IP Library › Patent Application 13337202

Patent Application

App. No. 13/337,202

N-BENZYL-4-METHYLENEAMINO-3-HYDROXY-2-PYRIDONES

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Patent No.: US None
App. No.: 13/337,202

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Abstract

Compounds of Formula (I) are effective in the treatment of a microbial infection.

Claims (108)

1 .- 20 . (canceled)

21 . A compound of formula (I)

wherein:

each R 1 is independently:

i) hydrogen;

ii) halogen;

iii) cyano; or

iv) C 1 -C 3 alkoxy;

R 3 and R 4 are taken together to form a piperazin-1-yl ring, wherein said ring can be optionally substituted at the 4-position nitrogen atom by a unit chosen from:

i) C 3 -C 9 monocyclic heterocycloalkyl; optionally substituted with C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, halogen, cyano, hydroxy, —C(═O)OH, —NH 2 ; —NHC(═O)R; —C(═O)NH 2 , phenyl, or combinations thereof; or

ii) C 5 -C 9 monocyclic heteroaryl; optionally substituted with C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, halogen, cyano, hydroxy, —C(═O)OH, —NH 2 ; —NHC(═)R; —C(═O)NH 2 , phenyl, or combinations thereof;

R 5 and R 6 are each independently:

i) C 1 -C 15 alkyl;

ii) C 3 -C 9 cycloalkyl;

iii) C 1 -C 12 haloalkyl;

iv) C 2 -C 15 alkenyl;

v) C 2 -C 15 alkynyl;

vi) halogen;

vii) cyano; or

viii) hydroxy; or

a pharmaceutically acceptable salt thereof.

22 . The compound according to claim 21 , wherein R 5 and R 6 are both hydrogen.

23 . The compound according to claim 21 , wherein the piperizin-1-yl ring formed when R 3 and R 4 are taken together is substituted at the 4-position nitrogen atom with a C 5 -C 9 monocyclic heteroaryl ring; wherein the monocyclic heteroaryl ring is optionally substituted with C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, halogen, cyano, hydroxy, —NH 2 ; —NHC(═O)R; —C(═O)NH 2 , phenyl, or combinations thereof.

24 . The compound according to claim 23 , wherein the piperazin-1-yl ring formed when R 3 and R 4 are taken together is substituted at the 4-position nitrogen atom with a unit chosen from:

i) pyridazinyl;

ii) pyridinyl; or

iii) pyrimidinyl;

wherein said units are optionally substituted with a unit chosen from C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, halogen, cyano, hydroxy, —C(═O)OH, —NH 2 ; —NHC(═O)R; —C(═O)NH 2 , phenyl, or combinations thereof.

25 . The compound according to claim 24 , wherein the monocyclic heteroaryl ring is a pyridazin-3-yl ring.

26 . The compound according to claim 21 , wherein the piperizin-1-yl ring formed when R 3 and R 4 are taken together is substituted at the 4-position nitrogen atom with a C 3 -C 9 monocyclic heterocycloalkyl; wherein the monocyclic heterocycloalkyl ring is optionally substituted with C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, halogen, cyano, hydroxy, —NH 2 ; —NHC(═O)R; —C(═O)NH 2 , phenyl, or combinations thereof.

27 . The compound according to claim 26 , wherein the piperazin-1-yl ring formed when R 3 and R 4 are taken together is substituted at the 4-position nitrogen atom with a unit chosen from:

i) pyrrolidinyl;

ii) piperidinyl; or

iii) piperazinyl;

28 . The compound according to claim 21 , chosen from:

1-benzyl-3-hydroxy-4-{[4-(6-chloropyridazin-3-yl)piperazin-1-yl]methyl}pyridine-2(1H)-one;

1-(3-methoxybenzyl)-3-hydroxy-4-{[4-(6-chloropyridazin-3-yl)piperazin-1-yl]methyl}pyridine-2(1H)-one;

1-(3-methylbenzyl)-3-hydroxy-4-{[4-(6-chloropyridazin-3-yl)piperazin-1-yl]methyl}pyridine-2(1H)-one; and

1-(3-chlorobenzyl)-3-hydroxy-4-{[4-(6-chloropyridazin-3-yl)piperazin-1-yl]methyl}pyridine-2(1H)-one.

29 . A composition comprising:

a) one or more compounds having the formula:

wherein:

each R 1 is independently:

i) hydrogen;

ii) halogen;

iii) cyano; or

iv) C 1 -C 3 alkoxy;

R 3 and R 4 are taken together to form a piperazin-1-yl ring, wherein said ring can be optionally substituted at the 4-position nitrogen atom by a unit chosen from:

ii) C 5 -C 9 monocyclic heteroaryl; optionally substituted with C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, halogen, cyano, hydroxy, —C(═O)OH, —NH 2 ; —NHC(═O)R; —C(═O)NH 2 , phenyl, or combinations thereof;

R 5 and R 6 are each independently:

i) C 1 -C 15 alkyl;

ii) C 3 -C 9 cycloalkyl;

iii) C 1 -C 12 haloalkyl;

iv) C 2 -C 15 alkenyl;

v) C 2 -C 15 alkynyl;

vi) halogen;

vii) cyano; or

viii) hydroxy; or

a pharmaceutically acceptable salt thereof; and

b) one or more pharmaceutically acceptable excipients.

