# US 10,369,130 B2 · Antibacterial compounds

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- Number: US 10,369,130 B2
- Document ID: US10369130B2
- Status: Granted
- Kind: B2
- Application number: 15/534,874
- Filed: 2015-12-11
- Published: 2017-12-28
- Granted: 2019-08-06
- Earliest claimed: 2014-12-17
- Assignees: AZIEN DE CHIMICHE RIUNITE ANGELINI FRANCESCO A.C.R.A.F. S.p.A.
- Applicants: AZIENDE CHIMICHE RIUNITE ANGELINI FRANCESCO A.C.R.A.F. S.p.A.
- Inventors: Rosella Ombrato; Barbara Garofalo; Giorgina Mangano; Alessandra Capezzone De Joannon; Gaia Corso; Gabriele Magaro′; Guido Furlotti; Tommaso Iacoangeli
- Web page: https://patentgrep.com/patent/US10369130B2

## CPC

- A61K 31/33: Heterocyclic compounds
- A61P 31/04: Antibacterial agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 401/04: directly linked by a ring-member-to-ring-member bond
- C07D 401/14: containing three or more hetero rings
- C07D 405/12: linked by a chain containing hetero atoms as chain links
- C07D 405/14: containing three or more hetero rings
- C07D 407/14: containing three or more hetero rings
- C07D 409/14: containing three or more hetero rings
- C07D 413/14: containing three or more hetero 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
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

The present invention relates to novel antibacterial compounds, pharmaceutical compositions containing them and their use as antimicrobials.

## Claims

### Claim 1

A compound of formula (I)
A-L1-B-L2-Y-L3-C (I)
wherein
A is a group of the following formula:
wherein
R1 is H or halogen atom,
R2 is H, halogen atom, OH, (C1-3)alkyl or (C1-3)alkoxy, and
R3 is H, (C1-3)alkyl or (C1-3)alkoxy;
L1 is σ bond, —O— or —N(R′)—, wherein R′ is H or (C1-3)alkyl;
B is a divalent residue of a piperazine or piperidine ring;
L2 is σ bond, —CH2—, —O—, or —N(R′)—, wherein R′ is H or (C1-3)alkyl;
Y is a (C1-6)alkylenyl, (C2-6)alkenylenyl, (C2-6)alkynylenyl, or (C3-6)cycloalkylenyl group, said group being optionally substituted with one or more groups selected from —OH, (C1-3)alkyl, (C3-6)cycloalkyl, 3- to 5-membered oxacycloalkyl, —COOR′, —NR′R″ wherein R′ and R″, identical or different each other, are hydrogen atom or (C1-3)alkyl;
L3 is —O—, —(CH2)2—, —N(R′)—, —N(R′)—C(═O)—, —N(R′)—C(═S)—, —N(R′)—(C1-6)alkylenyl-, —C(═O)—N(R′)—, —C(═O)—N(R′)—(C1-6)alkylenyl-, —SO2—N(R′)—, —N(R′)—SO2—, wherein R′ is hydrogen atom or (C1-3)alkyl;
C is a group of formula (V), (VI), or (VIII):
wherein
n is an integer from 0 to 3
P1 and P2, equal or different each other, are CH or N
P3 is O, S or NH;
R6 and R7 together form a 5- or 6-membered aliphatic or aromatic ring, optionally comprising at least one heteroatom selected from N and O,
R8 and R9, equal or different each other, are a hydrogen atom or an aryl group, or together form a 5- or 6-membered aliphatic or aromatic ring, optionally comprising at least one heteroatom selected from N and O,
R10 and R11 together form a 5- or 6-membered aliphatic or aromatic ring,
and wherein each hydrogen atom linked to a carbon or nitrogen atom forming the ring of formulae (V), (VI), or (VIII) is optionally substituted with at least one substituent selected from the group consisting of halogen atom, (C1-3)alkyl or (C1-3)alkoxy;
or an addition salt with a pharmaceutically acceptable organic or inorganic acid or base, an enantiomer, N-oxide, or quaternary ammonium salt of said compound of formula (I).

### Claim 2 (depends on 1)

The compound according to claim 1, wherein B is a group having the following formula (III)
wherein
G3 and G4, identical or different each other, are C(R4) or N, provided that that at least one of G3 and G4 is N,
R4 is hydrogen atom, —OH, —CN, —COOH, —NR′R″ wherein R′ and R″, identical or different each other, are hydrogen atom or (C1-3)alkyl;
G5 is C(═O) or C(H)(R5);
wherein R5 is hydrogen atom, CF3, —(C1-3)alkyl-CF3, —COOR′ and —CONR′R″, wherein R′ and R″, identical or different each other, are hydrogen atom or (C1-3)alkyl.

