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Usage

Uses

Used in Pharmaceutical Synthesis:
3-(4-Fluorobenzoyl)propionic acid is used as a key intermediate in the synthesis of various pharmaceutical compounds, such as 7-fluoro-1-tetralone and LM-1507 sodium salt. It plays a crucial role in the development of new drugs with potential therapeutic applications.
Used in the Synthesis of 7-Fluoro-1-Tetralone:
3-(4-Fluorobenzoyl)propionic acid is used as a starting material for the synthesis of 7-fluoro-1-tetralone, which is achieved through Wolff-Kishner reduction followed by ring closure with polyphosphoric acid. 3-(4-Fluorobenzoyl)propionic acid is an important intermediate in the development of new pharmaceuticals.
Used in the Synthesis of LM-1507 Sodium Salt:
3-(4-Fluorobenzoyl)propionic acid is used as a precursor in the synthesis of 4-(4-fluorophenyl)-1-butanol, which is then used to produce LM-1507 sodium salt. 3-(4-Fluorobenzoyl)propionic acid has potential applications in the treatment of certain medical conditions.
Used in the Synthesis of Penfluridol:
3-(4-Fluorobenzoyl)propionic acid is used in the synthesis of penfluridol, a compound with the chemical formula C28H27ClF5NO and a molecular weight of 523.99. Penfluridol is obtained by reducing the ketone of 3-(4-fluorobenzoyl)propionic acid into a lactone, and it has potential applications in the medical field.

InChI:InChI=1/C10H9FO3/c11-8-3-1-7(2-4-8)9(12)5-6-10(13)14/h1-4H,5-6H2,(H,13,14)

Upstream product

• 108-30-5 succinic acid anhydride 
• 462-06-6 fluorobenzene 
• 10457-90-6 bromperidol 
• 352-34-1 4-fluoro-1-iodobenzene 
• 352-13-6 4-flourophenylmagnesium bromide 
• 86798-58-5 α-<4-(1H-imidazol-1-yl)phenyl>-4-morpholineacetonitrile 
• 88427-81-0 4-(1H-imidazol-1-yl)-β-methyl-γ-oxobenzenebutanoic acid 

Downstream Products

• 589-06-0 4-(4-fluorophenyl)butanoic acid 
• 97150-72-6 4oxo-4(4-pyrazol-1-yl-phenyl)butyric acid 
• 86798-53-0 4-(4-hydroxymethyl-1H-imidazol-1-yl)-γ-oxobenzenebutanoic acid 
• 1026187-68-7 C₁₃H₁₃FO₅ 
• 116910-58-8 3a-(4-fluorophenyl)-2,3,3a,4-tetrahydro-1H-pyrrolo<1,2-a>benzimidazol-1-one 
• 39560-31-1 methyl 3-(4-fluorobenzoyl)-propionate 
• 81198-15-4 acido 3-(p.fluorobenzoil)-3-butenoico 
• 81198-14-3 4-(4-Fluorbenzoyl)-4,5-dihydro-2(3H)-furanon 
• 145879-02-3 N-Decyl-4-(4-fluoro-phenyl)-4-oxo-butyramide 
• 138688-84-3 4-(4-Fluoro-phenyl)-N-((1R,4aS,10aR)-7-isopropyl-1,4a-dimethyl-1,2,3,4,4a,9,10,10a-octahydro-phenanthren-1-ylmethyl)-4-oxo-butyramide 
• 154770-69-1 4-<6-Fluor-9-(4-fluorphenyl)-2,3,4,9-tetrahydro-1H-pyrido<3,4-b>indol-2-yl>-1-(4-fluorphenyl)-1,4-butandion 
• 1496-23-7 dimethyl α-(p-fluorophenyl)succinate 
• 39499-62-2 6-(4-Fluoro-phenyl)-4,5-dihydro-2H-pyridazin-3-one 
• 1693-05-6 ethyl 4-(4'-fluorophenyl)butanoate 

