61881-50-3

Upstream product

• 61881-49-0 Diethyl 2-methyl-2-(4-nitrophenyl)malonate 
• 350-46-9 4-Fluoronitrobenzene 
• 609-08-5 Diethyl methylmalonate 
• 100-00-5 4-chlorobenzonitrile 

Downstream Products

• 132483-77-3 Diethyl 2-(4-cyanophenyl)-2-methylmalonate 
• 76510-82-2 diethyl (4-hydroxyphenyl)methylmalonate 
• 88975-48-8 2-[4-(3-Benzoyl-thioureido)-phenyl]-2-methyl-malonic acid diethyl ester 
• 88975-37-5 2-Methyl-2-[4-(2,2,2-trifluoro-acetylamino)-phenyl]-malonic acid diethyl ester 
• 138568-92-0 2-(3-Bromo-4-nitro-phenyl)-2-methyl-malonic acid diethyl ester 
• 34645-72-2 (RS)-2-(4'-iodophenyl)propanoic acid 
• 56355-17-0 2-[4-(2-thiazolyloxy)phenyl]propionic acid 
• 57648-11-0 2-<4-(2-thiazolylamino)phenyl>propionic acid 
• 88975-18-2 diethyl (4-methylaminophenyl)methylmalonate 
• 56355-16-9 ethyl 2-[4-(2-thiazolyloxy)-phenyl]propionate 
• 88975-83-1 2-(4-Cyanato-phenyl)-2-methyl-malonic acid diethyl ester 
• 88975-96-6 2-[3,5-Dichloro-4-(thiazol-2-yloxy)-phenyl]-propionic acid 
• 88975-46-6 diethyl (3,5-dichloro-4-hydroxyphenyl)methylmalonate 
• 88975-84-2 2-Methyl-2-(4-thiocarbamoyloxy-phenyl)-malonic acid diethyl ester 

Relevant academic research and scientific papers

TRICYCLIC PYRIDINE DERIVATIVES, MEDICAMENTS CONTAINING SUCH COMPOUNDS, THEIR USE AND PROCESS FOR THEIR PREPARATION

The present invention relates to compounds defined by formula I wherein the variables R1-R8 are defined as in the description, possessing valuable pharmacological activity. Particularly, the compounds are inhibitors of cholesterol ester transfer protein (CETP) and thus are suitable for treatment and prevention of diseases which can be influenced by inhibition of this enzyme.

Inhibitors of protein kinases

Compounds of general Formula (I): wherein R1, R2, R3, Ra, A, B and x are as defined herein are inhibitors of protein kinases in particular members of the cyclin-dependent kinase family and/or the glycogen synthase kinase 3 family and are useful in preventing and/or treating any type of pain, inflammatory disorders, cancer, immunological diseases, proliferative diseases, infectious diseases, cardiovascular diseases, metabolic disorders, renal diseases, neurologic and neuropsychiatric diseases and neurodegenerative diseases.

Synthesis and biological activity of flurbiprofen analogues as selective inhibitors of β-amyloid1-42 secretion

Flurbiprofen, a nonsteroidal antiinflammatory drug (NSAID), has been recently described to selectively inhibit β-amyloid1-42 (Aβ42) secretion, the most toxic component of the senile plaques present in the brain of Alzheimer patients. The use of this NSAID in Alzheimer's disease (AD) is hampered by a significant gastrointestinal toxicity associated with cyclooxygenase (COX) inhibition. New flurbiprofen analogues were synthesized, with the aim of increasing Aβ42 inhibitory potency while removing anti-COX activity. In vitro ADME developability parameters were taken into account in order to identify optimized compounds at an early stage of the project. Appropriate substitution patterns at the alpha position of flurbiprofen allowed for the complete removal of anti-COX activity, while modifications at the terminal phenyl ring resulted in increased inhibitory potency on Aβ42 secretion. In rats, some of the compounds appeared to be well absorbed after oral administration and to penetrate into the central nervous system. Studies in a transgenic mice model of AD showed that selected compounds significantly decreased plasma Aβ42 concentrations. These new flurbiprofen analogues represent potential drug candidates to be developed for the treatment of AD.

Preparation and biological activity of 2-[4-(thiazol-2-yl)phenyl]propionic acid derivatives inhibiting cyclooxygenase

A series of 2-[4-(thiazol-2-yl)phenyl]propionic acids substituted at various positions were prepared by the reaction of diethyl 2-methyl-2-(4-thiocarbamoylphenyl)malonates with α-bromoaldehyde diethyl acetals or α-haloketones followed by hydrolysis of esters. The inhibition of prostaglandin H synthetase (cyclooxygenase) was assayed by use of an enzyme preparation from guinea pig polymorphonuclear leukocytes. Examination of the structure-activity relationship of these compounds indicated that the substitution pattern with halogens at position 3 (R1) of the benzene ring and a methyl group in position 4 (R2) and/or 5 (R3) of the thiazole ring were favorable for inhibitory activity. The compounds bearing bulky alkyl or polar functional groups at the R2 position were weak inhibitors. The potent inhibitors of cyclooxygenase were tested for their ability to reduce carrageenin-induced inflammation of rat paws. These derivatives had strong anti-inflammatory activity based on their strong inhibition of cyclooxygenase, with some exceptions, including those with a thiomethyl group at R1.