Discovery of a Highly Potent, Orally Active Mitosis/Angiogenesis Inhibitor R1530 for the Treatment of Solid Tumors

被引：20

作者：

Liu, Jin-Jun ^{[1
]}

Higgins, Brian ^{[2
]}

Ju, Grace ^{[2
]}

Kolinsky, Kenneth ^{[2
]}

Luk, Kin-Chun ^{[1
]}

Packman, Kathryn ^{[2
]}

Pizzolato, Giacomo ^{[1
]}

Ren, Yi ^{[3
]}

Thakkar, Kshitij ^{[1
]}

Tovar, Christian ^{[2
]}

Zhang, Zhuming ^{[1
]}

Woykulich, Peter M. ^{[1
]}

机构：

[1] Hoffmann La Roche Inc, Discovery Chem, Nutley, NJ 07110 USA

[2] Hoffmann La Roche Inc, Discovery Oncol, Nutley, NJ 07110 USA

[3] Hoffmann La Roche Inc, Chem Synth, Nutley, NJ 07110 USA

来源：

ACS MEDICINAL CHEMISTRY LETTERS | 2013年 / 4卷 / 02期

关键词：

pyrazolobenzodiazepines; mitosis/angiogenesis inhibitor; antitumor effect; VGFr-2; FGFr and PDGFr-beta; ORTHO-SUBSTITUTION-REACTION; ORGANIC-SYNTHESIS; ANGIOGENESIS; CANCER; AMINOHALOBORANE; COMBINATION; THERAPY;

D O I：

10.1021/ml300351e

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A new series of 7,8-disubstituted pyrazolobenzodiazepines based on the lead compound 1 have been synthesized and evaluated for their effects on mitosis and angiogenesis. Described herein is the design, synthesis, SAR, and antitumor activity of these compounds leading to the identification of R1530, which was selected for clinical evaluation.

