90221-70-8

Upstream product

• 99-02-5 3'-Chloroacetophenone 
• 41011-01-2 2-bromo-1-(3-chloro-phenyl)-ethanone 
• 33167-21-4 3-(3-chloro-phenyl)-3-oxo-propionic acid ethyl ester 
• 2039-85-2 3-Chlorostyrene 

Downstream Products

• 40733-92-4 C₈H₈ClFO 
• 1446417-90-8 1-(3-chlorophenyl)-2-fluoroethan-1-ol 
• 1446417-96-4 1-(3-chlorophenyl)-2-fluoroethan-1-ol 
• 99-02-5 3'-Chloroacetophenone 

Relevant academic research and scientific papers

Double Enzyme-Catalyzed One-Pot Synthesis of Enantiocomplementary Vicinal Fluoro Alcohols

A double-enzyme-catalyzed strategy for the synthesis of enantiocomplementary vicinal fluoro alcohols through a one-pot, three-step process including lipase-catalyzed hydrolysis, spontaneous decarboxylative fluorination, and subsequent ketoreductase-catalyzed reduction was developed. With this approach, β-ketonic esters were converted to the corresponding vicinal fluoro alcohols with high isolated yields (up to 92percent) and stereoselectivities (up to 99percent). This new cascade process addresses some issues in comparison with traditional methods such as environmentally hazardous reaction conditions and low stereoselectivity outcome.

Design, Synthesis, and Pharmacological Characterization of a Neutral, Non-Prodrug Thrombin Inhibitor with Good Oral Pharmacokinetics

Despite extensive research on small molecule thrombin inhibitors for oral application in the past decades, only a single double prodrug with very modest oral bioavailability has reached human therapy as a marketed drug. We have undertaken major efforts to identify neutral, non-prodrug inhibitors. Using a holistic analysis of all available internal data, we were able to build computational models and apply these for the selection of a lead series with the highest possibility of achieving oral bioavailability. In our design, we relied on protein structure knowledge to address potency and identified a small window of favorable physicochemical properties to balance absorption and metabolic stability. Protein structure information on the pregnane X receptor helped in overcoming a persistent cytochrome P450 3A4 induction problem. The selected compound series was optimized to a highly potent, neutral, non-prodrug thrombin inhibitor by designing, synthesizing, and testing derivatives. The resulting optimized compound, BAY1217224, has reached first clinical trials, which have confirmed the desired pharmacokinetic properties.

SUBSTITUTED BENZOXAZOLES

The invention relates to substituted benzoxazoles and to processes for their preparation and to their use for preparing medicaments for the treatment and/or prophylaxis of diseases, in particular of cardiovascular disorders, preferably of thrombotic or thromboembolic disorders.

TRIAZOLOPYRIDINES AS THROMBIN INHIBITORS FOR THE TREATMENT OF THROMBOEMBOLIC DISEASES

The invention relates to substituted triazolopyridines and to processes for their preparation and to their use for preparing medicaments for the treatment and/or prophylaxis of diseases, in particular of cardiovascular disorders, preferably of thrombotic or thromboembolic disorders.

SUBSTITUTED BENZOXAZOLES

The invention relates to substituted benzoxazoles and to processes for their preparation and to their use for preparing medicaments for the treatment and/or prophylaxis of diseases, in particular of cardiovascular disorders, preferably of thrombotic or thromboembolic disorders.

Triazolopyridines as thrombin inhibitors for the treatment of thromboembolic diseases

The invention relates to substituted triazolopyridines and methods for the production thereof, as well as to the use thereof in the production of drugs for treating and/or preventing diseases, especially diseases of the cardiovascular system, preferably thrombotic or thromboembolic diseases.

Metal-free, efficient oxyfluorination of olefins for the synthesis of α-fluoroketones

A novel oxyfluorination of olefin reactions has been developed. The reactions involve a metal-free and green catalytic system for the synthesis of α-fluoroketones which is an important building block for organic synthesis. Moreover, this reaction system exhibits great functional group tolerance.

Synthesis of α-fluoroketones and α-fluoroenones in aqueous media

An efficient synthesis of α-fluoroketones via the nucleophilic fluorination of α-bromoketones in water with TBAF·3H2O as the fluorinating agent was developed in this paper. In addition, a simple and efficient synthesis of α-fluoroenones through the condensation of α-fluoroketones with aldehydes promoted by sodium hydroxide in water was also discovered.

Synthesis of enantiopure fluorohydrins using alcohol dehydrogenases at high substrate concentrations

The use of purified and overexpressed alcohol dehydrogenases to synthesize enantiopure fluorinated alcohols is shown. When the bioreductions were performed with ADH-A from Rhodococcus ruber overexpressed in E. coli, no external cofactor was necessary to obtain the enantiopure (R)-derivatives. Employing Lactobacillus brevis ADH, it was possible to achieve the synthesis of enantiopure (S)-fluorohydrins at a 0.5 M substrate concentration. Furthermore, due to the activated character of these substrates, a huge excess of the hydrogen donor was not necessary.