55507-05-6

Usage

Chemical Properties

Yellow Solid

InChI:InChI=1/C16H15NO4/c1-20-15-8-7-13(9-10-17(18)19)11-16(15)21-12-14-5-3-2-4-6-14/h2-11H,12H2,1H3/b10-9-

Upstream product

• 75-52-5 nitromethane 
• 6346-05-0 3-benzyloxy-4-methoxybenzaldehyde 
• 2426-87-1 3-methoxy-4-(phenylmethoxy)benzaldehyde 
• 621-59-0 isovanillin 
• 100-44-7 benzyl chloride 
• 100-39-0 benzyl bromide 

Downstream Products

• 36455-21-7 3-benzyloxy-4-methoxyphenylethylamine 
• 29973-92-0 2-(benzyloxy)-1-methoxy-4-(1-methoxy-2-nitroethyl) Benzene 
• 31493-49-9 N-(Boc)-3'-hydroxy-4'-methoxyphenethylamine 
• 36455-20-6 tert-butyl N-[2-(3-benzyloxy-4-methoxy-phenyl)ethyl]carbamate 
• 1418126-68-7 2-(3-(benzyloxy)-2-fluorophenyl)-N-(3-(benzyloxy)-4-methoxyphenethyl)-N-methylacetamide 
• 1418126-69-8 6-(benzyloxy)-1-(3-(benzyloxy)-2-fluorobenzyl)-7-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline 
• 1418126-28-9 C₁₈H₁₉NO₃ 
• 1418126-35-8 C₁₈H₁₉NO₃ 
• 1418126-58-5 C₁₈H₁₈FNO₃ 
• 1432216-67-5 C₁₈H₂₀FNO₃ 
• 1418126-26-7 1-(2-fluoro-3-hydroxybenzyl)-7-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinolin-6-ol 
• 1418126-37-0 ethyl 3-benzyloxy-4-methoxyphenethylcarbamate 
• 106149-04-6 N-methyl-β-(3-benzyloxy-4-methoxyphenyl)ethylamine 
• 1418126-38-1 N-(3-benzyloxy-4-methoxyphenethyl)-2-(3-benzyloxyphenyl)-N-methylacetamide 

Relevant academic research and scientific papers

Design, Synthesis and Structure-Activity Relationship Studies of Glycosylated Derivatives of Marine Natural Product Lamellarin D

Lamellarin D, a marine natural product, acts as a potent inhibitor of DNA topoisomerase I (Topo I). To modify its physicochemical property and biological activity, a series of mono- and di-glycosylated derivatives were designed and synthesized through 22–26 multi-steps. Their inhibition of human Topo I was evaluated, and most of the glycosylated derivatives exhibited high potency in inhibiting Topo I activity as well as lamellarin D. All the 15 target compounds were evaluated for their cytotoxic activities against five human cancer cell lines. The typical lamellarin derivative ZL?3 exhibited the best activity with IC50 values of 3 nM, 10 nM, and 15 nM against human lung cancer A549 cells, human colon cancer HCT116 cells and human hepatocellular carcinoma HepG2 cells. Compound ZL?1 exhibited anti-cancer activity with IC50 of 14 nM and 24 nM against human colon cancer HCT116 cells and human hepatocellular carcinoma HepG2 cells, respectively. Cell cycle analysis in MDA-MB-231 suggested ZL?3 inhibited cell growth through arresting cells at the G2/M phase of the cell cycle. Further tests showed a significant improvement in aqueous solubility of ZL?1 and ZL?7. This study suggested that glycosylation could be utilized as a useful strategy to optimize lamellarin D derivatives as Topo I inhibitors and anticancer agents.

Asymmetric total synthesis of tetrahydroprotoberberine derivatives and evaluation of their binding affinities at dopamine receptors

Cocaine addiction remains a serious challenge for clinical and medical research because there is no effective pharmacological treatment. L-THP, a natural product isolated from Corydalis yanhusuo W.T. Wang, is one of the most frequently used traditional herbs to treat drug addiction in China. Our laboratory first reported that its demethylated metabolites L-ICP, L-CD, and L-CP had high affinity at dopamine D1, D2, and D5 receptors. Here we report the chemical synthesis of these metabolites and other derivatives and their binding affinities at dopamine receptors. The synthesis of these bioactive metabolites will allow further in vivo study of their potential in treating cocaine addiction.

Synthesis and biological evaluation of a D-ring-contracted analogue of lamellarin D

A D-ring contracted analogue of the strongly cytotoxic marine pyrrole alkaloid lamellarin D was synthesized and investigated for its antiproliferative action towards a wild type and a multidrug resistant (MDR) cancer cell line. The compound was found to inhibit tumor cell growth at submicromolar concentrations and showed a lower relative resistance in the MDR cell line than the antitumor drug camptothecin to which lamellarin D shows cross resistance and with which lamellarin D shares the same binding site.

ZrCl4-mediated synthesis of 1,2,3-triazoles from vinyl nitrates and their biological evaluation

A ZrCl4-mediated simple method for the conversion of vinyl nitrates to 1,2,3-triazoles in excellent yields is developed. The obtained new triazoles were evaluated for their antimicrobial activity.

ANTI-HIV COMPOUNDS

This invention provides, among other things, tetrahydroisoquinolines useful for treating viral infections, pharmaceutical formulations containing such compounds, as well as methods of inhibiting the replication of a virus, such as HIV, or treating a disease, such as AIDS.

