3998-28-5

Upstream product

• 2486-69-3 3-methoxy-4-aminobenzoic acid 
• 89-75-8 2,4-dichlorobenzoyl chloride 
• 50-84-0 2,4 dichlorobenzoic acid 
• 79-37-8 oxalyl dichloride 
• 2447-79-2 2,4-dichlorobenzamide 

Downstream Products

• 866329-48-8 acetic acid 3-[3-(2,4-dichlorobenzoyl)ureido]phenyl ester 
• 127085-54-5 1-(2,4-dichlorobenzoyl)-3-isobutyl-3-<1-(1'-benzyl-4'-imidazolyl)-3-hydroxyprop-2(S)-yl>urea 
• 127064-15-7 1-(2,4-dichlorobenzoyl)-3-ethyl-3-<1-(1'-benzyl-4'-imidazolyl)-3-hydroxyprop-2(S)-yl>urea 
• 1267610-50-3 2,4-dichloro-N-((4-(N-(2-(diethylamino)ethyl)-N-(4,6-dimethylpyrimidin-2-yl)sulfamoyl)phenyl)carbamoyl)benzamide 
• 66913-71-1 1-(N-2,4-dichlorobenzoyl-carbamoyl)-2-cyanoaziridine 
• 127064-23-7 3-Benzyl-5-[(S)-1-(2,4-dichloro-benzoyl)-3-isobutyl-2-oxo-imidazolidin-4-ylmethyl]-1-methyl-3H-imidazol-1-ium; iodide 
• 127064-12-4 3-Benzyl-5-[(S)-1-(2,4-dichloro-benzoyl)-3-ethyl-2-oxo-imidazolidin-4-ylmethyl]-1-methyl-3H-imidazol-1-ium; iodide 
• 127064-22-6 N-[(S)-4-(1-Benzyl-1H-imidazol-4-ylmethyl)-3-isobutyl-oxazolidin-(2Z)-ylidene]-2,4-dichloro-benzamide 
• 127064-21-5 (S)-1-(2,4-dichlorobenzoyl)-3-isobutyl-4-<(1'-benzyl-4'-imidazolyl)-methyl>-2-imidazolidinone 

Relevant academic research and scientific papers

Aroyl Isocyanates as 1,4-Dipoles in a Formal [4 + 1]-Cycloaddition Approach toward Oxazolone Construction

A formal phosphine-mediated [4 + 1]-cycloaddition between a 1,2-dicarbonyl and an aroyl isocyanate to provide oxazolones bearing a disubstituted C5 center is described. By exploiting the carbene-like reactivity of oxyphosphonium enolates as C1 synthons and aroyl isocyanates as formal 1,4-dipoles, oxazolones and spiroooxindole oxazolones are constructed in high yields (39-99%).

2-OXOQUINAZOLINE DERIVATIVES AS METHIONINE ADENOSYLTRANSFERASE 2A INHIBITORS

Disclosed herein are certain 2-oxoquinazoline derivatives of Formula (IA): (IA) that are methionine adenosyltransferase 2A (MAT2A) inhibitors. Also disclosed are pharmaceutical compositions comprising such compounds and methods of treating diseases treatable by inhibition of MAT2A such as cancer, including cancers characterized by reduced or absence of methylthioadenosine phosphorylase (MTAP) activity.

Novel acyl carbamates and acyl / diacyl ureas show in vitro efficacy against Toxoplasma gondii and Cryptosporidium parvum

Toxoplasma gondii and Cryptosporidium parvum are protozoan parasites that are highly prevalent and opportunistically infect humans worldwide, but for which completely effective and safe medications are lacking. Herein, we synthesized a series of novel small molecules bearing the diacyl urea scaffold and related structures, and screened them for in vitro cytotoxicity and antiparasitic activity against T. gondii and C. parvum. We identified one compound (GMG-1-09), and four compounds (JS-1-09, JS-2-20, JS-2-35 and JS-2-49) with efficacy against C. parvum and T. gondii, respectively, at low micromolar concentrations and showed appreciable selectivity in human host cells. Among the four compounds with efficacy against T. gondii, JS-1-09 representing the diacyl urea scaffold was the most effective, with an anti-Toxoplasma IC50 concentration (1.21 μM) that was nearly 53-fold lower than its cytotoxicity IC50 concentration, indicating that this compound has a good selectivity index. The other three compounds (JS-2-20, JS-2-35 and JS-2-49) were structurally more divergent from JS-1-09 as they represent the acyl urea and acyl carbamate scaffold. This appeared to correlate with their anti-Toxoplasma activity, suggesting that these compounds’ potency can likely be enhanced by selective structural modifications. One compound, GMG-1-09 representing acyl carbamate scaffold, depicted in vitro efficacy against C. parvum with an IC50 concentration (32.24 μM) that was 14-fold lower than its cytotoxicity IC50 concentration in a human intestinal cell line. Together, our studies unveil a series of novel synthetic acyl/diacyl urea and acyl carbamate scaffold-based small molecule compounds with micromolar activity against T. gondii and C. parvum that can be explored further for the development of the much-needed novel anti-protozoal drugs.

