IP Library Granted Patent US 8,951,536
Granted Patent B2
US 8,951,536 · App. 13/780,510 · Granted Feb 10, 2015

N-hydroxyamidinoheterocycles as modulators of indoleamine 2,3-dioxygenase

Inventors: Andrew P. Combs (Kennett Square, PA); Amy Takvorian (Newnan, GA); Wenyu Zhu (Media, PA); Richard B. Sparks (Wilmington, DE)
Assignee: Incyte Corporation
A61K31/541C07D271/08C07D285/06C07D413/06C07D413/12C07D413/14C07D417/06C07D417/12A61K31/4245A61K31/427A61K31/433A61K31/4439A61K31/454A61K31/4725A61K31/496A61K31/5377A61K45/06
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Quick Facts
Patent No.
US 8,951,536
App. No.
13/780,510
Granted
Feb 10, 2015
Kind
B2
Abstract

The present invention is directed to N-hydroxyamidino compounds which are modulators of indoleamine 2,3-dioxygenase (IDO), as well as pharmaceutical compositions thereof and methods of use thereof relating to the treatment of cancer and other diseases.

Claims (298)

1. A method of inhibiting immunosuppression or treating a cancer selected from melanoma, ovarian cancer, and breast cancer, in a patient comprising administering to said patient an effective amount of a compound of Formula Ia:

or a pharmaceutically acceptable salt thereof, wherein:

U is N;

V is O;

W is N, wherein the five-membered ring containing U, V, and W is an aromatic heterocycle;

A is aryl, or heteroaryl, each optionally substituted by 1, 2, 3, 4, or 5 substituents independently selected from halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 cyanoalkyl, Cy 1 , CN, NO 2 , OR a , SR a , C(O)R b , C(O)NR c R d , C(O)OR a , OC(O)R b , OC(O)NR c R d , NR c R d , NR c C(O)R b , NR c C(O)NR c R d , NR c C(O)OR a , C(═NR i )NR c R d , NR c C(═NR i )NR c R d , P(R f ) 2 , P(OR e ) 2 , P(O)R e R f , P(O)OR e OR f , S(O)R b , S(O)NR c R d , S(O) 2 R b , NR c S(O) 2 R b , and S(O) 2 NR c R d , wherein said C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl is optionally substituted with 1, 2, or 3 substitutents independently selected from Cy 1 , CN, NO 2 , OR a , SR a , C(O)R b , C(O)NR c R d , C(O)OR a , OC(O)R b , OC(O)NR c R d , NR c R d , NR c C(O)R b , NR c C(O)NR c R d , NR c C(O)OR a , C(═NR i )NR c R d , NR c C(═NR i )NR c R d , P(R f ) 2 , P(OR e ) 2 , P(O)R e R f , P(O)OR e OR f , S(O)R b , S(O)NR c R d , S(O) 2 R b , NR c S(O) 2 R b , and S(O) 2 NR c R d ;

R is H;

R A and R B are each H;

Q is OR Q , OC(O)R Q , OC(O)NR 4 R Q , NR 4 R Q , NR 4 C(O)R Q , NR 4 C(O)NR 4 R Q , NR 4 C(O)OR Q , NR 4 S(O)R Q , NR 4 S(O) 2 R Q , NR 4 C(═NR i )NR 4 R Q , SR Q , S(O)R Q , S(O)NR 4 R Q , S(O) 2 R Q , S(O) 2 NR 4 R Q , C(O)R Q , C(O)OR Q , C(O)NR 4 R Q , halo, cyano, azido, or nitro;

