IP Library › Granted Patent US 9,663,488

Granted Patent B2

US 9,663,488 · App. 14/763,468 · Granted May 30, 2017

Metalloenzyme inhibitor compounds

Inventors: William J. Hoekstra (Durham, NC); Christopher M. Yates (Raleigh, NC); Stephen W. Rafferty (Lake Worth, FL)

C07D401/04 A61K31/4375 A61K31/444 A61K31/4545 A61K31/47 A61K31/4709 A61K31/496 A61K31/5377 A61K31/541 A61K45/06 C07D215/14 C07D215/52 C07D471/04

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Quick Facts

Patent No.: US 9,663,488
App. No.: 14/763,468
Granted: May 30, 2017
Kind: B2

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Abstract

The instant invention describes compounds having metalloenzyme modulating activity, and methods of treating diseases, disorders or symptoms thereof mediated by such metalloenzymes.

Claims (475)

1. A compound of formula (I), (II), (III), (IV), or salt thereof, wherein:

U is O or S;

each X is independently O; S; NR 4 ; or H and R 4 ;

each R 1 is independently selected from:

b) heteroaryl optionally substituted with alkoxy wherein alkoxy is optionally substituted with 1, 2, or 3 OR 4 ; c) C≡C—R 13 ; d) C(═O)NR 4 R 7 ; e) N(R 7 )C(═O)R 4 ; f) SO 2 NR 4 R 7 ; g) N(R 7 )SO 2 R 4 ; h) hydrogen; i) hydroxy; j) optionally substituted alkoxy; k) SO 2 NHR 4 ;

1) optionally substituted alkenyl; or m) optionally substituted arylalkyl;

each R 8 , R 9 , R 10 , R 11 , and R 12 is independently selected from:

a) H; b) hydroxyalkylamino; c) alkoxy optionally substituted with 1, 2, or 3 independent heterocycloalkoxy, heterocycloalkylcarbonyl, hydroxy, amino, NHSO 2 R 4 , NHC(═O)R 4 , C(═O)OR 4 , C(═O)NHNHR 4 , or C(═O)NR 4 OH; d) halogen; e) SO 2 NHR 18 ; f) NHSO 2 R 4 ; g) NHC(═O)R 4 ; h) C(═O)NHR 4 ; i) heterocycloalkyl containing 5 to 6 ring atoms, optionally substituted with 1, 2, or 3 independent C(═O)OR 4 , C(═O)NR 4 R 7 , or SO 2 NR 4 R 7 ; j) heteroaryl containing 5 to 6 ring atoms optionally substituted with 1, 2, or 3 independent:

(1) C(═O)OR 17 ;

(2) heterocycloalkylcarbonyl optionally substituted with 1, 2, or 3 independent C(═O)OR 17 , C(═O)NR 4 R 7 , or SO 2 NR 4 R 7 ;

(3) alkyl optionally substituted with 1, 2, or 3 independent OC(═O)NHR 4 , NHC(═O)NHR 4 , NHSO 2 R 4 , hydroxy, or C(═O)NHR 4 ; or

(4) C(═O)NHR 4 ;

k) cyano; l) hydroxy; m) SO 2 R 4 ; n) heterocycloalkylcarbonyl optionally substituted with 1, 2, or 3 independent C(═O)OR 4 , C(═O)NR 4 R 7 , or SO 2 NR 4 R 7 ; o) heterocycloalkylsulfonyl optionally substituted with 1, 2, or, 3 independent C(═O)OR 4 , C(═O)NR 4 R 7 , or SO 2 NR 4 R 7 ; p)

q) mercapto; r) thioalkoxy; s) alkylamino; t) alkyl optionally substituted with 1, 2, or 3 independent heterocycloalkylcarbonyl, heterocycloalkyl, or heterocycloalkylsulfonyl, each optionally substituted with independent C(═O)OR 4 , C(═O)NR 4 R 7 , or SO 2 NR 4 R 7 ; u) dialkylamino; or v) —O—CH 2 ) n —C(═O)-heterocycloalkyl optionally substituted with 1, 2, or 3 independent C(═O)OR 4 , C(═O)NR 4 R 7 , or SO 2 NR 4 R 7 ;

R 2 is H, alkyl, fluoroalkyl, alkoxy, fluoroalkoxy, halogen, aryl, or heteroaryl;

R 3 is CH(R 4 )NHR 4 , CH(R 4 )NHSO 2 R 4 , CH(R 4 )SH, CH(R 4 )OH, CH(R 4 )CO 2 R 4 , CH(R 4 )CONHR 4 ; CH(R 4 )CONHOH; CH(R 4 )CONHNHR 4 ; C(═O)R 4 , CO 2 R 4 , C(═O)NHR 4 , C(═O)NHNHR 4 , C(═S)NHR 4 , C(═S)NHNHR 4 , C≡N, C(═NH)NH 2 , NHC(═NH)NH 2 , N(R 4 )OH, N(OH)C(═O)R 4 , NHR 4 , NHNHR 4 , NHC(═O)R 4 , N(R 4 )NHC(═O)R 4 , NHC(═O)NHR 4 , NHC(═S)NHR 4 , NHSO 2 R 4 , NHSO 2 NHR 4 ; NHNHSO 2 R 4 , NO 2 , SO 2 NHR 4 (only in the case of formula I), SO 2 NHOH (only in the case of formula I), SO 3 H (only in the case of formula I), OR 4 , OSO 2 R 4 , OSO 2 NHR 4 , SR 4 , B(OR 4 ) 2 , CH 2 B(OR 4 ) 2 , P(═O)OH, P(═O) 2 OH, Se(═O)OH, Se(═O) 2 OH, a heterocycle that is preferably a 5-membered ring with 1-4 heteroatoms, or a 5-membered heterocycle that is connected through a CH 2 ;

Y is O or null;

Z is N;

each R 4 is independently a) H; b) alkyl optionally substituted with 1, 2, or 3 independent hydroxy, halogen, C(═O)OR 27 , amino, alkylthio, or optionally substituted aryl; c) fluoroalkyl; d) optionally substituted aryl; e) optionally substituted heteroaryl; or f) heterocycloalkyl optionally substituted with 1, 2, or 3 independent C(═O)OR 27 , C(═O)NR 27 R 27 , or SO 2 NR 27 R 27 ;

each R 5 is independently H, alkyl, fluoroalkyl, halogen, alkoxy, fluoroalkoxy, substituted amino, aryl, or heteroaryl;

A is O, S, CH 2 or N(R 4 );

A may also be the following when R 6 is null: an optionally substituted heterocycle that is preferably a 5-membered ring with 1-4 heteroatoms, B(OR 4 ) 2 , P(═O)OH, P(═O) 2 OH, Se(═O)OH, Se(═O) 2 OH;

R 6 is null, CH(R 4 )CO 2 R 4 , CH(R 4 )CONHR 4 ; CH(R 4 )CONHOH; CH(R 4 )CONHNHR 4 ; C(═O)R 4 , CO 2 R 4 , C(═O)NHR 4 , C(═O)NR 4 OH, C(═O)NHNHR 4 , C(═S)NHR 4 , C(═S)NR 4 OH, C(═S)NHNHR 4 , C≡N, C(═NH)NH 2 , SO 2 NHNR 4 (with the proviso that A cannot be S), SO 2 NHR 4 (with the proviso that A cannot be S), SO 2 NHOH (with the proviso that A cannot be S); a heterocycle that is preferably a 5-membered ring with 1-4 heteroatoms, or a (preferably 5-membered) heterocycle that is connected through a CH 2 ; and

each R 7 is independently H; alkyl; alkoxy; hydroxy; C(═O)OR 4 ; NHSO 2 R 4 ; N(alkyl)SO 2 R 4 ; NHR 4 ; NHC(═O)R 4 ; N(alkyl)C(═O)R 4 ; C(═O)NR 27 R 4 ; SO 2 NR 27 R 4 ; C(═O)NR 27 NHR 4 ; C(═O)NR 27 OR 4 ; halogen; optionally substituted aryl; optionally substituted heteroaryl; heterocycloalkyl optionally substituted with 1, 2, or 3 independent OR 4 , C(═O)OR 4 , or NHSO 2 R 4 ; or heterocycloalkylcarbonyl optionally substituted with 1, 2, or 3 independent OR 4 , C(═O)OR 4 , or NHSO 2 R 4 ;

