5448-45-3

Usage

Uses

Used in Pharmaceutical Industry:
4-Benzyloxy-2-hydroxy-benzoic acid is used as an intermediate in the synthesis of 4-Hydroxy Flecainide (H942485), which is an analogue of Flecainide (F390000). Flecainide is a Class I antiarrhythmic agent used to treat various types of arrhythmias, including atrial fibrillation and ventricular tachycardia. The synthesis of 4-Hydroxy Flecainide involves the use of 4-Benzyloxy-2-hydroxy-benzoic acid as a key building block, highlighting its importance in the development of novel antiarrhythmic drugs.

InChI:InChI=1/C14H12O4/c15-13-8-11(6-7-12(13)14(16)17)18-9-10-4-2-1-3-5-10/h1-8,15H,9H2,(H,16,17)

Upstream product

• 89-86-1 4-hydroxysalicylic acid 
• 100-44-7 benzyl chloride 
• 5427-29-2 methyl 2-hydroxy-4-benzyloxybenzoate 
• 85607-79-0 4-(benzyloxy)-2-methoxybenzoic acid 
• 100-39-0 benzyl bromide 
• 97476-06-7 benzyl 4-(benzyloxy)-2-hydroxybenzoate 
• 2150-47-2 methyl 2,4-dihydroxybenzoate 
• 85593-77-7 2,4-bis(benzyloxy)benzoic acid 

Downstream Products

• 77376-41-1 4-benzyloxy-2-(9-hydroxynonyloxy)benzoic acid lactone 
• 77376-44-4 4-benzyloxy-2-(9-hydroxy-5-oxononyloxy)benzoic acid lactone 
• 77376-42-2 4-benzyloxy-2-(9-hydroxy-5-oxanonyloxy)benzoic acid lactone 

Relevant academic research and scientific papers

Design of HIV-1 integrase inhibitors targeting the catalytic domain as well as its interaction with LEDGF/p75: A scaffold hopping approach using salicylate and catechol groups

HIV-1 integrase (IN) is a validated therapeutic target for antiviral drug design. However, the emergence of viral strains resistant to clinically studied IN inhibitors demands the discovery of novel inhibitors that are structurally as well mechanistically different. Herein, we describe the design and discovery of novel IN inhibitors targeting the catalytic domain as well as its interaction with LEDGF/p75, which is essential for the HIV-1 integration as an IN cofactor. By merging the pharmacophores of salicylate and catechol, the 2,3-dihydroxybenzamide (5a) was identified as a new scaffold to inhibit the strand transfer reaction efficiently. Further structural modifications on the 2,3-dihydroxybenzamide scaffold revealed that the heteroaromatic functionality attached on the carboxamide portion and the piperidin-1-ylsulfonyl substituted at the phenyl ring are beneficial for the activity, resulting in a low micromolar IN inhibitor (5p, IC50 = 5 μM) with more than 40-fold selectivity for the strand transfer over the 3′-processing reaction. More significantly, this active scaffold remarkably inhibited the interaction between IN and LEDGF/p75 cofactor. The prototype example, N-(cyclohexylmethyl)-2,3- dihydroxy-5-(piperidin-1-ylsulfonyl) benzamide (5u) inhibited the IN-LEDGF/p75 interaction with an IC50 value of 8 μM. Using molecular modeling, the mechanism of action was hypothesized to involve the chelation of the divalent metal ions inside the IN active site. Furthermore, the inhibitor of IN-LEDGF/p75 interaction was properly bound to the LEDGF/p75 binding site on IN. This work provides a new and efficient approach to evolve novel HIV-1 IN inhibitors from rational integration and optimization of previously reported inhibitors.

Regioselective dealkylation of 2-alkoxybenzoic acid and its amide derivatives with aliphatic amines

The methoxy group of o-anisic acid was cleaved with aliphatic amines in aprotic dipolar solvents. This cleavage reaction was especially smooth when piperazine in dimethylacetamide was used. This method was applicable to a variety of dealkylations of o-alkoxybenzoic acid and ist amide derivatives with high regio-selectivity.

Selective endothelin A receptor ligands. 1. Discovery and structure-activity of 2,4-disubstituted benzoic acid derivatives

This paper describes the discovery of a new non-peptide endothelin A (ET(A)) selective ligand, 2,4-dibenzyloxybenzoic acid 3, which inhibits the binding of [125I]ET-1 to ET(A) receptors with an IC50 of 9 μM (ET-1 = endothelin-1). Optimisation of 3 resulted in compound 52 which had an IC50 of 1 μM. One of the analogues of 3, compound 15, was examined in a functional assay and shown to antagonise ET-1-induced contraction of rat aorta. The identification of 3 was made through the application of ChemDBS-3D searching of our corporate database. The 3D query, using an aromatic ring to a carboxylic acid group separated by 10.2 ± 1.1 A, was derived from an examination of common pharmacophoric distances found in the low energy conformations of two known ET(A) antagonists, the cyclic pentapeptide BQ 123 1 and myriceron caffeoyl ester 2.