65340-70-7

Usage

InChI:InChI=1/C9H5BrClN/c10-6-1-2-9-7(5-6)8(11)3-4-12-9/h1-5H

Upstream product

• 145369-94-4 6-bromoquinolin-4-ol 
• 98948-95-9 6-bromo-4-hydroxyquinoline-3-carboxylic acid 
• 1320361-74-7 ethyl 3-(4-bromoanilino)propenoate 
• 98948-95-9 6-bromo-1,4-dihydro-4-oxo-3-quinoline carboxylic acid 
• 79607-23-1 ethyl 6-bromo-4-oxo-1,4-dihydro-quinoline-3-carboxylate 
• 19056-84-9 diethyl 2-[(p-tolylamino)methylidene]malonate 
• 187278-01-9 5-(((4-bromophenyl)amino)methylene)-2,2-dimethyl-1,3-dioxane-4,6-dione 
• 145369-94-4 6-bromo-3-quinolinecarboxylic acid-4-ol 
• 106-40-1 4-bromo-aniline 
• 101937-44-4 diethyl 2-((4-bromophenylamino)methylene)malonate 
• 122794-99-4 6-bromo-4-hydroxyquinoline-3-carboxylic acid ethyl ester 
• 29124-64-9 N-(2-acetyl-4-bromophenyl)acetamide 
• 68-12-2 N,N-dimethyl-formamide 

Downstream Products

• 766557-83-9 4-chloro-6-(phenylethynyl)quinoline 
• 878276-92-7 4-chloro-6-(4-chlorophenyl)quinoline 
• 500127-41-3 4-chloro-6-(4-methoxyphenyl)quinoline 
• 474707-20-5 6-bromo-4-(morpholin-4-yl)quinoline 
• 879324-21-7 6-bromo-4-phenoxyquinoline 
• 676256-25-0 4-chloroquinoline-6-carbaldehyde 
• 879323-85-0 6-bromo-4-cyclohexylmethoxy-quinoline 
• 1208116-16-8 C₂₀H₁₄N₂ 
• 1086056-63-4 C₂₅H₁₇F₂N₅O₂S 
• 1086057-39-7 C₂₅H₁₆F₂N₄O₂S 
• 1086061-45-1 C₂₅H₁₆F₂N₄O₂S 
• 1201841-63-5 N-(2-chloro-5-(4-chloroquinolin-6-yl)pyridin-3-yl)-4-fluorobenzenesulfonamide 
• 1201843-85-7 N-(2-chloro-5-(4-(dimethylamino)quinolin-6-yl)pyridin-3-yl)-4-fluorobenzenesulfonamide 
• 1201843-87-9 N-(2-chloro-5-(4-(2-methoxyethylamino)quinolin-6-yl)pyridin-3-yl)-4-fluorobenzenesulfonamide 

Relevant academic research and scientific papers

QUINOLINE-BASED COMPOUNDS AND METHODS OF INHIBITING CDK8/19

Disclosed herein are quinoline-based compounds and method for inhibiting CDK8 or CDK19 for the intervention in diseases, disorders, and conditions. The quinoline-based composition comprise substituents at quinoline ring positions 4 and 6, wherein the substituent at position 4 is selected from a substituted or unsubstituted arylalkylamine or a substituted or unsubstituted arylhetrocyclylamine. Pharmaceutical compositions comprising the substituted qunioline compositions, methods of inhibiting CDK8 or CDK19, and methods of treating CDK8/19-associated diseases, disorders, or conditions are also disclosed.

6-bromo-4-chloroquinoline preparation method

The invention discloses a 6-bromo-4-chloroquinoline preparation method. 4-bromaniline, ethyl propiolate, phosphorus trichloride and the like are used as raw materials to obtain a target product 6-bromo-4-chloroquinoline through three-step reaction. The 6-bromo-4-chloroquinoline preparation method is convenient and simple in operation and environment friendly, the comprehensive yield is 70% or above and remarkably increased as compared with existing yield which is 26-42%, existing medicine production cost is sharply reduced, and the 6-bromo-4-chloroquinoline preparation method is suitable for industrial mass production.

Combination of mTOR inhibitors and P13-kinase inhibitors, and uses thereof

The present invention provides for a method for treating a disease condition associated with PI3-kinase α and/or mTOR in a subject. In another aspect, the invention provides for a method for treating a disease condition associated with PI3-kinase α and/or mTOR in a subject. In yet another aspect, a method of inhibiting phosphorylation of both Akt (S473) and Akt (T308) in a cell is set forth.

PI3 kinase modulators and methods of use thereof, and use thereof

The invention belongs to the field of medicines, concretely relates to a compound for treating cancer, a composition and an application of the composition and particularly relates to a PI3 kinase regulator as well as a use method and application of the PI3 kinase regulator. The invention provides a compound as shown in the formula (I), a pharmaceutically accepted salt of the compound and a pharmaceutical preparation of the compound, wherein the compound is used for regulating the activity of protein kinase and intercellular or intracellular signal response. The invention also relates to a pharmaceutical composition containing the compound and a method for treating high-proliferative diseases of mammals and particularly human beings by using the pharmaceutical composition as shown in the formula (I).