each R 13 is independently selected from:

b) heterocycloalkyl optionally substituted with 1, 2, or 3 independent alkyl wherein alkyl is optionally substituted with independent:

i) OR 4 ;

ii) NHC(═O)R 4 ;

iii) C(═O)OR 4 ; or

iv) C(═O)NHR 4 ;

c) heteroaryl optionally substituted with 1, 2, or 3 independent 1) heterocycloalkylcarbonyl, 2) NR 27 SO 2 R 4 , 3) alkylaminocarbonyl, each optionally substituted with 1, 2, or 3 independent C(═O)OR 4 , C(═O)NR 4 R 7 , or SO 2 NR 4 R 7 , 4) (heterocycloalkyl)alkyl; or 5) NR 27 C(═O)R 4 ; or

d) cycloalkyl optionally substituted with 1, 2, or 3 independent C(═O)OR 4 , C(═O)NR 4 R 7 , hydroxyalkyl, or SO 2 NR 4 R 7 ;

each R 14 is independently selected from heterocycloalkylcarbonyl, heterocycloalkylsulfonyl, or heterocycloalkyl, each optionally substituted with 1, 2, or 3 independent C(═O)OR 4 , C(═O)NR 4 R 7 , or SO 2 NR 4 R 7 ;

each R 15 is independently H; alkyl; fluoroalkyl; aryl; arylalkyl; or heteroaryl;

each R 16 is independently hydrogen; alkyl; alkoxy; hydroxy; NHR 4 ; NHC(═O)R 4 ; halogen; optionally substituted aryl; optionally substituted heteroaryl; heterocycloalkyl optionally substituted with 1, 2, or 3 independent C(═O)OR 4 , C(═O)NR 4 R 7 , or SO 2 NR 4 R 7 ; or NHSO 2 R 4 ;

each R 17 is independently a) H; b) alkyl optionally substituted with 1, 2, or 3 independent hydroxy, halogen, C(═O)OR 4 , C(═O)NR 4 R 7 , SO 2 NR 4 R 7 , amino, alkylthio, or optionally substituted aryl; c) fluoroalkyl; d) aryl; or e) heteroaryl;

each R 18 is independently a) H; b) alkyl optionally substituted with 1, 2, or 3 independent hydroxy, halogen, C(═O)OR 4 , C(═O)NR 4 R 7 , SO 2 NR 4 R 7 , amino, alkylthio, or optionally substituted aryl; c) fluoroalkyl; d) aryl; or e) heteroaryl;

each R 19 is independently a) H; b) alkyl optionally substituted with 1, 2, or 3 independent hydroxy, halogen, C(═O)OR 4 , C(═O)NR 4 R 7 , SO 2 NR 4 R 7 , amino, alkylthio, or optionally substituted aryl; c) fluoroalkyl; d) aryl; or e) heteroaryl;

each R 20 is independently a) H; b) alkyl optionally substituted with 1, 2, or 3 independent hydroxy, halogen, C(═O)OR 4 , C(═O)NR 4 R 7 , SO 2 NR 4 R 7 , amino, alkylthio, optionally substituted heteroaryl, or optionally substituted aryl; c) fluoroalkyl; d) aryl optionally substituted with 1, 2, or 3 independent C(═O)OR 4 or OR 4 ; or e) heteroaryl;

each R 21 is independently a) H; b) alkyl optionally substituted with 1, 2, or 3 independent hydroxy, halogen, C(═O)OR 4 , C(═O)NR 4 R 7 , SO 2 NR 4 R 7 , amino, alkylthio, or optionally substituted aryl; c) fluoroalkyl; d) aryl; or e) heteroaryl;

each R 22 , R 23 , R 24 , R 25 , and R 26 is independently selected from

i) hydrogen; ii) NHC(═O)R 4 ; iii) NHSO 2 R 4 ; iv) heterocycloalkylcarbonyl optionally substituted with 1, 2, or 3 independent alkyl, CH 2 C(═O)OR 19 , CH 2 C(═O)NR 4 R 7 , OR 4 , CH 2 SO 2 NR 4 R 7 , C(═O)OR 19 , C(═O)NR 4 R 7 , or SO 2 NR 4 R 7 ; v) heterocycloalkylsulfonyl optionally substituted with 1, 2, or 3 independent C(═O)OR 4 , C(═O)NR 4 R 7 , or SO 2 NR 4 R 7 , or alkyl; vi) halogen; vii) alkyl optionally substituted with heterocycloalkyl wherein heterocycloalkyl is optionally substituted with 1, 2, or 3 independent C(═O)OR 4 , C(═O)NR 4 R 7 , or SO 2 NR 4 R 7 ; viii) hydroxyalkylamino; ix) C(═O)NR 15 R 20 ; x) alkoxy optionally substituted with 1, 2, or 3 independent hydroxy, halogen, C(═O)OR 4 , C(═O)NR 4 R 7 , SO 2 NR 4 R 7 , amino, alkylthio, or optionally substituted aryl; xi) haloalkoxy; xii) haloalkyl; xiii) hydroxy; xiv) SO 2 NR 4 R 21 ; or xv) heterocycloalkyl optionally substituted with 1, 2, or 3 independent C(═O)OR 4 , C(═O)NR 4 R 7 , SO 2 NR 4 R 7 , or CH 2 C(═O)OR 4 ;

each R 27 is independently a) H; b) alkyl optionally substituted with 1, 2, or 3 independent hydroxy, halogen, amino, alkylthio, or optionally substituted aryl; c) fluoroalkyl; d) optionally substituted aryl; or e) optionally substituted heteroaryl;

each n is independently 0, 1, 2, 3, or 4; and

Q 1 and Q 2 are each independently CH or N.

2. The compound of claim 1 , wherein R 1 is

and each R 8 , R 9 , R 10 , R 11 , and R 12 is independently selected from:

a) hydrogen; b) hydroxyalkylamino; c) alkoxy optionally substituted with 1, 2, or 3 independent hydroxy, C(═O)OR 4 , C(═O)NHNHR 4 , or C(═O)NR 4 OH; d) halogen; e) heterocycloalkyl containing 5 to 6 ring atoms, optionally substituted with 1, 2, or 3 independent C(═O)OR 4 , C(═O)NR 4 R 7 , or SO 2 NR 4 R 7 ; f) heteroaryl optionally substituted with 1, 2, or 3 independent:

i) C(═O)OR 17 ; or

ii) heterocycloalkylcarbonyl optionally substituted with 1, 2, or 3 independent C(═O)OR 17 , C(═O)NR 4 R 7 , or SO 2 NR 4 R 7 ; or

iii) alkyl optionally substituted with 1, 2, or 3 independent OC(═O)NHR 4 , NHC(═O)NHR 4 , NHSO 2 R 4 , hydroxy, or C(═O)NHR 4 ;

g) alkyl optionally substituted with 1, 2, or 3 heterocycloalkylcarbonyl substituted with C(═O)OR 4 , C(═O)NR 4 R 7 , or SO 2 NR 4 R 7 ; h) heterocycloalkylcarbonyl optionally substituted with 1, 2, or 3 independent C(═O)OR 4 , C(═O)NR 4 R 7 , or SO 2 NR 4 R 7 ; or i) heterocycloalkylsulfonyl optionally substituted with 1, 2, or 3 independent C(═O)OR 4 , C(═O)NR 4 R 7 , or SO 2 NR 4 R 7 .

3. The compound of claim 2 wherein each R 8 , R 9 , R 10 , R 11 , and R 12 is independently selected from halogen, hydrogen,

each o is independently 1, 2, 3, or 4; and

each p is independently 1, 2, 3, or 4.

4. The compound of claim 3 , wherein each R 8 , R 9 , R 10 , R 11 , and R 12 is independently selected from hydrogen,

5. The compound of formulae (I) or (IV) in claim 1 , wherein X is O and R 3 is selected from NHNHR 4 , NHNHSO 2 R 4 , C(═O)NR 4 OH, or C(═O)OR 4 .

6. The compound of claim 5 , wherein R 3 is NHNH 2 .

7. The compound of claim 6 , wherein R 3 is NHNH 2 , R 1 is

R 10 is selected from

and R 8 , R 9 , R 11 , and R 12 are each H.

