22091-39-0

Usage

InChI:InChI=1/C10H7ClFNO/c11-5-9-6-14-10(13-9)7-1-3-8(12)4-2-7/h1-4,6H,5H2

Upstream product

• 824-75-9 p-fluorobenzamide 
• 534-07-6 1,3-Dichloroacetone 
• 459-57-4 4-fluorobenzaldehyde 
• 1065102-64-8 methyl 2-(4-fluorophenyl)-1,3-oxazole-4-carboxylate 
• 456-22-4 4-Fluorobenzoic acid 
• 403-43-0 4-fluorobenzoyl chloride 
• 885273-80-3 (2-(4-fluorophenyl)oxazol-4-yl)methanol 

Downstream Products

• 1589081-04-8 4-amino-6-(benzo[d][1,3]dioxol-5-yl)-2-((2-(4-fluorophenyl)oxazol-4-yl)methylthio)pyrimidine-5-carbonitrile 
• 1314887-18-7 4-(2-(4-fluorophenyl)oxazol-4-yl)-1-methylpiperidine-4-carbonitrile 
• 885272-89-9 (2-(4-fluorophenyl)oxazol-4-yl)methanamine 
• 1016734-82-9 2-(2-(4-fluorophenyl)oxazol-4-yl)ethanamine 
• 1314887-16-5 3-(2-(4-fluorophenyl)oxazol-4-yl)-N₁,N₁-dimethylbutane-1,4-diamine 
• 1314887-15-4 4-(dimethylamino)-2-(2-(4-fluorophenyl)oxazol-4-yl)butanenitrile 
• 22087-28-1 2-(2-(4-fluorophenyl)oxazol-4-yl)acetonitrile 

Relevant academic research and scientific papers

Structural and Activity Relationships of 6-Sulfonyl-8-Nitrobenzothiazinones as Antitubercular Agents

The benzothiazinone (BTZ) scaffold compound PBTZ169 kills Mycobacterium tuberculosis by inhibiting the essential flavoenzyme DprE1, consequently blocking the synthesis of the cell wall component arabinans. While extraordinarily potent against M. tuberculosis with a minimum inhibitory concentration (MIC) less than 0.2 ng/mL, its low aqueous solubility and bioavailability issues need to be addressed. Here, we designed and synthesized a series of 6-methanesulfonyl substituted BTZ analogues; further exploration introduced five-member aromatic heterocycles as linkers to attach an aryl group as the side chain. Our work led to the discovery of a number of BTZ derived compounds with potent antitubercular activity. The optimized compounds 6 and 38 exhibited MIC 47 and 30 nM, respectively. Compared to PBTZ169, both compounds displayed increased aqueous solubility and higher stability in human liver microsomes. This study suggested that an alternative side-chain modification strategy could be implemented to improve the druglike properties of the BTZ-based compounds.

Discovery of the disubstituted oxazole analogues as a novel class anti-tuberculotic agents against MDR- and XDR-MTB

A high-throughput screening effort on 45,000 compounds resulted in the discovery of a disubstituted oxazole as a new structural class inhibitor of Mycobacterium tuberculosis (Mtb). In order to improve the activity and investigate the SAR of this scaffold, a series of disubstituted azole analogues have been designed and synthesized. The newly synthesized compounds 1a-y were evaluated for their in vitro anti-TB activity versus replicating, multi- and extensive drug resistant Mtb strains. All the compounds, except 1o, 1p and 1q, showed potent anti-TB activity with MIC of 1-64 mg/L. The test of broad spectrum panel revealed that this series are specific to Mtb. The cytotoxicity assessment indicated that the compounds were not cytotoxic against HEK 293 cells. The compounds could have a novel mechanism to anti-Mtb as they can inhibit drug sensitive and drug resistant Mtb.

COMPOUNDS AND METHODS for the inhibition of HDAC

Disclosed are compounds having the formula: wherein X1, X2, X3, R1, R2, R3, R4, Y, A, Z, L and n are as defined herein, and methods of making and using the same.