R Q is H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, cycloalkylalkyl, heteroarylalkyl, or heterocycloalkylalkyl, wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, cycloalkylalkyl, heteroarylalkyl, or heterocycloalkylalkyl is optionally substituted by 1, 2, 3, 4, or 5 substituents independently selected from halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 cyanoalkyl, halosulfanyl, Cy, —(C 1-4 alkyl)-Cy, CN, NO 2 , OR a2 , SR a2 , C(O)R b2 , C(O)NR c2 R d2 , C(O)OR a2 , OC(O)R b2 , OC(O)NR c2 R d2 , NR c2 R d2 , NR c2 C(O)R b2 , NR c2 C(O)NR c2 R d2 , NR c2 C(O)OR a2 , C(═NR i )NR c2 R d2 , NR c2 C(═NR i )NR c2 R d2 , P(R f2 ) 2 , P(OR e2 ) 2 , P(O)R e2 R f2 , P(O)OR e2 OR f2 , S(O)R b2 , S(O)NR c2 R d2 , S(O) 2 R b2 , NR c2 S(O) 2 R b2 , and S(O) 2 NR c2 R d2 ;

or R 4 and R Q together with the N atom to which they are attached form a 4-20 membered heterocycloalkyl group or 5-20 membered heteroaryl group, each optionally substituted by 1, 2, 3, 4, or 5 substituents independently selected from halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 cyanoalkyl, halosulfanyl, Cy, —(C 1-4 alkyl)-Cy, CN, NO 2 , OR a2 , —(C 1-4 alkyl)-OR a2 , SR a2 , —(C 1-4 alkyl)-SR a2 , C(O)R b2 , —(C 1-4 alkyl)-C(O)R b2 , C(O)NR c2 R d2 , —(C 1-4 alkyl)-C(O)NR c2 R d2 , C(O)OR a2 , —(C 1-4 alkyl)-C(O)OR a2 , OC(O)R b2 , —(C 1-4 alkyl)-OC(O)R b2 , OC(O)NR c2 R d2 , —(C 1-4 alkyl)-OC(O)NR c2 R d2 , NR c2 R d2 , —(C 1-4 alkyl)-NR c2 R d2 , NR c2 C(O)R b2 , —(C 1-4 alkyl)-NR c2 C(O)R b2 , NR c2 C(O)NR c2 R d2 , —(C 1-4 alkyl)-NR c2 C(O)NR c2 R d2 , NR c2 C(O)OR a2 , —(C 1-4 alkyl)-NR c2 C(O)OR a2 , C(═NR i )NR c2 R d2 , NR c2 C(═NR i )NR c2 R d2 , P(R f2 ) 2 , P(OR e2 ) 2 , P(O)R e2 R f2 , P(O)OR e2 OR f2 , S(O)R b2 , —(C 1-4 alkyl)-S(O)R b2 , S(O)NR c2 R d2 , —(C 1-4 alkyl)-S(O)NR c2 R d2 , S(O) 2 R b2 , —(C 1-4 alkyl)-S(O) 2 R b2 , NR c2 S(O) 2 R b2 , —(C 1-4 alkyl)-NR c2 S(O) 2 R b2 , S(O) 2 NR c2 R d2 , and —(C 1-4 alkyl)-S(O) 2 NR c2 R d2 ;

Cy, Cy 1 , and Cy 2 are independently selected from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, each optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from halo, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 haloalkyl, halosulfanyl, CN, NO 2 , OR a3 , SR a3 , C(O)R b3 , C(O)NR c3 R d3 , C(O)OR a3 , OC(O)R b3 , OC(O)NR c3 R d3 , NR c3 R d3 , NR c3 C(O)R b3 , NR c3 C(O)OR a3 , C(═NR i )NR c3 R d3 , NR c3 C(═NR i )NR c3 R d3 , P(R f3 ) 2 , P(OR e3 ) 2 , P(O)R e3 R f3 , P(O)OR e3 OR f3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , and S(O) 2 NR c3 R d3 ;

R 1 is H or C 1-4 alkyl;

