1219-35-8

Usage

InChI:InChI=1/C15H20FNO/c16-14-8-6-13(7-9-14)15(18)5-4-12-17-10-2-1-3-11-17/h6-9H,1-5,10-12H2

Upstream product

• 1219-36-9 1-(4-fluorophenyl)-4-(piperidin-1-yl)butan-1-one hydrochloride 
• 110-89-4 piperidine 
• 40132-01-2 1-(4-fluorophenyl)-4-bromo-1-butanone 
• 3874-54-2 4-(4-fluorophenyl)-4-oxo-n-butyl chloride 

Relevant academic research and scientific papers

Structure-based design of haloperidol analogues as inhibitors of acetyltransferase Eis from: Mycobacterium tuberculosis to overcome kanamycin resistance

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is a deadly bacterial disease. Drug-resistant strains of Mtb make eradication of TB a daunting task. Overexpression of the enhanced intracellular survival (Eis) protein by Mtb confers resistance to the second-line antibiotic kanamycin (KAN). Eis is an acetyltransferase that acetylates KAN, inactivating its antimicrobial function. Development of Eis inhibitors as KAN adjuvant therapeutics is an attractive path to forestall and overcome KAN resistance. We discovered that an antipsychotic drug, haloperidol (HPD, 1), was a potent Eis inhibitor with IC50 = 0.39 ± 0.08 μM. We determined the crystal structure of the Eis-haloperidol (1) complex, which guided synthesis of 34 analogues. The structure-activity relationship study showed that in addition to haloperidol (1), eight analogues, some of which were smaller than 1, potently inhibited Eis (IC50 ≤ 1 μM). Crystal structures of Eis in complexes with three potent analogues and droperidol (DPD), an antiemetic and antipsychotic, were determined. Three compounds partially restored KAN sensitivity of a KAN-resistant Mtb strain K204 overexpressing Eis. The Eis inhibitors generally did not exhibit cytotoxicity against mammalian cells. All tested compounds were modestly metabolically stable in human liver microsomes, exhibiting 30-60% metabolism over the course of the assay. While direct repurposing of haloperidol as an anti-TB agent is unlikely due to its neurotoxicity, this study reveals potential approaches to modifying this chemical scaffold to minimize toxicity and improve metabolic stability, while preserving potent Eis inhibition. This journal is

Antifungal Compositions

Provided herein are antifungal compositions and methods of use thereof. The antifungal compositions include an antifungal agent and an antipsychotic agent or an antihistamine. The methods of use thereof include administering a composition including an antifungal agent and an antipsychotic or an antihistamine to a plant or animal in need thereof.

HETEROAROMATIC COMPOUNDS, METHOD FOR PREPARING THE COMPOUNDS, PHARMACEUTICAL COMPOSITIONS, USES AND METHOD FOR TREATING ACUTE AND CHRONIC PAIN

The present invention refers to a compound of formula (I) or a pharmaceutically acceptable salt thereof, having analgecic activity. Particularly, the compounds of the instant invention are useful to treat or prevent acute and chronic pain, especially neuropathic pain. Additionally, the present invention provides a procces for preparing the compounds, a pharmaceutical composition that comprises a compound of formula (I), and a method for treatment of acute and chronic pain.

18F-Labeled 1,4-Dioxa-8-azaspiro[4.5]decane Derivative: Synthesis and Biological Evaluation of a σ1 Receptor Radioligand with Low Lipophilicity as Potent Tumor Imaging Agent