8. The compound of claim 1 , wherein R 1 is C≡C—R 13 and

R 13 is independently selected from:

b) heterocycloalkyl optionally substituted with 1, 2, or 3 independent alkyl wherein alkyl is optionally substituted with independent:

i) OR 4 ;

ii) NHC(═O)R 4 ;

iii) C(═O)OR 4 ; or

iv) C(═O)NHR 4 ;

c) heteroaryl optionally substituted with 1, 2, or 3 independent 1) heterocycloalkylcarbonyl, 2) NH 2 SO 4 , 3) alkylaminocarbonyl, each optionally substituted with 1, 2, or 3 independent C(═O)OR 4 , C(═O)NR 4 R 7 , or SO 2 NR 4 R 7 , or 4) (heterocycloalkyl)alkyl; or

d) cycloalkyl optionally substituted with 1, 2, or 3 independent C(═O)OR 4 , C(═O)NR 4 R 7 , or SO 2 NR 4 R 7 .

9. The compound of claim 8 , wherein R 13 is

and each R 22 , R 23 , R 24 , R 25 , and R 26 is independently selected from halogen, hydrogen,

each M is independently O, CH 2 , or S;

each o is independently 1, 2, 3, or 4; and

each p is independently 1, 2, 3, or 4.

10. The compound of claim 9 , wherein each R 22 , R 23 , R 24 , R 25 , and R 26 is independently selected from hydrogen,

11. The compound of claim 6 , wherein R 3 is NHNH 2 , R 1 is C≡C—R 13 , R 13 is

R 24 is independently selected from hydrogen,

and

R 22 , R 23 , R 25 , and R 26 are each independently hydrogen or halogen.

12. The compound of formula (I) in claim 1 , wherein each R 7 is independently C(═O)OR 4 ; NHSO 2 R 4 ; N(alkyl)SO 2 R 4 ; NHC(═O)R 4 ; N(alkyl)C(═O)R 4 ; C(═O)NR 27 R 4 ; SO 2 NR 27 R 4 ; C(═O)NR 27 NHR 4 ; C(═O)NR 27 OR 4 ; or heterocycloalkylcarbonyl optionally substituted with 1, 2, or 3 independent OR 4 , C(═O)OR 4 , or NHSO 2 R 4 .

13. The compound of claim 12 , wherein each R 7 is independently

14. The compound of claim 12 , wherein R 1 is

and each R 8 , R 9 , R 10 , R 11 , and R 12 is independently selected from:

i) C(═O)OR 17 ; or

ii) heterocycloalkylcarbonyl optionally substituted with 1, 2, or 3 independent C(═O)OR 17 , C(═O)NR 4 R 7 , or SO 2 NR 4 R 7 ;

iii) alkyl optionally substituted with 1, 2, or 3 independent OC(═O)NHR 4 , NHC(═O)NHR 4 , NHSO 2 R 4 , hydroxy, or C(═O)NHR 4 ;

15. The compound of claim 12 , wherein R 1 is C≡C—R 13 and

R 13 is independently selected from:

b) heterocycloalkyl optionally substituted with 1, 2, or 3 independent alkyl wherein alkyl is optionally substituted with independent:

i) OR 4 ;

ii) NHC(═O)R 4 ;

iii) C(═O)OR 4 ; or

iv) C(═O)NHR 4 ;

d) cycloalkyl optionally substituted with 1, 2, or 3 independent C(═O)OR 4 , C(═O)NR 4 R 7 , or SO 2 NR 4 R 7 .

16. The compound of formula (III) in claim 1 , wherein A is an optionally substituted heterocycle that is preferably a 5-membered ring with 1-4 heteroatoms and R 6 is null.

17. A compound which is:

5-(2-(4′-((2-hydroxyethyl)amino)-[1,1′-biphenyl]-4-yl)-1,6-naphthyridin-4-yl)-5-methylimidazolidine-2,4-dione (1);

1-hydroxy-3-(2-(4′-((2-hydroxyethyl)amino)-[1,1′-biphenyl]-4-yl)-1,6-naphthyridin-4-yl)urea (2);

2-(4′4(2-hydroxyethyl)amino)-[1,1′-biphenyl]-4-yl)-1,6-naphthyridine-4-carboxylic acid (3);

2-(4′4(2-hydroxyethyl)amino)-[1,1′-biphenyl]-4-yl)-1,6-naphthyridine-4-carbohydrazide (4);

N-(2-((4′-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)-[1,1′-biphenyl]-4-yl)oxy)ethyl)isobutyramide (5);

N-(2-((4′-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)-[1,1′-biphenyl]-4-yl)oxy)ethyl)methanesulfonamide (6);

2-(4′-(5-(hydroxymethyl)isoxazol-3-yl)-[1,1′-biphenyl]-4-yl)-1,6-naphthyridine-4-carbohydrazide (7);

3-(2-(4′-(4-((tetrahydro-2H-pyran-2-yl)oxy)butoxy)-[1,1′-biphenyl]-4-yl)-1,6-naphthyridin-4-yl)imidazolidine-2,4-dione (8);

3-(2-(4′-(4-hydroxybutoxy)-[1,1′-biphenyl]-4-yl)-1,6-naphthyridin-4-yl)imidazolidine-2,4-dione (9);

3-(2-(4′-(4-((tetrahydro-2H-pyran-2-yl)oxy)butoxy)-[1,1′-biphenyl]-4-yl)-1,6-naphthyridin-4-yl)-2-thioxoimidazolidin-4-one (10);

3-(2-(4′-(4-hydroxybutoxy)-[1,1′-biphenyl]-4-yl)-1,6-naphthyridin-4-yl)-2-thioxoimidazolidin-4-one (11);

2-(4′-(3-aminopropoxy)-[1,1′-biphenyl]-4-yl)-1,6-naphthyridine-4-carbohydrazide (13);

N-(3-((4′-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)-[1,1′-biphenyl]-4-yl)oxy)propyl)methanesulfonamide (14);

N-(3-((4′-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)-[1,1′-biphenyl]-4-yl)oxy)propyl)acetamide (15);

N′-(2-(4′-((2-hydroxyethyl)amino)-[1,1′-biphenyl]-4-yl)-1,6-naphthyridine-4-carbonyl)methanesulfonohydrazide (17);

1-(2-(4′-fluoro-[1,1′-biphenyl]-4-yl)-1,6-naphthyridin-4-yl)imidazolidin-2-one (19);

1-(2-(4′-fluoro-[1,1′-biphenyl]-4-yl)-1,6-naphthyridin-4-yl)imidazolidine-2,4-dione (20);

5-(2-(4′-fluoro-[1,1′-biphenyl]-4-yl)-1,6-naphthyridin-4-yl)-1,3 ,4-oxadiazol-2-amine (21);

4′-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)-N-methyl-[1,1′-biphenyl]-4-sulfonamide (22);

N-(4′-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)-[1,1′-biphenyl]-4-yl)methanesulfonamide (23);

N-(4′-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)-[1,1′-biphenyl]-4-yl)acetamide (24);

4′-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)-N-methyl-[1,1′-biphenyl]-4-carboxamide (25);

1-(4′-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)-[1,1′-biphenyl]-4-yl)pyrrolidine-3 -carboxylic acid (26);

2-(4′-(2-morpholino-2-oxoethyl)-[1,1′-biphenyl]-4-yl)-1,6-naphthyridine-4-carbohydrazide (27);

2-(4′-(2-morpholino-2-oxoethoxy)-[1,1′-biphenyl]-4-yl)-1,6-naphthyridine-4-carbohydrazide (28);

2-(4′-((morpholino sulfonyl)methyl)-[1,1′-biphenyl]-4-yl)-1,6-naphthyridine-4-carbohydrazide (29);

3-(4′-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)-[1,1′-biphenyl]-4-yl)isoxazole-5-carboxylic acid (30);

(R)-1-(3-(4′-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)-[1,1′-biphenyl]-4-yl)isoxazole-5-carbonyl)pyrrolidine-2-carboxylic acid (31);

(3-(4′-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)-[1,1′-biphenyl]-4-yl)isoxazol-5-yl)methyl methylcarbamate (32);

1-((3-(4′-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)-[1,1′-biphenyl]-4-yl)isoxazol-5-yl)methyl)-3-methylurea (33);

N-((3-(4′-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)-[1,1′-biphenyl]-4-yl)isoxazol-5-yl)methyl)acetamide (34);