R 4 is H, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C(O)—R 4a , SO 2 —R 4a , aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, cycloalkylalkyl, heteroarylalkyl, or heterocycloalkylalkyl, wherein said C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, cycloalkylalkyl, heteroarylalkyl, or heterocycloalkylalkyl is optionally substituted by 1, 2, 3, 4, or 5 substituents independently selected from halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 cyanoalkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, halosulfanyl, CN, NO 2 , OR a4 , SR a4 , C(O)R b4 , C(O)NR c4 R d4 , C(O)OR a4 , OC(O)R b4 , OC(O)NR c4 R d4 , NR c4 R d4 , NR c4 C(O)R b4 , NR c4 C(O)NR c4 R d4 , NR c4 C(O)OR a4 , C(═NR i )NR c4 R d4 , NR c4 C(═NR i )NR c4 R d4 , P(R f4 ) 2 , P(OR e4 ) 2 , P(O)R e4 R f4 , P(O)OR e4 OR f4 , S(O)R b4 , S(O)NR c4 R d4 , S(O) 2 R b4 , NR c4 S(O) 2 R b4 , and S(O) 2 NR c4 R d4 ;

R 4a is H, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, cycloalkylalkyl, heteroarylalkyl, or heterocycloalkylalkyl;

R a , R a3 , R a4 , and R a5 are independently selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl, wherein said C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl or heterocycloalkylalkyl is optionally substituted with OH, amino, halo, C 1-6 alkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, or heterocycloalkyl;

R b , R b3 , R b4 , and R b5 are independently selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl, wherein said C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl is optionally substituted with OH, amino, halo, C 1-6 alkyl, C 1-6 haloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, or heterocycloalkyl;

R a2 is H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, Cy 2 , or Cy 2 -(C 1-6 alkyl)-, wherein said C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, or C 2-6 alkynyl, is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 cyanoalkyl, halosulfanyl, Cy 2 , CN, NO 2 , OR a5 , SR a5 , C(O)R b5 , C(O)NR c5 R d5 , C(O)OR a5 , OC(O)R b5 , OC(O)NR c5 R d5 , NR c5 R d5 , NR c5 C(O)R b5 , NR c5 C(O)NR c5 R d5 , NR c5 C(O)OR a5 , C(═NR i )NR c5 R d5 , NR c5 C(═NR i )NR c5 R d5 , P(R f5 ) 2 , P(OR e5 ) 2 , P(O)R e5 R f5 , P(O)OR e5 OR f5 , S(O)R b5 , S(O)NR c5 R d5 , R b2 , S(O) 2 R b5 , NR c5 S(O) 2 R b5 , and S(O) 2 NR c5 R d5 ;

R b2 is H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, Cy 2 , or Cy 2 -(C 1-6 alkyl)-, wherein said C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, or aryl is optionally substituted with 1,2, 3,4, or 5 substituents independently selected from halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 cyanoalkyl, halosulfanyl, Cy 2 , CN, NO 2 , OR a5 , SR a5 , C(O)R b5 , C(O)NR c5 R d5 , C(O)OR a5 , OC(O)R b5 , OC(O)NR c5 R d5 , NR c5 R d5 , NR c5 C(O)R b5 , NR c5 C(O)NR c c5 R d5 , NR c5 C(O)OR a5 , C(═NR i )NR c5 R d5 , NR c5 C(═NR i )NR c5 R d5 , P(R f5 ) 2 , P(OR e5 ) 2 , P(O)R e5 R f5 , P(O)OR e5 OR f5 , S(O)R b5 , S(O)NR c5 R d5 , S(O) 2 R b5 , NR c5 S(O) 2 R b5 , and S(O) 2 NR c5 R d5 ;

R c and R d are independently selected from H, C 1-10 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl, wherein said C 1-10 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl is optionally substituted with OH, amino, halo, C 1-6 alkyl, C 1-6 haloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, or heterocycloalkyl;

or R c and R d together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group;

R c2 and R d2 are independently selected from H, C 1-10 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, Cy 2 and Cy 2 -(C 1-6 alkyl)-, wherein said C 1-10 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, and C 2-6 alkynyl, is optionally substituted with 1, 2, or 3, substitutents independently selected from halo, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 haloalkyl, halosulfanyl, CN, NO 2 , OR a3 , SR a3 , C(O)R b3 , C(O)NR c 3 R d3 , C(O)OR a3 , OC(O)R b3 , OC(O)NR c3 R d3 , NR c3 R d3 , NR c3 C(O)R b3 , NR c3 C(O)OR a3 , C(═NR i )NR c3 R d3 , NR c3 C(═NR i )NR c3 R d3 , P(R f3 ) 2 , P(OR e3 ) 2 , P(O)R e3 R f3 , P(O)OR e3 OR f3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , and S(O) 2 NR c3 R d3 ;

