22116-33-2

Usage

Uses

Used in Pharmaceutical Industry:
2-(4-FLUOROBENZYLAMINO)ETHANOL is used as a pharmaceutical intermediate for the synthesis of mosapride citrate, a prokinetic agent used to treat gastrointestinal motility disorders. Its unique structure allows for the development of drugs with improved efficacy and selectivity.
Used in Organic Synthesis:
2-(4-FLUOROBENZYLAMINO)ETHANOL is used as an organic synthesis intermediate in the preparation of (Fluorobenzyl)aminomethylmorpholine salt, which is a key component in the synthesis of various organic compounds. This versatile intermediate enables the development of new chemical entities with potential applications in various industries.
Used in Research and Development:
2-(4-FLUOROBENZYLAMINO)ETHANOL is utilized in laboratory research and development processes, where it can be employed to explore new chemical reactions, synthesize novel compounds, and investigate the properties of related molecules. Its unique structure and reactivity make it a valuable tool for advancing scientific knowledge and discovering new applications.

Synthesis

P-fluorobenzaldehyde (24.8 g, 0.2 mol) and 2-aminoethanol (15.3 g, 0.25 mol) were added to a reaction flask containing methanol (250 ml), heated to reflux, and kept at 65 ° C for 4 h.The temperature was lowered, sodium borohydride (9.2 g 0.24 mol) was added, and the reaction was stirred, the reaction was completed, filtered, and concentrated.The fraction was collected to give 2-(4-fluorobenzylamino)ethanol as a colorless oily liquid (yield: 90.2%, purity 98.7%).

InChI:InChI=1/C9H12FNO/c10-9-3-1-8(2-4-9)7-11-5-6-12/h1-4,11-12H,5-7H2

Upstream product

• 459-57-4 4-fluorobenzaldehyde 
• 141-43-5 ethanolamine 
• 635283-50-0 2-{[1-(4-Fluoro-phenyl)-meth-(E)-ylidene]-amino}-ethanol 

Downstream Products

• 156816-53-4 1-Chloro-3-[(4-fluoro-benzyl)-(2-hydroxy-ethyl)-amino]-propan-2-ol 
• 24466-34-0 4-Fluor-N-<2-fluor-aethyl>-N-<2-hydroxy-aethyl>-benzylamin 
• 172419-86-2 4-(4-fluorobenzyl)-2-morpholinecarbonitrile 
• 112914-13-3 2-aminomethyl-4-(4-fluoro-benzyl) morpholine 
• 172419-87-3 ethyl 4-(4-fluorobenzyl)-2-morpholinecarboxylate 
• 172419-89-5 <2-2H2>-N-<<4-(4-fluorobenzyl)-2-morpholinyl>methyl>phthalimide 
• 172419-90-8 <2-2H2>-2-(aminomethyl)-4-(4-fluorobenzyl)morpholine 
• 172419-88-4 <2-2H2>-4-(4-fluorobenzyl)-2-hydroxymethylmorpholine 
• 156334-89-3 (S)-(-)-<4-(4-fluorobenzyl)-2-morpholinyl>methylamine 
• 156334-90-6 (R)-(+)-<4-(4-fluorobenzyl)-2-morpholinyl>methylamine 
• 156816-54-5 (+/-)-4-(4-fluorobenzyl)-2-morpholinylmethanol 
• 156925-17-6 (+/-)-2-(chloromethyl)-4-(4-fluorobenzyl)morpholine 
• 156816-57-8 (S)-2-Azidomethyl-4-(4-fluoro-benzyl)-morpholine 
• 156816-52-3 (+/-)-<4-(4-fluorobenzyl)-2-morpholinyl>methyl p-toluenesulfonate 

Relevant academic research and scientific papers

Method for preparing mosapride citrate intermediate

The invention belongs to the technical field of medicines and particularly relates to a method for preparing a mosapride citrate intermediate IV 4-(4-fluorophenyl)-2-aminomethyl morpholine. The methodcomprises the following steps: phthalimide potassium salt and dichloro-2-propanol react to produce an intermediate II N-(2-hydroxy-3-chloropropyl) phthalimide, then the produced intermediate II and an intermediate I 2-(4-fluorphenylamine)ethyl alcohol are condensed to prepare an intermediate III N-3-[4-fluorophenyl-2-(hydroxy-ethylamine)-2-hydroxypropyl]phthalic diamide, and the intermediate IIIis subjected to cyclization and hydrolysis to obtain the intermediate IV 4-(4-fluorophenyl)-2-aminomethyl morpholine. The method is short in route, lower in production cost and suitable for industrialproduction.

Citric acid mosapride intermediate product and application

The invention belongs to the field of medical chemistry synthesis, and provides a preparation method of citric acid mosapride intermediate product IV 4-[(4-fluorophenyl)methyl]-2-morpholinemethanaminesalt and citric acid mosapride. The 2-(4-fluorobenzoamido)ethanol and 1H-Isoindole-1,3(2H)-dione,2-(2-oxiranylmethyl) are taken as raw materials, and the intermediate product IV 4-[(4-fluorophenyl)methyl]-2-morpholinemethanamine salt is obtained after acid treating is conducted; the intermediate product IV and an intermediate V 2-oxethyl-4-acetamido-5-Chlorobenzoic acid ethyl ester compounds aretaken as raw materials, dichloromethane is taken as a solvent, and EDCI and DMAP are taken as catalysts to prepare mosapride salt; the mosapride salt is reacted with citric acid aqueous solution to prepare citric acid mosapride. The intermediate product has the advantages that products are high in yield, raw materials are easy to obtain, the production cost is low, and the intermediate product issuitable for industrialized production.