We report the syntheses and evaluation of series of novel piperidine compounds with low lipophilicity as σ1 receptor ligands. 8-(4-(2-Fluoroethoxy)benzyl)-1,4-dioxa-8-azaspiro[4.5]decane (5a) possessed high affinity (Ki = 5.4 ± 0.4 nM) for σ1 receptors and selectivity for σ2 receptors (30-fold) and the vesicular acetylcholine transporter (1404-fold). [18F]5a was prepared using a one-pot, two-step labeling procedure in an automated synthesis module, with a radiochemical purity of >95%, and a specific activity of 25-45 GBq/μmol. Cellular association, biodistribution, and autoradiography with blocking experiments indicated specific binding of [18F]5a to σ1 receptors in vitro and in vivo. Small animal positron emission tomography (PET) imaging using mouse tumor xenograft models demonstrated a high accumulation in human carcinoma and melanoma. Treatment with haloperidol significantly reduced the accumulation of the radiotracer in tumors. These findings suggest that radiotracer with suitable lipophilicity and appropriate affinity for σ1 receptors could be used for tumor imaging.

Antagonism of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane stimulus with a newly identified 5-HT2- versus 5-HT(1C)-selective antagonist

DOM [i.e., 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane] is a 5- HT(1C/2) serotonin agonist that exerts stimulus control of behavior in animals. In order to determine if the discriminative stimulus effect of DOM is 5-HT(1C)- or 5-HT2-mediated, it would be informative to conduct tests of stimulus antagonism with a 5-HT(1C)- or 5-HT2-selective antagonist. To date, no such agents exist. Although the neuroleptic agent spiperone binds at D2 dopamine receptors and 5-HT(1A) serotonin receptors, (a) it displays about a 1000-fold selectivity for 5-HT2 versus 5-HT(1C) sites and (b) it has been used as a '5-HT2-selective' antagonist. Because spiperone is a behaviorally disruptive agent, it is not suitable for use in drug-discrimination studies. Using the spiperone molecule as a starting point, a limited structure- affinity investigation was conducted in order to identify a suitable antagonist with high affinity and selectivity for 5-HT2 receptors, and yet an antagonist that might lack the disruptive actions of spiperone. Various modifications of the spiperone molecule were examined, but most resulted in decreased 5-HT2 affinity or in loss of selectivity. One compound, 8-[3-(4- fluorophenoxy)propyl]-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one (26), was shown to bind at 5-HT2 sites with high affinity (K(i) = 2 nM) and >2,000- fold selectivity versus 5-HT(1C) sites. In tests of stimulus antagonism using rats trained to discriminate 1 mg/kg of DOM from saline vehicle, 26 behaved as a potent antagonist (ED50 = 0.003 mg/kg) and lacked the disruptive effects associated with spiperone. As such, (a) it would appear that the DOM stimulus is primarily a 5-HT2-mediated, and not 5-HT(1C)-mediated, phenomenon, and (b) compound 26 may find application in other pharmacologic investigations where spiperone may not be a suitable antagonist.

N-substituted alpha-aminoalkylacrylophenones and some related compounds: a new class of spermicidal agents.

The results of a screening program to test the spermicidal effectiveness of several compounds is presented. The program was initiated after N-substituted 3-aminoacrylophenones were found to have unexpected spermicidal activity. The compounds had been synthesized as possible antiinflammatory agents. This result prompted the synthesis and screening of N-substituted alpha-aminomethylacrylophenones, alpha-(2-aminomethyl)acrylophenones and 3-N-substituted-2-methyleneindan-1-ones. The starting materials, substituted acetophenones, for the synthesis of N-substituted alpha-aminomethylacrylophenones were either commercial products or obtained by standard methods. N-substituted amino-butyrophenone was reacted with paraformaldehyde to yield the alpha-(2 aminoethyl)acrylophenones. A series of reactions was undertaken to synthesize 2-methyleneindan-1-ones. The preparation of each is detailed and molecular formulas are provided. Spermicidal activity was assessed by dissolving the compound in physiological saline at different concentrations. 2 drops of rat sperm suspension or human semen were placed on a slide, followed by 2 drops of a compound solution. Control slides of physiological saline were prepared. The contents were mixed for approximately 5 seconds and examined under a phase contrast microscope. The results were considered positive if 100% of the spermatozoa became immotile instantaneously. Several of the compounds showed marked spermicidal activity.