or R c2 and R d2 together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3, substitutents independently selected from Cy 2 , Cy 2 -(C 1-6 alkyl)-, halo, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 haloalkyl, halosulfanyl, CN, NO 2 , OR a3 , SR a3 , C(O)R b3 , C(O)NR c3 R d3 , C(O)OR a3 , OC(O)R b3 , OC(O)NR c3 R d3 , NR c3 R d3 , NR c3 C(O)R b3 , NR c3 C(O)OR a3 , C(═NR i )NR c3 R d3 , NR c3 C(═NR i )NR c3 R d3 , P(R f3 ) 2 , P(OR e3 ) 2 , P(O)R e3 R f3 , P(O)OR e3 OR f3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , and S(O) 2 NR c3 R d3 ;

R c3 and R d3 are independently selected from H, C 1-10 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl, wherein said C 1-10 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl is optionally substituted with OH, amino, halo, C 1-6 alkyl, C 1-6 haloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, or heterocycloalkyl;

or R c3 and R d3 together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group;

R c4 and R d4 are independently selected from H, C 1-10 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl, wherein said C 1-10 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl is optionally substituted with OH, amino, halo, C 1-6 alkyl, C 1-6 haloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, or heterocycloalkyl;

or R c4 and R d4 together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group;

R c5 and R d5 are independently selected from H, C 1-10 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl, wherein said C 1-10 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl is optionally substituted with OH, amino, halo, C 1-6 alkyl, C 1-6 haloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, or heterocycloalkyl;

or R c5 and R d5 together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group;

R e , R e2 , R e3 , R e4 , and R e5 are independently selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, (C 1-6 alkoxy)-C 1-6 alkyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, cycloalkylalkyl, heteroarylalkyl, and heterocycloalkylalkyl;

R f , R f2 , R f3 , R f4 , and R f5 are independently selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl, and heterocycloalkyl;

R i is H, CN, C(O)NH 2 , or NO 2 ; and

p is 1, 2, 3, 4, 5.

2. The method of claim 1 , wherein A is phenyl optionally substituted by 1, 2, 3, 4, or 5 substituents selected from halo, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 cyanoalkyl, CN, NO 2 , OR a , SR a , C(O)R b , C(O)NR c R d , C(O)OR a , OC(O)R b , OC(O)NR c R d , NR c R d , NR c C(O)R b , NR c C(O)NR c R d , NR c C(O)OR a , S(O)R b , S(O)NR c R d , S(O) 2 R b , NR c S(O) 2 R b , and S(O) 2 NR c R d .

3. The method of claim 1 , wherein A is phenyl optionally substituted by 1, 2, 3, 4, or 5 substituents selected from halo, C 1-6 alkyl, and C 1-6 haloalkyl.

4. The method of claim 1 , wherein Q is OR Q .

5. The method of claim 1 , wherein Q is NR 4 R Q .

6. The method of claim 1 , wherein R Q is C 1-6 alkyl optionally substituted by 1, 2, 3, 4, or 5 substituents selected from halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 cyanoalkyl, Cy, —(C 1-4 alkyl)-Cy, CN, NO 2 , OR a2 , SR a2 , C(O)R b2 , C(O)NR c2 R d2 , C(O)OR a2 , OC(O)R b2 , OC(O)NR c2 R d2 , NR c2 R d2 , NR c2 C(O)R b2 , NR c2 C(O)NR c2 R d2 , NR c2 C(O)OR a2 , C(═NR i )NR c2 R d2 , NR c2 C(═NR i )NR c2 R d2 , P(R f2 ) 2 , P(OR e2 ) 2 , P(O)R e2 R f2 , P(O)OR e2 OR f2 , S(O)R b2 , S(O)NR c2 R d2 , S(O) 2 R b2 , NR c2 S(O) 2 R b2 , and S(O) 2 NR c2 R d2 .

