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Usage

Uses

Anticonvulsant L.

InChI:InChI=1/C15H16N2O/c1-10-4-3-5-11(2)14(10)17-15(18)12-6-8-13(16)9-7-12/h3-9H,16H2,1-2H3,(H,17,18)

Upstream product

• 64594-44-1 4-Nitro-N-(2,6-dimethylphenyl)benzamide 
• 122-04-3 4-nitro-benzoyl chloride 
• 87-62-7 2,6-dimethylaniline 
• 62-23-7 4-nitro-benzoic acid 
• 150-13-0 4-amino-benzoic acid 
• 16106-38-0 4-aminobenzoyl chloride 

Downstream Products

• 794-98-9 4-(Acetylamino)-N-(2,6-dimethylphenyl)benzamide 
• 51616-07-0 4-Hydroxy-N-(2,6-dimethylphenyl)benzamide 
• 1620147-03-6 N-(2,6-dimethylphenyl)-4-(9-(4-methoxybenzyl)-6-(4-(trifluoromethoxy)phenyl)-9H-purine-2-aminyl) benzamide 
• 1059735-13-5 N-(2,6-dimethylphenyl)-4-((4-phenylpyrido[2,3-d]pyrimidin-2-yl)amino)benzamide 
• 1059735-14-6 N-(2,6-dimethylphenyl)-4-[(4-phenyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)amino]benzamide 
• 1620147-51-4 N-(2,6-dimethylphenyl)-4-((4-(4-(trifluoromethoxy)phenyl)furo[3,2-d]pyrimidin-2-yl)amino)benzamide 
• 1620147-50-3 N-(2,6-dimethylphenyl)-4-((4-(4-(trifluoromethoxy)phenyl)thieno[2,3-d]pyrimidin-2-yl)amino)benzamide 
• 1620147-49-0 N-(2,6-dimethylphenyl)-4-((4-(4-(trifluoromethoxy)phenyl)thieno[3,2-d]pyrimidin-2-yl)amino)benzamide 
• 1620147-24-1 N-(2,6-dimethylphenyl)-4-((4-(4-(trifluoromethoxy)phenyl)-5H-pyrrolo[3,2-d]pyrimidin-2-yl)amino)benzamide 
• 1620147-20-7 N-(2,6-dimethylphenyl)-4-((5-methyl-4-(4-(trifluoromethoxy)phenyl)-5H-pyrrolo[3,2-d]pyrimidin-2-yl)amino)benzamide 
• 1620147-15-0 N-(2,6-dimethylphenyl)-4-((7-p-toluenesulfonyl)4-(4-(trifluoromethoxy)phenyl)-7H-pyrrole[2,3-d]pyrimidin-2-yl)amino benzamide 
• 1620147-17-2 N-(2,6-dimethylphenyl)-4-((7-methyl-4-(4-(trifluoromethoxy)phenyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)benzamide 
• 1620147-16-1 N-(2,6-dimethylphenyl)-4-((4-(4-(trifluoromethoxy)phenyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)benzamide 
• 1620147-11-6 N-(2,6-dimethylphenyl)-4-(9-methyl-6-(4-(trifluoromethoxy)phenyl)-9H-purin-2-ylamino)benzamide 

Relevant academic research and scientific papers

Ligand-based rational design, synthesis and evaluation of novel potential chemical chaperones for opsin

Inherited blinding diseases retinitis pigmentosa (RP) and a subset of Leber's congenital amaurosis (LCA) are caused by the misfolding and mistrafficking of rhodopsin molecules, which aggregate and accumulate in the endoplasmic reticulum (ER), leading to photoreceptor cell death. One potential therapeutic strategy to prevent the loss of photoreceptors in these conditions is to identify opsin-binding compounds that act as chemical chaperones for opsin, aiding its proper folding and trafficking to the outer cell membrane. Aiming to identify novel compounds with such effect, a rational ligand-based approach was applied to the structure of the visual pigment chromophore, 11-cis-retinal, and its locked analogue 11-cis-6mr-retinal. Following molecular docking studies on the main chromophore binding site of rhodopsin, 49 novel compounds were synthesized according to optimized one-to seven-step synthetic routes. These agents were evaluated for their ability to compete for the chromophore binding site of opsin, and their capacity to increase the trafficking of the P23H opsin mutant from the ER to the cell membrane. Different new molecules displayed an effect in at least one assay, acting either as chemical chaperones or as stabilizers of the 9-cis-retinal-rhodopsin complex. These compounds could provide the basis to develop novel therapeutics for RP and LCA.

Chemoselective One-Pot Synthesis of Functionalized Amino-azaheterocycles Enabled by COware

Functionalized bicyclic amino-azaheterocycles are rapidly accessed in a one-pot cross-coupling/reduction sequence enabled by the use of COware. Incompatible reagents are physically separated in a single reaction vessel to effect two chemoselective transformations - Suzuki-Miyaura cross-coupling and heteroarene reduction. The developed method allows access to novel heterocyclic templates, including semisaturated Hedgehog and dual PI3K/mTOR inhibitors, which show enhanced physicochemical properties compared to their unsaturated counterparts.

Five-membered heteroaromatic ring fused-pyrimidine derivatives: Design, synthesis, and hedgehog signaling pathway inhibition study

A series of novel five-membered heteroaromatic ring fused-pyrimidine derivatives including purines, pyrrolo[2,3-d]pyrimidines, pyrrolo[3,2-d] pyrimidines, thieno[2,3-d]pyrimidines, thieno[3,2-d]pyrimidines and furo[3,2-d]pyrimidines have been identified to be potent inhibitors of hedgehog signaling pathway. The synthesis and SAR of these compounds are described. Among this new series of hedgehog signaling pathway inhibitors, most compounds exhibited significant inhibitory activity compared to vismodegib, indicating that the five-membered heteroaromatic ring fused-pyrimidines stand out as encouraging scaffolds among the currently reported structural skeletons for hedgehog signaling pathway inhibitors, deserving more exploration and further investigation.

QUINAZOLINONES AS PROLYL HYDROXYLASE INHIBITORS

Quinazolinone compounds of formula (I) are described, which are useful as prolyl hydroxylase inhibitors. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by prolyl hydroxylase activity. Thus, the compounds may be administered to treat, e.g., anemia, vascular disorders, metabolic disorders, and wound healing.

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.

Anticonvulsant method and formulations

This invention relates to certain aminobenzanilide compounds, and to the use, in the treatment of mammals, of certain aminobenzanilide compounds as anticonvulsant agents.