Relevant academic research and scientific papers

Role of CYP3A in bromperidol metabolism in rat in vitro and in vivo

1. The aim was to identify whether CYP3A metabolizes bromperidol (BP), an antipsychotic drug, to form 4-fluorobenzoyl-propionic acid (FBPA) in hepatic microsomes from 8-week-old male Sprague-Dawley rats and to investigate whether an inhibitor or an inducer of CYP3A affects BP pharmacokinetics in rat. 2. In an in vitro study, only troleandomycin showed marked inhibition of FBPA formation among several specific CYP isozyme inhibitors studied including troleandomycin, diethyldithiocarbamate, furafylline and quinine. Anti-rat CYP3A2 serum inhibited FBPA formation by 80%, whereas other anti-rat CYP sera (1A1, 1A2, 2B1, 2C11, 2E1) only slightly inhibited it. 3. In a pharmacokinetic study, BP half-life was prolonged to 137% of the average control value by 7-day treatment with erythromycin, a CYP3A inhibitor, and shortened to 58% of the control by 2-day treatment with dexamethasone, a CYP3A inducer. BP clearance was reduced to 68% of the control by erythromycin and was increased to 145% of control by dexamethasone. 4. These results suggested that BP biotransformation is catalysed mainly by CYP3A to form FBPA in rat and that the modification of this enzyme activity would affect the pharmacokinetics of BP.

Design and Synthesis of Butenolide-based Novel Benzyl Pyrrolones: Their TNF-α based Molecular Docking with in vivo and in vitro Anti-inflammatory Activity

A focused library of novel benzyl pyrrolones has been synthesized and their in silico molecular docking studies carried out against TNF-α target. Among all the docked molecules, compound 3f showed best glide score of -6.89. All the synthesized compounds were evaluated for in vivo anti-inflammatory activity by carrageenan-induced paw edema model. Compounds showing significant anti-inflammatory activity were further tested for their in vitro TNF α expression. Compounds 3b and 2b were found to show significant inhibition of 76.22% and 71.47%, respectively after 5 h in comparison with standard drug indomethacin, which showed 80.98% inhibition of inflammation. Compounds 3b and 2b also suppressed TNF α level by 65.03% and 60.90% as compared indomethacin, which showed 68.84% of inhibition. Compound 3b showed significant analgesic activity of 60.04%, and its activity was comparable with indomethacin (64.04%). Compounds 3b and 2b were also tested for their effect on protein expression of COX-2 and NF-κB in the liver tissues. Compounds 3b and 2b were further evaluated for their gastric risk and lipid peroxidation action and showed superior GI safety along with reduction of LPO as compared to indomethacin. Hepatotoxicity study showed that these two compounds did not cause any damage to liver.

Method for synthesizing 4-(4-fluorobenzoyl) butyric acid and analogues thereof in continuous flow microreactor

The invention relates to a method for synthesizing 4-(4-fluorobenzoyl) butyric acid and analogues thereof in a continuous flow microreactor, which comprises the following steps: (1) uniformly mixing a compound 1 and a compound 2 to obtain a homogeneous phase solution A; (2) uniformly mixing aluminum trichloride, a compound 1 and an organic solvent to obtain a homogeneous phase solution B; (3) diluting concentrated hydrochloric acid with water to prepare a solution C; and (4) transferring the homogeneous phase solution A and the homogeneous phase solution B into a first micro-reaction module for a Friedel-Crafts acylation reaction, after the reaction is finished, transferring the obtained reaction solution and the solution C into a second micro-reaction module for quenching reaction, and then performing liquid separation, washing and vacuum concentration to obtain a target compound 3; wherein the specific synthesis route is as follows. By adopting the method disclosed by the invention, the target product can be continuously and rapidly synthesized, aluminum trichloride is not needed for treatment, the reaction condition is mild, the reaction time is short, and the yield is high and reaches 90% or above.

Practical Synthesis of (3a R, 9b R)-8-Fluoro-7-(perfluoropropan-2-yl)-9b-(phenylsulfonyl)-2,3,3a,4,5,9b-hexahydro-1 H-benzo[e]indole: An Advanced Intermediate to Access the RORγt Inverse Agonist BMT-362265

A practical and scalable route to (3aR, 9bR)-8-fluoro-7-(perfluoropropan-2-yl)-9b-(phenylsulfonyl)-2,3,3a,4,5,9b-hexahydro-1H-benzo[e]indole 10, an advanced intermediate en route to the synthesis of the RORγt inverse agonist, BMT-362265, is described starting from fluorobenzene. The synthesis involved the screening of multiple synthetic routes for their feasibility and scalability. We also demonstrate the utility of an annulating reagent, (R)-N-(2-chloroethyl)-2-methylpropane-2-sulfinamide, for the diastereoselective synthesis of tricyclic pyrrolidine intermediates 24 and 36 on a multigram scale.

