385784-84-9

Upstream product

• 4421-08-3 3-methoxy-4-hydroxybenzonitrile 
• 100-39-0 benzyl bromide 
• 52805-46-6 2-methoxy-5-cyanophenol 
• 100-44-7 benzyl chloride 
• 2426-87-1 3-methoxy-4-(phenylmethoxy)benzaldehyde 
• 52805-34-2 4-(benzyloxy)-3-methoxybenzonitrile 

Downstream Products

• 385784-85-0 2-nitro-4-hydroxy-5-methoxybenzonitrile 
• 1320288-38-7 7-(benzyloxy)-2-cyclohexyl-6-methoxyquinazolin-4(3H)-one 
• 1320288-39-8 7-(benzyloxy)-4-chloro-2-cyclohexyl-6-methoxyquinazoline 
• 1320288-41-2 7-(benzyloxy)-2-cyclohexyl-N-(1-isopropylpiperidin-4-yl)-6-methoxyquinazolin-4-amine 
• 1255580-76-7 2-cyclohexyl-6-methoxy-N-[1-(1-methylethyl)-4-piperidinyl]-7-[3-(1-pyrrolidinyl)propoxy]-4-quinazolinamine 
• 1320288-42-3 C₂₃H₃₄N₄O₂ 
• 1320288-63-8 2-cyclohexyl-N-(1-isopropylpiperidin-4-yl)-6-methoxy-7-(3-(piperidin-1-yl)propoxy)quinazolin-4-amine 
• 1320288-64-9 2-cyclohexyl-7-(2-(2-(dimethylamino)ethoxy)ethoxy)-N-(1-isopropylpiperidin-4-yl)-6-methoxyquinazolin-4-amine 
• 60771-18-8 7-(benzyloxy)-2,4-dichloro-6-methoxyquinazoline 
• 60547-98-0 2-amino-4-benzyloxy-5-methoxybenzamide 
• 443913-73-3 vandetanib 
• 338992-12-4 N-Desmethylvandetanib 
• 338992-20-4 4-(((4-((4-bromo-2-fluorophenyl)amino)-6-methoxyquinazolin-7-yl)oxy)methyl)piperidine-1-carboxylic acid tert-butyl ester 
• 723283-25-8 (E)-tert-butyl 4-((4-cyano-5-(((dimethylamino)methylene)amino)-2-methoxyphenoxy)methyl)piperidine-1-carboxylate 

Relevant academic research and scientific papers

Tyrosine kinase inhibitors implant he loni and its key intermediate for the preparation of

The invention discloses tyrosine kinase inhibitor implant he loni and its key intermediate of the preparation method, which belongs to the medicine, in the field of fine chemicals. The invention of the preparation method of gefitinib, is a brand-new preparation scheme, from whatever a intermediate starting, can be obtained in accordance with the requirements of the target compound. The method of the invention has short steps, the reaction operation is simple, safe and reliable, high yield, low cost, high purity, pollution little and simple operation and the like.

An alternative synthesis of Vandetanib (Caprelsa) via a microwave accelerated Dimroth rearrangement

Vandetanib is an orally available tyrosine kinase inhibitor used in the treatment of cancer. The current synthesis proceeds via an unstable 4-chloroquinazoline, using harsh reagents, in addition to requiring sequential protection and deprotection steps. In the present work, use of the Dimroth rearrangement in the key quinazoline forming step enabled the synthesis of Vandetanib in nine steps (compared to the previously reported 12–14).

Cellular Compositions Used To Restore Stem Cell or Progenitor Cell Function and Methods Related Thereto

This disclosure relates to compounds, compositions and methods of epigenetically transforming cells. In certain embodiments, the disclosure relates to methods of generating epigenetically altered cells comprising mixing isolated cells with compositions di

BLOCKING TOLL-LIKE RECEPTOR 9 SIGNALING WITH SMALL MOLECULE ANTAGONIST

The present invention relates to small molecule4-(piperazin-1-yl)quinazolin-2-amino compounds with formula (I) useful for inhibiting signalling by certain toll-like receptors (TLRs), especially TLR9. Toll-like receptors (TLRs) are members of the larger family of evolutionarily conserved pattern recognition receptors which are critical first line of defence for self-nonself discrimination by the host immune response. Aberrant TLR9 activation is implicated in autoreactive inflammation in different autoimmune diseases. The invention depicts compounds with formula (I), composition and methods can be used in a number of clinical applications, including as pharmaceutical agents and methods for treating conditions involving unwanted immune activity due to TLR9 activation.

