Discovery of Pyrazolopyridones as a Novel Class of Gyrase B Inhibitors Using Structure Guided Design

被引：36

作者：

Cross, Jason B. ^{[1
]}

Zhang, Jing ^{[1
]}

Yang, Qingyi ^{[1
]}

Mesleh, Michael F. ^{[1
]}

Romero, Jan Antoinette C. ^{[1
]}

Wang, Bin ^{[1
]}

Bevan, Doug ^{[1
]}

Poutsiaka, Katherine M. ^{[1
]}

Epie, Felix ^{[1
]}

Moy, Terence ^{[1
]}

Daniel, Anu ^{[1
]}

Shotwell, Joseph ^{[1
]}

Chamberlain, Brian ^{[1
]}

Carter, Nicole ^{[1
]}

Andersen, Ole ^{[2
]}

Barker, John ^{[2
]}

Ryan, M. Dominic ^{[1
]}

Metcalf, Chester A., III ^{[1
]}

Silverman, Jared ^{[1
]}

Nguyen, Kien ^{[1
]}

Lippa, Blaise ^{[1
]}

Dolle, Roland E. ^{[1
]}

机构：

[1] Cubist Pharmaceut Inc, 65 Hayden Ave, Lexington, MA 02421 USA

[2] Evotec UK Ltd, 114 Innovat Dr,Milton Pk, Abingdon OX14 4RZ, Oxon, England

来源：

ACS MEDICINAL CHEMISTRY LETTERS | 2016年 / 7卷 / 04期

关键词：

Antibacterials; DNA gyrase B; fragment-based drug design; structure-based drug design; DNA GYRASE; ANTIBACTERIAL ACTIVITY; LEAD DISCOVERY; AGENTS; GYRB; OPTIMIZATION; MECHANISM; SCAFFOLD; POTENT;

D O I：

10.1021/acsmedchemlett.5b00368

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The ATPase subunit of DNA gyrase B is an attractive antibacterial target due to high conservation across bacteria and the essential role it plays in DNA replication. A novel class of pyrazolopyridone inhibitors was discovered by optimizing a fragment screening hit scaffold using structure guided design. These inhibitors show potent Gram-positive antibacterial activity and low resistance incidence against clinically important pathogens.

引用

下载

页码：374 / 378

页数：5

共 50 条

[1] Discovery of lndazole Derivatives as a Novel Class of Bacterial Gyrase B Inhibitors
Zhang, Jing
Yang, Qingyi
Romero, Jan Antoinette C.
Cross, Jason
Wang, Bin
Poutsiaka, Katherine M.
Epie, Felix
Bevan, Douglas
Wu, Yuchuan
Moy, Terence
Daniel, Anu
Chamberlain, Brian
Carter, Nicole
Shotwell, Joseph
Arya, Anu
Kumar, Vipul
Silverman, Jared
Kien Nguyen
Metcalf, Chester A., III
Ryan, Dominic
Lippa, Blaise
Dolle, Roland E.
ACS MEDICINAL CHEMISTRY LETTERS, 2015, 6 (10): : 1080 - 1085
[2] Discovery of Azaindole Ureas as a Novel Class of Bacterial Gyrase B Inhibitors
Zhang, Jing
Yang, Qingyi
Cross, Jason B.
Romero, Jan Antoinette C.
Poutsiaka, Katherine M.
Epie, Felix
Bevan, Douglas
Wang, Bin
Zhang, Yanzhi
Chavan, Ajit
Zhang, Xin
Moy, Terence
Daniel, Anu
Kien Nguyen
Chamberlain, Brian
Carter, Nicole
Shotwell, Joseph
Silverman, Jared
Metcalf, Chester A., III
Ryan, Dominic
Lippa, Blaise
Dolle, Roland E.
JOURNAL OF MEDICINAL CHEMISTRY, 2015, 58 (21) : 8503 - 8512
[3] Discovery of pyrazolthiazoles as novel and potent inhibitors of bacterial gyrase
Ronkin, Steven M.
Badia, Michael
Bellon, Steve
Grillot, Anne-Laure
Gross, Christian H.
Grossman, Trudy H.
Mani, Nagraj
Parsons, Jonathan D.
Stamos, Dean
Trudeau, Martin
Wei, Yunyi
Charifson, Paul S.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2010, 20 (09) : 2828 - 2831
[4] Discovery of Novel Mycobacterial DNA Gyrase B Inhibitors: In Silico and In Vitro Biological Evaluation
Saxena, Shalini
Renuka, Janupally
Yogeeswari, Perumal
Sriram, Dharmarajan
MOLECULAR INFORMATICS, 2014, 33 (09) : 597 - 609
[5] Discovery of Novel DNA Gyrase Inhibitors Against Salmonella Typhi using Structure Based Drug Delivery Approach
Kapil, Arti
Sharma, Priyanka
Kaur, Punit
Kumar, Manoj
Dahiya, Sushila
Sood, Seema
Das, Bimal
BIOPHYSICAL JOURNAL, 2020, 118 (03) : 72A - 73A
[6] Mechanism of Action of Mycobacterium tuberculosis Gyrase Inhibitors: A Novel Class of Gyrase Poisons
Gibson, Elizabeth G.
Blower, Tim R.
Cacho, Monica
Bax, Ben
Berger, James M.
Osheroff, Neil
ACS INFECTIOUS DISEASES, 2018, 4 (08): : 1211 - 1222
[7] Biological activities of novel gyrase inhibitors of the aminocoumarin class
Anderle, Christine
Stieger, Martin
Burrell, Matthew
Reinelt, Stefan
Maxwell, Anthony
Page, Malcolm
Heide, Lutz
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2008, 52 (06) : 1982 - 1990
[8] Discovery of Furanoquinone Derivatives as a Novel Class of DNA Polymerase and Gyrase Inhibitors for MRSA Eradication in Cutaneous Infection
Yang, Shih-Chun
Tang, Kai-Wei
Lin, Chih-Hung
Alalaiwe, Ahmed
Tseng, Chih-Hua
Fang, Jia-You
FRONTIERS IN MICROBIOLOGY, 2019, 10
[9] Recent progress in the discovery and development of DNA gyrase B inhibitors
Barancokova, Michaela
Kikelj, Danijel
Ilas, Janez
FUTURE MEDICINAL CHEMISTRY, 2018, 10 (10) : 1207 - 1227
[10] Discovery of Novel Inhibitors of Bacterial DNA Gyrase Using a QSAR-Based Approach
Jakhar, Ritu
Khichi, Alka
Kumar, Dev
Dangi, Mehak
Chhillar, Anil Kumar
ACS OMEGA, 2022, 7 (36): : 32665 - 32678

← 1 2 3 4 5 →