23095-05-8Relevant articles and documents
Design, synthesis, and biological activity evaluation of a series of novel sulfonamide derivatives as BRD4 inhibitors against acute myeloid leukemia
Chen, Aiping,Feng, Ziying,Huang, Wenlong,Li, Jieming,Liu, Xinhong,Qian, Hai,Qiu, Qianqian,Shi, Jing,Shi, Wei,Zhang, Wenjie,Zhou, Daoguang
supporting information, (2021/07/22)
Accumulating researches have contributed much effect to discover novel chemotherapeutic drug for leukemia with expeditious curative effect, of which bromodomain-containing protein 4 (BRD4) inhibitor is considered as a eutherapeutic drug which has presented efficient cell proliferation suppression effect. In this study, we disclosed a series of phenylisoxazole sulfonamide derivatives as potent BRD4 inhibitors. Especially, compound 58 exhibited robust inhibitory potency toward BRD4-BD1 and BRD4-BD2 with IC50 values of 70 and 140 nM, respectively. In addition, compound 58 significantly suppressed cell proliferation of leukemia cell lines HL-60 and MV4-11 with IC50 values of 1.21 and 0.15 μM. In-depth study of the biological mechanism of compound 58 exerted its tumor suppression effect via down-regulating the level of oncogene c-myc. Moreover, in vivo pharmacokinetics (PK) study was conducted and the results demonstrated better pharmacokinetics features versus (+)-JQ1. In summary, our study discovers that compound 58 represents as a novel BRD4 inhibitor for further investigation in development of leukemia inhibitor with potentiality.
Discovery of 5-((5-chloro-2-methoxyphenyl)sulfonamido)nicotinamide (SBI-425), a potent and orally bioavailable tissue-nonspecific alkaline phosphatase (TNAP) inhibitor
Pinkerton, Anthony B.,Sergienko, Eduard,Bravo, Yalda,Dahl, Russell,Ma, Chen-Ting,Sun, Qing,Jackson, Michael R.,Cosford, Nicholas D.P.,Millán, José Luis
, p. 31 - 34 (2017/11/27)
Tissue-nonspecific alkaline phosphatase (TNAP) is an ectoenzyme crucial for bone matrix mineralization via its ability to hydrolyze extracellular inorganic pyrophosphate (ePPi), a potent mineralization inhibitor, to phosphate (Pi). B
1,3,5-TRIAZINE-2-AMINE DERIVATIVES, PREPARATION THEREOF AND DIAGNOSTIC AND THERAPEUTIC USE THEREOF
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Page/Page column 14-15, (2013/07/05)
The present invention relates to compounds corresponding to formula (I) in which: - R1 represents a substituted phenyl; - R2 represents: - a substituted phenyl; - a heteroaromatic group, the said group being unsubstituted or substituted one or more times; - R3 represents a group Alk; - R4 represents a hydrogen atom or a (C1-C4)alkyl; - R5 represents a hydrogen atom, a (C3-C6)cycloalkyl or a (C1-C4)alkyl-O-Alk; - or alternatively R4 and R5, together with the nitrogen atom to which they are attached, constitute a heterocyclic radical chosen from: azetidin-1-yl, pyrrolidin-1-yl, piperid-1-yl, morpholin-4-yl; - R6 represents a group -COOAlk, a group -CONH2 or a group -NHSO2 Alk; - Alk represents a (C1-C4)alkyl, which is unsubstituted or substituted one or more times with a halogen atom; in the form of the base or of an acid-addition salt. Preparation process and diagnostic and therapeutic use