### Claim 3 (depends on 1)

The compound according to claim 1, wherein R6 and R7 together form a ring selected from the group consisting of benzene, furan, tetrahydrofuran, dioxolane, piperidine and piperazine.

### Claim 4 (depends on 1)

The compound according to claim 1, wherein R8 and R9, equal or different each other, are a hydrogen atom or an aryl group, or together form a ring selected from the group consisting of benzene, pyridine, and piperidine.

### Claim 5 (depends on 1)

The compound according to claim 1, wherein C is a group having one of the following formulas:

### Claim 6 (depends on 1)

The compound according to claim 1, wherein said Y is a (C1-4)alkylenyl, (C2-4)alkynylenyl, or (C5-6)cycloalkylenyl group, said group being optionally substituted with one or more groups selected from —OH, methyl, (C3-4)cycloalkyl, 3- or 4-membered oxacycloalkyl, —COOH, —NR′R″ wherein R′ and R″, identical or different each other, are hydrogen atom or methyl.

### Claim 7 (depends on 6)

The compound according to claim 6, wherein said Y is a (C1-4)alkylenyl, (C2-4)alkynylenyl, or cyclohexylenyl group, said group being optionally substituted with one or more hydroxy groups.

### Claim 8 (depends on 1)

The compound according to claim 1, wherein said L3 is —O—, —(CH2)2—, —N(R′)— wherein R′ is H or (C1-3)alkyl, —NH—C(═O)—, —NH—(C1-3)alkylenyl-, —C(═O)—NH—or —C(═O)—NH—(C1-3)alkylenyl-.

### Claim 9 (depends on 8)

The compound according to claim 8, wherein said L3 is —O—, —(CH2)2—, or —N(R′)— wherein R′ is H or methyl, —NH—C(═O)—, —NH—CH2—, —C(═O)—NH—, or —C(═O)—NH—CH2—.

### Claim 10 (depends on 1)

A pharmaceutical composition comprising at least one compound of formula (I) according to claim 1, a salt thereof with a pharmaceutically acceptable organic or inorganic acid or base, or an enantiomer thereof, or a quaternary ammonium salt thereof, or a N-oxide thereof, and at least one inert pharmaceutically acceptable excipient.

### Claim 11 (depends on 1)

A method for treating a bacterial infection, comprising the administration of a compound of formula (I) according to claim 1 to a patient in need thereof.

### Claim 12

A method for treating a bacterial infection, comprising administering, to a subject in need thereof, an effective amount of compound of formula (I)
A-L1-B-L2-Y-L3-C (I)
wherein
A is a group of the following formula:
wherein
R1 is H or halogen atom,
R2 is H, halogen atom, OH, (C1-3)alkyl or (C1-3)alkoxy, and
R3 is H, (C1-3)alkyl or (C1-3)alkoxy;
L1 is σ bond, —O— or —N(R′)—, wherein R′ is H or (C1-3)alkyl;
B is a divalent residue of a piperazine or piperidine ring;
L2 is σ bond, —CH2—, —O—, or —N(R′)—, wherein R′ is H or (C1-3)alkyl;
Y is a (C1-6)alkylenyl, (C2-6)alkenylenyl, (C2-6)alkynylenyl, or (C3-6)cycloalkylenyl group, said group being optionally substituted with one or more groups selected from —OH, (C1-3)alkyl, (C3-6)cycloalkyl, 3- to 5-membered oxacycloalkyl, —COOR′, —NR′R″ wherein R′ and R″, identical or different each other, are hydrogen atom or (C1-3)alkyl;
L3 is —O—, —(CH2)2—, —N(R′)—, —N(R′)—C(═O)—, —N(R′)—C(═S)—, —N(R′)—(C1-6)alkylenyl-, —C(═O)—N(R′)—(C1-6)alkylenyl-, —SO2—N(R′)—, —N(R′)—SO2—, wherein R′ is hydrogen atom or (C1-3)alkyl;
C is a group having a 5- or 6-membered saturated or unsaturated ring, or a 9- or 10-membered fused bicyclic ring;
or an addition salt with a pharmaceutically acceptable organic or inorganic acid or base, an enantiomer, N-oxide, or quaternary ammonium salt of said compound of formula (I).

### Claim 13 (depends on 12)

The method according to claim 12, wherein said bacterial infection is selected from the group consisting of a skin infection, a mucosal infection, a gynaecological infection, a respiratory tract infection (RTI), a CNS infection, a gastro-intestinal infection, a bone infection, a cardiovascular infection, a sexually transmitted infection, and a urinary tract infection.