776291-03-3

Upstream product

• 10540-31-5 4-cyano-4'-fluorobiphenyl 
• 518357-40-9 (4′-fluorobiphenyl-4-yl)methylammonium chloride 
• 1765-93-1 4-fluoroboronic acid 
• 3959-07-7 4-Bromobenzylamine 
• 60992-98-5 4-(4-fluorophenyl)benzaldehyde 

Downstream Products

• 937724-03-3 (4'-fluoro-4-biphenylmethyl)-{2-[1-(4-methylbenzyl)-4-piperidinyl]ethyl}amine 
• 1383484-22-7 1-((4'-fluoro-[1,1'-biphenyl]-4-yl)methyl)-3-hydroxy-2-methylpyridine-4(1H)-thione 
• 1394431-58-3 5-bromo-N-((4'-fluorobiphenyl-4-yl)methyl)-1-(phenylsulfonyl)-1H-indole-2-sulfonamide 
• 518357-40-9 (4′-fluorobiphenyl-4-yl)methylammonium chloride 
• 937724-29-3 C₃₈H₄₈FN₃O₅ 
• 937724-24-8 C₃₅H₄₄FN₃O₃ 

Relevant academic research and scientific papers

Solvent-controlled synthesis of bulky and polar-bulky galactonoamidines

The goal of this study was the design and synthesis of bulky and polar-bulky galactonoamidines that have a potential to interact with both catalytic amino acids in the active site of human α-galactosidase. While a library of more than 25 compounds was previously synthesized following established protocols, the coupling of the selected amines with activated perbenzylated galactothionolactam yielded only small amounts for some of the perbenzylated targets. A computational approach disclosed relative energy differences of selected adducts and suggested a solvent change that then allowed a successful synthesis of the precursor compounds in 20–75%. Subsequent attempts to globally deprotect perbenzylated galactonoamidines by Pd catalyzed hydrogenation resulted in unwanted Pd coordination, incomplete debenzylation reactions, partial compound hydrolysis, and even complete decomposition. A lengthy protocol was elaborated to purify the targeted carbohydrate derivatives after modified debenzylation conditions.

Probing structural requirements for human topoisomerase I inhibition by a novel N1-Biphenyl fluoroquinolone

Fluoroquinolones substituted with N-1 biphenyl and napthyl groups were discovered to act as catalytically inhibitors of human topoisomerases I and II, and to possess anti-proliferative activity in vivo. Structural requirements for these novel quinolones t

Development of indole sulfonamides as cannabinoid receptor negative allosteric modulators

Existing CB1 negative allosteric modulators (NAMs) fall into a limited range of structural classes. In spite of the theoretical potential of CB1 NAMs, published in vivo studies have generally not been able to demonstrate the expected therapeutically-relevant CB1-mediated effects. Thus, a greater range of molecular tools are required to allow definitive elucidation of the effects of CB1 allosteric modulation. In this study, we show a novel series of indole sulfonamides. Compounds 5e and 6c (ABD1075) had potencies of 4 and 3?nM respectively, and showed good oral exposure and CNS penetration, making them highly versatile tools for investigating the therapeutic potential of allosteric modulation of the cannabinoid system.

Substituted N -(biphenyl-4′-yl)methyl (R)-2-acetamido-3- methoxypropionamides: Potent anticonvulsants that affect frequency (Use) dependence and slow inactivation of sodium channels

We prepared 13 derivatives of N-(biphenyl-4′-yl)methyl (R)-2-acetamido-3-methoxypropionamide that differed in type and placement of a R-substituent in the terminal aryl unit. We demonstrated that the R-substituent impacted the compound's whole animal and cellular pharmacological activities. In rodents, select compounds exhibited excellent anticonvulsant activities and protective indices (PI = TD50/ED50) that compared favorably with clinical antiseizure drugs. Compounds with a polar, aprotic R-substituent potently promoted Na+ channel slow inactivation and displayed frequency (use) inhibition of Na+ currents at low micromolar concentrations. The possible advantage of affecting these two pathways to decrease neurological hyperexcitability is discussed.

(Biphenyl-4-yl)methylammonium chlorides: Potent anticonvulsants that modulate Na+ currents

We have reported that compounds containing a biaryl linked unit (Ar-X-Ar′) modulated Na+ currents by promoting slow inactivation and fast inactivation processes and by inducing frequency (use)-dependent inhibition of Na+ currents. These electrophysiological properties have been associated with the mode of action of several antiepileptic drugs. In this study, we demonstrate that the readily accessible (biphenyl-4-yl)methylammonium chlorides (compound class B) exhibited a broad range of anticonvulsant activities in animal models, and in the maximal electroshock seizure test the activity of (3′-trifluoromethoxybiphenyl-4- yl)methylammonium chloride (8) exceeded that of phenobarbital and phenytoin upon oral administration to rats. Electrophysiological studies of 8 using mouse catecholamine A-differentiated cells and rat embryonic cortical neurons confirmed that 8 promoted slow and fast inactivation in both cell types but did not affect the frequency (use)-dependent block of Na+ currents.

Novel series of substituted biphenylmethyl urea derivatives as MCH-R1 antagonists for the treatment of obesity

We have designed and synthesized two novel series of MCH-R1 antagonists based on a substituted biphenylmethyl urea core. SAR was explored, suggesting that optimal binding with the receptor was achieved when the biphenylmethyl group and the linker were sub

Pyrimidinone compounds

Pyrimidinone compounds of formula (I) are inhibitors of the enzyme Lp-PLA2 and of use in therapy, in particular for treating atherosclerosis.

Potent, orally active inhibitors of lipoprotein-associated phospholipase A2: 1-(biphenylmethylamidoalkyl)-pyrimidones

A series of 1-(biphenylmethylamidoalkyl)-pyrimidones has been designed as nanomolar inhibitors of recombinant lipoprotein-associated phospholipase A2 with high potency in whole human plasma. 5-(Pyrazolylmethyl) derivative 16 and 5-(methoxypyrimidinylmethyl) derivative 27 demonstrated excellent pharmacodynamic profiles which correlated well with their pharmacokinetic effects.