COMBINATION OF KINASE INHIBITORS AND USES THEREOF

The present invention provides for a method for treating a disease condition associated with PI3-kinase a and/or a receptor tyrosine kinase (RTK) in a subject. In another aspect, the invention provides for a method for treating a disease condition associated with PI3-kinase α and/or an RTK in a subject. In yet another aspect, a method of inhibiting phosphorylation of Akt (S473) in a cell is set forth.

Indolo[3,2-c]quinoline G-quadruplex stabilizers: A structural analysis of binding to the human telomeric G-quadruplex

A library of 5-methylindolo[3,2-c]quinolones (IQc) with various substitution patterns of alkyldiamine side chains were evaluated for G-quadruplex (G4) binding mode and efficiency. Fluorescence resonance energy transfer melting assays showed that IQcs with a positive charge in the heteroaromatic nucleus and two weakly basic side chains are potent and selective human telomeric (HT) and gene promoter G4 stabilizers. Spectroscopic studies with HT G4 as a model showed that an IQc stabilizing complex involves the binding of two IQc molecules (2,9-bis{[3-(diethylamino)propyl]amino}-5-methyl-11H-indolo[3,2-c]quinolin-5-ium chloride, 3 d) per G4 unit, in two non-independent but equivalent binding sites. Molecular dynamics studies suggest that end-stacking of 3 d induces a conformational rearrangement in the G4 structure, driving the binding of a second 3 d ligand to a G4 groove. Modeling studies also suggest that 3 d, with two three-carbon side chains, has the appropriate geometry to participate in direct or water-mediated hydrogen bonding to the phosphate backbone and/or G4 loops, assisted by the terminal nitrogen atoms of the side chains. Additionally, antiproliferative studies showed that IQc compounds 2 d (2-{[3-(diethylamino)propyl]amino}-5-methyl-11H-indolo[3,2-c]quinolin-5-ium chloride) and 3 d are 7- to 12-fold more selective for human malignant cell lines than for nonmalignant fibroblasts.

Design, synthesis and biological evaluation of novel 4-alkynyl-quinoline derivatives as PI3K/mTOR dual inhibitors

Abstract A novel series of 4-alkynyl-quinoline derivatives were designed, synthesized and biologically evaluated for their PI3Kα inhibitory activities and anti-proliferative effects against two cancer cell lines PC-3 and HCT-116. Most of them showed potent PI3Kα inhibitory activities with IC50 values at low nanomolar level and good to excellent anti-proliferative effects against both cell lines. Among them, compound 15d, the most potent one, was selected for further biological evaluation. As a result, 15d displayed strong inhibitory activity against other class I PI3K isoforms (PI3Kβ, PI3Kγ and PI3Kδ) and mTOR with an acceptable kinase selectivity profile. Moreover, the western blot assay indicated that the phosphorylation of Akt, another downstream effector of PI3K, can be remarkably suppressed by 15d at cellular level. All these experimental results suggested that 15d is a potent PI3K/mTOR dual inhibitor and could serve as a promising lead compound for the development of anticancer agents.

HETEROCYCLIC COMPOUNDS AND USES THEREOF

Heterocyclic entities that modulate PI3 kinase activity, pharmaceutical compositions containing the heterocyclic entities, and methods of using these chemical entities for treating diseases and conditions associated with PI3 kinase activity are described herein.

Protozoan Parasite Growth Inhibitors Discovered by Cross-Screening Yield Potent Scaffolds for Lead Discovery

Tropical protozoal infections are a significant cause of morbidity and mortality worldwide; four in particular (human African trypanosomiasis (HAT), Chagas disease, cutaneous leishmaniasis, and malaria) have an estimated combined burden of over 87 million disability-adjusted life years. New drugs are needed for each of these diseases. Building on the previous identification of NEU-617 (1) as a potent and nontoxic inhibitor of proliferation for the HAT pathogen (Trypanosoma brucei), we have now tested this class of analogs against other protozoal species: T. cruzi (Chagas disease), Leishmania major (cutaneous leishmaniasis), and Plasmodium falciparum (malaria). Based on hits identified in this screening campaign, we describe the preparation of several replacements for the quinazoline scaffold and report these inhibitors' biological activities against these parasites. In doing this, we have identified several potent proliferation inhibitors for each pathogen, such as 4-((3-chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)-6-(4-((4-methyl-1,4-diazepan-1-yl)sulfonyl)phenyl)quinoline-3-carbonitrile (NEU-924, 83) for T. cruzi and N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)-7-(4-((4-methyl-1,4-diazepan-1-yl)sulfonyl)phenyl)cinnolin-4-amine (NEU-1017, 68) for L. major and P. falciparum.

COMBINATION OF KINASE INHIBITORS AND USES THEREOF

The present invention provides for a method for treating a disease condition associated with PI3-kinase a and/or mTOR in a subject. In another aspect, the invention provides for a method for treating a disease condition associated with PI3-kinase a and/or mTOR in a subject. In yet another aspect, a method of inhibiting phosphorylation of both Akt (S473) and Akt (T308) in a cell is set forth. The present invention also provides a pharmaceutical kit effective for treating a disease condition associated with PI3 -kinase α and/or mTOR in a subject.