83642-03-9

Upstream product

• 167091-96-5 4-(4'-fluorophenoxy)benzylalcohol 
• 371-41-5 4-Fluorophenol 
• 137736-06-2 4-(4-fluorophenoxy)benzaldehyde 
• 459-57-4 4-fluorobenzaldehyde 

Downstream Products

• 1145683-33-5 2-(5-{1-[4-(4-Fluoro-phenoxy)-benzyl]-piperidin-3-yl}-4'-trifluoromethyl-biphenyl-3-yl)-4-methyl-pentanoic acid ethyl ester 
• 361146-55-6 (4R)-1-[4-(4-fluorophenoxy)benzyl]-2-oxo-imidazolidine-4-carboxylic acid (2-trimethylsilanylethoxy)amide 
• 361146-54-5 (4R)-1-[4-(4-fluorophenoxy)benzyl]-2-oxo-imidazolidine-4-carboxylic acid tert-butyl ester 
• 352665-63-5 (4R)-1-[4-(4-fluorophenoxy)benzyl]-2-oxo-imidazolidine-4-carboxylic acid 
• 352665-53-3 3-[4-(4-fluoro-phenoxy)-benzyl]-2-oxo-imidazolidine-1,5-dicarboxylic acid 1-benzyl ester 5-tert-butyl ester 

Relevant academic research and scientific papers

Discovery and structural optimization of 4-(4-(benzyloxy)phenyl)-3,4-dihydropyrimidin-2(1H)-ones as RORc inverse agonists

Aim: Retinoic acid receptor-related orphan nuclear receptors (RORs) are orphan nuclear receptors that show constitutive activity in the absence of ligands. Among 3 subtypes of RORs, RORc is a promising therapeutic target for the treatment of Th17-mediated autoimmune diseases. Here, we report novel RORc inverse agonists discovered through structure-based drug design. Methods: Based on the structure of compound 8, a previously described agonist of RORa, a series of 4-(4-(benzyloxy)phenyl)-3,4-dihydropyrimidin-2(1H)-one derivatives were designed and synthesized. The interaction between the compounds and RORc was detected at molecular level using AlphaScreen assay. The compounds were further examined in 293T cells transfected with RORc and luciferase reporter gene. Thermal stability shift assay was used to evaluate the effects of the compounds on protein stability. Results: A total of 27 derivatives were designed and synthesized. Among them, the compound 22b was identified as the most potent RORc inverse agonist. Its IC50 values were 2.39 μmol/L in AlphaScreen assay, and 0.82 μmol/L in inhibition of the cell-based luciferase reporter activity. Furthermore, the compound 22b displayed a 120-fold selectivity for RORc over other nuclear receptors. Moreover, a molecular docking study showed that the structure-activity relationship was consistent with the binding mode of compound 22b in RORc. Conclusion: 4-(4-(Benzyloxy)phenyl)-3,4-dihydropyrimidin-2(1H)-one derivatives are promising candidates for the treatment of Th17-mediated autoimmune diseases, such as rheumatoid arthritis, psoriasis, and multiple sclerosis.

Synthesis and Structure-Activity Relationships for Extended Side Chain Analogues of the Antitubercular Drug (6 S)-2-Nitro-6-{[4-(trifluoromethoxy)benzyl]oxy}-6,7-dihydro-5 H -imidazo[2,1- b ][1,3]oxazine (PA-824)

Novel extended side chain nitroimidazooxazine analogues featuring diverse linker groups between two aryl rings were studied as a potential strategy to improve solubility and oral activity against chronic infection by Mycobacterium tuberculosis. Both lipop

THIAZOLE COMPOUNDS AS ACTIVATORS OF SOLUBLE GUANYLATE CYCLASE

Disclosed are compounds of formula (I) wherein R1 and R2 are independently selected from hydrogen, halo, C1-4alkyl, C1-4alkoxy, CF3 and OCF3; -Y- represents formula (IA) R3 represents hydrogen, fluoro, chloro or C1-4alkyl; R4a and R4b each independently represent hydrogen, C1-4alkyl, C1-4alkoxy, CF3 or halo; and R5 represents a group Z-X; wherein Z is absent or represents (CH2)2 or O; and X represents formula (IB) wherein: J and L both represent CH, or one of J and L represents CH and the other represents N; when both J and L represent CH, R6 represents hydrogen, halo, CF3, C1-4alkyl or C1-4alkoxy in a meta or ortho position relative to the R7 substituent and R7 represents hydrogen, halo, CF3, OCF3, C1-4alkyl, C1-4alkoxy, CH2OH, CN, CONR8R9 or CO2H; or when one of J or L represents N, R6 represents hydrogen or halo in a meta or ortho position relative to the R7 substituent and R7 represents hydrogen, halo, CF3, C1-4alkyl, C1-4alkoxy, CH2OH, CN, CONR8R9 or CO2H; and R8 and R9 are independently selected from hydrogen and C1-4alkyl; or salts thereof which activate soluble guanylate cyclase (sGC), pharmaceutical compositions containing them, their use in medicine, and processes for their preparation.

2,6-DISUBSTITUTED PYRIDINES AS SOLUBLE GUANYLATE CYCLASE ACTIVATORS

Disclosed are compounds of formula (I) wherein R1 and R2 are independently selected from hydrogen, halo, CF3, C1-4alkyl and allyl; Y represents (II), (III), (IV) or (V) wherein R3 represents CF3 or C1-4alkyl; and R3a represents CF3 or C1-4alkyl.

PYRAZOLES AS HUMAN NON-PANCREATIC SECRETORY PHOSPHOLIPASE A2 INHIBITORS

A class of novel pyrazoles is disclosed together with the use of such compounds for inhibiting sPLA2 mediated release of fatty acids for treatment of conditions such as septic shock

Pyrazoles as human non-pancreatic secretory phospholipase A2 inhibitors

A class of novel pyrazoles is disclosed together with the use of such compounds for inhibiting sPLA2mediated release of fatty acids for treatment of conditions such as septic shock.