N-((3-(4′-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)-[1,1′-biphenyl]-4-yl)isoxazol-5-yl)methyl)methanesulfonamide (35);

(R)-1-(3-(4′-(4-(hydroxy(methyl)carbamoyl)-1,6-naphthyridin-2-yl)-[1,1′-biphenyl]-4-yl)isoxazole-5-carbonyl)pyrrolidine-2-carboxylic acid (36);

2-(4′-((2-hydroxyethyl)amino)-[1,1′-biphenyl]-4-yl)-3-methyl-1,6-naphthyridine-4-carbohydrazide (39);

N′-(2-(4′-((2-hydroxyethyl)amino)-[1,1′-biphenyl]-4-yl)-3-methyl-1,6-naphthyridine-4-carbonyl)methanesulfonohydrazide (40);

N-(2-(4′4(2-hydroxyethyl)amino)-[1,1′-biphenyl]-4-yl)-1,6-naphthyridin-4-yl)hydrazinecarboxamide (41);

2-(4′4(2-hydroxyethyl)amino)-[1,1′-biphenyl]-4-yl)-3-methoxy-1,6-naphthyridine-4-carbohydrazide (44);

2-(4′4(2-hydroxyethyl)amino)-[1,1′-biphenyl]-4-yl)-3-methoxy-1,6-naphthyridine-4-carboxylic acid (45);

2-(4′-((2-hydroxyethyl)amino)-[1,1′-biphenyl]-4-yl)-3-methyl-1,6-naphthyridine-4-carboxylic acid (46);

N-hydroxy-2-(4′-((2-hydroxyethyl)amino)-[1,1′-biphenyl]-4-yl)-N-methyl-1,6-naphthyridine-4-carboxamide (49);

2-(4′-fluoro-[1,1′-biphenyl]-4-yl)-4-(hydrazinecarbonyl)-1,6-naphthyridine 6-oxide (50);

4-(hydrazinecarbonyl)-2-(4′-((2-hydroxyethyl)amino)-[1,1′-biphenyl]-4-yl)-1,6-naphthyridine 6-oxide (51);

2-(4′-(4-hydroxybutoxy)-[1,1′-biphenyl]-4-yl)-1,6-naphthyridine-4-carbohydrazide (53);

2-(4′-cyano-[1,1′-biphenyl]-4-yl)-1,6-naphthyridine-4-carbohydrazide (54);

2-(5-(4-((2-hydroxyethyl)amino)phenyl)pyridin-2-yl)-1,6-naphthyridine-4-carbohydrazide (55);

2-(6-(4-((2-hydroxyethyl)amino)phenyl)pyridin-3-yl)-1,6-naphthyridine-4-carbohydrazide (56);

2-(4-(pyridin-3-yl)phenyl)-1,6-naphthyridine-4-carbohydrazide (57);

2-(4-(pyridin-2-yl)phenyl)-1,6-naphthyridine-4-carbohydrazide (58);

2-(4-(pyridin-4-yl)phenyl)-1,6-naphthyridine-4-carbohydrazide (59);

2-(4-(1H-pyrazol-3-yl)phenyl)-1,6-naphthyridine-4-carbohydrazide (60);

2-(4-(1H-pyrazol-4-yl)phenyl)-1,6-naphthyridine-4-carbohydrazide (61);

2-(4-(oxazol-2-yl)phenyl)-1,6-naphthyridine-4-carbohydrazide (62);

2-(4-(oxazol-5-yl)phenyl)-1,6-naphthyridine-4-carbohydrazide (63);

2-([1,1′-biphenyl]-4-yl)-1,6-naphthyridine-4-carbohydrazide (64);

2-(4′-fluoro-[1,1′-biphenyl]-4-yl)-1,6-naphthyridine-4-carbohydrazide (65);

2-(4′-(morpholinomethyl)-[1,1′-biphenyl]-4-yl)-1,6-naphthyridine-4-carbohydrazide (66);

2-(4-(5-(4-hydroxybutoxy)pyridin-2-yl)phenyl)-1,6-naphthyridine-4-carbohydrazide (67);

2-(2′-hydroxy-[1,1′-biphenyl]-4-yl)-1,6-naphthyridine-4-carbohydrazide (68);

2-(4-(thiazol-2-yl)phenyl)-1,6-naphthyridine-4-carbohydrazide (69);

3-(2-(4′-fluoro-[1,1′-biphenyl]-4-yl)-1,6-naphthyridin-4-yl)imidazolidine-2,4-dione (70);

3-(2-(4′-fluoro-[1,1′-biphenyl]-4-yl)-1,6-naphthyridin-4-yl)-2-thioxoimidazolidin-4-one (71);

2-(4′-(methylsulfonyl)-[1,1′-biphenyl]-4-yl)-1,6-naphthyridine-4-carbohydrazide (72);

4′-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)-N-(2-hydroxyethyl)-[1,1′-biphenyl]-4-sulfonamide (73);

4′-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)-N-(3-hydroxypropyl)-[1,1′-biphenyl]-4-sulfonamide (74);

3-(2-(4-(5-(4-hydroxybutoxy)pyridin-2-yl)phenyl)-1,6-naphthyridin-4-yl)-2-thioxoimidazolidin-4-one (75);

4-((4′-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)-[1,1′-biphenyl]-4-yl)oxy)butanoic acid (76);

2-(4′-(4-hydrazinyl-4-oxobutoxy)-[1,1′-biphenyl]-4-yl)-1,6-naphthyridine-4-carbohydrazide (77);

4-((4′-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)-[1,1′-biphenyl]-4-yl)oxy)-N-hydroxybutanamide (78);

4-((4′-(4-(2,5-dioxoimidazolidin-1-yl)-1,6-naphthyridin-2-yl)-[1,1′-biphenyl]-4-yl)oxy)-N-hydroxybutanamide (79);

4-((4′-(4-(2,5-dioxoimidazolidin-1-yl)-1,6-naphthyridin-2-yl)-[1,1′-biphenyl]-4-yl)oxy)butanoic acid (80);

ethyl 4-((4′-(4-(2,5-dioxoimidazolidin-1-yl)-1,6-naphthyridin-2-yl)-[1,1′-biphenyl]-4-yl)oxy)butanoate (81);

N-hydroxy-4-((4′-(4-(5-oxo-2-thioxoimidazolidin-1-yl)-1,6-naphthyridin-2-yl)-[1,1′-biphenyl]-4-yl)oxy)butanamide (82);

4-((4′-(4-(5-oxo-2-thioxoimidazolidin-1-yl)-1,6-naphthyridin-2-yl)-[1,1′-biphenyl]-4-yl)oxy)butanoic acid (83);

ethyl 4-((4′-(4-(5-oxo-2-thioxoimidazolidin-1-yl)-1,6-naphthyridin-2-yl)-[1,1′-biphenyl]-4-yl)oxy)butanoate (84);

2-(4′-(2-aminoethoxy)-[1,1′-biphenyl]-4-yl)-1,6-naphthyridine-4-carbohydrazide (85);

N-(2-((4′-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)-[1,1′-biphenyl]-4-yl)oxy)ethyl)acetamide (86);

(R)-1-(4′-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)-[1,1′-biphenyl]-4-yl)pyrrolidine-2-carboxylic acid (87);

(S)-1-(4′-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)-[1,1′-biphenyl]-4-yl)pyrrolidine-2-carboxylic acid (88);

1-(4′-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)-[1,1′-biphenyl]-4-yl)piperidine-3-carboxylic acid (89);

1-(4′-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)-[1,1′-biphenyl]-4-yl)piperidine-4-carboxylic acid (90);

N-(3-((4′-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)-[1,1′-biphenyl]-4-yl)oxy)propyl)propionamide (91);

N-(3-((4′-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)-[1,1′-biphenyl]-4-yl)oxy)propyl)isobutyramide (92);

2,2,2-trifluoro-N-(3-((4′-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)-[1,1′-biphenyl]-4-yl)oxy)propyl)acetamide (93);

N-(3-((4′-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)-[1,1′-biphenyl]-4-yl)oxy)propyl)ethanesulfonamide (94);

N-(3-((4′-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)-[1,1′-biphenyl]-4-yl)oxy)propyl)propane-2-sulfonamide (95);

1,1,1-trifluoro-N-(3-((4′-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)-[1,1′-biphenyl]-4-yl)oxy)propyl)methanesulfonamide (96);

