1580-37-6

Upstream product

• 89-55-4 5-bromosalicyclic acid 
• 98-16-8 3-trifluoromethylaniline 

Downstream Products

• 1552270-21-9 4-bromo-2-{[3-(trifluoromethyl)phenyl]carbamoyl}phenyl diethyl phosphate 

Relevant academic research and scientific papers

Salicylanilide diethyl phosphates as cholinesterases inhibitors

Based on the presence of dialkyl phosphate moiety, we evaluated twenty-seven salicylanilide diethyl phosphates (diethyl [2-(phenylcarbamoyl)phenyl] phosphates) for the inhibition of acetylcholinesterase (AChE) from electric eel (Electrophorus electricus L.) and butyrylcholinesterase (BChE) from equine serum. Ellman's spectrophotometric method was used. The inhibitory activity (expressed as IC50 values) was compared with that of the established drugs galantamine and rivastigmine. Salicylanilide diethyl phosphates showed significant activity against both cholinesterases with IC50 values from 0.903 to 86.3 μM. IC50s for BChE were comparatively lower than those obtained for AChE. All of the investigated compounds showed higher inhibition of AChE than rivastigmine, and six of them inhibited BChE more effectively than both rivastigmine and galantamine. In general, derivatives of 4-chlorosalicylic acid showed enhanced activity when compared to derivatives of 5-halogenated salicylic acids, especially against BChE. The most effective inhibitor of AChE was O-{5-chloro-2-[(3-bromophenyl)carbamoyl]phenyl} O,O-diethyl phosphate with IC50 of 35.4 μM, which is also one of the most potent inhibitors of BChE. O-{5-Chloro-2-[(3,4-dichlorophenyl)carbamoyl]phenyl} O,O-diethyl phosphate exhibited in vitro the strongest inhibition of BChE (0.90 μM). Salicylanilide diethyl phosphates act as pseudo-irreversible cholinesterases inhibitors.

2-Hydroxy-N-Phenylbenzamides and their esters inhibit acetylcholinesterase and Butyrylcholinesterase

The development of novel inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) represents a viable approach to alleviate Alzheimer’s disease. Thirty-six halogenated 2-hydroxy-N-phenylbenzamides (salicylanilides) with various substitution patterns and their esters with phosphorus-based acids were synthesized in yields of 72% to 92% and characterized. They were evaluated for in vitro inhibition of AChE from electric eel and BuChE from equine serum using modified Ellman’s spectrophotometric method. The benzamides exhibited a moderate inhibition of AChE with IC50 values in a narrow concentration range from 33.1 to 85.8 μM. IC50 values for BuChE were higher (53.5–228.4 μM). The majority of derivatives inhibit AChE more efficiently than BuChE and are comparable or superior to rivastigmine—an established cholinesterases inhibitor used in the treatment of Alzheimer’s disease. Phosphorus-based esters especially improved the activity against BuChE with 5-chloro-2-{[4-(trifluoromethyl)phenyl]carbamoyl}phenyl diethyl phosphite 5c superiority (IC50 = 2.4 μM). This derivative was also the most selective inhibitor of BuChE. It caused a mixed inhibition of both cholinesterases and acted as a pseudo-irreversible inhibitor. Several structure-activity relationships were identified, e.g., favouring esters and benzamides obtained from 5-halogenosalicylic acids and polyhalogenated anilines. Both 2-hydroxy-N-phenylbenzamides and esters share convenient physicochemical properties for blood-brain-barrier penetration and thus central nervous system delivery.

Salicylanilide diethyl phosphates: Synthesis, antimicrobial activity and cytotoxicity

A series of 27 salicylanilide diethyl phosphates was prepared as a part of our on-going search for new antimicrobial active drugs. All compounds exhibited in vitro activity against Mycobacterium tuberculosis, Mycobacterium kansasii and Mycobacterium avium strains, with minimum inhibitory concentration (MIC) values of 0.5-62.5 μmol/L. Selected salicylanilide diethyl phosphates also inhibit multidrug-resistant tuberculous strains at the concentration of 1 μmol/L. Salicylanilide diethyl phosphates also exhibited mostly the activity against Gram-positive bacteria (MICs ≥1.95 μmol/L), whereas their antifungal activity is significantly lower. The IC50 values for Hep G2 cells were within the range of 1.56-33.82 μmol/L, but there is no direct correlation with MICs for mycobacteria.

Diethyl 2-(phenylcarbamoyl)phenyl phosphorothioates: Synthesis, antimycobacterial activity and cholinesterase inhibition

A new series of 27 diethyl 2-(phenylcarbamoyl)phenyl phosphorothioates (thiophosphates) was synthesized, characterized by NMR, IR and CHN analyses and evaluated against Mycobacterium tuberculosis H37Rv, Mycobacterium avium and two strains of Mycobacterium kansasii. The best activity against M. tuberculosis was found for O-{4-bromo-2-[(3,4-dichlorophenyl)carbamoyl]phenyl} O,O-diethyl phosphorothioate (minimum inhibitory concentration of 4 iM). The highest activity against nontuberculous mycobacteria was exhibited by O-(5-chloro-2-{[4-(trifluoromethyl)phenyl]carbamoyl}- phenyl) O,O-diethyl phosphorothioate with MIC values from 16 iM. Prepared thiophosphates were also evaluated against acetylcholinesterase from electric eel and butyrylcholinesterase from equine serum. Their inhibitory activity was compared to that of the known cholinesterases inhibitors galanthamine and rivastigmine. All tested compounds showed a higher (for AChE inhibition) and comparable (for BChE inhibition) activity to that of rivastigmine, with IC50s within the 8.04 to 20.2 iM range.