In silico designing, in vitro and in vivo evaluation of potential PPAR-γ agonists derived from aryl propionic acid scaffold

Attributed to several side effects, especially on hepatic tissues and body weight, there is always an urge of innovation and upgrading in already existing medication being used in maintaining diabetic condition. Therefore, in the present work, forty-eight molecules derived from arylpropionic acid scaffold were synthesized and their evaluation against diabetes was carried out. The synthesis of these molecules attributed to excellent dock score displayed by all the structures performed against PPAR-γ receptor site. Subsequently, all the derivatives were primarily deduced for their antidiabetic potential by OGTT. The compounds that showed significant antidiabetic activity in OGT Test and also exhibited high dock scores were assessed further by in vitro PPAR transactivation assay to assure analogy between in vivo and in vitro studies. The antidiabetic activity of these active compounds was then evaluated on STZ induced diabetic model in vivo. The most active compounds were scrutinized for its effect on PPAR-γ gene expression and hepatotoxic effect. Finally, it was recapitulated that these derivatives can provide a new prospect towards the development of antidiabetic agents with fewer side effects.

Synthesis, anti-convulsant activity and molecular docking study of novel thiazole pyridazinone hybrid analogues

Pyridazinone analogues have been known to be potential candidates for anticonvulsant agents. We have identified several pyridazinone-based anticonvulsant agents. As a continuation to our previous research, a series of hybrid pyridazinone-thiazole connected through amide linkage were designed and synthesized. Among these, compound SP-5F demonstrated significant anticonvulsant activity with median effective dose of 24.38 mg/kg (MES) and 88.23 mg/kg (scPTz). Results of GABA estimation showed a marked increase in the GABA level when compared with control. Molecular docking studies at the active site of GABA receptor, further confirmed the GABA modulatory effects of SP-5F.

A class of histone acetylase p300 inhibitors, and application thereof

The invention discloses a class of histone acetylase p300 inhibitors, and application thereof, and belongs to the technical field of medicinal chemistry. The invention discloses a compound representedby a formula (I), or a stereochemical isomer, a solvate or a pharmaceutically acceptable salt thereof. According to the invention, the compound can effectively inhibit the activity of histone acetylase p300 and can effectively inhibit the proliferation activity of various tumor cells; the compound is combined with a CDK4/6 inhibitor to play a synergistic role in inhibiting proliferation of tumorcells; and the compound has good application prospects in preparation of histone acetylase inhibitors, preparation of drugs for preventing and/or treating cancers, metabolic diseases, neurological diseases or inflammations, and combination of drugs.

Direct Synthesis of Chiral NH Lactams via Ru-Catalyzed Asymmetric Reductive Amination/Cyclization Cascade of Keto Acids/Esters

Lactams with a stereogenic center adjacent to the N atom have existed in many medicinal agents and bioactive alkaloids. Herein we report a broadly applicable synthesis of enantioenriched NH lactams through a one-pot asymmetric reductive amination/cyclization sequence of easily available keto acids/esters. Such cascade processes alleviate the demand for protecting group manipulations as well as intermediate purification. This strategy is capable of constructing enantioenriched lactams and benzo-lactams of a five-, six-, or seven-membered ring in generally high yield and with excellent enantioselectivities (up to 97% ee). Scalable and concise syntheses of key drug intermediates have further displayed the importance of this methodology.

Synthesis of Enantiopure γ-Lactones via a RuPHOX-Ru Catalyzed Asymmetric Hydrogenation of γ-Keto Acids

A RuPHOX?Ru catalyzed asymmetric hydrogenation of γ-keto acids has been developed, affording the corresponding enantiopure γ-lactones in high yields and with up to 97% ee. The reaction could be performed on a gram scale with a relatively low catalyst loading (up to 10000 S/C) under the indicated reaction conditions and the resulting products can be transformed to several enantiopure building blocks, biologically active compounds and enantiopure drugs. (Figure presented.).

Synthesis of Novel Pterocarpen Analogues via [3?+?2] Coupling-Elimination Cascade of α,α-Dicyanoolefins with Quinone Monoimines

By employing triethylamine as a catalyst, [3?+?2] coupling-elimination cascade of α,α-dicyanoolefins with quinone monoimines was realized. The reactions afforded various novel pterocarpen analogues with generally moderate yields (up to 75%). In addition, a plausible reaction mechanism was proposed.