IP Library Granted Patent US 9,023,865
Granted Patent B2
US 9,023,865 · App. 14/353,381 · Granted May 5, 2015

Compounds that are ERK inhibitors

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Quick Facts
Patent No.
US 9,023,865
App. No.
14/353,381
Granted
May 5, 2015
Kind
B2
Abstract

Disclosed are the ERK inhibitors of formula (1): and the pharmaceutically acceptable salts thereof. Also disclosed are methods of treating cancer using the compounds of formula (1).

Claims (281)

1. A compound of formula (1):

or a pharmaceutically acceptable salt thereof, wherein:

X is S or O;

R 1 is selected from the group consisting of: H, halo, —CF 3 , —CN, (C 1 -C 6 )alkyl, substituted (C 1 -C 6 )alkyl, (C 1 -C 6 )alkenyl, (C 3 -C 6 )cycloalkyl, substituted (C 3 -C 6 )cycloalkyl, heteroaryl, substituted heteroaryl, heterocycloalkenyl-, substituted heterocycloalkenyl, —(C 1 -C 6 )alkyl-O—(C 1 -C 6 )alkyl, aryl, substituted aryl, —C(O)NH(C 1 -C 6 )alkyl, —C(O)N((C 1 -C 6 )alkyl) 2 wherein each alkyl is independently selected, —C(O)—(C 1 -C 6 )alkyl-C(O)—(C 1 -C 6 )alkyl, —(C 1 -C 4 )alkyl-C(O)—O—(C 1 -C 4 )alkyl, —N((C 1 -C 6 )alkyl-S(O) 2 —(C 1 -C 6 )alkyl, —N((C 1 -C 6 )alkyl) -(C 1 -C 6 )alkyl-O—(C 1 -C 6 )alkyl, —C(O)NH—(C 1 -C 2 )alkyl-fused heteroarylheteroaryl, —C(O)NH—(C 1 -C 2 )alkyl -(substituted fused heteroarylheteroaryl), —C(O)NH—(C 1 -C 2 )alkyl-(C 3 -C 6 )cycloalkyl-N(R 6 ) 2 , —C(O)NH—(C 1 -C 2 )alkyl-(substituted(C 3 -C 6 )cycloalkyl)-N(R 6 ) 2 , —C(O)NH—(C 1 -C 2 )alkylheterocycloalkyl, —C(O)NH—(C 1 -C 2 )alkyl(substituted heterocycloalkyl), —C(O)NH—(C 1 -C 2 )alkylheteroaryl, —C(O)NH—(C 1 -C 2 )alkyl(substituted heteroaryl), —C(O)NH—(C 1 -C 6 )alkyl-(C 3 -C 6 )cycloalkyl, —C(O)NH—(C 1 -C 6 )alkyl-(substituted (C 3 -C 6 )cycloalkyl), —C(O)NH—(C 1 -C 6 )alkyl -O—(C 1 -C 6 )alkyl, —C(O)NH—(C 1 -C 6 )alkylheterocycloalkyl, —C(O)NH—(C 1 -C 6 )alkyl(substituted heterocycloalkyl), —C(O)NH—(C 1 -C 2 )-(bridged multicyclic cycloalkyl), —C(O)NH—(C 1 -C 2 )-(substituted bridged multicyclic cycloalkyl), —C(O)-heterocycloalkyl-S—(C 1 -C 6 )alkyl, —C(O)-(substituted heterocycloalkyl-S—(C 1 -C 6 )alkyl, —C(O)-heterocycloalkyl, —C(O)-(substituted heterocycloalkyl), fused arylheteroaryl, fused (substituted arylheteroaryl), fused heteroarylheteroaryl, fused (substituted heteroarylheteroaryl), —(C 1 -C 4 )alkyl-S(O) 2 —(C 1 -C 6 )alkyl, and —(C 1 -C 4 )alkyl-NH—(C 1 -C 6 )alkyl;

and wherein said substituted R 1 groups, other than said substituted (C 1 -C 6 )alkyl, are substituted with 1 to 3 substituents independently selected from the group consisting of: —(C 1 -C 6 )alkyl, —(C 1 -C 6 )alkoxy, halo, CN, —OH, —CF 3 , ═O, —NH 2 , —NH(C 1 -C 6 )alkyl, —S(O) 2 (C 1 -C 6 )alkyl, —(C 3 -C 6 )cycloalkyl, —((C 1 -C 6 )alkyl)OH, —(C 3 -C 6 )cycloalkyl-S—(C 3 -C 6 )cycloalkyl, —N((C 1 -C 6 )alkyl) 2 wherein each alkyl is independently selected, —C(O)O—(C 1 -C 6 )alkyl, —C(O)OH, —OCF 3 , —C(O)NH(C 1 -C 6 )alkyl, heteroaryl, —(C 1 -C 6 )alkyl)-O—(C 1 -C 6 )alkyl, fused heteroarylaryl-, heterocycloalkyl, and heterocycloalkenyl;

and wherein said substituted (C 1 -C 6 )alkyl R 1 group is substituted with 1 to 3 substituents independently selected from the group consisting of: —(C 1 -C 6 )alkoxy, halo, CN, —OH, ═O, —CF 3 , —NH 2 , —NH(C 1 -C 6 )alkyl, —S(O) 2 (C 1 -C 6 )alkyl, fused heteroarylaryl-, heterocycloalkyl, and heterocycloalkenyl;

and wherein the alkyl moieties of the R 1 groups, other than (C 1 -C 6 )alkyl and substituted (C 1 -C 6 )alkyl, are optionally substituted with 1 to 3 substituents independently selected from the group consisting of: —(C 1 -C 6 )alkoxy, halo, CN, —OH, ═O, —CF 3 , —NH 2 , —NH(C 1 -C6)alkyl, —S(O) 2 (C 1 -C 6 )alkyl, fused heteroarylaryl-, heterocycloalkyl, and heterocycloalkenyl;