Identification and Structure–Activity Relationship Studies of Small-Molecule Inhibitors of the Methyllysine Reader Protein Spindlin1

The methyllysine reader protein Spindlin1 has been implicated in the tumorigenesis of several types of cancer and may be an attractive novel therapeutic target. Small-molecule inhibitors of Spindlin1 should be valuable as chemical probes as well as potential new therapeutics. We applied an iterative virtual screening campaign, encompassing structure- and ligand-based approaches, to identify potential Spindlin1 inhibitors from databases of commercially available compounds. Our in silico studies coupled with in vitro testing were successful in identifying novel Spindlin1 inhibitors. Several 4-aminoquinazoline and quinazolinethione derivatives were among the active hit compounds, which indicated that these scaffolds represent promising lead structures for the development of Spindlin1 inhibitors. Subsequent lead optimization studies were hence carried out, and numerous derivatives of both lead scaffolds were synthesized. This resulted in the discovery of novel inhibitors of Spindlin1 and helped explore the structure–activity relationships of these inhibitor series.

Compounds and compositions used to epigenetically transform cells and methods related thereto

This disclosure relates to compounds, compositions and methods of epigenetically transforming cells. In certain embodiments, the disclosure relates to methods of generating epigenetically altered cells comprising mixing isolated cells with compositions di

Optimization of cellular activity of G9a inhibitors 7-aminoalkoxy- quinazolines

Protein lysine methyltransferase G9a plays key roles in the transcriptional repression of a variety of genes via dimethylation of lysine 9 on histone H3 (H3K9me2) of chromatin as well as dimethylation of nonhistone proteins including tumor suppressor p53. We previously reported the discovery of UNC0321 (3), the most potent G9a inhibitor to date, via structure-based design and structure-activity relationship (SAR) exploration of the quinazoline scaffold represented by BIX01294 (1). Despite its very high in vitro potency, compound 3 lacks sufficient cellular potency. The design and synthesis of several generations of new analogues aimed at improving cell membrane permeability while maintaining high in vitro potency resulted in the discovery of a number of novel G9a inhibitors such as UNC0646 (6) and UNC0631 (7) with excellent potency in a variety of cell lines and excellent separation of functional potency versus cell toxicity. The design, synthesis, and cellular SAR of these potent G9a inhibitors are described.

Protein lysine methyltransferase g9a inhibitors: Design, synthesis, and structure activity relationships of 2,4-diamino-7-aminoalkoxy-quinazolines.

Protein lysine methyltransferase G9a, which catalyzes methylation of lysine 9 of histone H3 (H3K9) and lysine 373 (K373) of p53, is overexpressed in human cancers. Genetic knockdown of G9a inhibits cancer cell growth, and the dimethylation of p53 K373 results in the inactivation of p53. Initial SAR exploration of the 2,4-diamino-6,7-dimethoxyquinazoline template represented by 3a (BIX01294), a selective small molecule inhibitor of G9a and GLP, led to the discovery of 10 (UNC0224) as a potent G9a inhibitor with excellent selectivity. A high resolution X-ray crystal structure of the G9a?10 complex, the first cocrystal structure of G9a with a small molecule inhibitor, was obtained. On the basis of the structural insights revealed by this cocrystal structure, optimization of the 7-dimethylaminopropoxy side chain of 10 resulted in the discovery of 29 (UNC0321) (Morrison Ki = 63 pM), which is the first G9a inhibitor with picomolar potency and the most potent G9a inhibitor to date.

Discovery of a 2,4-diamino-7-aminoalkoxyquinazoline as a potent and selective inhibitor of histone lysine methyltransferase G9a

SAR exploration of the 2,4-diamino-6,7-dimethoxyquinazoline template led to the discovery of 8 (UNC0224) as a potent and selective G9a inhibitor. A high resolution X-ray crystal structure of the G9a-8 complex, the first cocrystal structure of G9a with a small molecule inhibitor, was obtained. The cocrystal structure validated our binding hypothesis and will enable structure-based design of novel inhibitors. 8 is a useful tool for investigating the biology of G9a and its roles in chromatin remodeling.

Discovery of novel and potent thiazoloquinazolines as selective Aurora A and B kinase inhibitors

The synthesis of a novel series of quinazolines substituted at C4 by five-membered ring aminoheterocycles is reported. Their in vitro structure-activity relationships versus Aurora A and B serine-threonine kinases is discussed. Our results demonstrate tha