# US 2019/0167609 A1 · Antibacterial compounds

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- Number: US 2019/0167609 A1
- Document ID: US20190167609A1
- Status: Published application
- Kind: A1
- Application number: 16/324,509
- Filed: 2017-08-09
- Published: 2019-06-06
- Earliest claimed: 2016-08-11
- Assignees: María Alejandra Nieves BOSCH; Consejo Nacional De Investigaciones Cientificas Y Tecnicas (Conicet); Universidad Nacional De La Plata (Unlp); Quaid-I-Azam University
- Applicants: Consejo Nacional De Investigaciones Cientificas Y TéCnicas (Conicet); Universidad Nacional De La Plata (Unlp); Quaid-I-Azam University
- Inventors: Aamer SAEED BHATTI; María Alejandra Nieves BOSCH; Yanina Andrea LAMBERTI; Mauricio Federico ERBEN
- Web page: https://patentgrep.com/patent/US20190167609A1

## CPC

- A61K 31/155: Amidines ([IMAGE cpc-sch-A61K-1029.gif]), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
- A61P 31/04: Antibacterial agents
- C07C 279/18: having nitrogen atoms of guanidine groups bound to carbon atoms of six-membered aromatic rings
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS

## Abstract

An antibacterial compound of formula I, wherein X is selected from fluoro or bromo, effective against Gram negative and Gram positive bacteria, and in particular against non-fermenting multiresistant bacteria affecting patients suffering from cystic fibrosis and which are responsible of severe hospital-acquired infections in immunodepressed patients; its preparation process and pharmaceutical composition comprising said compound.

## Claims

### Claim 1

An antibacterial compound of formula I
wherein X is selected from fluoro or bromo.

### Claim 2 (depends on 1)

A process for preparing the antibacterial compound of claim 1, said process comprising the steps of:
a) adding an amine and trietilamine to an acyl thiourea in solvent;
b) slowly adding HgCl2 to the mixture of step a); and
c) allowing the reaction to proceed at room temperature for at least 6 hours.

### Claim 3 (depends on 2)

The process of claim 2, wherein the acyl thiourea has the formula II
wherein R is the adamantyl group C10H15; R1 is H and R2 is 2-Br-4,6-F2—C6H2.

### Claim 4 (depends on 2)

The process of claim 2, wherein the solvent comprises dimethylformamide.

### Claim 5 (depends on 2)

The process of claim 2, wherein steps a) and b) are carried out under agitation and overheating is avoided using refrigeration means.

### Claim 6 (depends on 2)

The process of claim 2, wherein the amine of step a) is R3—NH2, wherein R3 is selected from the group comprising 2-bromo-4,6-difluoro-phenyl (2-Br-4,6-F2—C6H2) and 2,6-dibromo-4-fluoro-phenyl (2,6-Br2-4-F—C6H2).

### Claim 7 (depends on 2)

The process of claim 2, wherein after step c) the obtained guanidine is purified by performing the additional steps of:
d) removing by filtration the HgS formed during the reaction, which is an highly insoluble solid;
e) removing by filtration the Et3NH+Cl− salt, which is the other solid formed during the reaction, by an extraction process consisting of water addition and ethyl acetate to the reaction mixture under vigorous agitation;
f) allowing to settle and separating the ethyl acetate organic layer;
g) optionally, repeating the extraction process of steps e) and f);
h) drying the organic phase by adding MgSO4 or CaCl2 and removing the solvent under negative pressure;
i) the obtained solid is purified by standard ethanol re-crystallization methods.

### Claim 8 (depends on 1)

A bactericidal pharmaceutical composition comprising the compound of claim 1.

### Claim 9 (depends on 1)

A bactericidal pharmaceutical composition against Gram positive bacteria comprising the compound of claim 1.

### Claim 10 (depends on 1)

A bactericidal pharmaceutical composition for the treatment of infections affecting patients suffering from cystic fibrosis, said composition comprising the compound of claim 1.

### Claim 11 (depends on 1)

A bactericidal pharmaceutical composition for the treatment of infections caused by non-fermenting multiresistant Gram negative bacteria, said composition comprising the compound of claim 1.