101367-16-2

Upstream product

• 439691-95-9 2-(4-(hydroxymethyl)benzyl)isoindoline-1,3-dione 
• 623-24-5 1,4-bis(bromomethyl)benzene 
• 136918-14-4 phthalimide 
• 16473-35-1 4-(hydroxymethyl)benzyl chloride 
• 101207-45-8 2-(4-methylbenzyl)-1H-isoindol-1,3(2H)-dione 
• 1074-82-4 potassium phtalimide 

Downstream Products

• 164148-48-5 [6-(4-Aminomethyl-benzyloxy)-1-oxo-3,4-dihydro-1H-isoquinolin-2-yl]-acetic acid tert-butyl ester 
• 164148-49-6 6-{[4-({[N,N'-bis[(1,1-dimethylethoxy)carbonyl]aminoiminomethyl]amino}methyl)phenyl]methoxy}-3,4-dihydro-1-oxo-2(1H)-isoquinolineacetic acid 1,1-dimethylethyl ester 
• 1218909-37-5 [4-(1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)phenyl]acetonitrile 
• 1301740-34-0 1-(p-phthalimidoxylyl)-4,7-bis(tert-butoxycarbonyl)-1,4,7-triazacyclononane 
• 1301740-37-3 1-(p-aminoxylyl)-4,7-bis(tert-butoxycarbonyl)-1,4,7-triazacyclononane 
• 1301740-40-8 1-{p-[bis(tert-butoxycarbonyl)guanidino]xylyl}-4,7-bis(tert-butoxycarbonyl)-1,4,7-triazacyclononane 
• 101205-78-1 4-phthalimidomethylbenzyltriphenylphosphonium bromide 

Relevant academic research and scientific papers

Isoindoline-1,3-dione derivatives targeting cholinesterases: Design, synthesis and biological evaluation of potential anti-Alzheimer's agents

Alzheimer's disease is a fatal neurodegenerative disorder with a complex etiology. Because the available therapy brings limited benefits, the effective treatment for Alzheimer's disease remains the unmet challenge. Our aim was to develop a new series of donepezil-based compounds endowed with inhibitory properties against cholinesterases and β-amyloid aggregation. We designed the target compounds as dual binding site acetylcholinesterase inhibitors with N-benzylamine moiety interacting with the catalytic site of the enzyme and an isoindoline-1,3-dione fragment interacting with the peripheral anionic site of the enzyme. The results of pharmacological evaluation lead us to identify a compound 3b as the most potent and selective human acetylcholinesterase inhibitor (hAChE IC50 = 0.361 μM). Kinetic studies revealed that 3b inhibited acetylcholinesterase in non-competitive mode. The result of the parallel artificial membrane permeability assay for the blood-brain barrier indicated that the compound 3b would be able to cross the blood-brain barrier and reach its biological targets in the central nervous system. The selected compound 3b represents a potential lead structure for further development of anti-Alzheimer's agents.

ω-Imidazolyl- and ω-Tetrazolylalkylcarbamates as Inhibitors of Fatty Acid Amide Hydrolase: Biological Activity and in vitro Metabolic Stability

Fatty acid amide hydrolase (FAAH) is a serine hydrolase that terminates the analgesic and anti-inflammatory effects of endocannabinoids such as anandamide. Herein, structure-activity relationship studies on a new series of aryl N-(ω-imidazolyl- and ω-tetrazolylalkyl)carbamate inhibitors of FAAH were investigated. As one result, a pronounced increase in inhibitory potency was observed if a phenyl residue attached to the carbamate oxygen atom was replaced by a pyridin-3-yl moiety. The most active compounds exhibited IC50 values in the low nanomolar range. In addition, investigations on the metabolic properties of these inhibitors were performed. In rat liver homogenate and in porcine plasma, the extent of their degradation was shown to be strongly dependent on the kind of aryl residue bound to the carbamate as well as on the length and type of the alkyl spacer connecting the carbamate group with the heterocyclic system. With the aid of esterase inhibitors it was shown that in porcine plasma, carboxylesterase-like enzymes and paraoxonase are involved in carbamate cleavage. Moreover, it was found that highly active pyridin-3-yl carbamates reacted with albumin, which led to covalent albumin adducts.

