Discovery of Pyrazolopyrimidine Derivatives as Novel Dual Inhibitors of BTK and PI3Kδ

被引：17

作者：

Pujala, Brahmam ^{[2
]}

Agarwal, Anil K. ^{[2
]}

Middya, Sandip ^{[3
]}

Banerjee, Monali ^{[3
]}

Surya, Arjun ^{[3
]}

Nayak, Anjan K. ^{[2
]}

Gupta, Ashu ^{[2
]}

Khare, Sweta ^{[2
]}

Guguloth, Rambabu ^{[2
]}

Randive, Nitin A. ^{[2
]}

Shinde, Bharat U. ^{[2
]}

Thakur, Anamika ^{[2
]}

Patel, Dhananjay I. ^{[2
]}

Raja, Mohd. ^{[2
]}

Green, Michael J. ^{[1
]}

Alfaro, Jennifer ^{[4
]}

Avila, Patricio ^{[4
]}

Perez de Arce, Felipe ^{[4
,5
]}

Almirez, Ramona G. ^{[1
]}

Kanno, Stacy ^{[1
]}

Bernales, Sebastian ^{[1
]}

Hung, David T. ^{[1
]}

Chakravarty, Sarvajit ^{[1
]}

McCullagh, Emma ^{[1
]}

Quinn, Kevin P. ^{[1
]}

Rai, Roopa ^{[1
]}

Pham, Son M. ^{[1
]}

机构：

[1] Medivation Inc, 525 Market St,36th Floor, San Francisco, CA 94105 USA

[2] Integral BioSci Pvt Ltd, C-64,Hosiery Complex Phase 2 Extens, Noida 201306, Uttar Pradesh, India

[3] Curadev Pvt Ltd, Sect 83, Noida 201305, Uttar Pradesh, India

[4] Fdn Ciencia & Vida, Ave Zanartu 1482, Santiago 7780272, Chile

[5] Univ Andres Bello, Fac Ciencias Biol, Dept Ciencias Biol, Santiago 8370146, Chile

来源：

ACS MEDICINAL CHEMISTRY LETTERS | 2016年 / 7卷 / 12期

关键词：

BTK; PI3K; p110; delta; inhibitor; B-cell; BCR; pyrazolopyrimidine; CHRONIC LYMPHOCYTIC-LEUKEMIA; BRUTONS TYROSINE KINASE; SIGNAL-TRANSDUCTION; TARGETING BTK; IBRUTINIB; CLL; RESISTANCE; MECHANISMS; P110-DELTA; LYMPHOMA;

D O I：

10.1021/acsmedchemlett.6b00356

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The aberrant activation of B-cells has been implicated in several types of cancers and hematological disorders. BTK and PI3K delta are kinases responsible for B-cell signal transduction, and inhibitors of these enzymes have demonstrated clinical benefit in certain types of lymphoma. Simultaneous inhibition of these pathways could result in more robust responses or overcome resistance as observed in single agent use. We report a series of novel compounds that have low nanomolar potency against both BTK and PI3K delta as well as acceptable PK properties that could be useful in the development of treatments against B-cell related diseases.