N-(2-((4′-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)-[1,1′-biphenyl]-4-yl)oxy)ethyl)propionamide (97);

2,2,2-trifluoro-N-(2-((4′-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)-[1,1′-biphenyl]-4-yl)oxy)ethyl)acetamide (98);

N-(2-((4′-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)-[1,1′-biphenyl]-4-yl)oxy)ethyl)ethanesulfonamide (99);

N-(2-((4′-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)-[1,1′-biphenyl]-4-yl)oxy)ethyl)propane-2-sulfonamide (100);

1,1,1-trifluoro-N-(2-((4′-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)-[1,1′-biphenyl]-4-yl)oxy)ethyl)methanesulfonamide (101);

2-(3′,4′-dihydroxy-[1,1′-biphenyl]-4-yl)-1,6-naphthyridine-4-carbohydrazide (102);

(R)-1-(2-(4′-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)-[1,1′-biphenyl]-4-yl)acetyl)pyrrolidine-2-carboxylic acid (103);

(R)-1-(2-((4′-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)-[1,1′-biphenyl]-4-yl)oxy)acetyl)pyrrolidine-2-carboxylic acid (104);

(R)-1-(((4′-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)-[1,1′-biphenyl]-4-yl)methyl)sulfonyl)pyrrolidine-2-carboxylic acid (105);

2-(4′-(morpholine-4-carbonyl)-[1,1′-biphenyl]-4- yl)-1,6-naphthyridine-4-carbohydrazide (106);

(R)-1-(4′-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)-[1,1′-biphenyl]-4-carbonyl)pyrrolidine-2-carboxylic acid (107);

1-(4′-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)-[1,1′-biphenyl]-4-carbonyl)piperidine-3-carboxylic acid (108);

2-(4′-(5-(morpholine-4-carbonyl)isoxazol-3-yl)-[1,1′-biphenyl]-4-yl)-1,6-naphthyridine-4-carbohydrazide (109);

2-(4′-(morpholinosulfonyl)-[1,1′-biphenyl]-4-yl)-1,6-naphthyridine-4-carbohydrazide (110);

(R)-1-((4′-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)-[1,1′-biphenyl]-4-yl)sulfonyl)pyrrolidine-2-carboxylic acid (111);

1-((4′-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)-[1,1′-biphenyl]-4-yl)sulfonyl)piperidine-3-carboxylic acid (112);

3-(4′-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)-[1,1′-biphenyl]-4-yl)-N-methylisoxazole-5-carboxamide (113);

1-(3-(4′-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)-[1,1′-biphenyl]-4-yl)isoxazole-5-carbonyl)piperidine-3-carboxylic acid (114);

1-(3-(4′-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)-[1,1′-biphenyl]-4-yl)isoxazole-5-carbonyl)piperidine-2-carboxylic acid (115);

N-(4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)phenyl)acetamide (116);

N-(4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)phenyl)methanesulfonamide (117);

2-(4-((4-(morpholine-4-carbonyl)phenyl)ethynyl)phenyl)-1,6-naphthyridine-4-carbohydrazide (118);

(R)-1-((4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)phenyl)sulfonyl)pyrrolidine-2-carboxylic acid (119);

2-(4-((1-(2-hydroxyethyl)-2-oxo-1,2-dihydropyridin-4-yl)ethynyl)phenyl)-1,6-naphthyridine-4-carbohydrazide (120);

N-(2-(4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)-2-oxopyridin-1(2H)-yl)ethyl)acetamide (121);

1-(3-fluoro-4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)benzoyl)piperidine-2-carboxylic acid (122);

1-(4-((2-fluoro-4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)benzoyl)piperidine-2-carboxylic acid (123);

2-(4-((4-(morpholinomethyl)phenyl)ethynyl)phenyl)-1,6-naphthyridine-4-carbohydrazide (124);

2-(4-((4-((2-hydroxyethyl)amino)phenyl)ethynyl)phenyl)-1,6-naphthyridine-4-carbohydrazide (125);

2-(4-(pyridin-3-ylethynyl)phenyl)-1,6-naphthyridine-4-carbohydrazide (126);

3-(2-(4-((4-(morpholinomethyl)phenyl)ethynyl)phenyl)-1,6-naphthyridin-4-yl)-2-thioxoimidazolidin-4-one (127);

4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)-N-methylbenzamide (128);

4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)-N-methylbenzenesulfonamide (129);

(S)-1-(4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)benzoyl)pyrrolidine-2-carboxylic acid (130);

(R)-1-(4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)benzoyl)pyrrolidine-2-carboxylic acid (131);

1-(4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)benzoyl)piperidine-3-carboxylic acid (132);

(−)-1-(4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)benzoyl)piperidine-3-carboxylic acid (133);

(+)-1-(4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)benzoyl)piperidine-3-carboxylic acid (134);

1-(4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)benzoyl)pyrrolidine -3-carboxylic acid (135);

1-(4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)benzoyl)piperidine-4-carboxylic acid (136);

2-(4-((4-(4-methylpiperazine-1-carbonyl)phenyl)ethynyl)phenyl)-1,6-naphthyridine-4-carbohydrazide (137);

4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)-N-(2-hydroxyethyl)benzamide (138);

4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)-N-(3-hydroxypropyl)benzamide (139);

2-(4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)benzamido)acetic acid (140);

(S)-1-((4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)phenyl)sulfonyl)pyrrolidine-2-carboxylic acid (141);

1-((4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)phenyl)sulfonyl)piperidine-3-carboxylic acid (142);

1-((4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)phenyl)sulfonyl)pyrrolidine-3-carboxylic acid (143);

1-((4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)phenyl)sulfonyl)piperidine-4-carboxylic acid (144);

2-(4-((4-(morpholinosulfonyl)phenyl)ethynyl)phenyl)-1,6-naphthyridine-4-carbohydrazide (145);

2-(4-((4-((4-methylpiperazin-1-yl) sulfonyl)phenyl)ethynyl)phenyl)-1,6-naphthyridine-4-carbohydrazide (146);

4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)-N-(2-hydroxyethyl)benzenesulfonamide (147);

4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)-N-(3-hydroxypropyl)benzenesulfonamide (148);

2-(4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)phenylsulfonamido)acetic acid (149);

N-(2-aminoethyl)-4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)benzamide (150);

N-(2-aminoethyl)-4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)benzenesulfonamide (151);

(R)-1-((4-((4-(4-(5-oxo-2-thioxoimidazolidin-1-yl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)phenyl)sulfonyl)pyrrolidine-2-carboxylic acid (152);

(R)-1-((4-((4-(4-(2,5-dioxoimidazolidin-1-yl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)phenyl)sulfonyl)pyrrolidine-2-carboxylic acid (153);

1-(4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-l)phenyl)ethynyl)benzoyl)azetidine-2-carboxylic acid (154);

1-(4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)benzoyl)piperidine-2-carboxylic acid (155);

(−)-1-(4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)benzoyl)piperidine-2-carboxylic acid (156);

(+)-1-(4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)benzoyl)piperidine-2-carboxylic acid (157);

1-((4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)phenyl)sulfonyl)azetidine-2-carboxylic acid (158);

1-((4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)phenyl)sulfonyl)piperidine-2-carboxylic acid (159);

4-(4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)benzoyl)morpholine-3-carboxylic acid (160);

4-(4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)benzoyl)morpholine-2-carboxylic acid (161);

2-(4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)-2-oxopyridin-1(2H)-yl)acetic acid (162);

2-(4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)-2-oxopyridin-1(2H)-yl)-N-methylacetamide (163);

1-(5-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)thiophene-2-carbonyl)piperidine-3-carboxylic acid (164);

1-(5-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)thiophene-2-carbonyl)piperidine-2-carboxylic acid (165);

1-(5-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)furan-2-carbonyl)piperidine-2-carboxylic acid (166);

1-(5-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)furan-2-carbonyl)piperidine-3-carboxylic acid (167);

1-(5-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)picolinoyl)piperidine -2-carboxylic acid (168);

1-(2-fluoro -4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)benzoyl)piperidine-2-carboxylic acid (169);

2-(4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)benzamido)propanoic acid (170);

2-(4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)benzamido)-3-methylbutanoic acid (171);

2-(4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)benzamido)-3-methylpentanoic acid (172);

