380843-81-2

Basic information

• Product Name: 4-((2,4-dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(piperazin-1-yl)propoxy)quinoline-3-carbonitrile
• CAS NO: 380843-81-2
• Molecular Weight: 516.427
• Mol File: 380843-81-2.mol
• Article Data: 5

Chemical Properties

• CAS DataBase Reference: 4-((2,4-dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(piperazin-1-yl)propoxy)quinoline-3-carbonitrile(CAS DataBase Reference)
• NIST Chemistry Reference: 4-((2,4-dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(piperazin-1-yl)propoxy)quinoline-3-carbonitrile(380843-81-2)
• EPA Substance Registry System: 4-((2,4-dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(piperazin-1-yl)propoxy)quinoline-3-carbonitrile(380843-81-2)

Safety Data

• Hazardous Substances Data: 380843-81-2(Hazardous Substances Data)

Usage

Uses

Proteolysis Targeting Chimera (PROTAC) is a novel approach to modern drug development programs that utilizes small compounds to target proteins for ubiquitination and degradation by proteasome. 4-[(2,4-Dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(1-piperazinyl)propoxy]-3-quinolinecarbonitrile is a PROTAC compound, which has the potential to target oncogenic BCR-ABL for degradation. 4-[(2,4-Dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(1-piperazinyl)propoxy]-3-quinolinecarbonitrile has also been employed in ligand-based pharmacophore modelling to identify c-Src inhibitors.

Upstream product

• 110-85-0 piperazine 
• 380844-49-5 7-(3-chloropropoxy)-4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-3-quinolinecarbonitrile 
• 263149-10-6 4-chloro-7-hydroxy-6-methoxyquinolin-3-carbonitrile 
• 214470-68-5 7-(3-chloro-propoxy)-4-chloro-6-methoxy-quinoline-3-carbonitrile 
• 98446-49-2 2,4-dichloro-5-methoxyaniline 

Relevant articles and documents

Compound capable of degrading Bcr-Abl or PARP as well as preparation method and pharmaceutical application thereof

The invention relates to a compound shown in a general formula (Ia), (Ib), (Ic), (Id), (Ie), (If) or (Ig) or a stereoisomer, a deuterated compound, a solvate, a prodrug, a metabolite, a pharmaceutically acceptable salt or a co-crystal of the compound, an intermediate and a preparation method of the compound, and application of the compound in Bcr-Abl or PARP related diseases such as tumors. The chemical formula is B-K(Ia)B-Cy1-K(Ib)B-Cy1-Cy2-K(Ic)B-Cy1-Cy2-Cy3-K(Id)B-Cy1-Cy2-Cy3-Cy4-K(Ie).

COMPOUNDS TARGETING AND DEGRADING BCR-ABL PROTEIN AND ITS ANTITUMOR APPLICATION

The present disclosure provides a compound of formula (I) targeting and degrading BCR-ABL protein and its use in the field of antitumor. The compound of formula (I) shows degradation and inhibitory effects on BCR-ABL target protein, which is mainly comprised of four moieties, wherein the first moiety (BCR-ABL-TKIs) is compound moiety with BCR-ABL tyrosine kinase inhibited activity; the second moiety (the LIN) is link units; the third moiety (the ULM) is a small molecule ligand for VHL or CRBN proteases with ubiquitination; and the four moiety (the group A) is carbonyl group that covalently binds to BCR-ABL-TKIs and LIN, and the LIN is further covalently bonded to ULM. A series of compounds designed and synthesized by the present disclosure shows extensive pharmacological effective, which function to degrade BCR-ABL protein and inhibit BCR-ABL effective, and can be utilized for treating relevant tumor.

Optimization of 4-phenylamino-3-quinolinecarbonitriles as potent inhibitors of Src kinase activity

Subsequent to the discovery of 4-[(2,4-dichlorophenyl)amino] -6,7-dimethoxy-3-quinolinecarbonitrile (1a) as an inhibitor of Src kinase activity (IC50 = 30 nM) several additional analogues were prepared. Optimization of the C-4 anilino group of la led to lc which contains a 2,4-dichloro-5-methoxy- substituted aniline. Replacement of the methoxy group at C-7 of 1c with a 3-(morpholin-4-yl)propoxy group provided 2c resulting in increased inhibition of both Src kinase activity and Src-mediated cell proliferation. Analogues of 2c with other trisubstituted anilines at C-4 were also potent Src inhibitors and the propoxy group of 2c was preferred over ethoxy butoxy or pentoxy. Replacement of the morpholine group of 2c with a 4-methylpiperazine group provided 31a which had an IC50 of 1.2 nM in the Src enzymatic assay an IC50 of 100 nM for the inhibition of Src-dependent cell proliferation and was selective for Src over non-Src family kinases. Compound 31a which had higher 1 and 4 h plasma levels than 2c effectively inhibited tumor growth in xenograft models.