474707-20-5

Upstream product

• 110-91-8 morpholine 
• 65340-70-7 6-bromo-4-chloroquinoline 
• 145369-94-4 6-bromoquinolin-4-ol 

Downstream Products

• 1201842-32-1 2,6-dichloro-N-(2-chloro-5-(4-(4-morpholinyl)-6-quinolinyl)-3-pyridinyl)benzenesulfonamide 
• 1201842-28-5 N-(2-chloro-5-(4-(4-morpholinyl)-6-quinolinyl)-3-pyridinyl)-2-fluorobenzenesulfonamide 
• 1201841-60-2 N-(2-chloro-5-(4-morpholinoquinolin-6-yl)pyridin-3-yl)-4-fluorobenzenesulfonamide 
• 1404227-77-5 3-(2,4-difluorophenylsulfonamino)-2-methoxy-5-(4-morpholinoquinolin-6-yl)benzamide 
• 1404227-75-3 3-(4-fluorophenylsulfonamino)-2-methoxy-5-(4-morpholinoquinolin-6-yl)benzamide 

Relevant academic research and scientific papers

DERIVATIVES OF QUINOLINE AS INHIBITORS OF DYRK1A AND/OR DYRK1B KINASES

The present invention relates to the compound of formula (I) and salts, stereoisomers, tautomers or N-oxides thereof. The present invention is further concerned with the use of such a compound or salt, stereoisomer, tautomer or N-oxide thereof as medicament and a pharmaceutical composition comprising said compound.

Structure-based optimization leads to the discovery of NSC765844, a highly potent, less toxic and orally efficacious dual PI3K/mTOR inhibitor

The phosphoinositide 3-kinase (PI3K) family is one of the most frequently activated enzymes in a wide range of human cancers; thus, inhibition of PI3K represents a promising strategy for cancer therapy. Herein, a series of benzylamine substituted arylsulfonamides were designed and synthesized as dual PI3K/mTOR inhibitors using a strategy integrating focused library design and virtual screening, resulting in the discovery of 13b (NSC765844). The compound 13b exhibits highly potent enzyme inhibition with IC50s of 1.3, 1.8, 1.5, 3.8 and 3.8?nM for PI3Kα, β, γ, δ, and mTOR, respectively. 13b was further evaluated in NCI by an in?vitro cytotoxic screening program. Broad-spectrum antitumor activities with mean GI50value of 18.6?nM against approximately 60 human tumor cell lines were found. 13b displayed favorable physicochemical properties and superior pharmacokinetic profiles for animal studies. It significantly inhibited tumor growth when administered orally in an A549 non-small-cell lung carcinoma xenograft and BEL7404 human hepatocellular carcinoma xenograft models. On the basis of its excellent in?vivo efficacy and superior pharmacokinetic profiles, 13b has been selected for further preclinical investigation as a promising anticancer drug candidate.

Fused ring compound and preparation method, application and intermediate compound thereof

The invention relates to a fused ring compound and a preparation method, application and intermediate compound thereof. The fused ring compound can be used as an inhibitor of phosphatidylinositol 3-kinase.

2,3-DISUBSTITUTED PYRIDINE COMPOUNDS AS TGF-BETA INHIBITORS AND METHODS OF USE

The invention described herein comprises compounds of formula (IV) and a method of treating cancer comprising administering to a subject having cancer one of the compounds in conjunction with another therapeutic treatment of cancer. The compounds (IV) inhibit signaling by a member of the TGF-β superfamily such as Nodal or Activin.

Discovery of 2-methoxy-3-phenylsulfonamino-5-(quinazolin-6-yl or quinolin-6-yl)benzamides as novel PI3K inhibitors and anticancer agents by bioisostere

2-Substituted-3-sulfonamino-5-(quinazolin-6-yl or quinolin-6-yl)benzamides have been proposed as novel structures of PI3K inhibitors and anticancer agents based on bioisostere. In the present study, 2-substituted-3-sulfonamino-5-(4- morpholinoquinazolin-6-yl)benzamides and 2-methoxy-3-sulfonamino-5-(4- morpholinoquinolin-6-yl)benzamides were synthesized. Their antiproliferative activities in vitro were evaluated via MTT assay against four human cancer cell lines, including A549, HCT-116, U-87 MG and KB. The SAR of the title compounds was preliminarily discussed. Compound 1a with potent antiproliferative activity was tested for its inhibitory activity against PI3K and mTOR and its effect on the AKT and p-AKT473. The anticancer effect of 1a was evaluated in established nude mice U-87 MG xenograft model. The results suggest that compound 1a can significantly inhibit PI3K/AKT/mTOR pathway and tumor growth. These findings strongly support the assumption that title compounds are potent PI3K inhibitors and anticancer agents.

Phospshoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) dual inhibitors: Discovery and structure-activity relationships of a series of quinoline and quinoxaline derivatives

The phosphoinositide 3-kinase (PI3K) family catalyzes the ATP-dependent phosphorylation of the 3′-hydroxyl group of phosphatidylinositols and plays an important role in cell growth and survival. There is abundant evidence demonstrating that PI3K signaling is dysregulated in many human cancers, suggesting that therapeutics targeting the PI3K pathway may have utility for the treatment of cancer. Our efforts to identify potent, efficacious, and orally available PI3K/mammalian target of rapamycin (mTOR) dual inhibitors resulted in the discovery of a series of substituted quinolines and quinoxalines derivatives. In this report, we describe the structure-activity relationships, selectivity, and pharmacokinetic data of this series and illustrate the in vivo pharmacodynamic and efficacy data for a representative compound.

INHIBITORS OF PI3 KINASE

The present invention relates to compounds of Formula (I), or a pharmaceutically acceptable salt thereof; methods of treating diseases or conditions, such as cancer, using the compounds; and pharmaceutical compositions containing the compounds, wherein Q, X1, X2, R1 and Z are as defined herein.

Thiazolinone 4-monosubstituted quinolines

Thiazolinone monosubstituted quinoline derivatives where the quinoline ring is mono-substituted at the 4 positions which derivatives demonstrates CDK1 antiproliferative activity and are useful as anti-cancer agents.

NITROGENOUS FUSED?RING COMPOUND HAVING PYRAZOLYL GROUP AS SUBSTITUENT AND MEDICINAL COMPOSITION THEREOF

The present invention provides a compound having an excellent inhibitory action on activation of STAT6 and a pharmaceutical composition thereof. Inparticular, it provides a compound represented by the following formula (I), a salt thereof or a hydrate of them. In the formula, X represents a nitrogen-containing condensed aromatic heterocyclic group such as imidazo[1,2-a]pyridine, benzimidazole, quinazoline, quinoline, or 2,1-benzisoxazole and has (R4)n as substituent groups; Y represents a C3-8 cycloalkyl group, C4-8 cycloalkenyl group, 5- to 14-membered non-aromatic heterocyclic group, C6-14 aromatic hydrocarbon cyclic group or 5- to 14-membered aromatic heterocyclic group; n in (R4)n is 0, 1, 2 or 3, and Z groups independently represent (1) hydrogen atom, (2) amino group, (3) halogen atom, (4) hydroxyl group, (5) nitro group, (6) cyano group, (7) azido group, (8) formyl group, (9) hydroxyamino group, (10) sulfamoyl group, (11) guanodino group, (12) oxo group, (13) C2-6 alkenyl group, (14) C1-6 alkoxy group, (15) C1-6 alkylhydroxyamino group, (16) halogenated C1-6 alkyl group, (17) halogenated C2-6 alkenyl group, (18) (i) C3-7cycloalkyl group, (ii) C3-7cycloalkenyl group, (iii) 5- to 14-membered non-aromatic heterocyclic group, each of which may have one or more substituent groups Q, or (19) formula -M1-M2-M3, R1 represents (1) hydrogen atom, (2) halogen atom, (3) hydroxyl group, (4) nitro group, (5) cyano group, (6) halogenated C1-6 alkyl group, (7) C2-6 alkyl group substituted with a hydroxyl or cyano group, (8) C2-6 alkenyl group, or (9) formula -L1-L2-L3, and R2 represents a hydrogen atom or a protecting group; and R3 represents a hydrogen atom, halogen atom, cyano group, amino group, C1-4 alkyl group or halogenated C1-4 alkyl group.