104-32-5

Basic information

• Product Name: Propamidine
• Synonyms: propamidine;4,4'-(1,3-Propanediylbis(oxy))bisbenzenecarboximidamide;4,4'-(1,3-Propanediyl)bis(oxy)bisbenzamidine;4,4'-[1,3-Propanediylbis(oxy)]bis(benzenecarbimidamide);Brolene;DAPP;BenzenecarboxiMidaMide,4,4'-[1,3-propanediylbis(oxy)]bis-;4,4'-[1,3-Propanediylbis(oxy)]dibenzenecarboximidamide
• CAS NO: 104-32-5
• Molecular Formula: C₁₇H₂₀N₄O₂
• Molecular Weight: 312.37
• EINECS: 203-195-2
• Mol File: 104-32-5.mol
• Article Data: 3

Chemical Properties

• Boiling Point: 497.3 °C at 760 mmHg
• Flash Point: 254.6 °C
• Appearance: /
• Density: 1.25 g/cm³
• Vapor Pressure: 4.99E-10mmHg at 25°C
• Refractive Index: 1.608
• PKA: 12.75±0.50(Predicted)
• CAS DataBase Reference: Propamidine(CAS DataBase Reference)
• NIST Chemistry Reference: Propamidine(104-32-5)
• EPA Substance Registry System: Propamidine(104-32-5)

Safety Data

• Hazardous Substances Data: 104-32-5(Hazardous Substances Data)

Usage

Uses

as isethionate.

Definition

ChEBI: A polyether that is the bis(4-guanidinophenyl) ether of propane-1,3-diol. Used (as its isethionate salt) for the treatment of minor eye or eyelid infections, such as conjunctivitis and blepharitis.

Pharmaceutical Applications

A synthetic diamidine formulated as the isethionate or as dibromopropamidine isethionate for topical administration to the eye. Resistant clinical isolates of Acanthamoeba have been identified. It is available over the counter in eye drops. Its activity against bacterial pathogens is poor, but it exhibits specific activity against Acanthamoeba spp. Reduction in sensitivity of Acanthamoeba during encystation might reflect changes in drug uptake. It is still recommended for aggressive treatment of amebic keratitis (in combination with neomycin or other agents), but is not well tolerated.

InChI:InChI=1/C17H20N4O2/c18-16(19)12-2-6-14(7-3-12)22-10-1-11-23-15-8-4-13(5-9-15)17(20)21/h2-9H,1,10-11H2,(H3,18,19)(H3,20,21)

Synthetic route

1,3-bis(4-cyanophenoxy)propane (7476-06-4) → propamidine (104-32-5)

Conditions	Yield
With lithium hexamethyldisilazane In tetrahydrofuran at 20℃;	89%
Multi-step reaction with 2 steps 1: HCl (gas) / benzene / 72 h / Ambient temperature 2: ethanol. NH3 / 6 h / 50 °C View Scheme

1,3-bis(4-cyanophenoxy)propane (7476-06-4) + ammonium thiocyanate (1147550-11-5) → propamidine (104-32-5)

Conditions	Yield
at 180 - 195℃;

1,3-bis(4-cyanophenoxy)propane (7476-06-4) + ammonium benzenesulfonate (19402-64-3) → propamidine (104-32-5)

Conditions	Yield
at 260 - 270℃;

4,4'-propanediyldioxy-bis-benzimidic acid diethyl ester (1448-61-9) → propamidine (104-32-5)

Conditions	Yield
With ethanol; ammonium chloride

C21H26N2O4*2ClH → propamidine (104-32-5)

Conditions	Yield
With ammonia at 50℃; for 6h;

1.3-bis-<4-ethoxycarboximidoyl-phenoxy>-propane dihydrochloride → propamidine (104-32-5)

Conditions	Yield
With ammonia

1.3-bis-<4-(N-phenyl-carbamimidoyl)-phenoxy>-propane-bis-benzenesulfonate → propamidine (104-32-5)

Conditions	Yield
With ammonia; aniline at 100 - 110℃;

4-cyanophenol (767-00-0) → propamidine (104-32-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: 82 percent / ethanol. NaOEt / 48 h / Heating 2: HCl (gas) / benzene / 72 h / Ambient temperature 3: ethanol. NH3 / 6 h / 50 °C View Scheme
Multi-step reaction with 2 steps 1: potassium carbonate / acetonitrile / Reflux 2: lithium hexamethyldisilazane / tetrahydrofuran / 20 °C View Scheme

4-nitro-phenol (100-02-7) → propamidine (104-32-5)

Conditions	Yield
Multi-step reaction with 4 steps 1: ethanolic NaOH 2: aqueous sodium sulfide 3: ueber die Diazonium-Verbindung dargestellt 4: 180 - 195 °C View Scheme

1-nitro-4-(3-(4-nitrophenoxy)propoxy)benzene (3722-79-0) → propamidine (104-32-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: aqueous sodium sulfide 2: ueber die Diazonium-Verbindung dargestellt 3: 180 - 195 °C View Scheme

1,3-bis(4-aminophenoxy)propane (52980-20-8) → propamidine (104-32-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: ueber die Diazonium-Verbindung dargestellt 2: 180 - 195 °C View Scheme

Upstream product

• 52980-20-8 1,3-bis(4-aminophenoxy)propane 
• 3722-79-0 1-nitro-4-(3-(4-nitrophenoxy)propoxy)benzene 
• 100-02-7 4-nitro-phenol 
• 767-00-0 4-cyanophenol 
• 7476-06-4 1,3-bis(4-cyanophenoxy)propane 
• 1448-61-9 4,4'-propanediyldioxy-bis-benzimidic acid diethyl ester 
• 19402-64-3 ammonium benzenesulfonate 
• 1147550-11-5 ammonium thiocyanate 

Relevant articles and documents

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.

Analogues of 1,5-bis(4-amidinophenoxy)pentane (pentamidine) in the treatment of experimental Pneumocystis carinii pneumonia

A series of 33 analogues of the anti-Pneumocystis carinii drug 1,5-bis(4-amidinophenoxy)pentane (pentamidine) was synthesized for screening against a rat model of P. carinii pneumonia (PCP). Twenty-five of the compounds showed efficacy against PCP when compared to a saline-treated control group. Two compounds, 1,4-bis(4-amidinophenoxy)butane (butamidine, 6) and 1,3-bis(4-amidino-2-methoxyphenoxy)propane (DAMP, 16), were statistically more effective than the parent drug in treating PCP in the rat model of infection. In addition to their activity against PCP, the compounds were also evaluated for antitrypsin activity, ability to inhibit thymidylate synthetase, affinity for DNA, and toxicity. No correlation was observed between the tested molecular interactions of the diamidines and their effectiveness against PCP.