- As the PI3K/mTOR inhibitor tricyclic compound, its preparation and use
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The invention discloses a tricyclic compound as a PI3K/mTOR inhibitor. The tricyclic compound is a compound with the general formula (I) in the specification, wherein Ar is selected from aryl or heteroaryl; X, Y and Z are independently selected from O, CR2R3 and NR4 respectively; Q is selected from O, CR2R3 and NR4 or does not exists; R1 represents C1-C6 alkyl; n is selected from integers from 0 to 4; when n is more than or equal to 2, two R1 and a morpholine cycle can be combined into a combined cycle, a bridge cycle or a spiral cycle; R2 and R3 are selected from hydrogen and C1-C6 alkyl; R4 is selected from hydrogen, C1-C6 alkyl, C3-C7 cycloalkyl, heterocyclic radical, acyl and sulfonyl. The invention further discloses a perpetration method of the compound with the general formula (I) as well as a pharmaceutical composition and application of the compound with the general formula (I).
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Paragraph 0168; 0170
(2017/08/25)
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- Pyrido-pyrimidines, its preparation and use
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The invention discloses pyridopyrimidine compounds with a general formula (I), wherein Ar is aryl or heteroaryl; R1 is hydrogen, halogen, amino, heterocyclic group, alkyl, aminoalkyl, heterocyclic alkyl, aryl, heteroaryl, cyano, alkenyl or alkynyl; R2 is
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- Having a spiro ring substituent of aryl morpholine compound, its preparation and use
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The invention discloses arylmorpholine compounds with spiro substituents. The arylmorpholine compounds are compounds having the following general formula (I), wherein X is N or CH; R1 is hydrogen, hydroxyl, alkoxy, halogen, amino, amido, acylamino, sulfam
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- Discovery of 4-morpholino-6-aryl-1H-pyrazolo[3,4-d]pyrimidines as highly potent and selective ATP-competitive inhibitors of the mammalian target of rapamycin (mTOR): Optimization of the 6-aryl substituent
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Design and synthesis of a series of 4-morpholino-6-aryl-1H-pyrazolo[3,4-d] pyrimidines as potent and selective inhibitors of the mammalian target of rapamycin (mTOR) are described. Optimization of the 6-aryl substituent led to the discovery of inhibitors carrying 6-ureidophenyl groups, the first reported active site inhibitors of mTOR with subnanomolar inhibitory concentrations. The data presented in this paper show that 6-arylureidophenyl substituents led to potent mixed inhibitors of mTOR and phosphatidylinositol 3-kinase α (PI3K-α), whereas 6-alkylureidophenyl appendages gave highly selective mTOR inhibitors. Combination of 6-alkylureidophenyl groups with 1-carbamoylpiperidine substitution resulted in compounds with subnanomolar IC50 against mTOR and greater than 1000-fold selectivity over PI3K-α. In addition, structure based drug design resulted in the preparation of several 6-arylureidophenyl-1H-pyrazolo[3,4-d]pyrimidines, substituted in the 4-position of the arylureido moiety with water solubilizing groups. These compounds combined potent mTOR inhibition (IC50501 nM). 2009 American Chemical Society.
- Verheijen, Jeroen C.,Richard, David J.,Curran, Kevin,Kaplan, Joshua,Lefever, Mark,Nowak, Pawel,Malwitz, David J.,Brooijmans, Natasja,Toral-Barza, Lourdes,Zhang, Wei-Guo,Lucas, Judy,Hollander, Irwin,Ayral-Kaloustian, Semiramis,Mansour, Tarek S.,Yu, Ker,Zask, Arie
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supporting information; experimental part
p. 8010 - 8024
(2010/07/04)
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