2-(4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)benzamido)-4-methylpentanoic acid (173);

2-(4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)benzamido)succinic acid (174);

2-(4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)benzamido)pentanedioic acid (175);

2-(4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)benzamido)-3-hydroxypropanoic acid (176);

2-(4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)benzamido)-3-hydroxybutanoic acid (177);

2-(4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)benzamido)-4-(methylthio)butanoic acid (178);

2-(4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)benzamido)-3-phenylpropanoic acid (179);

2-(4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)benzamido)-3-(4-hydroxyphenyl)propanoic acid (180);

4-(4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)benzoyl)thiomorpholine-3-carboxylic acid (181);

2-(4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)benzamido)-2-methylpropanoic acid (182);

N-(4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)phenyl)ethanesulfonamide (183);

N-(4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)phenyl)propane-2-sulfonamide (184);

1,1,1-trifluoro-N-(4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)phenyl)methanesulfonamide (185);

2-(N-(4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)phenyl)sulfamoyl)acetic acid (186);

2-(1-(4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)benzoyl)pyrrolidin-2-yl)acetic acid (187);

2-(1-(4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)benzoyl)piperidin-2-yl)acetic acid (188);

2-(4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)-N-methylbenzamido)acetic acid (189);

2-(4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)-N-methylbenzamido)propanoic acid (190);

3-(4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)benzamido)propanoic acid (191);

3-(4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)-N-methylbenzamido)propanoic acid (192);

3-(4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)benzamido)-2-methylpropanoic acid (193);

3-(4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)benzamido)butanoic acid (194);

3-(4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)-N-methylbenzamido)-2-methylpropanoic acid (195);

3-(4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)-N -methylbenzamido)butanoic acid (196);

3-(4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)benzamido)-2-phenylpropanoic acid (197);

3-(4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)benzamido)-3-phenylpropanoic acid (198);

5-(4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)benzamido)-2-hydroxybenzoic acid (199);

3-(4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)benzamido)benzoic acid (200);

2-(4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)benzamido)malonic acid (201); or

(S)-1-(3-chloro-4-((4-(4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl)phenyl)ethynyl)benzoyl)piperidine-2-carboxylic acid (202);

2-[4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)benzamido]benzoic acid (203);

1-[4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)-3-methoxybenzoyl]piperidine-2-carboxylic acid (204);

1-[4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)-3-hydroxybenzoyl]piperidine-2-carboxylic acid (205);

1-[4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)-3-(trifluoromethyl)benzoyl]piperidine-2-carboxylic acid (206);

1-[4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)benzoyl]-4-hydroxypiperidine-3-carboxylic acid (207);

(2R)-1-[3-fluoro-4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)benzoyl]piperidine-2-carboxylic acid (208);

(2S)-1-[3-fluoro-4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)benzoyl]piperidine-2-carboxylic acid (209);

1-[2,5-difluoro-4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)benzoyl]piperidine-2-carboxylic acid (210);

2-(4-{2-[4-(2-oxo-1,3-oxazolidin-5-yl)phenyl]ethynyl}phenyl)-1,6-naphthyridine-4-carbohydrazide (211);

1-[3-chloro-4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)benzoyl]piperidine-2-carboxylic acid (212);

2-{1-[4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)phenyl]-N-methylformamido}-3-phenylprop anoic acid (213);

2-{[3-fluoro-4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)phenyl]formamido}-3-phenylpropanoic acid (214);

4-[4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)benzamido]-2-hydroxybenzoic acid (215);

2-{1-[3-fluoro-4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)phenyl]-N-methylformamido}-3-phenylpropanoic acid (216);

2-{1-[4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)phenyl]-N-methylformamido}-3-methylpentanoic acid (217);

1-[2,3-difluoro-4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)benzoyl]piperidine-2-carboxylic acid (218);

2-{1-[4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)phenyl]-N-methylformamido}-4-methylpentanoic acid (219);

2-{1-[3-fluoro-4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)phenyl]formamido}-3-methylpentanoic acid (220);

2-{1-[4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)phenyl]-N-methylformamido}-3-methylbutanoic acid (221);

2-{1-[4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)phenyl]-N-methylformamido}pentanedioic acid (222);

N-hydroxy-N-methyl-2-(4-{4-[5-(morpholine-4-carbonyl)-1,2-oxazol-3-yl]phenyl}phenyl)-1,6-naphthyridine-4-carboxamide (223);

2-{1-[3-fluoro-4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)phenyl]-N-methylformamido}-3-methylpentanoic acid (224);

2-{1-[4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)phenyl]-N-methylformamido}butanedioic acid (225);

1-[4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)-2-methoxybenzoyl]piperidine-2-carboxylic acid (226);

1-[2-chloro-4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)benzoyl]piperidine-2-carboxylic acid (227);

1-[4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)-2-(trifluoromethyl)benzoyl]piperidine-2-carboxylic acid (228);

1-[4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)-2-hydroxybenzoyl]piperidine-2-carboxylic acid (229);

1-[6-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)pyridine-3-carbonyl]piperidine-2-carboxylic acid (230);

N-hydroxy-2-(4-{4-[5-(methanesulfonamidomethyl)-1,2-oxazol-3-yl]phenyl}phenyl)-N-methyl-1,6-naphthyridine-4-carboxamide (231);

2-{1-[3-chloro-4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)phenyl]formamido}-3-phenylpropanoic acid (232);

2-[4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)benzenesulfonamido]-3-phenylpropanoic acid (233);

2-[N-methyl4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)benzenesulfonamido]-3-phenylpropanoic acid (234);

1-[3 ,5-difluoro-4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)benzoyl]piperidine-2-carboxylic acid (235);

2-{1-[3-chloro-4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)phenyl]formamido}-3-methylpentanoic acid (236);

2-{N-ethyl-1-[4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)phenyl]formamido}acetic acid (237);

2-{1-[4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)phenyl]-N-propylformamido}acetic acid (238);

2-[4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)benzenesulfonamido]-3-methylpentanoic acid (239);

3-methyl-2-[N-methyl4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)benzenesulfonamido]pentanoic acid (240);

2-{N-benzyl-1-[4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)phenyl]formamido}acetic acid (241);

N-hydroxy-N-methyl-2-{4-[2-(6-trifluoromethanesulfonamidopyridin-3-yl)ethynyl]phenyl}-1,6-naphthyridine-4-carboxamide (242);

2-{1-[4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)phenyl]-N-(propan-2-yl)formamido}acetic acid (243);

2-{1-[4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)phenyl]-N-(2-methylpropyl)formamido}acetic acid (244);

N-hydroxy-N-methyl-2-{4-[2-(4-trifluoromethanesulfonamidophenyl)ethynyl]phenyl}-1,6-naphthyridine-4-carboxamide (245);

2-[3-fluoro-4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)benzenesulfonamido]-3-methylpentanoic acid (246);

2-{N-benzyl-1-[4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)phenyl]formamido}-3-phenylpropanoic acid (247);

3-methyl-2-[N-methyl3-fluoro-4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)benzenesulfonamido]pentanoic acid (248);

(2R)-1-[3-fluoro-4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)benzenesulfonyl]piperidine-2-carboxylic acid (249);

(2S)-1-[3-fluoro-4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)benzenesulfonyl]piperidine-2-carboxylic acid (250);

2-[3-fluoro-4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)benzenesulfonamido]-3-phenylpropanoic acid (251);

2-[N-methyl3-fluoro-4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)benzenesulfonamido]-3-phenylpropanoic acid (252);

1-[4-(2-{5-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]pyridin-2-yl}ethynyl)benzoyl]piperidine-2-carboxylic acid (253);

1-[3-fluoro-4-(2-{2-fluoro-4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)benzoyl]piperidine-2-carboxylic acid (254);

2-{N-ethyl-1-[4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)phenyl]formamido}-3-phenylpropanoic acid (255);

2-{1-[4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)phenyl]-N-(propan-2-yl)formamido}-3-phenylpropanoic acid (256);

1-{3-fluoro-4-[2-(4-{4-[hydroxy(methyl)carbamoyl]-1,6-naphthyridin-2-yl}phenyl)ethynyl]benzoyl}piperidine-2-carboxylic acid (257);

(2R)-1-{[5-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)pyridin-2-yl]methyl}pyrrolidine-2-carboxylic acid (258);

