- Synthesis and SAR of 4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline derivatives as potent and selective CDK4/6 inhibitors
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CDK4/6 pathway is an attractive target for development of anti-cancer drugs. Herein, we reported the design and synthesis of a series of 4,5-dihydro-1H-pyrazolo [4,3-h]quinazoline derivatives as selective CDK4/6 inhibitors. Applied with the optimizing strategy to the initial scaffold, it is found that compound 13n is able to selectively inhibit CDK4 and CDK6 with IC50 values 0.01 and 0.026 μM, respectively. The compound showed good anti-proliferative activity when tested in a panel of tumor cell lines with CDK4/6 related mechanism of action, the results clearly suggest that compound 13n works much better than Ly2385219 which is a selective CDK4/6 inhibitor. This compound was also found to have favorable pharmacokinetic parameters. Taken together, compound 13n could be selected for further preclinical evaluation.
- Zhao, Hui,Hu, Xiaoxia,Cao, Kai,Zhang, Yue,Zhao, Kuantao,Tang, Chunlei,Feng, Bainian
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p. 935 - 945
(2018/09/04)
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- 2-BENZOYLIMIDAZOPYRIDINE DERIVATIVES, PREPARATION AND THERAPEUTIC USE THEREOF
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The present invention is related to a compound of formula (I) wherein R1, R2, R3, R4 and X are as defined herein, or an acid-addition salt thereof, its preparation and therapeutic use in the treatment or prevention of diseases involving the Nurr-1 nuclear receptors, also known as NR4A2, NOT, TINUR, RNR-1 and HZF3.
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Page/Page column 8
(2009/06/27)
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- DERIVATIVES OF IMIDAZO[1,2-a]PYRIDINE-2-CARBOXAMIDES, PREPARATION METHOD THEREOF AND USE OF SAME IN THERAPEUTICS
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The present invention is related to a compound of formula (I): wherein R1, R2, R3, R4 and X are as defined herein, or an addition salt with an acid thereof, its pharmaceutical composition or use for treating or preventing diseases involving Nurr-1 nuclear receptors, also known as NR4A2, NOT, TINUR, RNR-1 and HZF3.
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Page/Page column 8
(2009/06/27)
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- QUINAZOLINE DERIVATIVES
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The invention concerns quinazoline derivatives of Formula (I) or a pharmaceutically-acceptable salt thereof, wherein each of X1, p, R1, q, R2, R3, R4, R5, Ring A, r and R6 has any of the meanings defined hereinbefore in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use in the treatment of cell proliferative disorders.
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Page/Page column 102
(2008/06/13)
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- QUINAZOLINE DERIVATIVES
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The invention concerns quinazoline derivatives of Formula (I) or a pharmaceutically-acceptable salt, solvate or pro-drug thereof, wherein each of X1, p, R1, q, R2, R3, R4, R5, Ring A, r and R6 has any of the meanings defined hereinbefore in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use in the treatment of cell proliferative disorders or in the treatment of disease states associated with angiogenesis and/or vascular permeability.
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Page/Page column 106
(2008/06/13)
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- QUINOLINE DERIVATIVES
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The invention concerns quinoline derivatives of Formula (I) or a pharmaceutically-acceptable salt, solvate or pro-drug thereof, wherein each of p, R1, q, R2, R3, R4, R5, Ring A, r and R6 has any of the meanings defined in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use in the treatment of cell proliferative disorders or in the treatment of disease states associated with angiogenesis and/or vascular permeability.
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Page/Page column 88
(2008/06/13)
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- 5-SUBSTITUTED-PYRAZINE OR PYRIDINE GLUCOKINASE ACTIVATORS
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The present invention provides a compound according to formula (I) where the substituent designations are provided in the specification. Pharmaceutical compositions comprising a compound according to formula (I) are also provided, said compounds being glucokinase activators which are useful in the treatment of type II diabetes.
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