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Synthesis and antiproliferative activity of 3-amino-N-phenyl-1H-indazole-1-carboxamides
- Publication Year :
- 2009
- Publisher :
- country:FR, 2009.
-
Abstract
- A series of new 3-amino-N-phenyl-1H-indazole-1-carboxamides 10 have been prepared from commercially available phenyl isocyanate precursors 8 and 3-aminoindazole 9. Some of the synthesized compounds were evaluated for their in vitro antineoplastic activity against 60 human cell lines derived from seven clinically isolated cancer types (lung, colon, melanoma, renal, ovarian, brain, and leukemia) according to the NCI standard protocol. The test results indicated that 3-amino-1H-indazole-1-carboxamides 10 were endowed with an interesting antiproliferative activity. The most active compounds of this series, 10d,e, were able to inhibit cell growth of many neoplastic cell lines at concentrations lower than 1 μM (0.0153 μM in SR leukemia) causing a block in G0–G1 phase of cell cycle. Analysis of pRb expression showed that these two compounds increased the ratio between underphosphorylated pRb and total pRb. The X-ray structure of 10w, confirmed the 3-amino-N-phenyl-1H-indazole-1-carboxamide structure of compounds 10.
- Subjects :
- Indazoles
Antineoplastic Agents
Crystallography, X-Ray
Retinoblastoma Protein
chemistry.chemical_compound
Structure-Activity Relationship
Cell Line, Tumor
Neoplasms
Drug Discovery
medicine
Humans
Cell Proliferation
G0-G1 arrest
Pharmacology
Indazole
Molecular Structure
Chemistry
Cell growth
Melanoma
Organic Chemistry
Cell Cycle
Cancer
1H-Indazole-1-carboxamides
Crystallographic study
pRb
1H-Indazole-1-carboxamide
General Medicine
Cell cycle
medicine.disease
Amides
Settore CHIM/08 - Chimica Farmaceutica
In vitro
Crystallographyc study
Leukemia
Biochemistry
Neoplastic cell
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....fdfd4287784d8bcf2c738542cf62acfe