引用

页码：1161 / 1166

页数：6

共 50 条

[1] Discovery of novel quinazolinone derivatives as high potent and selective PI3Kδ and PI3Kδ/γ inhibitors
Ma, Chen-Chen
Zhang, Cheng-Mei
Tang, Long-Qian
Liu, Zhao-Peng
[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2018, 151 : 9 - 17
[2] Discovery and in Vivo Evaluation of Dual PI3Kβ/δ Inhibitors
de Turiso, Felix Gonzalez-Lopez
Shin, Youngsook
Brown, Matthew
Cardozo, Mario
Chen, Yi
Fong, David
Hao, Xiaolin
He, Xiao
Henne, Kirk
Hu, Yi-Ling
Johnson, Michael G.
Kohn, Todd
Lohman, Julia
McBride, Helen J.
McGee, Lawrence R.
Medina, Julio C.
Metz, Daniela
Miner, Kent
Mohn, Deanna
Pattaropong, Vatee
Seganish, Jennifer
Simard, Jillian L.
Wannberg, Sharon
Whittington, Douglas A.
Yu, Gang
Cushing, Timothy D.
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 2012, 55 (17) : 7667 - 7685
[3] Discovery of novel and potent PARP/PI3K dual inhibitors for the treatment of cancer
Wu, Zhengyang
Bai, Ying
Jin, Jiaming
Jiang, Teng
Shen, Hui
Ju, Qiurong
Zhu, Qihua
Xu, Yungen
[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2021, 217
[4] Discovery of novel quinazoline derivatives as potent PI3Kδ inhibitors with high selectivity
Teng, Yu
Li, Xinyu
Ren, Shengnan
Cheng, Yu
Xi, Kun
Shen, Hongtao
Ma, Wenzhuo
Luo, Guoshun
Xiang, Hua
[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2020, 208
[5] Discovery, Optimization, and Evaluation of Potent and Highly Selective PI3Kγ-PI3Kδ Dual Inhibitors
Jia, Hong
Dai, Guangxiu
Su, Weiguo
Xiao, Kun
Weng, Jianyang
Zhang, Zhulin
Wang, Qing
Yuan, Tianhai
Shi, Fuying
Zhang, Zheng
Chen, Wei
Sai, Yang
Wang, Jian
Li, Xiong
Cai, Yu
Yu, Jun
Ren, Ping
Venable, Jennifer
Rao, Tadimeti
Edwards, James P.
Bembenek, Scott D.
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 2019, 62 (10) : 4936 - 4948
[6] Discovery of fluoroquinolone derivatives as potent, selective inhibitors of PI3Kγ
Sha, Shao
Han, Hong-Wei
Gao, Fei
Liu, Tian-Bao
Li, Zhen
Xu, Chi
Zhong, Wei-Qing
Zhu, Hai-Liang
[J]. MEDCHEMCOMM, 2015, 6 (11) : 2029 - 2035
[7] Discovery of pyrazolopyrimidine derivatives as potent BTK inhibitors with effective anticancer activity in MCL
Ran, Fansheng
Liu, Yang
Liu, Meixia
Zhang, Daoguang
Wang, Peng
Dong, Junze
Tang, Wendi
Zhao, Guisen
[J]. BIOORGANIC CHEMISTRY, 2019, 89
[8] Discovery of a novel aminopyrazine series as selective PI3Kα inhibitors
Barlaam, Bernard
Cosulich, Sabina
Fitzek, Martina
Germain, Herve
Green, Stephen
Hanson, Lyndsey L.
Harris, Craig S.
Hancox, Urs
Hudson, Kevin
Lambert-van der Brempt, Christine
Lamorlette, Maryannick
Magnien, Francoise
Ouvry, Gilles
Page, Ken
Ruston, Linette
Ward, Lara
Delouvrie, Benedicte
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2017, 27 (13) : 3030 - 3035
[9] Discovery of novel class of alpha selective PI3K inhibitors
Garland, Keira
Hanan, Emily
Staben, Steven
Braun, Marie-Gabrielle
Edgar, Kyle
Endres, Nick
Friedman, Lori
Nguyen, Amanda
Pang, Jodie
Purkey, Hans
Salphati, Laurent
Schmidt, Stephen
Song, Kyung
Ultsch, Mark
Jaochico, Allan
Chan, Connie
Eigenbrot, Charles
MacLeod, Calum
Jackson, Philip
Narukulla, Raman
Knight, Jamie
Yeap, Kuen
Messick, Kristen
Valle, Nicole
Heald, Robert
Nannini, Michelle
Hamilton, Pat
Clausen, Saundra
Young, Amy
Sampath, Deepak
Hong, Rebecca
Lee, Man-Ling
Blench, Toby
Elliott, Richard
Lu, Aijun
Gu, Xiao-Hu
Xin, Jianfeng
[J]. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2017, 254
[10] Discovery of novel PI3Kγ/δ inhibitors as potential agents for inflammation
Ellard, Katie
Sunose, Mihiro
Bell, Kathryn
Ramsden, Nigel
Bergamini, Giovanna
Neubauer, Gitte
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2012, 22 (14) : 4546 - 4549

← 1 2 3 4 5 →