2-{1-[4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)phenyl]-N-(2-methylpropyl)formamido}-3-phenylpropanoic acid (259);

(2R)-1-[3-chloro-4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)benzenesulfonyl]piperidine-2-carboxylic acid (260);

(2S)-1-[3-chloro-4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)benzenesulfonyl]piperidine-2-carboxylic acid (261);

2-amino-3-{1-[3-chloro-4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)phenyl]formamido}propanoic acid (262);

2-{1-[4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)phenyl]-N-propylformamido}-3-phenylpropanoic acid (263);

1-[4-(2-{2-chloro-4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)benzoyl]piperidine-2-carboxylic acid (264);

1-[3-fluoro-4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)benzoyl]piperidine-3-carboxylic acid (265);

(2R)-1-[3-fluoro-4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)benzoyl]pyrrolidine-2-carboxylic acid (266);

1-[3-chloro-4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)benzoyl]piperidine-3-carboxylic acid (267);

(2R)-1-[3-chloro-4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)benzoyl]pyrrolidine-2-carboxylic acid (268);

1-[3-fluoro-4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)benzenesulfonyl]piperidine-3-carboxylic acid (269);

(2R)-1-[3-fluoro-4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)benzenesulfonyl]pyrrolidine-2-carboxylic acid (270);

2-{1-[3-chloro-4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)phenyl]-N-(2-methylpropyl)formamido}acetic acid (271);

2-{1-[3-fluoro-4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)phenyl]-N-(2-methylpropyl)formamido}acetic acid (272);

2-[N-(2-methylpropyl)3-chloro-4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)benzenesulfonamido]acetic acid (273);

2-[N-(2-methylpropyl)3-fluoro-4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)benzenesulfonamido]acetic acid (274);

1-[3-chloro-4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)benzenesulfonyl]piperidine-3-carboxylic acid (275);

(2R)-1-[3-chloro-4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)benzenesulfonyl]pyrrolidine-2-carboxylic acid (276);

2-amino-3-[4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)phenoxy]propanoic acid (277);

1-[4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]-2-methoxyphenyl}ethynyl)benzoyl]piperidine-2-carboxylic acid (278);

2-{1-[4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)phenyl]-N-(2-methylpropyl)formamido}propanoic acid (279);

1-[4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]-2-hydroxyphenyl}ethynyl)benzoyl]piperidine-2-carboxylic acid (280);

2-[4-(2-{4-[(2S)-2-carboxypiperidine-1-carbonyl]-2-chlorophenyl}ethynyl)phenyl]-1,6-naphthyridine-4-carboxylic acid (281);

2-{1-[3-fluoro-4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)phenyl]-N-(2-methylpropyl)formamido}propanoic acid (282);

2-amino-3-{1-[3-chloro-4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)phenyl]-N-methylformamido}propanoic acid (283);

2-{1-[3-chloro-4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)phenyl]-N-(2-methylpropyl)formamido}propanoic acid (284);

2-{1-[4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)phenyl]-N-(2-methylpropyl)formamido}-3-hydroxyprop anoic acid (285);

2-[4-(2-{2-chloro-4-[(2S)-2-(hydrazinecarbonyl)piperidine-1-carbonyl]phenyl}ethynyl)phenyl]-1,6-naphthyridine-4-carbohydrazide (286);

2-[4-(2-{2-chloro-4-[(2S)-2-(hydrazinecarbonyl)piperidine-1-carbonyl]phenyl}ethynyl)phenyl]-1,6-naphthyridine-4-carboxylic acid (287);

(2S)-1-[3-chloro-4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)benzoyl]-N-hydroxypiperidine-2-carboxamide (288);

2-{1-[4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)phenyl]formamido}-3-(1H-imidazol-4-yl)propanoic acid (289);

2-{1-[4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)phenyl]-N-(2-methylpropyl)formamido}-3-(4-hydroxyphenyl)propanoic acid (290);

methyl 2-{1-[4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)phenyl]formamido}-3-(1H-imidazol-4-yl)propanoate (291);

2-{1-[3-fluoro-4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)phenyl]-N-(2-methylpropyl)formamido}-3-hydroxypropanoic acid (292);

2-{1-[3-fluoro-4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)phenyl]-N-(2-methylpropyl)formamido}-3-hydroxypropanoic acid (293);

2-{1-[3-fluoro-4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)phenyl]-N-(2-methylpropyl)formamido}-3-hydroxypropanoic acid (294);

methyl 2-{1-[3-chloro-4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)phenyl]formamido}-3-(1H-imidazol-4-yl)propanoate (295);

methyl 2-{1-[3-fluoro-4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)phenyl]formamido}-3-(1H-imidazol-4-yl)propanoate (296);

3-amino-2-{1-[4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)phenyl]formamido}propanoic acid (297);

3-amino-2-{1-[3-chloro-4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)phenyl]formamido}propanoic acid (298);

3-amino-2-{1-[3-fluoro-4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)phenyl]formamido}propanoic acid (299);

(2S)-1-[3-chloro-4-(2-{4-[7-chloro-4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)benzoyl]piperidine-2-carboxylic acid (300);

3-amino-2-{1-[4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)phenyl]-N-(2-methylpropyl)formamido}propanoic acid (301);

3-amino-2-{1-[3-chloro-4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)phenyl]-N-(2-methylpropyl)formamido}propanoic acid (302);

3-amino-2-{1-[3-fluoro-4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)phenyl]-N-(2-methylpropyl)formamido}propanoic acid (303);

2-{4-[2-(4-{1,3-dioxo-octahydroimidazolidino[1,5-a]pyridin-2-yl}phenyl)ethynyl]phenyl}-1,6-naphthyridine-4-carbohydrazide (304);

3-amino-2-{1-[4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)phenyl]-N-methylformamido}propanoic acid (305);

(2S)-1-[4-(2-{4-[7-amino-4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)-3-chlorobenzoyl]piperidine-2-carboxylic acid (306);

3-amino-2-{1-[3-fluoro-4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)phenyl]-N-methylformamido}propanoic acid (307);

1-[4-(2-{5-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]thiophen-2-yl}ethynyl)benzoyl]piperidine-2-carboxylic acid (308);

(2S)-1-[3-chloro-4-(2-{4-[4-(hydrazinecarbonyl)-7-methanesulfonamido-1,6-naphthyridin-2-yl]phenyl}ethynyl)benzoyl]piperidine-2-carboxylic acid (309);

(2S)-1-[3-chloro-4-(2-{4-[4-(hydrazinecarbonyl)-7-methoxy-1,6-naphthyridin-2-yl]phenyl}ethynyl)benzoyl]piperidine-2-carboxylic acid (310);

2-(4-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}buta-1,3-diyn-1-yl)cyclopropane-1-carboxylic acid (311);

(2S)-1-[3-chloro-4-(2-{4-[7-acetamido-4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)benzoyl]piperidine-2-carboxylic acid (312);

(2S)-1-[3-chloro-4-(2-{4-[4-(hydrazinecarbonyl)-7-(morpholin-4-yl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)benzoyl]piperidine-2-carboxylic acid (313);

1-[2-(4-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}buta-1,3-diyn-1-yl)cyclopropanecarbonyl]piperidine-2-carboxylic acid (314);

(2S)-1-[4-(2-{4-[7-(2-carboxyacetamido)-4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)-3-chlorobenzoyl]piperidine-2-carboxylic acid (315);

(2S)-1-[4-(2-{4-[7-carboxymethanesulfonamido-4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)-3-chlorobenzoyl]piperidine-2-carboxylic acid (316);

1-{[4-(2-{4-[4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)phenyl]carbamoyl}piperidine-2-carboxylic acid (317);

(2S)-1-[3-chloro-4-(2-{4-[4-(hydrazinecarbonyl)-7-(3-methoxypyrrolidin-1-yl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)benzoyl]piperidine-2-carboxylic acid (318);

4-(hydrazinecarbonyl)-2-{4-[4-(4-hydroxybutoxy)phenyl]phenyl}-1,6-naphthyridine-7-carboxylic acid (319);

N-[2-(4-{2-[2-chloro-4-(morpholine-4-carbonyl)phenyl]ethynyl}phenyl)-4-(hydrazinecarbonyl)-1,6-naphthyridin-7-yl]methanesulfonamide (320);

