41995-04-4

Upstream product

• 6280-88-2 4-chloro-2-nitro-benzoic acid 
• 89-59-8 4-chloro-2-nitrotoluene 
• 34662-32-3 4-chloro-2-nitrobenzonitrile 
• 89-63-4 4-Chloro-2-nitroaniline 

Downstream Products

• 859962-09-7 (4-chloro-2-nitro-phenyl)-[2]furyl ketone 
• 22978-09-2 4-Chloro-N-cyanomethyl-2-nitro-benzamide 
• 23082-51-1 4'-chloro-2'-nitroacetophenone 
• 20895-89-0 diethyl 2-(4-chloro-2-nitro-benzoyl)-malonate 
• 63931-26-0 2-[(4-Chloro-2-nitro-benzoyl)-methyl-amino]-malonic acid diethyl ester 
• 144485-98-3 4-Chloro-N-(3-methyl-isoxazol-5-yl)-2-nitro-benzamide 
• 1032-41-3 4-chloro-N-(2-chloro-pyridin-3-yl)-2-nitro-benzamide 
• 120123-76-4 4-Chloro-N-(2-imidazol-1-ylmethyl-phenyl)-2-nitro-benzamide 
• 211563-70-1 [5-(4-Chloro-2-nitro-benzoylamino)-1-methyl-1H-pyrazol-4-yl]-acetic acid ethyl ester 
• 229978-35-2 4-chloro-N-(5-methyl-isoxazol-3-yl)-2-nitro-benzamide 
• 223462-00-8 4-chloro-2-nitro-N-(3-phenyl-isoxazol-5-yl)-benzamide 
• 41994-91-6 4-chloro-2-nitrobenzoic amide 
• 349406-24-2 2-nitro-4-chlorobenzanilide 
• 611199-33-8 diethyl 2-(4-chloro-2-nitrobenzoyl)malonate 

Relevant academic research and scientific papers

AROMATIC DERIVATIVE, PREPARATION METHOD FOR SAME, AND MEDICAL APPLICATIONS THEREOF

The present invention relates to an aromatic derivative, a preparation method thereof and medical applications thereof. Particularly, the present invention relates to a novel compound as shown in the general formula (I) and a pharmaceutically acceptable s

2-Aminoquinazolin-4(3H)-one based plasmepsin inhibitors with improved hydrophilicity and selectivity

2-Aminoquinazolin-4(3H)-ones were previously discovered as perspective leads for antimalarial drug development targeting the plasmepsins. Here we report the lead optimization studies with the aim to reduce inhibitor lipophilicity and increase selectivity

INHIBITORS OF KRAS G12C

Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I): or a pharmaceutically acceptable salt, tautomer, prodrug or stereoisomer thereof, wherein R1, R2a, R3a, R3b, R4a, R4b, G1, G2, L1, L2, m1, m2, A, B, W, X, Y, Z and E are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided.

Structure-activity relationships for lipoprotein lipase agonists that lower plasma triglycerides in vivo

The risk of cardiovascular events increases in individuals with elevated plasma triglyceride (TG) levels, therefore advocating the need for efficient TG-lowering drugs. In the blood circulation, TG levels are regulated by lipoprotein lipase (LPL), an unstable enzyme that is only active as a non-covalently associated homodimer. We recently reported on a N-phenylphthalimide derivative (1) that stabilizes LPL in vitro, and moderately lowers triglycerides in vivo (Biochem. Biophys. Res. Commun. 2014, 450, 1063). Herein, we establish structure-activity relationships of 51 N-phenylphthalimide analogs of the screening hit 1. In vitro evaluation highlighted that modifications on the phthalimide moiety were not tolerated and that lipophilic substituents on the central phenyl ring were functionally essential. The substitution pattern on the central phenyl ring also proved important to stabilize LPL. However, in vitro testing demonstrated rapid degradation of the phthalimide fragment in plasma which was addressed by replacing the phthalimide scaffold with other heterocyclic fragments. The in vitro potency was retained or improved and substance 80 proved stable in plasma and efficiently lowered plasma TGs in vivo.