R 2 is selected from the group consisting of: H, (C 1 -C 6 )alkyl, —(C 1 -C 3 )alkyl-O—(C 1 -C 2 )alkyl, aryl, arylalkyl-, heteroaryl, heteroarylalkyl-, substituted —(C 1 -C 6 )alkyl, substituted aryl, substituted arylalkyl-, substituted heteroaryl, and substituted heteroarylalkyl-; wherein said substituted aryl, substituted arylalkyl, substituted heteroaryl and substituted heteroarylalkyl are substituted with 1 to 3 substitutents independently selected from the group consisting of: aryl, substituted aryl, arylalkyl-, substituted arylalkyl-, halo, —OH, —C(O)N(R 6 ) 2 , —(C 1 -C 6 )alkyl, —(C 1 -C 6 )alkoxy, —CF 3 , —(C 1 -C 6 )alkyl-OH, —(C 1 -C 6 )alkyl-NH 2 , and —NH—(CH 2 ) 1-4 —(C 6 -C 10 )aryl; and wherein said R 2 which is substituted —(C 1 -C 6 )alkyl is substituted with 1-3 substituents independently selected from the group consisting of: aryl, substituted aryl, arylalkyl-, substituted arylalkyl-, halo, —OH, —C(O)N(R 6 ) 2 , —(C 1 -C 6 )alkoxy, —CF 3 , —NH 2 and —NH—(CH 2 ) 1-4 —(C 6 -C 10 )aryl;

R 3 is selected from the group consisting of: H, —(C 1 -C 6 )alkyl, substituted —(C 1 -C 6 )alkyl, heterocycloalkyl-, substituted heterocycloalkyl-, aryl, substituted aryl, arylalkyl-, substituted arylalkyl-, heteroaryl, substituted heteroaryl, heteroarylalkyl-, substituted heteroarylalkyl-, cycloalkyl, substituted cycloalkyl, cycloalkylalkyl, substituted cycloalkylalkyl-, cycloalkylalkenyl-, substituted cycloalkenyl, heterocycloalkylalkyl-, substituted heterocycloalkylalkyl, —(C 1 -C 6 )alkyl(CF 3 )—C(O)O—(C 1 -C 6 )alkyl, cycloalkenylalkyl-, substituted cycloalkenyl, fused cycloalkylheteroaryl, substituted fused cycloalkylheteroaryl, fused heterocycloalkylaryl, substituted fused heterocycloalkylaryl, fused cycloalkylaryl, substituted fused cycloalkylaryl, fused heteroarylaryl, substituted fused heteroarylaryl, —(C 1 -C 6 )alkylheterocycloalkenyl, —(C 1 -C 6 )alkyl(substituted heterocyloalkenyl), —(C 1 -C 6 )alkylcycloalkyl-N—(—(C-C 6 )alkyl) 2 (wherein each alkyl is independently selected), —(C 1 -C 6 )alkylheterocycloalkyl, —C 1 -C 6 )alkyl(substituted heterocycloalkyl), —(C 1 -C 6 )alkylcycloalkylaryl, substituted —(C 1 C 6 )alkyl(substituted cycloalkylaryl), —(C 1 -C 6 )alkyl -(fused arylheteroaryl), —(C 1 -C 6 )alkyl-(substituted used arylheteroaryl), an oxygen bridged (C 3 -C 6 ) cycloalkyl ring, substituted oxygen bridged (C 3 -C 6 ) cycloalkyl ring, —(C1-C6)alkyl)-(fused heterocycloalkylaryl), —(C 1 -C 6 )alkyl)-(substituted fused heterocycloalkylaryl), —(C 1 -C 6 )alkyl) -(fused heteroarylaryl), —(C 1 -C 6 )alkyl)-(substituted fused heteroarylaryl), —(C 1 -C 6 )alkyl)-C(O)—NH-aryl, —(C 1 -C 6 )alkyl)-C(O)—NH-(substituted aryl), —(C 3 -C 6 )cycloalkyl-O-aryl, —(C 3 -C 6 )cycloalkyl-O-(substituted aryl), a 5 and 4 membered heterocycloalkyl spiro ring, a substituted 5 and 4 membered heterocycloalkyl spiro ring, and —(C 1 -C 6 )alkyl-O—(C 1 -C 6 )alkyl;

and wherein said R 3 5 and 4 membered heterocycloalkyl spiro ring comprises a 5 membered ring comprising one nitrogen, and a 4 membered (including the carbon common to both rings) ring comprising one oxygen atom;