30 . The composition according to claim 29 , wherein R 5 and R 6 are both hydrogen.

31 . The composition according to claim 29 , wherein the piperizin-1-yl ring formed when R 3 and R 4 are taken together is substituted at the 4-position nitrogen atom with a C 5 -C 9 monocyclic heteroaryl ring; wherein the monocyclic heteroaryl ring is optionally substituted with C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, halogen, cyano, hydroxy, —NH 2 ; —NHC(═O)R; —C(═O)NH 2 , phenyl, or combinations thereof.

32 . The composition according to claim 31 , wherein the piperazin-1-yl ring formed when R 3 and R 4 are taken together is substituted at the 4-position nitrogen atom with a unit chosen from:

i) pyridazinyl;

ii) pyridinyl; or

iii) pyrimidinyl;

33 . The composition according to claim 32 , wherein the monocyclic heteroaryl ring is a pyridazin-3-yl ring.

34 . The compound according to claim 29 , wherein the piperizin-1-yl ring formed when R 3 and R 4 are taken together is substituted at the 4-position nitrogen atom with a C 3 -C 9 monocyclic heterocycloalkyl; wherein the monocyclic heterocycloalkyl ring is optionally substituted with C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, halogen, cyano, hydroxy, —NH 2 ; —NHC(═O)R; —C(═O)NH 2 , phenyl, or combinations thereof.

35 . The composition according to claim 34 , wherein the piperazin-1-yl ring formed when R 3 and R 4 are taken together is substituted at the 4-position nitrogen atom with a unit chosen from:

i) pyrrolidinyl;

ii) piperidinyl; or

iii) piperazinyl;

36 . The composition according to claim 29 , wherein the compound is chosen from:

1-benzyl-3-hydroxy-4-{[4-(6-chloropyridazin-3-yl)piperazin-l-yl]methyl}pyridine-2(1H)-one;

1-(3-methoxybenzyl)-3-hydroxy-4-{[4-(6-chloropyridazin-3-yl)piperazin-1-yl]methyl}pyridine-2(1H)-one;

1-(3-methylbenzyl)-3-hydroxy-4-{[4-(6-chloropyridazin-3-yl)piperazin-1-yl]methyl}pyridine-2(1H)-one; and

1-(3-chlorobenzyl)-3-hydroxy-4-{[4-(6-chloropyridazin-3-yl)piperazin-1-yl]methyl}pyridine-2(1H)-one.

37 . A method of treating a microbial infection, comprising administering a safe and effective of amount of a compound having the formula:

wherein:

each R 1 is independently:

i) hydrogen;

ii) halogen;

iii) cyano; or

iv) C 1 -C 3 alkoxy;

R 3 and R 4 are taken together to form a piperazin-1-yl ring, wherein said ring can be optionally substituted at the 4-position nitrogen atom by a unit chosen from:

R 5 and R 6 are each independently:

i) C 1 -C 15 alkyl;

ii) C 3 -C 9 cycloalkyl;

iii) C 1 -C 12 haloalkyl;

iv) C 2 -C 15 alkenyl;

v) C 2 -C 15 alkynyl;

vi) halogen;

vii) cyano; or

viii) hydroxy; or

a pharmaceutically acceptable salt thereof.

38 . The method according to claim 37 , wherein the piperizin-1-yl ring formed when R 3 and R 4 are taken together is substituted at the 4-position nitrogen atom with a C 5 -C 9 monocyclic heteroaryl ring; wherein the monocyclic heteroaryl ring is optionally substituted with C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, halogen, cyano, hydroxy, —NH 2 ; —NHC(═O)R; —C(═O)NH 2 , phenyl, or combinations thereof.

39 . The method according to claim 37 , wherein the piperizin-1-yl ring formed when R 3 and R 4 are taken together is substituted at the 4-position nitrogen atom with a C 3 -C 9 monocyclic heterocycloalkyl; wherein the monocyclic heterocycloalkyl ring is optionally substituted with C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, halogen, cyano, hydroxy, —NH 2 ; —NHC(═O)R; —C(═O)NH 2 , phenyl, or combinations thereof.

40 . The method according to claim 37 , chosen from:

1-benzyl-3-hydroxy-4-{[4-(6-chloropyridazin-3-yl)piperazin-1-yl]methyl}pyridine-2(1H)-one;

1-(3-methoxybenzyl)-3-hydroxy-4-{[4-(6-chloropyridazin-3-yl)piperazin-1-yl]methyl}pyridine-2(1H)-one;

1-(3-methylbenzyl)-3-hydroxy-4-{[4-(6-chloropyridazin-3-yl)piperazin-1-yl]methyl}pyridine-2(1H)-one; and

1-(3-chlorobenzyl)-3-hydroxy-4-{[4-(6-chloropyridazin-3-yl)piperazin-1-yl]methyl}pyridine-2(1H)-one.