- Discovery and structure-activity relationship of N-phenyl-1H-pyrazolo[3,4-b]quinolin-4-amines as a new series of potent apoptosis inducers
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We report the discovery and SAR study of a series of N-phenyl-1H-pyrazolo[3,4-b]quinolin-4-amines as potent inducers of apoptosis. N-(3-Acetylphenyl)-2,3-dihydro-1H-cyclopenta[b]quinolin-9-amine (2) was discovered through our cell- and caspase-based HTS assays as an inducer of apoptosis. Compound 2 is active against cancer cells derived from several human solid tumors, with EC50 values ranging from 400 to 700 nM. SAR study of hit 2 led to the discovery of N-phenyl-1H-pyrazolo[3,4-b]quinolin-4-amines as a novel series of potent apoptosis inducers, with 1,3-dimethyl-N-(4-propionylphenyl)-1H-pyrazolo[3,4-b]quinolin-amine (6b) having EC50 values ranging from 30 to 70 nM in cancer cells. These compounds also demonstrated potent activity in the cell growth inhibition assay, with GI50 values of 16-42 nM for compound 6b.
- Zhang, Han-Zhong,Claassen, Gisela,Crogran-Grundy, Candace,Tseng, Ben,Drewe, John,Cai, Sui Xiong
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p. 222 - 231
(2008/09/16)
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- Method for inhibiting neoplastic cells by exposure to substituted N-cycloalkylmethyl-1-H-pyrazolo (3,4-B) quinolone-4 amines
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A method for inhibiting neoplastic cells and related conditions by exposing them to substituted N-cycloalkylmethyl-1H-pyrazolo?3,4-b!quinolin-4-amines.
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- Method for inhibiting neoplastic cells and related conditions by exposure to substituted N- arylmethyl and heterocyclmethyl-1H-pyrazolo (3,4-B) quinolin-4-amines
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A method for inhibiting neoplastic cells and related conditions by exposing them to substituted N-arylmethyl and heterocyclmethyl-1H-pyrazolo?3,4-B!quinolin-4-amines.
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- Substituted N-arylmethyl and heterocyclmethyl-1H-pyrazolo[3,4-b]quinolin-4-amines and compositions and methods of use thereof
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Substituted N-arylmethyl and heterocyclylmethyl-1H-pyrazolo[3,4-b]quinolin-4-amines, pharmaceutical compositions containing them and methods for a) effecting c-GMP-phosphodiesterase inhibition, b) treating heart failure and/or hypertension, c) reversing o
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- Substituted N-cycloalkylmethyl-1H-pyrazolo(3,4-b)quinolin-4 amines and compositions and methods of use thereof
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Substituted N-cycloalkylmethyl-1H-pyrazolo[3,4-b]quinolin-4-amines, pharmaceutical compositions containing them and methods for a) effecting c-GMP-phosphodiesterase inhibition, b) treating heart failure and/or hypertension, c) reversing or reducing nitrate-induced tolerance and d) treating angina pectoris, congestive heart disease and myocardial infarction utilizing them.
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