and wherein said substituted R 3 groups, other than substituted —(C 1 -C 6 )alkyl, are substituted with 1 to 3 substituents independently selected from the group consisting of: aryl, substituted aryl, arylalkyl-, substituted arylalkyl-, halo, —OH, —C(O)N(R 6 ) 2 , —(C 1 -C 6 )alkyl, —(C 1 -C 6 )alkoxy, —CF 3 , —(C 1 -C 6 )alkyl-OH, —(C 1 -C 6 )alkyl-NH 2 , —NH—(CH 2 ) 1-4 —(C 6 -C 10 )aryl, —NH 2 , ═O, —CN, —OCHF 2 , —OCF 3 , —(C 3 -C 6 )cycloalkyl, heterocycloalkyl, —(C 1 -C 6 )alkyl-CF 3 , —O—C(O)(C 1 -C 6 )alkyl, —NHS(O) 2 (C 1 -C 6 )alkyl, —S(O) 2 (C 1 -C 6 )alkyl, —NHaryl, heteroaryl, substituted heteroaryl, —O-heteroaryl, —O-(substituted heteroaryl), —(C 1 -C 6 )alkyl-N((C 1 -C 6 )alkyl) 2 wherein each alkyl is independently selected, —(C 1 -C 6 )alkyl-O—(C 1 -C 6 )alkyl, —N((C 1 -C 6 )alkyl) 2 wherein each alkyl is independently selected, —(C 1 -C 6 )alkyl-S(O) 2 —(C 1 -C 6 )alkyl, —((C 1 -C 6 )alkyl)(halo) 1-3 , —S(C 1 -C 6 )alkyl, —(C 1 -C 6 )alkyl-O—(C 1 -C 6 )alkyl-(C 3 -C 6 )cycloalkyl, —(C 1 -C 6 )alkyl-O—(C 1 -C 6 )alkyl-O—(C 1 -C 6 )alkyl, and —(C 1 -C 6 )alkyl-O—(C 1 -C 6 )alkyl(halo) 1-3 ;

and wherein said R 3 substituted —(C 1 -C 6 )alkyl group is substituted with 1-3 substituents independently selected from the group consisting of: aryl, substituted aryl, arylalkyl-, substituted arylalkyl-, halo, —OH, —C(O)N(R 6 ) 2 , —(C 1 -C 6 )alkoxy, —CF 3 , —NH 2 and —NH—(CH 2 ) 1-4 —(C 6 -C 10 )aryl, —N((C 1 -C 6 )alkyl) 2 wherein each alkyl is independently selected, —C(O)O(C 1 -C 6 )alkyl, —C(O)OH, —CN, —O-phenyl;

or said R 2 and said R 3 , taken together with the nitrogen to which they are bonded to, form a 4-6 membered heterocycloalkyl ring, said ring optionally comprising an additional heteroatom selected from the group consisting of: N and O, and wherein said ring is optionally substituted with 1-3 substituents independently selected from the group consisting of: C 1 -C 6 )alkyl, aryl, and substituted aryl wherein said substituted aryl is substituted with 1-3 substituents independently selected from the group consisting of halo;

R 4 is selected from the group consisting of: H, halo, —(C 1 -C 6 )alkyl, —OH and —NH 2 ; and

each R 6 is independently selected from the group consisting of: H and —(C 1 -C 6 )alkyl.

2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:

X is S or O;

R 1 is selected from the group consisting of: H, halo, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkenyl, (C 3 -C 6 )cycloalkyl, heteroaryl, substituted heteroaryl, heterocycloalkenyl-, substituted heterocycloalkenyl, —(C 1 -C 6 )alkyl-O—(C 1 -C 6 )alkyl, aryl, and substituted aryl, and wherein said substituted heteroaryl, substituted heterocycloalkenyl, and substituted aryl are substituted with 1 to 3 substituents independently selected from the group consisting of: —(C 1 -C 6 )alkyl, —(C 1 -C 6 )alkoxy, halo, CN, ═O, —NH 2 , —NH(C 1 -C 6 )alkyl, —S(O) 2 (C 1 -C 6 )alkyl, fused heteroarylaryl-, heterocycloalkyl, and heterocycloalkenyl;

R 2 is selected from the group consisting of: H, (C 1 -C 6 )alkyl, —(C 1 -C 3 )alkyl-O—(C 1 -C 2 )alkyl, aryl, arylalkyl-, heteroaryl, heteroarylalkyl-, substituted —(C 1 -C 6 )alkyl, substituted aryl, substituted arylalkyl-, substituted heteroaryl, and substituted heteroarylalkyl-; wherein said substituted aryl, substituted arylalkyl, substituted heteroaryl and substituted heteroarylalkyl are substituted with 1 to 3 substitutents independently selected from the group consisting of: aryl, substituted aryl, arylalkyl-, substituted arylalkyl-, halo, —OH, —C(O)N(R 6 ) 2 , —(C 1 -C 6 )alkyl, —(C 1 -C 6 )alkoxy, —CF 3 , —(C 1 -C 6 )alkyl-OH, —(C 1 -C 6 )alkyl-NH 2 , and —NH—(CH 2 ) 1-4 —(C 6 -C 10 )aryl; and wherein said R 2 which is substituted —(C 1 -C 6 )alkyl is substituted with 1-3 substituents independently selected from the group consisting of: aryl, substituted aryl, arylalkyl-, substituted arylalkyl-, halo, —OH, —C(O)N(R 6 ) 2 , —(C 1 -C 6 )alkoxy, —CF 3 , —NH 2 and —NH—(CH 2 ) 1-4 —(C 6 -C 10 )aryl;

