title: Discovery of a highly potent, orally active mitosis/angiogenesis inhibitor r1530 for the treatment of solid tumors.
abstract: 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.
authors.affiliation: Discovery Chemistry, Discovery Oncology, and Chemical Synthesis, Hoffmann-La Roche Inc. , 340 Kingsland Street, Nutley, New Jersey 07110, United States.
authors.forename: Jin-Jun
authors.initials: JJ
authors.lastname: Liu
authors.affiliation: Discovery Chemistry, Discovery Oncology, and Chemical Synthesis, Hoffmann-La Roche Inc. , 340 Kingsland Street, Nutley, New Jersey 07110, United States.
authors.forename: Brian
authors.initials: B
authors.lastname: Higgins
authors.affiliation: Discovery Chemistry, Discovery Oncology, and Chemical Synthesis, Hoffmann-La Roche Inc. , 340 Kingsland Street, Nutley, New Jersey 07110, United States.
authors.forename: Grace
authors.initials: G
authors.lastname: Ju
authors.affiliation: Discovery Chemistry, Discovery Oncology, and Chemical Synthesis, Hoffmann-La Roche Inc. , 340 Kingsland Street, Nutley, New Jersey 07110, United States.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Kolinsky
authors.affiliation: Discovery Chemistry, Discovery Oncology, and Chemical Synthesis, Hoffmann-La Roche Inc. , 340 Kingsland Street, Nutley, New Jersey 07110, United States.
authors.forename: Kin-Chun
authors.initials: KC
authors.lastname: Luk
authors.affiliation: Discovery Chemistry, Discovery Oncology, and Chemical Synthesis, Hoffmann-La Roche Inc. , 340 Kingsland Street, Nutley, New Jersey 07110, United States.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Packman
authors.affiliation: Discovery Chemistry, Discovery Oncology, and Chemical Synthesis, Hoffmann-La Roche Inc. , 340 Kingsland Street, Nutley, New Jersey 07110, United States.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Pizzolato
authors.affiliation: Discovery Chemistry, Discovery Oncology, and Chemical Synthesis, Hoffmann-La Roche Inc. , 340 Kingsland Street, Nutley, New Jersey 07110, United States.
authors.forename: Yi
authors.initials: Y
authors.lastname: Ren
authors.affiliation: Discovery Chemistry, Discovery Oncology, and Chemical Synthesis, Hoffmann-La Roche Inc. , 340 Kingsland Street, Nutley, New Jersey 07110, United States.
authors.forename: Kshitij
authors.initials: K
authors.lastname: Thakkar
authors.affiliation: Discovery Chemistry, Discovery Oncology, and Chemical Synthesis, Hoffmann-La Roche Inc. , 340 Kingsland Street, Nutley, New Jersey 07110, United States.
authors.forename: Christian
authors.initials: C
authors.lastname: Tovar
authors.affiliation: Discovery Chemistry, Discovery Oncology, and Chemical Synthesis, Hoffmann-La Roche Inc. , 340 Kingsland Street, Nutley, New Jersey 07110, United States.
authors.forename: Zhuming
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Discovery Chemistry, Discovery Oncology, and Chemical Synthesis, Hoffmann-La Roche Inc. , 340 Kingsland Street, Nutley, New Jersey 07110, United States.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Wovkulich
keywords: FGFr and PDGFr-β; VGFr-2; antitumor effect; mitosis/angiogenesis inhibitor; pyrazolobenzodiazepines