Synthesis and Preclinical Evaluation of Three Novel Fluorine-18 Labeled Radiopharmaceuticals for P-Glycoprotein PET Imaging at the Blood-Brain Barrier

P-Glycoprotein (P-gp), along with other transporter proteins at the blood-brain barrier (BBB), limits the entry of many pharmaceuticals into the brain. Altered P-gp function has been found in several neurological diseases. To study the P-gp function, many positron emission tomography (PET) radiopharmaceuticals have been developed. Most P-gp radiopharmaceuticals are labeled with carbon-11, while labeling with fluorine-18 would increase their applicability due to longer half-life. Here we present the synthesis and in vivo evaluation of three novel fluorine-18 labeled radiopharmaceuticals: 4-((6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)methyl)-2-(4-fluorophenyl)oxazole (1a), 2-biphenyl-4-yl-2-fluoroethoxy-6,7-dimethoxy-1,2,3,4-tetrahydro-isoquinoline (2), and 5-(1-(2-fluoroethoxy))-[3-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-propyl]-5,6,7,8-tetrahydronaphthalen (3). Compounds were characterized as P-gp substrates in vitro, and Mdr1a/b(-/-)Bcrp1(-/-) and wild-type mice were used to assess the substrate potential in vivo. Comparison was made to (R)-[11C]verapamil, which is currently the most frequently used P-gp substrate. Compound [18F]3 was performing the best out of the new radiopharmaceuticals; it had 2-fold higher brain uptake in the Mdr1a/b(-/-)Bcrp1(-/-) mice compared to wild-type and was metabolically quite stable. In the plasma, 69% of the parent compound was intact after 45 min and 96% in the brain. Selectivity of [18F]3 to P-gp was tested by comparing the uptake in Mdr1a/b(-/-) mice to uptake in Mdr1a/b(-/-)Bcrp1(-/-) mice, which was statistically not significantly different. Hence, [18F]3 was found to be selective for P-gp and is a promising new radiopharmaceutical for P-gp PET imaging at the BBB. (Chemical Equation).

6,7-DIOXYALKYLTETRAHYDROISOQUINOLINE COMPOUNDS

The present invention relates to a 6,7-dioxyalkyltetrahydroisoquinoline compound, or a salt or solvate thereof according to formula I: (formula I), (I) wherein R represents hydrogen or a fluorinated alkyl group, and R2 and R3 independently represents hydrogen or an alkyl group.

Synthesis and bioactivity of novel pyrazole oxime derivatives containing oxazole ring

Abstract A series of novel pyrazole oxime derivatives containing oxazole ring were designed and synthesized. The title compounds were structurally confirmed by 1H NMR, 13C NMR spectra and elemental analyses. Preliminary bioassay results showed that some of the title compounds displayed promising fungicidal activity besides insecticidal and acaricidal activity. Particularly, compound 8c exhibited potent fungicidal activity against cucumber Pseudoperonospora cubensis beyond good insecticidal activity against Aphis craccivora and Nilaparvata lugens.

Agonists for the adenosine A1 receptor with tunable residence time. a case for nonribose 4-amino-6-aryl-5-cyano-2-thiopyrimidines

We report the synthesis and evaluation of previously unreported 4-amino-6-aryl-5-cyano-2-thiopyrimidines as selective human adenosine A 1 receptor (hA1AR) agonists with tunable binding kinetics, this without affecting their nanomolar affinity for the target receptor. They show a very diverse range of kinetic profiles (from 1 min (compound 52) to 1 h (compound 43)), and their structure-affinity relationships (SAR) and structure-kinetics relationships (SKR) were established. When put in perspective with the increasing importance of binding kinetics in drug discovery, these results bring new evidence of the consequences of affinity-only driven selection of drug candidates, that is, the potential elimination of slightly less active compounds that may display preferable binding kinetics.

SUBSTITUTED ARYLOXAZOLES AND THEIR USE

The present application relates to novel substituted aryloxazole derivatives, a method for the production thereof, the use thereof for the treatment and/or prophylaxis of diseases and the use thereof for the production of drugs for the treatment and/or prophylaxis of diseases, preferably for the treatment and/or prevention of cardiovascular and metabolic disorders.

COMPOUNDS AND METHODS

Disclosed are compounds having the formula: wherein X1, X2, X3, R1, R2, R3, R4, Y, A, n and L are as defined herein, and methods of making and using the same.

Synthesis and structure-activity relationships of 2-aryl-4-oxazolylmethoxy benzylglycines and 2-aryl-4-thiazolylmethoxy benzylglycines as novel, potent PPARα selective activators- PPARα and PPARγ selectivity modulation

The synthesis and follow-up SAR studies of our development candidate 1 by incorporating 2-aryl-4-oxazolylmethoxy and 2-aryl-4-thiazolylmethoxy moieties into the oxybenzylglycine framework of the PPARα/γ dual agonist muraglitazar is described. SAR studies indicate that different substituents on the aryloxazole/thiazole moieties as well as the choice of carbamate substituent on the glycine moiety can significantly modulate the selectivity of PPARα versus PPARγ. Potent, highly selective PPARα activators 2a and 2l, as well as PPARα activators with significant PPARγ activity, such as 2s, were identified. The in vivo pharmacology of these compounds in preclinical animal models as well as their ADME profiles are discussed.