7221-33-2

Upstream product

• 100-83-4 meta-hydroxybenzaldehyde 
• 74-89-5 methylamine 
• 593-51-1 methylamine hydrochloride 

Downstream Products

• 123926-62-5 N-(3-hydroxybenzyl)methylamine 
• 90271-38-8 N-nitrozo(m-hydroxybenzyl)methylamine 
• 1224951-30-7 C₁₂H₁₂N₂O₂ 
• 142677-62-1 5-(3-benzyloxyphenyl)-1-methylimidazole 

Relevant academic research and scientific papers

Phenyl ether- and aniline-containing 2-aminoquinolines as potent and selective inhibitors of neuronal nitric oxide synthase

Excess nitric oxide (NO) produced by neuronal nitric oxide synthase (nNOS) is implicated in neurodegenerative disorders. As a result, inhibition of nNOS and reduction of NO levels is desirable therapeutically, but many nNOS inhibitors are poorly bioavailable. Promising members of our previously reported 2-aminoquinoline class of nNOS inhibitors, although orally bioavailable and brain-penetrant, suffer from unfavorable off-target binding to other CNS receptors, and they resemble known promiscuous binders. Rearranged phenyl ether- and aniline-linked 2-aminoquinoline derivatives were therefore designed to (a) disrupt the promiscuous binding pharmacophore and diminish off-target interactions and (b) preserve potency, isoform selectivity, and cell permeability. A series of these compounds was synthesized and tested against purified nNOS, endothelial NOS (eNOS), and inducible NOS (iNOS) enzymes. One compound, 20, displayed high potency, selectivity, and good human nNOS inhibition, and retained some permeability in a Caco-2 assay. Most promisingly, CNS receptor counterscreening revealed that this rearranged scaffold significantly reduces off-target binding.

4-Phenyl tetrahydroisoquinolines as dual norepinephrine and dopamine reuptake inhibitors

Novel 4-phenyl tetrahydroisoquinolines that inhibit both dopamine and norepinephrine transporters were designed and prepared. In this Letter, we describe the synthesis, in vitro activity and associated structure-activity relationships of this series. We also report the ex vivo NET occupancy of a representative compound, 41.

Efficient synthesis of new 4-arylideneimidazolin-5-ones related to the GFP chromophore by 2+3 cyclocondensation of arylideneimines with imidate ylides

A 2+3 condensation of a wide assortment of Schiff bases, prepared from aromatic aldehydes and primary amines, with methyl (1-ethoxyethylideneamino) acetate allows convenient access to an extensive family of substituted 4-arylideneimidazolin-5-one analogues of the green fluorescent protein (GFP) chromophore. Georg Thieme Verlag Stuttgart · New York.

N-Nitrosobenzylmethylamine hydroxylation and coumarin 7-hydroxylation: Catalysis by rat esophageal microsomes and cytochrome P450 2A3 and 2A6 enzymes

N-Nitrosobenzylmethylamine (NBzMA) is a potent and selective esophageal carcinogen in the rat and may be a causative agent for human esophageal cancer. This nitrosamine, like most, must be metabolically activated to exert its carcinogenic potential. NBzMA may be metabolized by P450-catalyzed methyl or methylene hydroxylation; the latter is believed to be the activation pathway. The sensitivity of the esophagus to NBzMA-induced tumorigenesis is believed to be due, at least in part, to the presence of efficient P450 catalysts in this tissue. However, while it was reported almost 20 years ago that the rat esophagus catalyzes the methylene hydroxylation of NBzMA, the P450 that catalyzes this reaction has yet to be identified. We report here that human P450 2A6 and the closely related extrahepatic rat enzyme P450 2A3 both efficiently catalyze NBzMA methylene hydroxylation, characterized as benzaldehyde formation. The catalytic efficiency of P450 2A3 in this reaction was 3-fold greater than that of P450 2A6, 7.6 (K(m) = 0.63 ± 0.18 μM and the V(max) = 4.8 nmol min-1 nmol of P450-1) versus 2.3 (K(m) = 6.7 ± 2.9 μM and the V(max) = 15.7 nmol min-1 nmol of P450-1), respectively. Both enzymes catalyzed methylene hydroxylation at least 4-fold more efficiently than methyl hydroxylation. In addition, P450 2A6, but not P450 2A3, catalyzed benzyl ring hydroxylation, generating N-(p-hydroxybenzyl)methylamine. The identity of this metabolite was confirmed by synthesis of a standard and LC/MS and LC/MS/MS analysis. P450 2A6 is an efficient coumarin 7-hydroxylase, and we report here that P450 2A3 is an equally good catalyst of this reaction (K(m) = 1.7 ± 0.41 μM and V(max) = 1.7 ± 0.08 nmol min-1 nmol of P450- 1). Rat esophageal microsomes (REM), like P450 2A3, were efficient catalysts of NBzMA methylene hydroxylation. However, in contrast to P450 2A3, the major product of this reaction was the product of benzaldehyde oxidation, benzoic acid. Antibody to the closely related mouse P450, 2A5, did not inhibit REM- catalyzed NBzMA metabolism, and most importantly, REM did not catalyze the 7- hydroxylation of coumarin. Therefore, P450 2A3 does not appear to be the P450 in the rat esophagus responsible for catalyzing the methylene hydroxylation of NBzMA.

Acetylcholinesterase inhibitors: Synthesis and structure-activity relationships of ω-[N-methyl-N-(3-alkylcarbamoyloxyphenyl)- methyl]aminoalkoxyheteroaryl derivatives

Acetylcholinesterase (ACHE) inhibitors are one of the most actively investigated classes of compounds in the search for an effective treatment of Alzheimer's disease. This work describes the synthesis, AChE inhibitory activity, and structure-activity relationships of some compounds related to a recently discovered series of AChE inhibitors: the ω-[N-methyl-N-(3- alkylcarbamoyloxyphenyl)methyl]aminoalkoxyxanthen-9-ones. The influence of structural variations on the inhibitory potency was carefully investigated by modifying different parts of the parent molecule, and a theoretical model of the binding of one representative compound to the enzyme was developed. The biological properties of the series were investigated in some detail by considering not only the activity on isolated enzyme but the selectivity with respect to butyrylcholinesterase (BuChE) and the in vitro inhibitory activity on rat cerebral cortex as well. Some of the newly synthesized derivatives, when tested on isolated and/or AChE-enriched rat brain cortex fraction, displayed a selective inhibitory activity and were more active than physostigmine. In particular, compound 13, an azaxanthone derivative, displayed the best rat cortex AChE inhibition (190-fold higher than physostigmine), as well as a high degree of enzyme selectivity (over 60-fold more selective for AChE than for BuChE). When tested in the isolated enzyme, compound 13 was less active, suggesting some differences either in drug availability/biotransformation or in the inhibitor-sensitive residues of the enzyme when biologically positioned in rat brain membranes.

Synthesis and Insect Growth Regulatory Activity of 1,5-Disubstituted Imidazoles with Non-terpene Chains

1-Isobutyl-5-(4-phenoxyphenyl)imidazole (KK-98), an inhibitor of juvenile hormone (JH) biosynthesis in the cockroach, and related imidazole compounds were evaluated against silkworm, Bombyx mori, for their activity to induce precocious metamorphosis.KK-98