Synthesis and Quantitative Structure-Activity Relationships of Selective BCRP Inhibitors

The breast cancer resistance protein (BCRP/ABCG2) is a member of the ABC transporter superfamily. This protein has a number of physiological functions, including protection of the human body from xenobiotics. The overexpression of BCRP in certain tumor cell lines causes cross-resistance against various drugs used in chemotherapeutic treatment. In a previous work we showed that a new class of compounds derived from XR9576 (tariquidar) selectively inhibits BCRP. In this work we synthesized more members of this class, with modification on the second and third aromatic rings. The inhibitory activities against BCRP and P-gp were assayed using a Hoechst 33342 assay for BCRP and a calcein AM assay for P-gp. Finally, quantitative structure-activity relationships for both aromatic rings were established. The results obtained show the importance of the electron density on the third aromatic ring, influenced by substituents, pointing to interactions with aromatic residues of the protein binding site. In the second aromatic ring the activity of compounds is influenced by the steric volume of the substituents.

New quinazoline derivatives for telomeric G-quadruplex DNA: Effects of an added phenyl group on quadruplex binding ability

To improve the selectivity of indoloquinoline or benzofuroquinoline derivatives, we previously reported several quinazoline derivatives [17]. These compounds could mimic a tetracyclic aromatic system through intramolecular hydrogen bond. Studies showed that these quinazoline derivatives were effective and selective telomeric G-quadruplex ligands. With this encouragement, here we synthesized a series of N-(2-(quinazolin-2-yl)phenyl)benzamide (QPB) compounds as modified quinazoline derivatives. In this modification, a phenyl group was introduced to the aromatic core. The evaluation results showed that part of QPB derivatives had stronger binding ability and better selectivity for telomeric G-quadruplex DNA than LZ-11, the most potential compound of reported quinazoline derivatives. Furthermore, telomerase inhibition of QPB derivatives and their cellular effects were studied.

Disubstituted quinazoline derivatives as a new type of highly selective ligands for telomeric G-quadruplex DNA

A series of 2,4-disubstituted quinazoline derivatives found to be a new type of highly selective ligand to bind with telomeric G-quadruplex DNA, and their biological properties were reported for the first time.Their interactions with telomeric G-quadruplex DNA were evaluated by using fluorescence resonance energy transfer (FRET) melting assay, circular dichroism (CD) spectroscopy, surface plasmon resonance (SPR), nuclear magnetic resonance (NMR), and molecular modeling. Our results showed that these derivatives could well recognize G-quadruplex and have high selectivity toward G-quadruplex over duplex DNA. The structure-activity relationships (SARs) study revealed that the disubstitution of quinazoline and the length of the amide side chain were important for its interaction with the G-quadruplex. Furthermore, telomerase inhibition of the quinazoline derivatives and their cellular effects were studied.

Synthesis, biological evaluation, and structure-activity relationships of 2-[2-(benzoylamino)benzoylamino]benzoic acid analogues as inhibitors of adenovirus replication

2-[2-Benzoylamino)benzoylamino]benzoic acid (1) was previously identified as a potent and nontoxic antiadenoviral compound (Antimicrob. Agents Chemother. 2010, 54, 3871). Here, the potency of 1 was improved over three generations of compounds. We found that the ortho, ortho substituent pattern and the presence of the carboxylic acid of 1 are favorable for this class of compounds and that the direction of the amide bonds (as in 1) is obligatory. Some variability in the N-terminal moiety was tolerated, but benzamides appear to be preferred. The substituents on the middle and C-terminal rings were varied, resulting in two potent inhibitors, 35g and 35j, with EC50 = 0.6 μM and low cell toxicity.

Synthesis and Preliminary Biologic Evaluation of 5-Substituted-2-(4-substituted phenyl)-1,3-Benzoxazoles as A Novel Class of Influenza Virus A Inhibitors

The diversity-oriented chemistry synthesis together with the random screening approach has permitted the discovery and optimization of novel antiviral lead compounds. In this paper, a series of novel 5-substituted-2-(4-substituted phenyl)-1,3-benzoxazoles was synthesized and evaluated for their in vitro anti-influenza A virus and anti-influenza B virus activity. The activity was monitored by the MTS assay in the Madin-Darby canine kidney cells. Compound 7h showed excellent inhibitory activity and selective index against A/H3N2 (EC50=37.03μm, SI>5), which were all higher than that of the reference drug oseltamivir (EC50>59.00μm, SI>1). However, no compound displays inhibitory activity against influenza B virus.

Efficient synthesis of naturally occurring skeleton 5-7-6 tricyclic pyrrolo[2,1- c ][1,4]benzodiazepin-5-one and its derivatives via cationic π-cyclization

An efficient method for the synthesis of a library based on the naturally occurring 5-7-6 tricyclic 5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one skeleton and its derivatives via cationic π-(7-endo) cyclization is described. Georg Thieme Verlag Stuttgart - New York.