7. The method of claim 1 , wherein R Q is aryl, heteroaryl, arylalkyl, or heteroarylalkyl, each optionally substituted by 1, 2, 3, 4, or 5 substituents selected from halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, C 1-6 cyanoalkyl, Cy, —(C 1-4 alkyl)-Cy, CN, NO 2 , OR a2 , SR a2 , C(O)R b2 , C(O)NR c2 R d2 , C(O)OR a2 , OC(O)R b2 , OC(O)NR c2 R d2 , NR c2 R d2 , NR c2 C(O)R b2 , NR c2 C(O)NR c2 R d2 , NR c2 C(O)OR a2 , C(═NR i )NR c2 R d2 , NR c2 C(═NR i )NR c2 R d2 , P(R f2 ) 2 , P(OR e2 ) 2 , P(O)R e2 R f2 , P(O)OR e2 OR f2 , S(O)R b2 , S(O)NR c2 R d2 , S(O) 2 R b2 , NR c2 S(O) 2 R b2 , and S(O) 2 NR c2 R d2 .

8. The method of claim 1 , wherein R 4 is H.

9. The method of claim 1 , wherein R 1 is H.

10. The method of claim 1 , wherein the compound is a compound having Formula II:

or pharmaceutically acceptable salt thereof.

11. The method of claim 1 , wherein the compound is selected from:

N-(3-chloro-4-fluoro-phenyl)-N′-hydroxy-4-hydroxymethyl-furazan-3-carboxamidine;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-(phenoxymethyl)-1,2,5-oxadiazole-3-carboximidamide;

4-[(E/Z)-[(3-chloro-4-fluorophenyl)amino](hydroxyimino)methyl]-1,2,5-oxadiazol-3-ylmethyl phenylcarbamate;

4-[(benzylamino)methyl]-N-(3-chloro-4-fluorophenyl)-N-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-4-[(2-chlorophenoxy)methyl]-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-4-[(3-chlorophenoxy)methyl]-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-4-[(4-chlorophenoxy)methyl]-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-[(2-methoxyphenoxy)methyl]-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-[(3-methoxyphenoxy)methyl]-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-[(4-methoxyphenoxy)methyl]-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-4-[(3-cyanophenoxy)methyl]-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-4-[(4-chloro-2-methoxyphenoxy)methyl]-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-4-[(3,4-dimethoxyphenoxy)methyl]-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

{4-[(E/Z)-[(3-chloro-4-fluorophenyl)amino](hydroxyimino)methyl]-1,2,5-oxadiazol-3-yl}methyl phenylcarbamate;

{4-[(E/Z)-[(3-chloro-4-fluorophenyl)amino](hydroxyimino)methyl]-1,2,5-oxadiazol-3-yl}methyl isopropylcarbamate;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-(piperidin-1-ylmethyl)-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-4-[(dimethylamino)methyl]-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-[(4-phenylpiperazin-1-yl)methyl]-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N-hydroxy-4-[(isoxazol-3-ylamino)methyl]-1,2,5-oxadiazole-3-carboximidamide;

4-{[(1-benzylpiperidin-4-yl)amino]methyl}-N-(3-chloro-4-fluorophenyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-{[4-(2-methoxyphenyl)piperazin-1-yl]methyl}-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-{[(pyridin-2-ylmethyl)amino]methyl}-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-{[(2-phenylethyl)amino]methyl}-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-{[(3-phenylpropyl)amino]methyl}-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4({[(1R)-1-phenylethyl]amino}methyl)-1,2,5-oxadiazole-3-carboximidamide;

4-{[(2-chlorobenzyl)amino]methyl}-N-(3-chloro-4-fluorophenyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-{[(4-phenylbutyl)amino]methyl}-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-4-(3,4-dihydroisoquinolin-2(1H)-ylmethyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-4-(2,3-dihydro-1H-indol-1-ylmethyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-(morpholin-4-ylmethyl)-1,2,5-oxadiazole-3-carboximidamide;

