# US 2011/0212080 A1 · Urea derivatives as antibacterial agents

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- Number: US 2011/0212080 A1
- Document ID: US20110212080A1
- Status: Published application
- Kind: A1
- Application number: 13/057,505
- Filed: 2009-07-28
- Published: 2011-09-01
- Earliest claimed: 2008-08-04
- Inventors: Umar Faruk Mansoor; Panduranga Adulla Reddy; M. Arshad Siddiqui
- Web page: https://patentgrep.com/patent/US20110212080A1

## CPC

- C07D 213/38: having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P 31/04: Antibacterial agents
- A61P 31/10: Antimycotics
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07C 275/24: containing six-membered aromatic rings
- C07D 207/06: with radicals, containing only hydrogen and carbon atoms, attached to ring carbon atoms
- C07D 211/16: with acylated ring nitrogen atom
- C07D 213/61: Halogen atoms or nitro radicals
- C07D 213/73: Unsubstituted amino or imino radicals
- C07D 213/74: Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
- C07D 231/12: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D 241/12: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D 295/215: Radicals derived from nitrogen analogues of carbonic acid
- C07D 333/20: by nitrogen atoms (nitro, nitroso radicals C07D333/12)
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS

## Abstract

This invention relates to compounds of the Formula (I): or a pharmaceutically acceptable salt, solvate, ester or isomer thereof, which is useful for the treatment of diseases or conditions mediated by LpxC.

## Claims

### Claim 1

A compound represented by Formula (I)
or a pharmaceutically acceptable salt, solvate, or ester thereof, wherein:
(i) T is selected from the group consisting of H, alkyl, alkenyl and alkynyl, wherein said alkyl, alkenyl and alkynyl can be unsubstituted or optionally independently substituted with one or more moieties selected from the group consisting of aryl, aralkyl, heteroaryl, heteroaralkyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, heterocyclyl, heterocyclenyl, heterocycloalkylalkyl, heterocyclenylalkyl, —OH, alkoxyl, —O-alkenyl, —O-alkynyl, hydroxyalkyl, hydroxyalkenyl, —O-aryl, —O-aralkyl, —SH, —S-alkyl, —S-alkenyl, —S-alkynyl, —S-aryl, —S-aralkyl, —NR1R2, -alkyl-NR1R2, -alkenyl-NR1R2,
wherein R1 and R2 are independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, aralkyl, cycloalkylalkyl, cycloalkenylalkyl, heteroaryl, heteroaralkyl, or
R1 and R2 together with the N atom to which each is attached form heterocyclyl, heterocyclenyl, or heteroaryl;or
T and H together with the C atom to which each is attached form spirocycloalkyl or spiroheterocyclyl, wherein each of said spirocycloalkyl and spiroheterocyclyl can be unsubstituted or optionally independently substituted with one or more moieties selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkenyl, cycloalkyl, aralkyl, aralkenyl, cycloalkenylalkyl, cycloalkylalkyl, halo and haloalkyl;
(ii) X is O, S or NH;
(iii) R4 and R5 are independently selected from the group consisting of hydrogen or (C1-C6)alkyl, wherein said (C1-C6)alkyl is substituted with aryl wherein said aryl can be unsubstituted or optionally independently substituted with alkynyl, halo, aryl, heteroaryl, heterocyclenyl or heterocyclyl, wherein said alkynyl, heteroaryl, heterocyclenyl or heterocyclyl can be unsubstituted or substituted with an additional aryl; or
R4 and R5 together with the N atom to which each is attached, form a heterocyclyl or heterocyclenyl, wherein each of said heterocyclyl and heterocyclenyl is substituted with A; or
R4 and R5 together with the N atom to which each is attached form a heterocyclic structure represented by the structure:
wherein Y, Q, Z, or V are each independently selected from the group consisting of C(O), C(S), C(NH), S(O), S(O)2 and C(R6R7), wherein q is 0-1, wherein each of R6 and R7 are independently selected from the group consisting of H, alkyl, and alkenyl, wherein each of said alkyl or alkenyl can be unsubstituted or optionally independently substituted with one or more moieties selected from the group consisting of H, alkyl, alkenyl, alkynyl, aryl, cycloalkenyl, cycloalkyl, aralkyl, aralkenyl, cycloalkenylalkyl, cycloalkylalkyl, halo and haloalkyl;
further wherein M is N or CR, wherein R is H, halo, alkyl, alkenyl, alkynyl, aryl, aralkyl, cycloalkenyl, cycloalkyl, heteroaryl, heterocyclenyl, heterocyclyl, OH, —O-alkyl, —O-alkenyl, —O-alkynyl, —O-aryl, —O-aralkyl, —O-cycloalkenyl, —O-cycloalkyl, —O-heteroaryl, —O-heterocyclenyl, —O-heterocyclyl, —SH, —S-alkyl, —S-alkenyl, —S-alkynyl, —S-aryl, —S-aralkyl, —S-cycloalkenyl, —S-cycloalkyl, —S-heteroaryl, —S-heterocyclenyl, or —S-heterocyclyl;
A is selected from the group consisting of, -aryl-alkynyl-aryl, -aryl-C(O)aralkyl, -aryl, -biaryl, -alkynyl-aryl, -aryl-heteroaryl and -aryl-alkynyl-heteroaryl, wherein said , -aryl-alkynyl-aryl, -aryl-C(O)aralkyl, -aryl, -biaryl, -alkynyl-aryl, -aryl-heteroaryl, and -aryl-alkynyl-heteroaryl can be unsubstituted or optionally independently substituted with one or more moieties selected from the group consisting of halo, haloalkyl, —N(R1)(R2), haloalkoxyl, -alkyl-CN, hydroxyalkyl, —OH, heterocyclyl, heterocyclenyl, alkyl, alkenyl, dialkylaminoalkoxyl and heterocyclylalkoxyl.