NF-KB ACTIVATION INHIBITORS

A medicament having inhibitory activity against NF-κB activation which comprises as an active ingredient a substance selected from the group consisting of a compound represented by the following general formula (I) and a pharmacologically acceptable salt thereof, and a hydrate thereof and a solvate thereof: wherein A represents hydrogen atom or acetyl group, E represents a 2,5-di-substituted or a 3,5-di-substituted phenyl group, or a monocyclic or a fused polycyclic heteroaryl group which may be substituted, provided that the compound wherein said heteroaryl group is 1○ a fused polycyclic heteroaryl group wherein the ring which binds directly to ―CONH― group in the formula (I) is a benzene ring, 2○ unsubstituted thiazol-2-yl group, or 3○ unsubstituted benzothiazol-2-yl group is excluded, ring Z represents an arene which may have one or more substituents in addition to the group represented by formula ―O―A wherein A has the same meaning as that defined above and the group represented by formula -CONH-E wherein E has the same meaning as that defined above, or a heteroarene which may have one or more substituents in addition to the group represented by formula ―O―A wherein A has the same meaning as that defined above and the group represented by formula ― CONH―E wherein E has the same meaning as that defined above.

INHIBITORS AGAINST THE ACTIVATION OF AP-1 AND NFAT

A medicament inhibiting the activation of AP-1 which comprises as an active ingredient a substance selected from the group consisting of a compound represented by the following general formula (I) and a pharmacologically acceptable salt thereof, and a hydrate thereof and a solvate thereof: wherein X represents a connecting group whose number of atoms in the main chain is 2 to 5 (said connecting group may be substituted), A represents hydrogen atom or acetyl group, E represents an aryl group which may be substituted or a hetero aryl group which may be substituted, ring Z represents an arene which may have one or more substituents in addition to the group represented by formula -O-A wherein A has the same meaning as that defined above and the group represented by formula -X-E wherein each of X and E has the same meaning as that defined above, or a heteroarene which may have one or more substituents in addition to the group represented by formula -O-A wherein A has the same meaning as that defined above and the group represented by formula -X-E wherein each of X and E has the same meaning as that defined above.

IMMUNITY-RELATED PROTEIN KINASE INHIBITORS

[From equivalent EP1510210A1] A medicament having an inhibitory activity against IKK-Aβ and/or MEKK-1 or other protein kinases structurally similar thereto, which comprises as an active ingredient a substance selected from the group consisting of a compound represented by the following general formula (I) and a pharmacologically acceptable salt thereof, and a hydrate thereof and a solvate thereof: wherein X represents a connecting group whose number of atoms in the main chain is 2 to 5 (said connecting group may be substituted), A represents hydrogen atom or acetyl group, E represents an aryl group which may be substituted or a hetero aryl group which may be substituted, ring Z represents an arene which may have one or more substituents in addition to the group represented by formula -O-A wherein A has the same meaning as that defined above and the group represented by formula -X-E wherein each of X and E has the same meaning as that defined above, or a heteroarene which may have one or more substituents in addition to the group represented by formula -O-A wherein A has the same meaning as that defined above and the group represented by formula -X-E wherein each of X and E has the same meaning as that defined above.

ANTIALLERGIC

A medicament for the preventive and/or therapeutic treatment of allergic diseases and/or endometriosis and/or hysteromyoma which comprises as an active ingredient a substance selected from the group consisting of a compound represented by the following general formula (I) and a pharmacologically acceptable salt thereof, and a hydrate thereof and a solvate thereof: wherein X represents a connecting group whose number of atoms in the main chain is 2 to 5 (said connecting group may be substituted), A represents hydrogen atom or acetyl group, E represents an aryl group which may be substituted or a hetero aryl group which may be substituted, ring Z represents an arene which may have one or more substituents in addition to the group represented by formula -O-A wherein A has the same meaning as that defined above and the group represented by formula -X-E wherein each of X and E has the same meaning as that defined above, or a heteroarene which may have one or more substituents in addition to the group represented by formula -O-A wherein A has the same meaning as that defined above and the group represented by formula -X-E wherein each ofX and E has the same meaning as that defined above.

INHIBITORS AGAINST THE PRODUCTION AND RELEASE OF INFLAMMATORY CYTOKINES

A medicament having inhibitory activity against NF- κ B activation, which comprises a compound represented by the following general formula (I) or a pharmacologically acceptable salt as an active ingredient: wherein X represents a connecting group, A represents hydrogen atom or acetyl group, E represents an aryl group or a heteroaryl group, and ring X represents an arene or a heteroarene.