Article

Optimization of 6,6-dimethyl pyrrolo[3,4-c]pyrazoles: Identification of PHA-793887, a potent CDK inhibitor suitable for intravenous dosing.

Nerviano Medical Sciences Srl, Business Unit Oncology, Viale Pasteur 10, 20014 Nerviano (MI), Italy.
Bioorganic & medicinal chemistry (impact factor: 2.82). 01/2010; 18(5):1844-53. DOI:10.1016/j.bmc.2010.01.042
Source: PubMed

ABSTRACT We have recently reported CDK inhibitors based on the 6-substituted pyrrolo[3,4-c]pyrazole core structure. Improvement of inhibitory potency against multiple CDKs, antiproliferative activity against cancer cell lines and optimization of the physico-chemical properties led to the identification of highly potent compounds. Compound 31 (PHA-793887) showed good efficacy in the human ovarian A2780, colon HCT-116 and pancreatic BX-PC3 carcinoma xenograft models and was well tolerated upon daily treatments by iv administration. It was identified as a drug candidate for clinical evaluation in patients with solid tumors.

0 0
 · 
0 Bookmarks
 · 
34 Views
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

6-substituted pyrrolo[3,4-c]pyrazole core structure
 
antiproliferative activity
 
clinical evaluation
 
colon HCT-116
 
drug candidate
 
good efficacy
 
optimization
 
physico-chemical properties
 
potent compounds
 
solid tumors