### Claim 2 (depends on 1)

The compound of claim 1, wherein T is hydroxyalkyl.

### Claim 3 (depends on 1)

The compound according to claim 1, wherein X is O.

### Claim 4 (depends on 1)

The compound according to claim 1, wherein each of said R4 and R5 is independently hydrogen or (C1-C6)alkyl, wherein said (C1-C6)alkyl is substituted with aryl, wherein said aryl can be unsubstituted or optionally independently substituted with alkynyl, halo or heteroaryl, wherein said alkynyl is substituted with an additional aryl.

### Claim 5 (depends on 4)

The compound according to claim 4, wherein said (C1-C6)alkyl can be straight chain alkyl or branched alkyl.

### Claim 6 (depends on 5)

The compound according to claim 5, wherein said alkyl is methyl, ethyl or branched ethyl.

### Claim 7 (depends on 4)

The compound according to claim 4, wherein said alkynyl is ethynyl.

### Claim 8 (depends on 4)

The compound according to claim 4, wherein said halo is bromo.

### Claim 9 (depends on 4)

The compound of claim 4, wherein said heteroaryl is N-pyrazole.

### Claim 10 (depends on 1)

The compound according to claim 1, wherein said R4 and R5 together with the N atom to which each is attached form heterocyclyl, substituted with A.

### Claim 11 (depends on 10)

The compound according to claim 10, wherein said heterocyclyl is piperazinyl, piperidinyl, pyrollidinyl.

### Claim 12 (depends on 10)

The compound according to claim 10, wherein A is phenyl-ethynyl-phenyl, ethynyl-phenyl, phenyl-C(O)-benzyl, phenyl, biphenyl, phenyl-heteroaryl, phenyl-heteroaryl-heterocyclyl or phenyl-ethynyl-heteroaryl,
wherein said phenyl can be unsubstituted or optionally independently substituted with one or more moieties selected from the group consisting of chloro, bromo, —NH2, dialkylamino, trihaloalkyl, —O-trihaloalkyl and cyanoalkyl;
wherein said biphenyl can be unsubstituted or optionally independently substituted with one or more moieties selected from the group consisting of propyl, fluro, heterocyclyl, dimethylaminoethoxyl and heterocyclylalkoxyl;
wherein said heteroaryl is selected from the group consisting of pyrimidinyl, pyridinyl, thiophenyl, thiazolyl, pyrazinyl and pyrazolyl, further wherein said heteroaryl can be unsubstituted or optionally independently substituted with one or more moieties selected from the group consisting of halo, alkyl, —NH2 and heterocyclyl; and
wherein said heterocyclyl is selected from the group consisting of morpholinyl, piperazinyl, piperidinyl and pyrrolidinyl.

### Claim 13 (depends on 12)

The compound according to claim 12, wherein said heteroaryl is selected from the group consisting of 5-pyrimidinyl, 4-pyridinyl, 3-thiophenyl, 5-thiazolyl, 2-pyrazinyl and 5-pyrazolyl.

### Claim 14 (depends on 12)

The compound according to claim 12, wherein said heterocyclyl is selected from the group consisting of 4-morpholinyl, piperazinyl, piperidinyl and pyrrolidinyl.

### Claim 15 (depends on 12)

The compound according to claim 12, wherein said biphenyl is substituted with 4-morpholinylethoxyl.

### Claim 16

A compound selected from the group consisting of:
or a pharmaceutically acceptable salt, solvate or ester thereof.

### Claim 17

(canceled)

### Claim 18 (depends on 1)

A pharmaceutical composition comprising at least one compound of claim 1, or a pharmaceutically acceptable salt, solvate or ester thereof, in combination with at least one pharmaceutically acceptable carrier.

### Claim 19 (depends on 18)

The pharmaceutical composition of claim 18, further comprising at least one additional agent, drug, medicament, antibody and/or inhibitor for treating a UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase (LpxC) receptor mediated disease.

### Claim 20 (depends on 18)

A method of treating a disorder associated with UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase (LpxC), said method comprising administering to a patient in need of such treatment a pharmaceutical composition of claim 18.

### Claim 21 (depends on 20)

The method of claim 20, wherein said disorder is a microbial infection.

### Claim at position 22

22-29. (canceled)