R 3 is selected from the group consisting of: H, —(C 1 -C 6 )alkyl, substituted —(C 1 -C 6 )alkyl, heterocycloalkyl-, substituted heterocycloalkyl-, aryl, substituted aryl, arylalkyl-, substituted arylalkyl-, heteroaryl, substituted heteroaryl, heteroarylalkyl-, substituted heteroarylalkyl-, cycloalkyl, substituted cycloalkyl, cycloalkylalkyl, substituted cycloalkylalkyl-, cycloalkylalkenyl-, substituted cycloalkenyl, and -alkyl-O-alkyl; and wherein said substituted heteroaryl, substituted heterocycloalkyl, substituted aryl, substituted arylalkyl, substituted heteroarylalkyl, substituted cycloalkyl, substituted cycloalkylalkyl, and substituted cycloalkenyl R 3 moieties are substituted with 1 to 3 substituents independently selected from the group consisting of: aryl, substituted aryl, arylalkyl-, substituted arylalkyl-, halo, —OH, —C(O)N(R 6 ) 2 , —(C 1 -C 6 )alkyl, —(C 1 -C 6 )alkoxy, —CF 3 , —(C 1 -C 6 )alkyl-OH, —(C 1 -C 6 )alkyl-NH 2 , and —NH—(CH 2 ) 1-4 —(C 6 -C 10 )aryl; and wherein said R 3 which is substituted —(C 1 -C 6 )alkyl is substituted with 1-3 substituents independently selected from the group consisting of: aryl, substituted aryl, arylalkyl-, substituted arylalkyl-, halo, —OH, —C(O)N(R 6 ) 2 , —(C 1 -C 6 )alkoxy, —CF 3 , —NH 2 and —NH—(CH 2 ) 1-4 —(C 6 -C 10 )aryl;

R 4 is selected from the group consisting of: H, halo, —(C 1 -C 6 )alkyl, —OH and —NH 2 ; and

each R 6 is independently selected from the group consisting of: —(C 1 -C 6 )alkyl.

3. The compound of claim 2 wherein X is O.

4. The compound of claim 2 wherein R 1 is selected from the group consisting of: propyl, pyridyl, pyridyl-N + —O −, 2-methylpyridyl, dihydropyran, pyrazolyl, N-methylpyrazolyl, fluorophenyl, phenyl, 2,6-dimethylpyridyl, fluoropyridyl, N-methylpyrazolyl-, N-methylpyrazolyl, N-methylindazolyl-, cyanophenyl, propenyl, Br, methyloxodihydropyridyl, pyrazolyl, chloropyridyl, aminopyrimindinyl, methylbenzothiazolyl, dihydrobenzodioxinyl, CH 3 SO 2 -phenyl-, and methylpyridazinyl.

5. The compound of claim 2 wherein R 1 is selected from the group consisting of R 1 groups (1) to (26).

6. The compound of claim 2 wherein R 2 is H.

7. The compound of claim 2 wherein R 3 is selected from the group consisting of: (a) piperidinyl, (b) substituted piperidinyl, (c) —CH 2 -phenyl, (d) substituted —CH 2 -phenyl, (e) —(CH 2 )-2-phenyl, (f) a hydroxy substituted —CH(CH 3 )-phenyl, (g) a monohalo substituted —CH(CH 3 )-phenyl, (h) a dihalo substituted —CH(CH 3 )-phenyl, (i) —CH 2 -pyridyl, (j) —CH 2 -oxadiazolyl, (k) substituted —CH 2 -oxadiazolyl (l) —CH 2 -naphthyl, (m) —CH 2 -cyclopropyl, (n) t-butyl, (o) cyclopropylmethanol, (p) cyclopropylmethylene-, (q) azetidinyl, (r) methoxyethyl, (s) cyclopropyl-CH(CF 3 )—, (t) N-methylimidazolyl-CH 2 —, (u) methylthiazolyl-CH 2 —, (v) pyrimindinyl-CH 2 —, (w) pyridyl-CH 2 —, (x) pyridyl-(CH 2 ) 2 —, (y) pyrazinyl-CH 2 —, (z) pyridyl -CH(CH 3 )—, (aa) fluoropyridyl-CH 2 —, (ab) phenylethylaminopyridazinyl-, (ac) phenyl, (ad) chlorophenyl-C(CH 3 ) 2 —, (ae) chlorophenyltetrahydropyranyl-, (af) dihydroindenyl, (ag) phenyl-CH(CH 3 )—, and (ah) chlorophenylcyclopropyl-.

8. The compound of claim 2 wherein R 3 is selected from the group consisting of R 3 groups (27) to (81).

9. The compound of claim 2 wherein R 4 is selected from the group consisting of H, Cl, and F.

10. The compound of claim 2 wherein R 4 is H.

11. The compound of claim 2 wherein R 2 is H and R 3 is other than H.

12. The compound of claim 2 wherein R 2 is H, R 3 is other than H, R 4 is H, and X is O.

13. The compound of claim 2 wherein R 3 is selected from the group consisting of: R 3 groups

R 1 is selected from the group consisting of R 1 groups

CH 3 CH 2 CH 2 —, CH 3 CH═CH—

R 2 is H, R 4 is H, and X is O.