3-(4-[(2-morpholin-4-ylethyl)amino]methyl-1,2,5-oxadiazol-3-yl)-4-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5(4H)-one;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-[(methylsulfonyl)(2-morpholin-4-ylethyl)amino]-methyl-1,2,5-oxadiazole-3-carboximidamide;

N-{4-[N-(3-chloro-4-fluoro-phenyl)-N′-hydroxy-carbamimidoyl]-furazan-3-ylmethyl}-benzamide;

N-(3-chloro-4-fluoro-phenyl)-N′-hydroxy-4-[(3-phenyl-ureido)-methyl]-furazan-3-carboxamidine;

4-(benzenesulfonylamino-methyl)-N-(3-chloro-4-fluoro-phenyl)-N′-hydroxy-furazan-3-carboxamidine;

benzyl({4-[(E/Z)-[(3-chloro-4-fluorophenyl)amino](hydroxyimino)methyl]-1,2,5-oxadiazol-3-yl}methyl)carbamate;

N-(3-cyanophenyl)-N′-hydroxy-4-methyl-1,2,5-oxadiazole-3-carboximidamide;

4-[(5-amino-1H-tetrazol-1-yl)methyl]-N-(3-chloro-4-fluorophenyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

4-[(5-amino-2H-tetrazol-2-yl)methyl]-N-(3-chloro-4-fluorophenyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-[(1H-tetrazol-5-ylamino)methyl]-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-({[3-(1 H-imidazol-1-yl)propyl]amino}methyl)-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-{[(2-morpholin-4-ylethyl)amino]methyl}-1,2,5-oxadiazole-3-carboximidamide;

{4-[({4-[(E/Z)-[(3-chloro-4-fluorophenyl)amino](hydroxyimino)methyl]-1,2,5-oxadiazol-3-yl}-methyl)amino]phenyl}acetic acid;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-[(4-hydroxypiperidin-1-yl)methyl]-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-{[4-(2-hydroxyethyl)piperazin-1-yl]methyl}-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-({[(1R)-2-hydroxy-1-phenylethyl]amino}methyl)-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-{[(2-hydroxyethyl)amino]methyl}-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-{[(2-pyridin-4-ylethyl)amino]methyl}-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-{[(tetrahydrofuran-2-ylmethyl)amino]methyl}-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-{[(1,3-thiazol-2-ylmethyl)amino]methyl}-1,2,5-oxadiazole-3-carboximidamide;

4-({[4-(aminosulfonyl)benzyl]amino}methyl)-N-(3-chloro-4-fluorophenyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

{4-[(E/Z)-[(3-chloro-4-fluorophenyl)amino](hydroxyimino)methyl]-1,2,5-oxadiazol-3-yl}methyl dimethylcarbamate;

4-{[4-(aminosulfonyl)phenoxy]methyl}-N-(3-chloro-4-fluorophenyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-{[4-(methylsulfonyl)phenoxy]methyl}-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4(1H-imidazol-1-ylmethyl)-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4(1H-1,2,4-triazol-1-ylmethyl)-1,2,5-oxadiazole-3-carboximidamide;

4-[({2-[4-(aminosulfonyl)phenyl]ethyl}amino)methyl]-N-(3-chloro-4-fluorophenyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-(2H-tetrazol-2-ylmethyl)-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4(1H-tetrazol-1-ylmethyl)-1,2,5-oxadiazole-3-carboximidamide;

{4-[(E/Z)-[(3-chloro-4-fluorophenyl)amino](hydroxyimino)methyl]-1,2,5-oxadiazol-3-yl}methyl morpholine-4-carboxylate;

2-[4-({4-[(E/Z)-[(3-chloro-4-fluorophenyl)amino](hydroxyimino)methyl]-1,2,5-oxadiazol-3-yl}-methoxy)phenyl]acetamide;

4-(aminomethyl)-N-(3-chloro-4-fluorophenyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

4-[(5-amino-1H-tetrazol-1-yl)methyl]-N-[3-(trifluoromethyl)phenyl]-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

4-[(5-benzyl-1H-tetrazol-1-yl)methyl]-N-(3-chloro-4-fluorophenyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

4-[(5-benzyl-2H-tetrazol-2-yl)methyl]-N-(3-chloro-4-fluorophenyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

