147807-45-2

Upstream product

• 79-04-9 chloroacetyl chloride 
• 147807-60-1 1-<4-(benzyloxy)benzoyl>-2-(cyanoethyl)hydrazine 
• 32122-11-5 4-benzyloxy-benzoic acid methyl ester 
• 128958-65-6 4-benzyloxyphenylhydrazide 
• 100-44-7 benzyl chloride 
• 56441-55-5 ethyl 4-(benzyloxy)benzoate 
• 120-47-8 Ethyl 4-hydroxybenzoate 
• 99-76-3 methyl 4-hydroxylbenzoate 
• 100-39-0 benzyl bromide 

Relevant academic research and scientific papers

Synthesis and biological screening of 2-substituted 5,6-dihydro-5-oxo-4H-1,3,4-oxadiazine-4-propanenitriles and of their intermediates

To evaluate the effect of substituents on biological activities of electron-rich N-containing heterocycles, the variably 2-substituted 5,6-dihydro-5-oxo-4H-1,3,4-oxadiazine-4-propanenitriles 26-33 were synthesized and evaluated for antibacterial, antifungal, and enzyme-inhibition activities. The target compounds were obtained from alkyl 4- or 3-hydroxy benzoates 1 and 2, respectively, and from methyl indoleacetate 3. The phenolic OH group of benzoates 1 and 2 were substituted with p-toluenesulfonyl (→ 4 and 5), benzoyl (→ 6 and 7), and benzyl groups (→ 8 and 9) and then converted to 5,6-dihydro-5-oxo-4H-1,3,4-oxadiazine-4-propanenitriles. To establish structure-activity relationships (SAR), a pharmacological screening of the intervening intermediates was also conducted, which revealed that the intermediate hydrazide 11 possesses significant antimicrobial and MAO-A inhibiting properties and intermediates 12, 24, 28, and 29 appreciable antifungal activities. Compound 7 inhibits α-chymotrypsin.

5-[4-(Benzyloxy)phenyl]-1,3,4-oxadiazol-2(3H)-one derivatives and related analogues: New reversible, highly potent, and selective monoamine oxidase type B inhibitors

Thirty-three new 5-[4-(benzyloxy)phenyl]-1,3,4-oxadiazol-2(3H)-one derivatives including related analogues, designed as inhibitors of monoamine oxidase type B (MAO B), were synthesized and investigated both in vitro and ex vivo for their abilities to inhibit selectively rat brain MAO B over MAO A. Three inhibitors were found to act as reversible, highly potent, and selective MAO B inhibitors, namely the nitrile derivative 5-[4- (benzyloxy)phenyl]-3-(2-cyanoethyl)-1,3,4-oxadiazol-2(3H)-one (12a) and two closely related homologues, the corresponding oxadiazolethione 13a and the alcohol 14b. Their IC50(MAO B) values are in the low nanomolar range of 1.4-4.6 nM and their selectivities, estimated by the ratio of IC50 values (A/B), are from 3200 to >71 400. Compound 12a exhibited the highest activity against MAO B. Its IC50 was evaluated to be 1.4 nM with a quasitotal selectivity (>71 400) toward this enzyme. In ex vivo studies, 12a showed a reversible and short duration of action. MAO B was markedly inhibited with the oral dose of 1 mg/kg without any alteration of MAO A, and the inhibition almost did not exceed 24 h. Its ED50 (1 h after oral administration) was evaluated to be 0.56 mg (1.7 μmol)/kg. Remarkably, MAO A was not affected at doses as high as 1500 mg/kg, po. In addition, no apparent toxicity or behavioral anomaly was observed during the treatment even at the maximum administrated dose. SAR studies emphasize the existence of three binding sites to the enzyme with a special importance of the terminal phenyl. Analysis of the inhibition kinetics indicated that 12a acts in a two-step mechanism as a competitive, slow, and tight-binding inhibitor of MAO B with a K(i) value of 0.22 μM and an overall K(i)* value at equilibrium of 0.7 nM.