14. The compound of claim 2 wherein said compound of formula (1) is a compound of formula (1A):

15. A compound selected from the group consisting of

1-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-piperidin-3-ylurea,

1-[(3R)-1-(2-fluoro-6-methoxybenzyl)-piperidin-3-yl]-3-[3-(2-methylpyridin-4-yl)-1H -pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[(3S)-1-(2-fluoro-6-methoxybenzyl)-piperidin-3-yl]-3-[3-(2-methylpyridin-4-yl)-1H -pyrazolo[4,3-c]pyridin-6-yl]urea

1-[1-(2-fluoro-6-methoxybenzyl)-piperidin-3-yl]-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-(2-phenylethyl)urea,

1-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[(1R)-1-phenylethyl]urea,

1-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[(1S)-1-phenylethyl]urea,

1-(3,4-dichlorobenzyl)-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-benzyl-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-(2-hydroxy-1-phenylethyl)-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[(1S)-1-(4-fluorophenyl)ethyl]-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-(pyridin-4-ylmethyl)urea,

1-[5-methyl-1,3,4-oxadiazol-2-yl)methyl]-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]urea,

1-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-(pyridin-3-ylmethyl)urea,

1-[(1S)-2-hydroxy-1-phenylethyl]-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[(1S)-2,2,2-trifluoro-1-phenylethyl]urea,

1-[(1R)-2-hydroxy-1-phenylethyl]-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[(1R)-2,2,2-trifluoro-1-phenylethyl]urea,

1-[(1R)-1-(4-chlorophenyl)ethyl]-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[3-(3,6-dihydro-2H-pyran-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[(1R)-1-phenylethyl]urea,

1[3-(3 -methoxypropyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[(1R)-1-phenylethyl]urea,

1-[(1R)-1-phenylethyl]-3-(3-propyl-1H-pyrazolo[4,3-c]pyridin-6-yl)urea,

1-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[(1R)-1-(4-fluorophenyl)ethyl]-3-(1H-pyrazolo[4,3-c]pyridin-6-yl)urea,

1-(3-cyclopropyl-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-[(1R)-1-phenylethyl]urea,

1-(4-chlorobenzyl)-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-(3-chlorobenzyl)-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-{3-[6-(1-methylethoxy)pyridin-3-yl]-1H-pyrazolo[4,3-c]pyridin-6-yl}-3-[(1R)-1-phenylethyl]urea,

1-[3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[(1R)-1-phenylethyl]urea,

1-[3-(4-fluorophenyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[(1R)-1-phenylethyl]urea,

1-[3-(2,6-dimethylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[(1R)-1-phenylethyl]urea,

1-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-(naphthalen-1-ylmethyl)urea,

1-(3,4-dimethoxybenzyl)-3-[3-(4-fluorophenyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[3-(4-fluorophenyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-(cyclopropylmethyl)-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-tert-butyl-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

hydroxycyclopropyl)methyl]-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-clpyridin-6-yl]urea,

1-(cyclopropylidenemethyl)-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-azetidin-3-yl-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-(2-methoxyethyl)-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-(1-cyclopropyl-2,2,2-trifluoroethyl)-3[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin -6-yl]urea,

1-[(1-methyl-1H-imidazol-5-yl)methyl]-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[(2-methyl-1,3-thiazol-4-yl)methyl]urea,

1-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-(pyrimidin-2-ylmethyl)urea,

1-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-(naphthalen-2-ylmethyl)urea,

1-methyl-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-1-(pyridin-3-ylmethyl)urea,

1-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-(2-pyridin-2-ylethyl)urea,

1-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-(pyrazin-2-ylmethyl)urea,

1-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-(1-pyridin-3-ylethyl)urea

1-(2-methoxyethyl)-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-1-(pyridin-3-ylmethyl)urea,

1-[(5-fluoropyridin-3-yl)methyl]-3[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-(2,6-difluorobenzyl)-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-(3-fluorobenzyl)-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[4-(trifluoromethyl) -benzyl]urea,

1[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-{6-[(2-phenylethyl) -amino]pyridazin-3-yl}urea,

1-(3-chloro-4-fluorobenzyl)-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[(1R)-1-(4-chlorophenyl)ethyl]-3-[3-(2-fluoropyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-(3-chloro-4-fluorobenzyl)-3-[3-(2-fluoropyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[(1R)-1-(4-chlorophenyl)ethyl]-3-[3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-(3-chloro-4-fluorobenzyl)-3-[3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-phenylurea,

1-[(1R)-1-(3-chlorophenyl)ethyl]-3-[3-(2-methyl-2H-indazol-5-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[(1R)-1-(4-fluorophenyl)ethyl]-3-[3-(2-methyl-2H-indazol-5-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-(3-chloro-4-fluorobenzyl)-3-[3-(2-methyl-2H-indazol-5-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[(1R)-1-(4-chlorophenyl)ethyl]-3-[3-(2-methyl-2H-indazol-5-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[3-(4-cyanophenyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[(1R)-1-phenylethyl]urea,

1-[(1R)-1-phenylethyl]-3-{3-[(1E)-prop-1-en-1-yl]-1H-pyrazolo[4,3-c]pyridin-6-yl}urea,

1-(3-bromo-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-[(1R)-1-(3-chloro-4-fluorophenyl)ethyl]urea,