Identification and in vivo evaluation of a fluorine-18 rolipram analogue, [18F]MNI-617, as a radioligand for PDE4 imaging in mammalian brain

Phosphodiesterase (PDE) 4 is the most prevalent PDE in the central nervous system (CNS) and catalyzes hydrolysis of intracellular cAMP, a secondary messenger. By therapeutic inhibition of PDE4, intracellular cAMP levels can be stabilized, and the symptoms of psychiatric and neurodegenerative disorders including depression, memory loss and Parkinson's disease can be ameliorated. Radiotracers targeting PDE4 can be used to study PDE4 density and function, and evaluate new PDE4 therapeutics, in vivo in a non-invasive way, as has been shown using the carbon-11 labeled PDE4 inhibitor R-(-)-rolipram. Herein we describe a small series of rolipram analogs that contain fluoro- or iodo-substituents that could be used as fluorine-18 PET or iodine-123 SPECT PDE4 radiotracers. This series was evaluated with an in vitro binding assay and a 4-(fluoromethyl) derivative of rolipram, MNI-617, was identified, with a five-fold increase in affinity for PDE4 (Kd = 0.26 nM) over R-(-)-rolipram (Kd = 1.6 nM). A deutero-analogue d2-[18F]MNI-617 was radiolabeled and produced in 23% yield with high (>5 Ci/μmol) specific activity and evaluated in non-human primate, where it rapidly entered the brain, with SUVs between 4 and 5, and with a distribution pattern consistent with that of PDE4.

PHENANTHRENE DERIVATIVES FOR USE AS MEDICAMENTS

The present invention refers to phenanthrene derivatives for use as medicaments, mainly in the prevention and/or treatment of Myotonic Dystrophy Type 1, Huntington's Disease Like 2, Spinocerebellar Ataxia Type 8, Myotonic Dystrophy Type 2, Spinocerebellar Ataxia Type 3, Fragile-X-Associated Tremor/Ataxia Syndrome, Frontotemporal Degeneration/Amyotrophic Lateral Sclerosis and Spinocerebellar Ataxia Type 31. In a preferred embodiment, phenanthrene derivatives of the invention are also used as antimyotonic agents. Therefore, this invention may be included either in the whole pharmaceutical or medical field.

Design and total synthesis of Mannich derivatives of marine natural product lamellarin D as cytotoxic agents

Enlightened by the modification route from Camptothecin (CPT) to Topotecan and based on classical drug design theory, a series of Mannich derivatives of lamellarin D were designed and synthesized in 26-27 steps starting from vanillin and isovanilin. All synthesized compounds were then biologically evaluated for their in vitro anti-cancer activities and Topo I inhibitory activities. The results showed that most target compounds exhibited Topo I inhibitory activities in equivalent level with that of lamellarin D. Compound SL-9 exhibited better Topo I inhibitory activity than that of lamellarin D. Compounds SL-2, SL-3, SL-4, SL-5 and SL-11 exhibited better anti-proliferative activity against HT-29 cells than that of lamellarin D.

Asymmetric total synthesis and identification of tetrahydroprotoberberine derivatives as new antipsychotic agents possessing a dopamine D1, D2 and serotonin 5-HT1A multi-action profile

An effective and rapid method for the microwave-assisted preparation of the key intermediate for the total synthesis of tetrahydroprotoberberines (THPBs) including l-stepholidine (l-SPD) was developed. Thirty-one THPB derivatives with diverse substituents on A and D ring were synthesized, and their binding affinity to dopamine D1, D2 and serotonin 5-HT 1A and 5-HT2A receptors were determined. Compounds 18k and 18m were identified as partial agonists at the D1 receptor with Ki values of 50 and 6.3 nM, while both compounds act as D2 receptor antagonists (Ki = 305 and 145 nM, respectively) and 5-HT1A receptor full agonists (Ki = 149 and 908 nM, respectively). These two THPBs compounds exerted antipsychotic actions in animal models. Further electrophysiological studies employing single-unit recording in intact animals demonstrated that 18k-excited dopaminergic (DA) neurons are associated with its 5-HT1A receptor agonistic activity. These results suggest that these two compounds targeted to multiple neurotransmitter receptors may present novel lead drugs with new pharmacological profiles for the treatment of schizophrenia.

(+)-9-Benzyloxy-α-dihydrotetrabenazine as an important intermediate for the VMAT2 imaging agents: Absolute configuration and chiral recognition

This article reports, for the first time, on the absolute configuration of (+)-9-benzyloxy-α-dihydrotetrabenazine (8), as determined from the perspective of X-ray crystallography. Compound 8 was prepared by a six-step reaction using 3-benzyloxy-4-methoxybenzaldehyde (1) as a starting material. The X-ray crystal diffraction structure of two compounds, racemic 9-benzyloxy-tetrabenazine (5) and the diastereomeric salt of compound 8, is also described for the first time in this article. The X-ray results and the chiral HPLC helped elucidate that compound 8 has an absolute configuration as 2R,3R,11bR. The crystal structure of racemic compound 5 contains two symmetry- independent molecules in the unit cell. Interestingly, while they are structural isomers, they are enantiomers, too, i.e., in solution, because they are not mirror images of each other in the crystal lattice. In order to elucidate the intermolecular interaction mechanism of the diastereomeric salt of compound 8, its crystal packing was investigated with regard to the weak interactions, such as salt bridge, OH.O and CH.O hydrogen bonds, and intermolecular CH.π interaction. The results showed that the carbonyl-assisted salt bridges and the OH.O hydrogen bonds formed polar columns in the crystal structure of the diastereomeric salt of compound 8, resembling butterflies with open wings as viewed along the c-axis. These polar columns were extended to three-dimensional network by intermolecular CH.O hydrogen bonds and intermolecular CH.π interactions. Chirality, 2013. 2013 Wiley Periodicals, Inc. Copyright