1627596-00-2Relevant articles and documents
Design, synthesis and biological evaluation of 7-methylimidazo[1,5-a]pyrazin-8(7H)-one derivatives as BRD4 inhibitors
Zhao, Leilei,Yang, Yifei,Guo, Yahui,Yang, Lingyun,Zhang, Jian,Zhou, Jinpei,Zhang, Huibin
, p. 2482 - 2490 (2017)
BRD4 is an attractive target for antitumor due to its important role in regulation of gene transcription. In this paper, we synthesized a series of 7-methylimidazo[1,5-a]pyrazin-8(7H)-one derivatives as potent BRD4 inhibitors and evaluated their BRD4 inhibitory activities in vitro and anti-proliferation effects on tumor cells. Gratifyingly, compound 10j exhibited robust potency of BRD4(1) and BRD4(2) inhibition with IC50 values of 130 and 76?nM respectively. Docking studies were performed to explain the structure-activity relationship. Furthermore, compound 10j potently inhibited cell proliferation in BRD4-sensitive cell lines HL-60 and MV4-11 with IC50 value of 0.57 and 0.18?μM respectively. Activity on BRD4-independent K562 cell was weaker than on BRD4-sensitive lines. Overall, these results suggest that compound 10j is a potential BRD4 inhibitor deserving further investigation for cancer treatment.
Development of 7-methylimidazo[1,5-a]pyrazin-8(7H)-one derivatives as a novel chemical series of BRD4 inhibitors
Liu, Xueting,Wu, Zhenwei,Tian, Jiping,Yuan, Xinrui,Zhao, Leilei,Chen, Pan,Zhang, Huibin,Zhou, Jinpei
, p. 2089 - 2099 (2018)
Bromodomain protein 4 (BRD4) is a member of the bromodomain and extra-terminal domain (BET) protein family. It binds to acetylated histones that regulate gene transcription preferentially at super-enhancer regions. Now BRD4 has been involved into several
beNZOdIAZEPINEdERIVATIVES USEfuL INtREATINGarESPIRATORY SYNcyTIAL VIRUS INFECTION
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Page/Page column 95, (2022/02/06)
benzodiazepinederivativesof formula(Ie) whereinoneofr1 andr2 isa benzodiazepinyl-containing groupof formula(II) in whichr8 is Hor halo;theotherofr1andr2 isa group Z selected from H,C3-C6 cycloalkyl,halo,-NHR9,benzyl,phenyl,4-to 10-membered heterocyclyland 4-to 10-membered heteroaryl,whereinphenyl,heterocyclyland heteroarylare unsubstitutedor substituted byoneortwo substituents selected from 4-to 10-membered heterocyclyl which is unsubstitutedor substituted byoR,and from C1-C6alkyl,C1-C6 hydroxyalkyl,C1-C6 haloalkyl,C3-C6 cycloalkyl,halo,-OR,-(ch2)mOR,-NR2,-(ch2)mNR2,-NHR",-SOmNR2,-SOmR,-SR,nitro,-CO2R,-CN,-CONR2,-NHCOR,-ch2NR10R11and-NR10R11,in whicheachr is independently Hor C1-C6alkyl,r" is C3-C6 cycloalkyland m is 1or 2;r9 is selected fromphenyland 4-to 10-membered heteroaryl whereinphenyland heteroarylare unsubstitutedor substituted by halo;r10 andr11areeach independently Hor C1-C6alkyl;orr10andr11 form,together withthenatomto whichtheyareattached,either(a)a morpholinering which isoptionally bridged bya-ch2-group linkingtworing carbonatomsthatarepositionedparatoeachother,or(b)a spiro groupofthe following formula(b):andringa isaringofoneofthe following structural formulae(I-1),(I-2)and(I-3):andringa isaringofoneofthe following structural formulae(I-1),(1-2)and(1-3): in which Y is selected fromo,S,SO2and NR,whereinr isasdefinedabove,andeachofr2tor7 is independently H,C1-C6alkyl,C1-C6 hydroxyalkyl,C3-C6 cycloalkyl,halo,-OR,-ch2OR,-NR2,-ch2NR12R13,-NRCOOR,-ch2OR,-SOmNR2,-SOmR,-ch2SOmR,nitro,-CO2R,-CN,-CONR2or-NHCOR,in whichrand mareasdefinedaboveandr12andr13areeach independently H,C1-C6alkyl,benzyl,4-to 10-membered heterocyclylorr12andr13 form,together withthenatomto whichtheyareattached,a 4-to 10-membered heteroaryl which is unsubstitutedora 4-to 10-membered heterocyclyl which is unsubstitutedor substituted with C1-C6alkylor halo,oranytwoofr2tor7that bondtothe same carbonatom forma spiroring selected froma C3-C6 cycloalkyl spiroringanda spirooxetaneringofthe following structure:(Formulaa)andthepharmaceuticallyacceptable saltsthereofare inhibitorsofrSVand cantherefore be usedtotreatorpreventanrSV infection.
Methylpyrrole inhibitors of BET bromodomains
Hasvold, Lisa A.,Sheppard, George S.,Wang, Le,Fidanze, Steven D.,Liu, Dachun,Pratt, John K.,Mantei, Robert A.,Wada, Carol K.,Hubbard, Robbert,Shen, Yu,Lin, Xiaoyu,Huang, Xiaoli,Warder, Scott E.,Wilcox, Denise,Li, Leiming,Buchanan, F. Greg,Smithee, Lauren,Albert, Daniel H.,Magoc, Terrance J.,Park, Chang H.,Petros, Andrew M.,Panchal, Sanjay C.,Sun, Chaohong,Kovar, Peter,Soni, Nirupama B.,Elmore, Steven W.,Kati, Warren M.,McDaniel, Keith F.
, p. 2225 - 2233 (2017/04/27)
An NMR fragment screen for binders to the bromodomains of BRD4 identified 2-methyl-3-ketopyrroles 1 and 2. Elaboration of these fragments guided by structure-based design provided lead molecules with significant activity in a mouse tumor model. Further mo
DIHYDRO-PYRROLOPYRIDINONE INHIBITORS
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, (2014/09/29)
The present invention provides for compounds of formula (I) wherein R1, R2, R3, R4, and R5 have any of the values defined in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of diseases and conditions, including inflammatory diseases, cancer, and AIDS. Also provided are pharmaceutical compositions comprising one or more compounds of formula (I).
BROMODOMAIN INHIBITORS
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Paragraph 0627, (2014/09/29)
The present invention provides for compounds of formula (I) wherein R1, R2, A1, A2, A3, A4, X, and Y have any of the values defined in the specification, and pharmaceutically acceptable sal