THERAPEUTIC MACROLIDE COMPOUNDS AND THEIR USE

The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain macrolide compounds (for convenience, collectively referred to herein as "MC compounds"), which, inter alia, are useful in treatment of cancer. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to treat proliferative conditions such as cancer, and in the treatment of diseases and conditions that are mediated by the regulation (e.g. inhibition) of cell proliferation, optionally in combination with another agent.

Discovery of highly potent and selective inhibitors of neuronal nitric oxide synthase by fragment hopping

Selective inhibition of neuronal nitric oxide synthase (nNOS) has been shown to prevent brain injury and is important for the treatment of various neurodegenerative disorders. This study shows that not only greater inhibitory potency and isozyme selectivity but more druglike properties can be achieved by fragment hopping. On the basis of the structure of lead molecule 6, fragment hopping effectively extracted the minimal pharmacophoric elements in the active site of nNOS for ligand hydrophobic and steric interactions and generated appropriate lipophilic fragments for lead optimization. More potent and selective inhibitors with better druglike properties were obtained within the design of 20 derivatives (compounds 7-26). Our structure - based inhibitor design for nNOS and SAR analysis reveal the robustness and efficiency of fragment hopping in lead discovery and structural optimization, which implicates a broad application of this approach to many other therapeutic targets for which known druglike small-molecule modulators are still limited.

ANTIVIRAL COMPOUNDS

The invention is related to phosphorus substituted anti-viral inhibitory compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

PROCESS FOR THE SYNTHESIS OF A BENZAMIDE DERIVATIVE

The invention relates to a process for the synthesis of mosapride citrate of formula (I), the chemical name: (R,S)-4-amino-5-chloro-2-ethoxy-N-{ [4-(4-fluoro-benzyl)-2- morpholinyl]-methyl}benzamide citrate dihydrate, (I), (II) reacting the compound of formula (II) with di-tert-butyl-dicarbonate in an alcohol in the presence of a base, the obtained product is ethylated in an inert solvent in the presence of a base, the obtained compound is hydrolyzed with an alkyl-hydroxide and the obtained salt neutralized with an acid, the obtained product is chlorinated, and the obtained compound of formula (VI) is reacted with the compound of formula (VII), (VI), (VII) where BOC is tert-butoxy-carbonyl protecting group and removing the protecting group from the obtained compound of formula (VIII) the mosapride base is prepared, (VIII) where BOC is defined as above and in desired case with an acid, preferably with citric acid a pharmaceutically acceptable salt, preferably the mosapride citrate dehydrate of formula (I) is produced.

Structural studies on bioactive compounds. 34.1 Design, synthesis, and biological evaluation of triazenyl-substituted pyrimethamine inhibitors of Pneumocystis carinii dihydrofolate reductase

The triazenyl-pyrimethamine derivative 3a (TAB), a potent and selective inhibitor of Pneumocystis carinii DHFR, was selected as the starting point for a lead optimization study. Molecular modeling studies, corroborated by a recent crystal structure determination of the ternary complex of P. carinii DHFR-NADPH bound to TAB, predicted that modifications to the acetoxy residue of the lead inhibitor could exploit binding opportunities in the vicinity of an active site pocket bounded by residues Ile33, Lys37, and Leu72. Substitutions in the benzyl moiety with electron-donating and electron-withdrawing groups were predicted to probe face-edge interactions with amino acid Phe69 unique to the P. carinii enzyme. New triazenes 10a-v and 12a-f were prepared by coupling the diazonium tetrafluoroborate salt 6b of aminopyrimethamine with substituted benzylamines or phenethylamines. The most potent of the new inhibitors against P. carinii DHFR was the naphthylmethyl-substituted triazene 10t (IC50: 0.053 μM), but a more substantial increase in potency against the rat liver DHFR led to a reduction in selectivity (ratio rat liver DHFR IC50/P. carinii DHFR IC50: 5.36) compared to the original lead structure 3a (ratio rat liver DHFR IC50/P. carinii DHFR IC50: 114).

Synthesis and biological activities of the optical isomers of (±)-4-amino-5-chloro-2-ethoxy-N-[[4-(4-fluorobenzyl)-2-morpholinyl]me thyl]benzamide (Mosapride)

The enantiomers, (S)-(-)-1 and (R)-(+)-1, of (+)-4-amino-5-chloro-2-ethoxy-N-[[4-(4-fluorobenzyl)-2-morpholinyl]met hyl]benzamide (mosapride) [(+)-1], a new and selective gastroprokinetic agent, were prepared from optically active [4-(4-fluorobenzyl)-2-morpholinyl]methylamines (S)-(-)-4 and (R)-(+)-4, respectively. The requisite (S)-(-)-4 and (R)-(+)-4 were prepared by optical resolution of [4-(4-fluorobenzyl)-2-morpholinyl]methyl p-toluenesulfonate [(+)-5] using (-)- and (+)-N-(p-toluenesulfonyl)glutamic acids, followed by amination of the tosyloxy groupe of (R)-(-)-5 and (S)-(+)-5, respectively. The absolute configurations of (R)-(-)-5 and (S)-(+)-5 were determined on the basis of an asymmetric synthesis of (R)-(-)-5 from (S)-(+)-benzyl glycidyl ether [(S)-(+)-11]. Mosapride and its enantiomers, (S)-(-)-1 and (R)-(+)-1, were essentially equipotent in serotonin 5-HT4 receptor agonistic activity on the electrically evoked contractions in isolated guinea pig ileum.