53658-03-0

Upstream product

• 623-24-5 1,4-bis(bromomethyl)benzene 
• 3328-57-2 sodium 4-cyanophenolate 
• 767-00-0 4-cyanophenol 

Downstream Products

• 118499-86-8 1,4-Bis(4-amidoximinophenoxymethyl)benzene 
• 53657-95-7 1,4-bis{(4-amidino)-phenoxymethyl}benzene dihydrochloride 
• 75846-17-2 4,4′-((1,4-phenylenebis(methylene))bis(oxy))dibenzimidamide 

Relevant academic research and scientific papers

Structure-Activity Studies with Bis-Amidines That Potentiate Gram-Positive Specific Antibiotics against Gram-Negative Pathogens

Pentamidine, an FDA-approved antiparasitic drug, was recently identified as an outer membrane disrupting synergist that potentiates erythromycin, rifampicin, and novobiocin against Gram-negative bacteria. The same study also described a preliminary structure-activity relationship using commercially available pentamidine analogues. We here report the design, synthesis, and evaluation of a broader panel of bis-amidines inspired by pentamidine. The present study both validates the previously observed synergistic activity reported for pentamidine, while further assessing the capacity for structurally similar bis-amidines to also potentiate Gram-positive specific antibiotics against Gram-negative pathogens. Among the bis-amidines prepared, a number of them were found to exhibit synergistic activity greater than pentamidine. These synergists were shown to effectively potentiate the activity of Gram-positive specific antibiotics against multiple Gram-negative pathogens such as Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli, including polymyxin- and carbapenem-resistant strains.

COMPOUNDS FOR THE TREATMENT OF BACTERIAL INFECTIONS AND POTENTIATION OF ANTIBIOTICS

Compounds and methods for use to treat a bacterial infection caused by, for example, gram positive bacteria, gram negative bacteria, and/or mycobacteria are provided herein. Also provided herein are compounds and methods for use in potentiating the effect of an antibiotic in the treatment of a bacterial infection. Pharmaceutical compositions including the compounds as described herein are also provided.

AMIDINES AND AMIDINE ANALOGS FOR THE TREATMENT OF BACTERIAL INFECTIONS AND POTENTIATION ANTIBIOTICS

Compounds and methods for the treatment of a bacterial infection or the potentiation of an antibiotic in treating a bacterial infection are described herein.

Synthesis and antiprotozoal activities of dicationic bis(phenoxymethyl)benzenes, bis(phenoxymethyl)naphthalenes, and bis(benzyloxy)naphthalenes

A series of 37 dicationically substituted bis(phenoxymethyl)benzene bis(phenoxymethyl)naphthalene, and bis(benzyloxy)naphthalene analogues of pentamidine was prepared and evaluated for antiprotozoal activities and cytotoxicity in in vitro. 1,3-Bis(4-amidinophenoxymethyl)benzene (1) was the most active against Trypanosoma brucei rhodesiense (IC50 = 2.1 nM). 1,3-Bis[4-(N-isopropylamidino)phenoxymethyl]benzene (2) was most active against Plasmodium falciparum (IC50 = 3.6 nM) and displayed a selectivity index more than 50 times greater than that of pentamidine. Several other compounds displayed lower antiplasmodial IC50 values and higher selectivity indices relative to pentamidine. 1,4-Bis(4-amidinophenoxymethyl)benzene (14) was the most active against Leishmania donovani (IC50 = 1.3 μM). Compound 2 displayed the greatest activity against T. b. rhodesiense in vivo, curing three of four infected mice dosed intraperitoneally at 5 mg/kg × 4 days.

Novel bisbenzamidines as potential drug candidates for the treatment of Pneumocystis carinii pneumonia

A series of pentamidine congeners has been synthesized and screened for their in vitro activity against Pneumocystis carinii. Among the tested compounds, bisbenzamidines linked by a flexible pentanediamide or hexanediamide chain (7 and 9) emerged as excep

Antiparasitic Agents: Part VI - Synthesis of 1,2-, 1,3,- and 1,4-Bis(4-substituted aryloxy)benzenes and their Biological Activities

Several 1,2-, 1,3-, 1,4-bis(4-amidinophenoxy)benzenes (8-10); 1,2-, 1,3-, 1,4-bis(4-amidinobenzyloxy)benzenes (14-16) and 1,2-, 1,3-, 1,4-bis(4-amidinophenoxymethyl)benzenes (26-28) and the corresponding amidoximes (17-19), (29-31) and 33 have been synthe