Investigation of novel pesticides with insecticidal and antifungal activities: Design, synthesis and SAR studies of benzoylpyrimidinylurea derivatives

In order to find pesticides with insecticidal and antifungal activities, a series of novel benzoyl pyrimidinylurea derivatives were designed and synthesized. All target compounds were identified by 1H-NMR spectroscopy and HRMS. Insecticidal and antifungal activity of these compounds were evaluated and the structure-activity relationships (SAR) were clearly and comprehensively illustrated. Compound 7, with low toxicity to zebrafish (LC50 = 378.387 μg mL?1) showed 100% inhibition against mosquito (Culex pipiens pallens) at 0.25 μg mL?1. Both compounds 19 and 25 exhibited broad-spectrum fungicidal activity (>50% inhibitory activities against 13 phytopathogenic fungi), which were better than those of the commercial pesticide pyrimethanil (>50% inhibitory activities against eight phytopathogenic fungi). Furthermore, compounds 19 and 25 exhibited protective activity against Sclerotinia sclerotiorum on leaves of Brassica oleracea L. during in vivo experiments.

Design, synthesis and fungicidal activity of N-substituted benzoyl-1,2,3,4-tetrahydroquinolyl-1-carboxamide

To find a new lead compound with high biological activity, a series of N-substituted benzoyl-1,2,3,4-tetrahydroquinolyl-1-carboxamide were designed using linking active substructures method. The target compounds were synthesized from substituted benzoic acid by four steps and their structures were confirmed by 1H NMR, IR spectrum and elemental analysis. The in vitro bioassay results indicated that some target compounds exhibited excellent fungicidal activities, and the position of the substituents played an important role in fungicidal activities. Especially, compound 5n, exhibited better fungicidal activities than the commercial fungicide flutolanil against two tested fungi Valsa Mali and Sclerotinia sclerotiorum, with EC50 values of 3.44 and 2.63 mg/L, respectively. And it also displayed good in vivo fungicidal activity against S. sclerotiorum with the EC50 value of 29.52 mg/L.

Synthesis, antitumor activity and mechanism of action of novel 1,3-thiazole derivatives containing hydrazide–hydrazone and carboxamide moiety

A series of novel 2,4,5-trisubstituted 1,3-thiazole derivatives containing hydrazide–hydrazine, and carboxamide moiety including 46 compounds T were synthesized, and evaluated for their antitumor activity in vitro against a panel of five human cancer cell lines. Eighteen title compounds T displayed higher inhibitory activity than that of 5-Fu against MCF-7, HepG2, BGC-823, Hela, and A549 cell lines. Especially, T1, T26 and T38 exhibit best cytotoxic activity with IC50values of 2.21?μg/mL, 1.67?μg/mL and 1.11?μg/mL, against MCF-7, BCG-823, and HepG2 cell lines, respectively. These results suggested that the combination of 1,3-thiazole, hydrazide–hydrazone, and carboxamide moiety was much favorable to cytotoxicity activity. Furthermore, the flow cytometry analysis revealed that compounds T1 and T38 could induce apoptosis in HepG2 cells, and it was confirmed T38 led the induction of cell apoptosis by S cell-cycle arrest.

PHOSPHATIDYLCHOLINE TRANSFER PROTEIN INHIBITORS

This invention relates to compounds of Formulas I, II, and III, and their use as inhibitors of phosphatidylcholine transfer protein (PC-TP). The invention further relates to pharmaceutical compositions and methods of treatment of disorders related to the

Acyl ureas as human liver glycogen phosphorylase inhibitors for the treatment of type 2 diabetes

Using a focused screening approach, acyl ureas have been discovered as a new class of inhibitors of human liver glycogen phosphorylase (hiGPa). The X-ray structure of screening hit 1 (IC50 = 2 μM) in a complex with rabbit muscle glycogen phosphorylase b reveals that 1 binds at the AMP site, the main allosteric effector site of the dimeric enzyme. A first cycle of chemical optimization supported by X-ray structural data yielded derivative 21, which inhibited hlGPa with an IC50 of 23 ± 1 nM, but showed only moderate cellular activity in isolated rat hepatocytes (IC50 = 6.2 μM). Further optimization was guided by (i) a 3D pharmacophore model that was derived from a training set of 24 compounds and revealed the key chemical features for the biological activity and (ii) the 1.9 A? crystal structure of 21 in complex with hlGPa. A second set of compounds was synthesized and led to 42 with improved cellular activity (hlGPa IC50 = 53 ± 1 nM; hepatocyte IC50 = 380 nM). Administration of 42 to anaesthetized Wistar rats caused a significant reduction of the glucagon-induced hyperglycemic peak. These findings are consistent with the inhibition of hepatic glycogenolysis and support the use of acyl ureas for the treatment of type 2 diabetes.

Acylcarboxylic-3-coarboxyphenyl urea derivatives, its manufacturing method and use thereof

The invention relates to acyl-3-carboxyphenylurea derivatives, physiologically-acceptable salts, physiologically-functional derivatives thereof and compounds of formula (I), where the groups have the given meanings, the physiologically-acceptable salts an

Carboxamide-substituted phenylurea derivatives, process for their preparation and their use as medicaments

The invention relates to carboxamide-substituted phenylurea derivatives and their physiologically tolerated salts and physiologically functional derivatives. Compounds of the formula I in which the radicals have the stated meanings, and the physiologicall