80708-77-6Relevant academic research and scientific papers
Optimization of imidazo[4,5- b ]pyridine-based kinase inhibitors: Identification of a dual FLT3/aurora kinase inhibitor as an orally bioavailable preclinical development candidate for the treatment of acute myeloid leukemia
Bavetsias, Vassilios,Crumpler, Simon,Sun, Chongbo,Avery, Sian,Atrash, Butrus,Faisal, Amir,Moore, Andrew S.,Brown, Nathan,Sheldrake, Peter W.,Bush, Katherine,Henley, Alan,Box, Gary,Valenti, Melanie,De Haven Brandon, Alexis,Raynaud, Florence I.,Workman, Paul,Eccles, Suzanne A.,Linardopoulos, Spiros,Blagg, Julian,Kosmopoulou, Magda,Bayliss, Richard
supporting information, p. 8721 - 8734,14 (2020/09/16)
Optimization of the imidazo[4,5-b]pyridine-based series of Aurora kinase inhibitors led to the identification of 6-chloro-7-(4-(4-chlorobenzyl)piperazin- 1-yl)-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine (27e), a potent inhibitor of Aurora kinases (Aurora-A Kd = 7.5 nM, Aurora-B K d = 48 nM), FLT3 kinase (Kd = 6.2 nM), and FLT3 mutants including FLT3-ITD (Kd = 38 nM) and FLT3(D835Y) (Kd = 14 nM). FLT3-ITD causes constitutive FLT3 kinase activation and is detected in 20-35% of adults and 15% of children with acute myeloid leukemia (AML), conferring a poor prognosis in both age groups. In an in vivo setting, 27e strongly inhibited the growth of a FLT3-ITD-positive AML human tumor xenograft (MV4-11) following oral administration, with in vivo biomarker modulation and plasma free drug exposures consistent with dual FLT3 and Aurora kinase inhibition. Compound 27e, an orally bioavailable dual FLT3 and Aurora kinase inhibitor, was selected as a preclinical development candidate for the treatment of human malignancies, in particular AML, in adults and children.
Discovery of novel thieno[2,3-d]pyrimidin-4-yl hydrazone-based inhibitors of Cyclin D1-CDK4: Synthesis, biological evaluation and structure-activity relationships. Part 2
Horiuchi, Takao,Nagata, Motoko,Kitagawa, Mayumi,Akahane, Kouichi,Uoto, Kouichi
experimental part, p. 7850 - 7860 (2010/04/02)
The design, synthesis and evaluation of novel thieno[2,3-d]pyrimidin-4-yl hydrazone analogues as cyclin-dependent kinase 4 (CDK4) inhibitor are described. Focusing on the optimization of the heteroaryl moiety at the hydrazone with substituted phenyl group
Design, synthesis and AChE inhibitory activity of indanone and aurone derivatives
Sheng, Rong,Xu, Yu,Hu, Chunqi,Zhang, Jing,Lin, Xiao,Li, Jingya,Yang, Bo,He, Qiaojun,Hu, Yongzhou
experimental part, p. 7 - 17 (2009/04/06)
A new series of indanone and aurone derivatives have been synthesized and tested for in vitro AChE inhibitory activity by modified Ellman method. Most of them exhibit AChE inhibitory activities superior to rivastigmine. Further, the most potent compound 1g was selected to evaluate the effect on the acquisition and memory impairment by mice step-down passive avoidance test.
HYDRAZONE DERIVATIVE
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Page/Page column 42, (2010/11/08)
A compound represented by the following formula (I): wherein R1 represents hydrogen, aryl which may have a substituent, a saturated or unsaturated 5- to 7-membered heterocyclic group which may have a substituent, etc.; R2 represents hydrogen, aryl which may have a substituent, a saturated or unsaturated 5- to 7-membered heterocyclic group which may have a substituent, etc.; R3 represents hydrogen, etc.; Ar represents a divalent group derived from aromatic hydrocarbon, etc.; X represents a single bond, linear or branched alkylene having from 1 to 3 carbon atoms which may have a substituent, etc.; and G represents halogen, a saturated or unsaturated 5- or 6-membered cyclic hydrocarbon group which may have a substituent, a saturated or unsaturated 5- to 7-membered heterocyclic group which may have a substituent, etc., a salt thereof or a solvate thereof; and an agent for inhibiting aggregation and/or deposition of an amyloid protein or an amyloid-like protein, which comprises the compound, a salt thereof or a solvate thereof
Aminoisoquinolines and aminotheinopyridine derivatives and their use as anti-inflammatory agents
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, (2008/06/13)
PCT No. PCT/SE97/00589 Sec. 371 Date Aug. 19, 1997 Sec. 102(e) Date Aug. 19, 1997 PCT Filed Apr. 9, 1997 PCT Pub. No. WO97/38977 PCT Pub. Date Oct. 23, 1997Compounds of formula I wherein R, R1, R2, and R3 and A are as defined herein, together with pharmaceutically acceptable salts, enantiomers or tautomers are useful as pharmaceuticals, particularly in the treatment of inflammatory disease.
Potential Antidepressants. Synthesis of 6,11-Dihydrodibenzothiepin-11-yl 4-(Dimethylaminomethyl)phenyl Ketone and of Some Related Compounds
Metysova, Jirina,Protiva, Miroslav
, p. 1325 - 1330 (2007/10/02)
Reactions of dibenzothiepin-11(6H)-one (4) with 2-, 3- and 4-(dimethylaminomethyl)phenylmagnesium bromide afforded the tertiary alcohols 5a,b,c.The aldehydes 7 and 8 gave similarly the secondary alcohols 9a,b,c and 10c.Numerous attempts to prepare the corresponding ketones, especially by oxidation of 9a,b,c and 10c were unsuccessful.Only the oxidation of 9c with tetrabutylammonium chromate in chloroform afforded the desired ketone 16.Its formation was accompanied by an important side reaction consisting in a cleavage of the "retro-ene-reaction" type leading to compound 11 and the aldehyde 13c which reacted with the chloroform present to give the alcohol 17.Compounds 5a,b,c, 9a,b,c and 16 were tested as potential antidepressants but with the exception of some effects in the test of potentiation of yohimbine toxicity in mice, they proved inactive in this line.
PYRIMIDONES HAVING HISTAMINE H2-ANTAGONIST ACTIVITY
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, (2008/06/13)
The compounds of this invention are 5-dialkylaminoalkylfuranyl (or thienyl, phenyl or pyridyl)!-4-pyrimidones having histamine H 2-antagonist activity. A specific compound of this invention is 2-2-(5-dimethylaminomethyl-2-furanylmethylthio) ethylamino!-5-(5-dimethylamino methyl-2-furanylmethyl)-4-pyrimidone.