引用

页码：259 / 263

页数：5

共 50 条

[41] SB930: A potent and orally active HDAC inhibitor for the treatment of hemaiological malignancies
Sangthongpitag, Kanda
Stunkel, Walter
Bonday, Zahid Q.
Goh, Kee C.
Wang, Xukun
Wu, Xiaofeng
Hu, Changyong
Wang, Haishan
Yu, Niefang
Sun, Eric
Entzeroth, Michael
Kantharaj, Ethirajulu
Chen, Chien-Shing
Wood, Jeanette M.
BLOOD, 2007, 110 (11) : 479A - 479A
[42] Discovery of a Highly Potent Lysine Methyltransferases G9a/NSD2 Dual Inhibitor to Treat Solid Tumors
Yang, Chunju
Li, Bang
Feng, Zongbo
Li, Huaxuan
Yang, Hong
Yang, Zhenjiao
Liu, Li
Shi, Qiongyu
Wang, Hong
Chen, Zhong-Zhu
Huang, Xun
Wang, Junjian
Wang, Yuanxiang
JOURNAL OF MEDICINAL CHEMISTRY, 2024, 67 (18) : 16072 - 16087
[43] Dasatinib: A potent SRC inhibitor in clinical development for the treatment of solid tumors
Araujo, John
Logothetis, Christopher
CANCER TREATMENT REVIEWS, 2010, 36 (06) : 492 - 500
[44] Discovery of LY444711: A novel, highly potent, and orally active growth hormone secretagogue.
Lugar, CW
Dodge, JA
Adrian, MD
Alt, CA
Bryant, HU
Clay, MP
Cohen, DM
Fahey, KJ
Heiman, ML
Jones, SA
Jungheim, LN
Muehl, BS
Osborne, JJ
Palkowitz, AD
Rhodes, GA
Robey, RL
Thrasher, KJ
Shepherd, TA
Short, LL
Surface, PL
Seyler, DE
Lindstrom, TD
ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 1999, 218 : U956 - U956
[45] THE DISCOVERY OF L-749,329, A HIGHLY POTENT, ORALLY-ACTIVE ANTAGONIST OF ENDOTHELIN RECEPTORS
WALSH, TF
FITCH, KJ
CHAKRAVARTY, PK
WILLIAMS, DL
MURPHY, KA
NOLAN, NA
OBRIEN, JA
LIS, EV
PETTIBONE, DJ
KIVLIGHN, SD
GABEL, RA
ZINGARO, GJ
KRAUSE, SM
SIEGL, PKS
CLINESCHMIDT, BV
GREENLEE, WJ
ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 1994, 208 : 145 - MEDI
[46] Discovery of Imidazoisoindole Derivatives as Highly Potent and Orally Active Indoleamine-2,3-dioxygenase Inhibitors
Tu, Wangyang
Yang, Fanglong
Xu, Guoji
Chi, Jiangtao
Liu, Zhiwei
Peng, Wei
Hu, Bing
Zhang, Lei
Wan, Hong
Yu, Nan
Jin, Fangfang
Hu, Qiyue
Zhang, Lianshan
He, Feng
Tao, Weikang
ACS MEDICINAL CHEMISTRY LETTERS, 2019, 10 (06): : 949 - 953
[47] Discovery of OAT-1441: Highly active, selective, and orally bioavailable inhibitor of human AMCase
Andryianau, Gleb
Kowalski, Michal
Piotrowicz, Michal
Dymek, Barbara
Salamon, Magdalena
Zagozdzon, Agnieszka
Rymaszewska, Aleksandra
Mazurkiewicz, Marcin
Klossowski, Szymon
Sklepkiewicz, Piotr
Mazur, Marzena
Olejniczak, Sylwia
Koralewski, Robert
Matyszewski, Krzysztof
Borek, Bartlomiej
Czestkowski, Wojciech
Niedziejko, Piotr
Bartoszewicz, Agnieszka
Pluta, Elzbieta
Gruza, Mariusz
Dzwonek, Karolina
Stefaniak, Filip
Olczak, Jacek
Golebiowski, Adam
ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2019, 258
[48] Discovery and preclinical profile of saxagliptin (BMS-477118): A highly potent, long-acting, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes
Augeri, DJ
Robl, JA
Betebenner, DA
Magnin, DR
Khanna, A
Robertson, JG
Wang, AY
Simpkins, LM
Taunk, P
Huang, Q
Han, SP
Abboa-Offei, B
Cap, M
Xin, L
Tao, L
Tozzo, E
Welzel, GE
Egan, DM
Marcinkeviciene, J
Chang, SY
Biller, SA
Kirby, MS
Parker, RA
Hamann, LG
JOURNAL OF MEDICINAL CHEMISTRY, 2005, 48 (15) : 5025 - 5037
[49] Discovery of Clinical Candidate BMS-906024: A Potent Pan-Notch Inhibitor for the Treatment of Leukemia and Solid Tumors
Gavai, Ashvinikumar V.
Quesnelle, Claude
Norris, Derek
Han, Wen-Ching
Gill, Patrice
Shan, Weifang
Balog, Aaron
Chen, Ke
Tebben, Andrew
Rampulla, Richard
Wu, Dauh-Rurng
Zhang, Yingru
Mathur, Arvind
White, Ronald
Rose, Anne
Wang, Haiqing
Yang, Zheng
Ranasinghe, Asoka
D'Arienzo, Celia
Guarino, Victor
Xiao, Lan
Su, Ching
Everlof, Gerry
Arora, Vinod
Shen, Ding Ren
Cvijic, Mary Ellen
Menard, Krista
Wen, Mei-Li
Meredith, Jere
Trainor, George
Lombardo, Louis J.
Olson, Richard
Baran, Phil S.
Hunt, John T.
Vite, Gregory D.
Fischer, Bruce S.
Westhouse, Richard A.
Lee, Francis Y.
ACS MEDICINAL CHEMISTRY LETTERS, 2015, 6 (05): : 523 - 527
[50] Discovery of BPI460372, a potent and selective inhibitor of TEAD for the treatment of solid tumors harboring Hippo pathway aberrations
Shen, Hongling
Xu, Xiaofeng
Rong, Hongfei
Song, Xizhen
Gao, Jinheng
Chen, Jie
Zhu, Di
Zhao, Xiangdong
Tong, Jun
Zou, Zhengyao
Liu, Xiaoyun
Guo, Jin
Xu, Yan
Li, Yabin
Liu, Xiangyong
Chen, Hong
Zhao, Jiayu
Liu, Yanju
Ju, Xuepeng
Chen, Haibo
Lan, Hong
Ding, Lieming
Wang, Jiabing
CANCER RESEARCH, 2023, 83 (07)

← 1 2 3 4 5 →