(2S)-1-[4-(2-{4-[7-(2-aminoacetamido)-4-(hydrazinecarbonyl)-1,6-naphthyridin-2-yl]phenyl}ethynyl)-3-chlorobenzoyl]piperidine-2-carboxylic acid (321);

2-{[2-(4-{2-[2-chloro-4-(morpholine-4-carbonyl)phenyl]ethynyl}phenyl)-4-(hydrazinecarbonyl)-1,6-naphthyridin-7-yl]sulfamoyl}acetic acid (322);

(2R)-1-[4-(hydrazinecarbonyl)-2-{4-[4-(4-hydroxybutoxy)phenyl]phenyl}-1,6-naphthyridine-7-carbonyl]pyrrolidine-2-carboxylic acid (323);

(2S)-1-[4-(hydrazinecarbonyl)-2-{4-[4-(4-hydroxybutoxy)phenyl]phenyl}-1,6-naphthyridine-7-carbonyl]pyrrolidine-2-carboxylic acid (324);

N-[4-(hydrazinecarbonyl)-2-{4-[4-(4-hydroxybutoxy)phenyl]phenyl}-1,6-naphthyridin-7-yl]methanesulfonamide (325);

2-{[4-(hydrazinecarbonyl)-2-{4-[4-(4-hydroxybutoxy)phenyl]phenyl}-1,6-naphthyridin-7-yl]sulfamoyl}acetic acid (326);

N-[4-(hydrazinecarbonyl)-2-(4-{4-[5-(hydroxymethyl)-1,2-oxazol-3-yl]phenyl}phenyl)-1,6-naphthyridin-7-yl]methanesulfonamide (327);

2-{1-[4-(hydrazinecarbonyl)-2-(4-{4-[5-(hydroxymethyl)-1,2-oxazol-3-yl]phenyl}phenyl)-1,6-naphthyridin-7-yl]sulfamoyl}acetic acid (328);

N-[2-(4-{2-[2-chloro-4-(morpholine-4-carbonyl)phenyl]ethynyl}phenyl)-4-(hydrazinecarbonyl)-1,6-naphthyridin-7-yl]-N-methylmethanesulfonamide (329); or

2-{[2-(4-{2-[2-chloro-4-(morpholine-4-carbonyl)phenyl]ethynyl}phenyl)-4-(hydrazinecarbonyl)-1,6-naphthyridin-7-yl](methyl)sulfamoyl}acetic acid (330);

or salt thereof.

18. A method of treating a subject suffering from or susceptible to a disorder or disease, comprising administering to the subject an effective amount of a compound of claim 1 , wherein the disease or disorder is bacterial infection.

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

20. The composition of claim 19 further comprising an additional therapeutic agent.

21. The method of claim 18 , wherein the bacterial infection is gram-negative bacterial infection.

22. A compound of formula (I), (II), (III), (IV), or salt thereof, wherein:

U is O or S;

each X is independently O; S; NR 4 ; or H and R 4 ;

each R 1 is independently selected from:

b) heteroaryl optionally substituted with alkoxy wherein alkoxy is optionally substituted with 1, 2, or 3 OR 4 ; c) C≡C—R 13 ; d) C(═O)NR 4 R 7 ; e) N(R 7 )C(═O)R 4 ; f) SO 2 NR 4 R 7 ; g) N(R 7 )S0 2 R 4 ; h) hydrogen; i) hydroxy; j) optionally substituted alkoxy; k) SO 2 NHR 4 ; l) optionally substituted alkenyl; m) optionally substituted arylalkyl; or n) C≡C—C≡C—R 13 ;

each R 8 , R 9 , R 10 , R 11 , and R 12 is independently selected from:

(1) C(═O)OR 17 ;

(2) heterocycloalkylcarbonyl optionally substituted with 1, 2, or 3 independent C(═O)OR 17 ,C(═O)NR 4 R 7 , or SO 2 NR 4 R 7 ;

(3) alkyl optionally substituted with 1, 2, or 3 independent OC(═O)NHR 4 , NHC(═O)NHR 4 , NHSO 2 R 4 , hydroxy, or C(═O)NHR 4 ; or

(4) C(═O)NHR 4 ;

q) mercapto; r) thioalkoxy; s) alkylamino; t) alkyl optionally substituted with 1, 2, or 3 independent heterocycloalkylcarbonyl, heterocycloalkyl, or heterocycloalkylsulfonyl, each optionally substituted with independent C(═O)OR 4 , C(═O)NR 4 R 7 , or SO 2 NR 4 R 7 ; u) dialkylamino; or v) —O—(CH 2 ) n —C(═O)-heterocycloalkyl optionally substituted with 1, 2, or 3 independent C(═O)OR 4 , C(═O)NR 4 R 7 , or SO 2 NR 4 R 7 ;

R 2 is H, alkyl, fluoroalkyl, alkoxy, fluoroalkoxy, halogen, aryl, or heteroaryl;

R 3 is CH(R 4 )NHR 4 , CH(R 4 )NHSO 2 R 4 , CH(R 4 )SH, CH(R 4 )OH, CH(R 4 )CO 2 R 4 , CH(R 4 )CONHR 4 ; CH(R 4 )CONHOH; CH(R 4 )CONHNHR 4 ; C(═O)R 4 , CO 2 R 4 , C(═O)NHR 4 , C(═O)NHNHR 4 , C(═S)NHR 4 , C(═S)NHNHR 4 , C≡N, C(═NH)NH 2 , NHC(═NH)NH 2 , N(OH)C(═O)R 4 , NHR 4 , NHNHR 4 , NHC(═O)R 4 , N(R 4 )NHC(═O)R 4 , NHC(═O)NHR 4 , NHC(═S)NHR 4 , NHSO 2 R 4 , NHSO 2 NHR 4 ; NHNHSO 2 R 4 , NO 2 , SO 2 NHR 4 (only in the case of formula I), SO 2 NHOH (only in the case of formula I), SO 3 H (only in the case of formula I), OR 4 , OSO 2 R 4 , OSO 2 NHR 4 , SR 4 , B(OR 4 ) 2 , CH 2 B(OR 4 ) 2 , P(═O)OH, P(═O) 2 OH, Se(═O)OH, Se(═O) 2 OH, a heterocycle that is preferably a 5-membered ring with 1-4 heteroatoms, or a 5-membered heterocycle that is connected through a CH 2 ;

Y is O or null;

Z is N;

each R 5 is independently H, alkyl, fluoroalkyl, halogen, alkoxy, fluoroalkoxy, substituted amino, aryl, or heteroaryl;

A is O, S, CH 2 or N(R 4 );

A may also be the following when R 6 is null: an optionally substituted heterocycle that is preferably a 5-membered ring with 1-4 heteroatoms, B(OR 4 ) 2 , P(═O) 2 OH, Se(═O)OH, Se(═O) 2 OH;

each R 13 is independently selected from:

b) heterocycloalkyl optionally substituted with 1, 2, or 3 independent alkyl wherein alkyl is optionally substituted with independent:

i) OR 4 ;

ii) NHC(═O)R 4 ;

iii) C(═O)OR 4 ; or

iv) C(═O)NHR 4 ;

d) cycloalkyl optionally substituted with 1, 2, or 3 independent C(═O)OR 4 , C(═O)NR 4 R 7 , hydroxyalkyl, or SO 2 NR 4 R 7 ;

each R 15 is independently H; alkyl; fluoroalkyl; aryl; arylalkyl; or heteroaryl;

each R 22 , R 23 , R 24 , R 25 , and R 26 is independently selected from

each n is independently 0, 1, 2, 3, or 4; and

Q 1 and Q 2 are each independently CH or N.

Assignments (3)

CHANGE OF NAME Recorded Jan 2, 2018

From: VIAMET PHARMACEUTICALS, INC.

To: VIAMET PHARMACEUTICALS (NC), INC.

Reel/Frame 044978/0893 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 2, 2018

From: VIAMET PHARMACEUTICALS (NC), INC.

To: VPS-3, INC.

Reel/Frame 044980/0541 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 3, 2015

From: HOEKSTRA, WILLIAM J.; YATES, CHRISTOPHER M.; RAFFERTY, STEPHEN W.

To: VIAMET PHARMACEUTICALS, INC.

Reel/Frame 036944/0034 →

Continuity (2)

Provisional Application 61757594 · Jan 28, 2013

Related Publication 20150353546A1 · Dec 10, 2015