1-[(1R)-1-(3-chloro-4-fluorophenyl)ethyl]-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[1-(4-chlorophenyl)-1-methylethyl]-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[(1R)-1-(4-fluorophenyl)ethyl]-3-[3-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-1H -pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[(1R)-1-(3-chloro-4-fluorophenyl)ethyl]-3-[3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[(1R)-1-(3-chloro-4-fluorophenyl)ethyl]-3-[3-(4-fluorophenyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[(1R)-1-(3-chloro-4-fluorophenyl)ethyl]-3-[3-(1H-pyrazol-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[(1R)-1-(3-chloro-4-fluorophenyl)ethyl]-3-[3-(2-chloropyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[(1R)-1-(3-chloro-4-fluorophenyl)ethyl]-3-[3-(3-chlorophenyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1[4-(4-chlorophenyl)tetrahydro-2H-pyran-4-yl]-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-(2,3-dihydro-1H-inden-1-yl)-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1[7-bromo-3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[(1R)-1-phenylethyl]urea,

1-[3-(2-aminopyrimidin-5-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[(1R)-1-(3-chloro-4-fluorophenyl)ethyl]urea,

1-[(1R)-1-(3-chloro-4-fluorophenyl)ethyl]-3-[3-(2-fluoropyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[(1R)-1-(3-chloro-4-fluorophenyl)ethyl]-3-(3-cyclopropyl-1H-pyrazolo[4,3-c]pyridin-6-yl)urea,

1-[3-(4-cyanophenyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[(1R)-1-(4-fluorophenyl)ethyl]urea,

1-[(1R)-1-(3-chlorophenyl)ethyl]-3-[3-(4-cyanophenyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[1-(4-chlorophenyl)cyclopropyl]-3[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[7-bromo-3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[(1R)-1-(4-chlorophenyl)ethyl]urea,

1-[3-(2-methyl-1,3-benzothiazol-6-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[(1R)-1-phenylethyl]urea,

1-[3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[1R)-1-phenylethyl]urea,

1-{3-[4-(methylsulfonyl)phenyl]-1H-pyrazolo[4,3-c]pyridin-6-yl}-3-[(1R)-1-phenylethyl]urea,

1-[3-(1-methyl-1H-pyrazol-3-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[(1R)-1-phenylethyl]urea,

1-[3-(6-methylpyridazin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[(1R)-1-phenylethyl]urea,

1-benzyl-3-[7-chloro-3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[3-(1-oxidopyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[(1R)-1-phenylethyl]urea,

1-benzyl-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]thiourea, and

1-[7-fluoro-3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl1-3-[(1R)-1-phenylethyl]urea.

16. The compound of claim 15 selected from the group consisting of

1-[(3R)-1-(2-fluoro-6-methoxybenzyl)-piperidin-3-yl]-3-[3-(2-methylpyridin-4-yl)-1H -pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[(3S)-1-(2-fluoro-6-methoxybenzyl)-piperidin-3-yl]-3-[3-(2-methylpyridin-4-yl)-1H -pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[1-(2-fluoro-6-methoxybenzyl)-piperidin-3-yl]-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-(2-phenylethyl)urea,

1[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[(1R)-1-phenylethyl]urea,

1-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[(1S)-1-phenylethyl]urea,

1-(3,4-dichlorobenzyl)-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-benzyl-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-(2-hydroxy-1-phenylethyl)-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[(1S)-1-(4-fluorophenyl)ethyl]-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-(pyridin-4-ylmethyl)urea,

1-[(5-methyl-1,3,4-oxadiazol-2-yl)methyl]-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]urea

1-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-(pyridin-3-ylmethyl)urea,

1-[(1R)-2-hydroxy-1-phenylethyl]-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[(1R)-2,2,2-trifluoro-1-phenylethyl]urea,

1-[1-(4-chlorophenyl)-1-methylethyl]-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[7-bromo-3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[(1R)-1-(4-chlorophenyl)ethyl]urea, and

1-benzyl-3-[7-chloro-3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea, and the free base form of

1[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-piperidin-3-ylurea,

1-[(1S)-2-hydroxy-1-phenylethyl]-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl[-3-[(1S)-2,2,2-trifluoro-1-phenylethyl]urea,

1-[(1R)-1-(4-chlorophenyl)ethyl]-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[3-(3,6-dihydro-2H-pyran-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[(1R)-1-phenylethyl]urea,

1-[3-(3-methoxypropyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[(1R)-1-phenylethyl]urea,

1-[(1R)-1-phenylethyl]-3-(3-propyl-1H-pyrazolo[4,3-c]pyridin-6-yl)urea,

1-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[(1R)-1-(4-fluorophenyl)ethyl]-3-(1H-pyrazolo [4,3-c]pyridin-6-yl)urea,

1-(3-cyclopropyl-1H-pyrazolo [4,3-c]pyridin-6-yl)-3-[(1R)-1-phenylethyl]urea,

1-(4-chlorobenzyl)-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-(3-chlorobenzyl)-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-{3-[6-(1-methylethoxy)pyridin-3-yl]-1H-pyrazolo[4,3-c]pyridin-6-yl}-3-[(1R)-1-phenylethyl]urea,

1-[3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[(1R)-1-phenylethyl]urea,