Exploration of a Au(i)-mediated three-component reaction for the synthesis of DNA-tagged highly substituted spiroheterocycles

We demonstrate a Au(i)-mediated three-component reaction to DNA-tagged highly substituted 6-oxa-1,2-diazaspiro[4.4]nonanes from either DNA-coupled aldehydes, hydrazides, or alkynols. The choice of the starting material coupled to the DNA tag was critial for the purity of the product as the DNA-aldehyde conjugate yielded the purest products, whereas the alkynol- and hydrazide conjugates returned complex product mixtures. The reaction was compatible with thymine-, cytosine-, and, surprisingly, with adenine-DNA, while guanine-containing DNA strands were degraded under the reaction conditions.

KCNT1 INHIBITORS AND METHODS OF USE

The present invention is directed to, in part, compounds and compositions useful for preventing and/or treating a neurological disease or disorder, a disease or condition relating to excessive neuronal excitability, and/or a gain-of-function mutation in a gene (e.g., KCNT1). Methods of treating a neurological disease or disorder, a disease or condition relating to excessive neuronal excitability, and/or a gain-of-function mutation in a gene such as KCNT1 are also provided herein.

PYRROLE AND PYRAZOLE COMPOUNDS AND METHODS OF USE THEREOF

The disclosure relates to anti-cancer compounds derived from nuclear steroid receptor binders, to products containing the same, as well as to methods of their use and preparation. The present disclosure provides compounds having hormone receptor antagonis

Mechanochemical N-alkylation of imides

The mechanochemical N-alkylation of imide derivatives was studied. Reactions under solvent-free conditions in a ball mill gave good yields and could be put in place of the classical solution conditions. The method is general and can be applied to various imides and alkyl halides. Phthalimides prepared under ball milling conditions were used in a mechanochemical Gabriel synthesis of amines by their reaction with 1,2-diaminoethane.

SULFONAMIDE DERIVATIVES AS INHIBITORS OF ION CHANNELS

Compounds, compositions and methods are provided which are useful in the treatment of diseases through the inhibition of sodium ion flux through voltage-gated sodium channels.

Search for cyclodextrin-based inhibitors of anthrax toxins: Synthesis, structural features, and relative activities

Recently, using structure-inspired drug design, we demonstrated that aminoalkyl derivatives of β-cyclodextrin inhibited anthrax lethal toxin action by blocking the transmembrane pore formed by the protective antigen (PA) subunit of the toxin. In the prese

Non-peptide RGD surrogates which mimic a Gly-Asp β-turn: Potent antagonists of platelet glycoprotein IIb-IIIa

Cyclic heptapeptide 1, which contains an Arg-Gly-Asp sequence, has good affinity for the platelet receptor GPIIb-IIIa and was chosen for study by 1H NMR techniques. The key RGD sequence of this molecule was found to reside in a conformationally defined type II' Gly-Asp β-turn, and this information was used in the design of simple non-peptide RGD mimics. Disubstituted isoquinolones, bearing an acidic side chain at position 2 and a basic side chain at position 6, were prepared and were found to have modest affinity for GPIIb-IIIa. Systematic modification of the basic residue contained in these molecules yielded compounds with high affinity for GPIIb-IIIa.

Amidine derivatives and cardiotonic compositions

Amidine derivatives of the formula STR1 wherein R1 and R2, which may be the same or different, represent each a hydrogen atom or a lower alkyl group, or R1 and R2 together with an intermediary carbon atom and/or hetero atom may form a ring; X represents STR2 (wherein R8 represents a hydrogen atom, a lower alkyl group, or --CH2 COOR9, where R9 represents a hydrogen atom or a lower alkyl group; Z represents a single bond, --CH2 --, --CH2 CH2 --, or --CH=CH--); R3 represents a hydrogen or chlorine atom, methoxy group, nitro group, or amino group; Y represents --CH2 CH2 --, --CH=CH--, --CH2 O--, or --OCH2 --; R4 represents a hydrogen atom, methoxy group, benzoyl group, nitro group, or amino group; and R5, R6 and R7, which may be the same or different, represent each a hydrogen atom, lower alkyl group, cycloalkyl group, aralkyl group, substituted alkyl group, substituted aralkyl group, or amino group, or R5 and R7 may form a ring, or salts thereof have an excellent cardiotonic activity and can be used as cardiotonics.