139549-11-4

Upstream product

• 52189-63-6 3,5-dimethoxyfluorobenzene 
• 93-61-8 N-methyl-N-phenylformamide 
• 68-12-2 N,N-dimethyl-formamide 
• 4885-02-3 Dichloromethyl methyl ether 

Relevant academic research and scientific papers

Enzymatic Incorporation of a Coumarin–Guanine Base Pair

Previous expansions beyond nature's preferred base-pairing interactions have utilized either nonpolar shape-fitting interactions or classical hydrogen bonding. Reported here is a hybrid of these systems. By replacing a single N?H with C?H at a Watson–Crick interface, the design space for new drug candidates and fluorescent nucleobase analogues is dramatically expanded, as demonstrated here by the new, highly fluorescent deoxycytidine mimic 3-glycosyl-5-fluoro-7-methoxy-coumarin-2′-deoxyribose (dCC). dGTP is selectively incorporated across from a template dCC during enzymatic DNA synthesis. Likewise, dCC is selectively incorporated across from a template guanine when dCC is provided as the triphosphate dCCTP. DNA polymerase I (Klenow fragment) exhibited about a 10-fold higher affinity for dCCTP than dCTP, allowing selective incorporation of dCC in direct competition experiments. These results demonstrate that a single C?H can replace N?H at a Watson–Crick-type interface with preservation of functional selectivity and enhanced activity.

Phenoxy-N-phenylaniline derivative and application thereof

The invention relates to a phenoxy-N-phenylaniline derivative and an application thereof, and belongs to the technical field of novel colorectal cancer drugs. The present invention addresses the problem of providing some novel compounds having c-Myc inhibitory activity. The structural formula of the compound is shown as a formula I in the specification. According to the invention, a series of novel phenoxy-N-phenylaniline derivatives are designed and synthesized, and the compounds can be used as c-Myc inhibitors, have a good inhibition effect on the proliferation of colorectal cancer cells, and provide a new choice for colorectal cancer drugs.

Discovery of 4-(3,5-dimethoxy-4-(((4-methoxyphenethyl)amino)methyl)phenoxy)-N-phenylaniline as a novel c-myc inhibitor against colorectal cancer in vitro and in vivo

Proto-oncogene c-Myc plays an essential role in the development of colorectal cancer (CRC), since downregulation of c-Myc inhibits intestinal polyposis, which is the most cardinal pathological change in the development of CRC. Herein, a series of novel phenoxy-N-phenylaniline derivatives were designed and synthesized. The cytotoxicity activities of all the derivatives were measured by MTT assay in different colon cancer cells, 4-(3,5-dimethoxy-4-(((4-methoxyphenethyl)amino)methyl)phenoxy)-N-phenylaniline (42) was discovered, the lead compound 42 with excellent cytotoxicity activity of IC50 = 0.32 μM, IC50 = 0.51 μM, in HT29 and HCT 15 cells, respectively. Compound 42 had a good inhibitory activity of c-Myc/MAX dimerization and DNA binding. Besides, compound 42 could effectively induce apoptosis and induced G2/M arrest in low concentration and G0/G1 arrest in high concentration to prevent the proliferation and differentiation in colon cancer cells. Western blot analysis confirmed the 42 strongly down-regulated expression of c-Myc. Furthermore, during 30 days treatment 42 exhibited excellent efficacy in HT29 tumor xenograft model without causing significant weight loss and toxicity. Consequently, 42 could be a promising drug candidate for CRC therapy.

2,4-DIHYDROXY-NICOTINAMIDES AS APJ AGONISTS

The present invention provides compounds of Formula (I): wherein all variables are as defined in the specification, and compositions comprising any of such novel compounds. These compounds are APJ agonists which may be used as medicaments.

PROCESSES FOR PREPARING (E)-STYRYLBENZYLSULFONE COMPOUNDS AND USES THEREOF FOR TREATING PROLIFERATIVE DISORDERS

Processes for preparing (E)-2,4,6-(Trimethoxystyryl)-3-O-Phosphate Disodium-4-Methoxybenzyl Sulfones and uses thereof as antiproliferative agents, including, for example, anticancer agents, and as radioprotective and chemoprotective agents.

Design, synthesis, and biological evaluation of (E)-styrylbenzylsulfones as novel anticancer agents

Cell cycle progression is regulated by cyclins and cyclin-dependent kinases, which are formed at specific stages of the cell cycle and regulate the G1/S and G2/M phase transitions, employing a series of "checkpoints" governed by phosphorylation of their substrates. Tumor development is associated with the loss of these checkpoint controls, and this provides an approach for the development of therapeutic agents that can specifically target tumor cells. Here, we describe the synthesis and SAR of a novel group of cytotoxic molecules that selectively induce growth arrest of normal cells in the G1 phase while inducing a mitotic arrest of tumor cells resulting in selective killing of tumor cell populations with little or no effect on normal cell viability. The broad spectrum of antitumor activity in vitro and xenograft models, lack of in vivo toxicity, and drug resistance suggest potential for use of these agents in cancer therapy.

Biosynthesis of angular furanocoumarins: Mechanism and stereochemistry of the oxidative dealkylation of columbianetin to angelicin in Heracleum mantegazzianum (Apiaceae)

Deuterium-labelled 5-fluorocolumbianetin 13 was synthesized as a metabolic probe to examine the stereochemical course of the bioconversion of (+)-columbianetin (12) into the angular furocoumarin angelicin (5). In leaves of Heracleum mantegazzianum, oxidative dealkylation of the specifically deuterated fluorocolumbianetin 13 proceeded by syn-elimination of a D-atom, from C(9), and the vicinal 1-hydroxy-1-methylethyl substituent, yielding 5- fluoroangelicin (23). This matches the stereochemical course of the related reaction converting (+)-marmesin (10) into the linear furocoumarin psoralen (1). Key steps in the synthesis of 5-fluorocolumbianetin (13) were the copper-catalysed alkynylation/cyclization of 5-fluoro-8-iodoumbelliferone (15) followed by a transfer hydrogenation, which established the cis- orientation of the D-Atom and the 1-hydroxy-1-methylethyl substituent.