1-[3-(4-fluorophenyl)-1H-pyrazolo[4,3 -c]pyridin-6-yl]-3-[(1R)-1-phenylethyl]urea,

1-[3-(2,6-dimethylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[(1R)-1-phenylethyl]urea,

1-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-(naphthalen-1-ylmethyl)urea,

1-(3,4-dimethoxybenzyl)-3-[3-(4-fluorophenyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[3-(4-fluorophenyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-(cyclopropylmethyl)-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-tert-butyl-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

hydroxycyclopropyl)methyl]-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-(cyclopropylidenemethyl)-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-azetidin-3-yl-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-(2-methoxyethyl)-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-(1-cyclopropyl-2,2,2-trifluoroethyl)-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[(1-methyl-1H-imidazol-5-yl)methyl]-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[(2-methyl-1,3-thiazol-4-yl)methyl]urea,

1-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-(pyrimidin-2-ylmethyl)urea,

1-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-(naphthalen-2-ylmethyl)urea,

1-methyl-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-1-(pyridin-3-ylmethyl)urea,

1-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-(2-pyridin-2-ylethyl)urea,

1-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-(pyrazin-2-ylmethyl)urea,

1-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-(1-pyridin-3-ylethyl)urea

1-(2-methoxyethyl)-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-1-(pyridin-3-ylmethyl)urea,

1-[(5-fluoropyridin-3-yl)methyl]-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-(2,6-difluorobenzyl)-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-(3-fluorobenzyl)-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[4-(trifluoromethyl) -benzyl]urea,

1-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-{6-[(2-phenylethyl) -amino]pyridazin-3-yl}urea,

1-(3-chloro-4-fluorobenzyl)-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[(1R)-1-(4-chlorophenyl)ethyl]-3-[3-(2-fluoropyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-(3-chloro-4-fluorobenzyl)-3-[3-(2-fluoropyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[(1R)-1-(4-chlorophenyl)ethyl]-3-[3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-(3-chloro-4-fluorobenzyl)-3-[3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-phenylurea,

1-[(1R)-1-(3-chlorophenyl)ethyl]-3-[3-(2-methyl-2H-indazol-5-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[(1R)-1-(4-fluorophenyl)ethyl]-3-[3-(2-methyl-2H-indazol-5-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-(3-chloro-4-fluorobenzyl)-3-[3-(2-methyl-2H-indazol-5-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[(1R)-1-(4-chlorophenyl)ethyl]-3-[3-(2-methyl-2H-indazol-5-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[3-(4-cyanophenyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[(1R)-1-phenylethyl]urea,

1-[(1R)-1-phenylethyl]-3-{3-[(1E)-prop-1-en-1-yl]-1H-pyrazolo[4,3-c]pyridin-6-yl}urea,

1-(3-bromo-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-[(1R)-1-(3-chloro-4-fluorophenyl)ethyl]urea,

1-[(1R)-1-(3-chloro-4-fluorophenyl)ethyl]-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[(1R)-1-(4-fluorophenyl)ethyl]-3-[3-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-1H -pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[(1R)-1-(3-chloro-4-fluorophenyl)ethyl]-3-[3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[(1R)-1-(3-chloro-4-fluorophenyl)ethyl]-3-[3-(4-fluorophenyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[(1R)-1-(3-chloro-4-fluorophenyl)ethyl]-3-[3-(1H-pyrazol-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[(1R)-1-(3-chloro-4-fluorophenyl)ethyl]-3-[3-(2-chloropyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[(1R)-1-(3-chloro-4-fluorophenyl)ethyl]-3-[3-(3-chlorophenyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[4-(4-chlorophenyl)tetrahydro-2H-pyran-4-yl]-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-(2,3-dihydro-1H-inden-1-yl)-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[7-bromo-3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[(1R)-1-phenylethyl]urea,

1-[3-(2-aminopyrimidin-5-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[(1R)-1-(3-chloro-4-fluorophenyl)ethyl]urea,

1-[(1R)-1-(3-chloro-4-fluorophenyl)ethyl]-3-[3-(2-fluoropyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[(1R)-1-(3-chloro-4-fluorophenyl)ethyl]-3-(3-cyclopropyl-1H-pyrazolo[4,3-c]pyridin-6-yl)urea,

1-[3-(4-cyanophenyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[(1R)-1-(4-fluorophenyl)ethyl]urea,

1-[(1R)-1-(3-chlorophenyl)ethyl]-3-[3-(4-cyanophenyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[1-(4-chlorophenyl)cyclopropyl]-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[3-(2-methyl-1,3-benzothiazol-6-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[(1R)-1-phenylethyl]urea,

1-[3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[(1R)-1-phenylethyl]urea,

1-{3-[4-(methylsulfonyl)phenyl]-1H-pyrazolo[4,3-c]pyridin-6-yl}-3-[(1R)-1-phenylethyl]urea, 1-[3-(1-methyl-1H-pyrazol-3-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[(1R)-1-phenylethyl]urea,

1-[3-(6-methylpyridazin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[(1R)-1-phenylethyl]urea,

1-[3-(1-oxidopyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[(1R)-1-phenylethyl]urea,

