161535-70-2

Upstream product

• 610-27-5 4-nitrophthalic acid 
• 19241-16-8 2,6-dimethylphenylisothiocyanate 
• 5466-84-2 4-nitrophthalic anhydride 
• 87-62-7 2,6-dimethylaniline 

Downstream Products

• 1059734-06-3 2-(2,6-dimethylphenyl)-5-[(4-phenylquinazolin-2-yl)amino]-1H-isoindole-1,3(2H)-dione 
• 158276-70-1 4-amino-N-(2,6-dimethylphenyl)phthalimide 

Relevant academic research and scientific papers

Mechanochemical synthesis of phthalimides with crystal structures of intermediates and products

A series of phthalimides have been successfully synthesized in the solid state by grinding (or kneading) of substituted phthalic anhydride and aniline derivatives. Selected products and intermediates were crystallized and characterized by crystallography leading to a potential rationale for the solid-state reactivity that suggests that co-crystals could serve as intermediates. This journal is

INHIBITORS OF THE HEDGEHOG PATHWAY

The present invention is directed to a compound of Formula (I) or a single isomer thereof; where the compound is optionally as a pharmaceutically acceptable salt, hydrate, solvate or combination thereof, in addition to methods of preparing a Compound of Formula I, and methods of using a Compound of Formula (I) to treat cancer.

Design, anticonvulsive and neurotoxic properties of retrobenzamides / N- (nitrophenyl)benzamides and N-(aminophenyl)benzamides

Design, anticonvulsant properties in maximal electroshock-reduced seizures [MES] and seizures reduced by subcutaneous administration of pentetrazole (scPtz), and neurotoxicity of retrobenzamides (N- (nitrophenyl)benzamides and N-(aminophenyl) benzamides are reported. These data are further compared with those on carbamazepine, phenytoin, ameltolide and other reference compounds. Studies on retrobenzamides in mice dosed intraperitoneally point out a good anticonvulsant potential in the MES test for the amino derivatives (N-(aminophenyl)benzamides) and moderate activity for corresponding 'nitro' derivatives. In rats dosed orally, aminoretrobenzamides were, however, less active in the MES test than in mice dosed intraperitoneally. Differences between experimental animal species and administration routes lead to hypothesize rapid metabolization of compounds, reduced intestinal resorption and increased removal from body. The presence of a methyl substitution on the N-phenyl moiety of aminoretrobenzamides attenuated these discrepancies between mice and rats. Present results indicate that pharmacological values - including the dose offering anticonvulsant protection in 50 % of tested animals (ED50) and protective indices - obtained on some retrobenzamides may compete with phenytoin and carbamazepine values. By contrast with phenytoin, some retrobenzamides further exhibit activity in the scPtz test.

Anticonvulsant activity and interactions with neuronal voltage- dependent sodium channel of analogues of ameltolide

Fifteen compounds related to ameltolide (LY 201116) were studied for (i) anticonvulsant potential in the maximal electroshock-induced seizures (MES) and the subcutaneous pentylenetetrazol (sc Ptz)tests in mice and rats and (ii) interactions with neuronal voltage-dependent sodium channels. Compounds were chosen ranging in anticonvulsant activity in mice from very active to inactive. The active compounds were defined as those protecting 50% of the animals at doses between 10 and 50 μmol/kg and inactive compounds as those protecting 50% of the animals at doses greater than 1 mmol/kg. The series studied included three N-(2,6-dimethylphenyl)benzamides (compounds 1, 2 (ameltolide), and 3), three N-(2,2,6,6-tetramethyl)piperidinyl-4-benzamides (compounds 4, 5, 6), one phenylthiourea (compound 7), five N-(2,6- dimethylphenyl)phthalimides (compounds 8, 9, 10, 13, and 14), two N- phenylphthalimide derivatives (compounds 11 and 12), and one N-(2,2,6,6- tetramethyl)piperidinyl-4-phthalimide (compound 15). Phenytoin (PHT) was employed as the reference prototype antiepileptic drug. After inital screening in mice, compounds 1, 2, 3, 5, 8, 9, 10, 13, and 14 were selected for further testing in rats. Anticonvulsant ED50s (effective doses in at least 50% of animals tested) of compounds in the MES test were determined in rats dosed orally and amounted to 52 (1), 135 (2), 284 (3), 231 (8), 131 (9), 25 (10), 369 (13), 354 (14), and 121 (PHT) μmol/kg, compound 5 presenting with an ED50 value higher than 650 μmol/kg. In our hands, the apparent IC50s (inhibitory concentrations 50) of compounds toward binding to rat brain synaptosomes of [3H]batrachotoxinin-A-20α-benzoate were 0.25 (1), 0.97 (2), 0.35 .(3), 25.8 (5), 161.3 (8), 183.5 (9), 0.11 (10), 1.86 (13), 47.8 (14), and 0.86 (PHT) μM. The relationship between the activity in the MES test and the capacity to interact in vitro with neuronal voltage- dependent sodium channels and the fact that the IC50 values obtained in the in vitro test are close to the brain concentrations at which anticonvulsant activities are reported to occur for ameltolide strongly suggest that the anticonvulsant properties of most compounds tested could be a direct result of their interaction with the neuronal voltage-dependent sodium channel.

Synthesis and anticonvulsant activity of some N-phenylphthalimides

The anticonvulsant potential of a series of N-phenylphthalimide derivatives has been screened in subcutaneous pentylenetetrazole seizure (scPTZ) and maximal electroshock seizure (MES) tests. Intraperitoneal 4-amino-N-phenylphthalimides were the most potent agents against MES in mice. Referring to the N-(2,6-dimethylphenyl)phthalimide structure, the order of anticonvulsant activity appears to correspond to the phthalimide ring substitution pattern of 4-amino > 4-nitro > 4-methyl; H > 3-nitro; 3-amino. The 4-amino-N-(2-methylphenyl)phthalimide displays an anti-MES ED50 of 47.61 μmol/kg with a protective index (PI) of 4.2. Oral administration to rats of the compounds found to be active in mice showed that the 4-amino-N-(2,6-dimethylphenyl)phthalimide is the most potent anti-MES agent in rats, exhibiting an ED50 of 25.2 μmol/kg and a PI greater than 75. Regarding the nature of the 2 and 6 substituents of the N-phenyl ring, the anticonvulsant efficiencies may be ordered as follows: 2,6-dimethyl > 2-methyl > 2-ethyl > 2-ethyl-6-methyl > 2,6-diethyl > unsubstituted phenyl ring. N-Phenylphthalimide derivatives seem to have great potential as candidate anticonvulsant drugs.