead Optimization Studies on FimH Antagonists: Discovery of Potent and Orally Bioavailable Ortho-Substituted Biphenyl Mannosides [J].

Han, Zhenfu ;

Pinkner, Jerome S. ;

Ford, Bradley ;

Chorell, Erik ;

Crowley, Jan M. ;

Cusumano, Corinne K. ;

Campbell, Scott ;

Henderson, Jeffrey P. ;

Hultgren, Scott J. ;

Janetka, James W. .

JOURNAL OF MEDICINAL CHEMISTRY, 2012, 55 (08) :3945-3959

[5] Structure-Based Drug Design and Optimization of Mannoside Bacterial FimH Antagonists [J].

Han, Zhenfu ;

Pinkner, Jerome S. ;

Ford, Bradley ;

Obermann, Robert ;

Nolan, William ;

Wildman, Scott A. ;

Hobbs, Doug ;

Ellenberger, Tom ;

Cusumano, Corinne K. ;

Hultgren, Scott J. ;

Janetka, James W. .

JOURNAL OF MEDICINAL CHEMISTRY, 2010, 53 (12) :4779-4792

[6] Uncomplicated Urinary Tract Infection [J].

Hooton, Thomas M. .

NEW ENGLAND JOURNAL OF MEDICINE, 2012, 366 (11) :1028-1037

[7] PALLADIUM(O)-CATALYZED CROSS-COUPLING REACTION OF ALKOXYDIBORON WITH HALOARENES - A DIRECT PROCEDURE FOR ARYLBORONIC ESTERS [J].

ISHIYAMA, T ;

MURATA, M ;

MIYAURA, N .

JOURNAL OF ORGANIC CHEMISTRY, 1995, 60 (23) :7508-7510

[8] Antivirulence Isoquinolone Mannosides: Optimization of the Biaryl Aglycone for FimH Lectin Binding Affinity and Efficacy in the Treatment of Chronic UTI [J].

Jarvis, Cassie ;

Han, Zhenfu ;

Kalas, Vasilios ;

Klein, Roger ;

Pinkner, Jerome S. ;

Ford, Bradley ;

Binkley, Jana ;

Cusumano, Corinne K. ;

Cusumano, Zachary ;

Mydock-McGrane, Laurel ;

Hultgren, Scott J. ;

Janetka, James W. .

CHEMMEDCHEM, 2016, 11 (04) :367-373

[9] Antimicrobial Resistance of Escherichia coli Causing Uncomplicated Urinary Tract Infections: A European Update for 2014 and Comparison with 2000 and 2008 [J].

Kahlmeter G. ;

Åhman J. ;

Matuschek E. .

Infectious Diseases and Therapy, 2015, 4 (4) :417-423

[10] FimH Antagonists: Bioisosteres To Improve the in Vitro and in Vivo PK/PD Profile [J].

Kleeb, Simon ;

Pang, Lijuan ;

Mayer, Katharina ;

Eris, Deniz ;

Sigl, Anja ;

Preston, Roland C. ;

Zihlmann, Pascal ;

Sharpe, Timothy ;

Jakob, Roman P. ;

Abgottspon, Daniela ;

Hutter, Aline S. ;

Scharenberg, Meike ;

Jiang, Xiaohua ;

Navarra, Giulio ;

Rabbani, Said ;

Smiesko, Martin ;

Luedin, Nathalie ;

Bezencon, Jacqueline ;

Schwardt, Oliver ;

Maier, Timm ;

Ernst, Beat .

JOURNAL OF MEDICINAL CHEMISTRY, 2015, 58 (05) :2221-2239

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