1-benzyl-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]thiourea, and

1-[7-fluoro-3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[(1R)-1-phenylethyl]urea,

or a pharmaceutically acceptable salt thereof

17. The compound of claim 15 selected from the group consisting of

1-[(3R)-1-(2-fluoro-6-methoxybenzyl)-piperidin-3-yl]-3-[3-(2-methylpyridin-4-yl)-1H -pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[1-(2-fluoro-6-methoxybenzyl)-piperidin-3-yl]-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-(2-phenylethyl)urea,

1-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[(1R)-1-phenylethyl]urea,

1-(3,4-dichlorobenzyl)-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-benzyl-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-(2-hydroxy-1-phenylethyl)-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[(1S)-1-(4-fluorophenyl)ethyl]-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea, and

1-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-(pyridin-3-ylmethyl)urea,

and the free base form of

1-[(1S)-2-hydroxy-1-phenylethyl]-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[(1R)-1-(4-chlorophenyl)ethyl]-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[3-(3,6-dihydro-2H-pyran-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[(1R)-1-phenylethyl]urea,

1-[(1R)-1-phenylethyl]-3-(3-propyl-1H-pyrazolo[4,3-c]pyridin-6-yl)urea,

1-(3-cyclopropyl-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-[(1R)-1-phenylethyl]urea, and

1-(4-chlorobenzyl)-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

or a pharmaceutically salt of thereof.

18. The compound of claim 15 selected from the group consisting of:

1-(3-chlorobenzyl)-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[(1R)-1-phenylethyl]urea,

1-[3-(4-fluorophenyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[(1R)-1-phenylethyl]urea,

1-[3-(2,6-dimethylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[(1R)-1-phenylethyl]urea, 1-[3-(4-fluorophenyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[(2-methyl-1,3-thiazol-4-yl)methyl]urea,

1-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-(1-pyridin-3-ylethyl)urea

1-[(5-fluoropyridin-3-yl)methyl]-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl ]urea,

1-(2,6-difluorobenzyl)-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-(3-fluorobenzyl)-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-(3-chloro-4-fluorobenzyl)-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[(1R)-1-(4-chlorophenyl)ethyl]-3-[1-(2-fluoropyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-(3-chloro-4-fluorobenzyl)-3-[3-(2-fluoropyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[(1R)-1-(4-chlorophenyl)ethyl]-3-[3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-(3-chloro-4-fluorobenzyl)-3-[3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[(1R)-1-(3-chlorophenyl)ethyl]-3-[3-(2-methyl-2H-indazol-5-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[(1R)-1-(4-fluorophenyl)ethyl]-3-[3-(2-methyl-2H-indazol-5-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-(3-chloro-4-fluorobenzyl)-3-[3-(2-methyl-2H-indazol-5-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[(1R)-1-(4-chlorophenyl)ethyl]-3-[3-(2-methyl-2H-indazol-5-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[3-(4-cyanophenyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[(1R)-1-phenylethyl]urea,

1-[(1R)-1-phenylethyl]-3-{3-[(1E)-prop-1-en-1-yl]-1H-pyrazolo[4,3-c]pyridin-6-yl}urea,

1-[(1R)-1-(3-chloro-4-fluorophenyl)ethyl]-3-[3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[(1R)-1-(4-fluorophenyl)ethyl]-3-[3-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-1H -pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[(1R)-1-(3-chloro-4-fluorophenyl)ethyl]-3-[3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[(1R)-1-(3-chloro-4-fluorophenyl)ethyl]-3-[3-(1H-pyrazol-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]urea,

1-[3-(2-methyl-1,3-benzothiazol-6-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[(1R)-1-phenylethyl]urea,

1-[3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[(1R)-1-phenylethyl]urea,

1-{3-[4-(methylsulfonyl)phenyl]-1H-pyrazolo[4,3-c]pyridin-6-yl}-3-[(1R)-1-phenylethyl]urea,

1-[3-(6-methylpyridazin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[(1R)-1-phenylethyl]urea,

1-[3-(1-oxidopyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[(1R)-1-phenylethyl]urea, and

1-[7-fluoro-3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-3-[(1R)-1-phenylethyl]urea,

or a pharmaceutically acceptable salt thereof.

19. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.

20. A method for inhibiting ERK2 in a patient in need of such inhibition, said method comprising administering to said patient an effective amount of at least one compound of claim 1 .

Assignments (2)
MERGER Recorded Aug 8, 2022
From: MERCK SHARP & DOHME CORP.
To: MERCK SHARP & DOHME LLC
Reel/Frame 061102/0145 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 15, 2014
From: LIM, JONGWON; KELLEY, ELIZABETH; METHOT, JOEY L.; ZHOU, HUA; PETROCCHI, ALESSIA; MANSOOR, UMAR FARUK; FISCHER, CHRISTIAN; O'BOYLE, BRENDAN M.; GUERIN, DAVID JOSEPH; BIENSTOCK, COREY E.; BOYCE, CHRISTOPHER W.; DANIELS, MATTHEW H.; FALCONE, DANIELLE; FERGUSON, RONALD D.; FEVRIER, SALEM; HUANG, XIANHAI; LIPFORD, KATHRYN ANN; SLOMAN, DAVID L.; WILSON, KEVIN J.; ZHOU, WEI; WITTER, DAVID J.; MALETIC, MILANA M.; SILIPHAIVANH, PHIENG
To: MERCK SHARP & DOHME CORP.
Reel/Frame 032899/0347 →