[2-({4-[(E/Z)-[(3-chloro-4-fluorophenyl)amino](hydroxyimino)methyl]-1,2,5-oxadiazol-3-yl}-methyl)-2H-tetrazol-5-yl]acetic acid;

N-(3-chloro-4-fluorophenyl)-4-(cyanomethyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-[(2-oxo-1,3-oxazolidin-3-yl)methyl]-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-4-({[2-(dimethylamino)ethyl]amino}methyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-{[(3-morpholin-4-ylpropyl)amino]methyl}-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-[(5-pyridin-4-yl-2H-tetrazol-2-yl)methyl]-1,2,5-oxadiazole-3-carboximidamide;

4-({[4-(aminosulfonyl)benzyl]amino}methyl)-N-[3-(trifluoromethyl)phenyl]-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-[3-(trifluoromethyl)phenyl]-N′-hydroxy-4-(1H-tetrazol-1-ylmethyl)-1,2,5-oxadiazole-3-carboximidamide;

N-[3-(trifluoromethyl)phenyl]-N′-hydroxy-4-(2H-tetrazol-2-ylmethyl)-1,2,5-oxadiazole-3-carboximidamide;

N-[3-(trifluoromethyl)phenyl]-N′-hydroxy-4-{[(2-morpholin-4-ylethyl)amino]methyl}-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-{[(pyridin-3-ylmethyl)amino]methyl}-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-{[(2-pyrrolidin-1-ylethyl)amino]methyl}-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-({[2-(1H-imidazol-4-yl)ethyl]amino}methyl)-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-({[2-(2-oxopyrrolidin-1-yl)ethyl]amino}methyl)-1,2,5-oxadiazole-3-carboximidamide;

N-(3-choro-4-fluorophenyl)-N′-hydroxy-4-[(5-methyl-1H-tetrazol-1-yl)methyl]-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-[(5-methyl-2H-tetrazol-2-yl)methyl]-1,2,5-oxadiazole-3-carboximidamide;

N-({4-[(E/Z)-[(3-chloro-4-fluorophenyl)amino](hydroxyimino)methyl]-1,2,5-oxadiazol-3-yl}-methyl)-N-(2-morpholin-4-ylethyl)acetamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-{[5-(methylthio)-2H-tetrazol-2-yl]methyl}-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-{[5-(methylthio)-1H-tetrazol-1-yl]methyl}-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-[(5-phenyl-1H-tetrazol-1-yl)methyl]-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-[(5-phenyl-2H-tetrazol-2-yl)methyl]-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-({5-[3-(trifluoromethoxy)phenyl]-2H-tetrazol-2-yl}-methyl)-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-[(5-pyridin-3-yl-2H-tetrazol-2-yl)methyl]-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-[(5-pyrrolidin-1-yl-2H-tetrazol-2-yl)methyl]-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-({5-[3-(trifluoromethoxy)phenyl]-1H-tetrazol-1-yl}-methyl)-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-[(5-pyridin-2-yl-1H-tetrazol-1-yl)methyl]-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-[(5-pyrrolidin-1-yl-1H-tetrazol-1-yl)methyl]-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-4-{[5-(4-fluorophenyl)-1H-tetrazol-1-yl]methyl}-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-4-({5-[2-(dimethylamino)ethyl]-1H-tetrazol-1-yl}methyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide

N-(3-chloro-4-fluorophenyl)-4-{[5-(4-fluorophenyl)-2H-tetrazol-2-yl]methyl}-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-4-({5-[2-(4-chlorophenoxy)ethyl]-2H-tetrazol-2-yl}methyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-({5-[5-(trifluoromethyl)pyridin-2-yl]-2H-tetrazol-2-yl}methyl)-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-4-({5-[2-(4-chlorophenoxy)ethyl]-1H-tetrazol-1-yl}methyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-4-[({2-[(2R,6S)-2,6-dimethylmorpholin-4-yl]ethyl}amino)methyl]-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-({[2-(2-methylpiperidin-l-yOethyl]amino}methyl)-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-4-{[(1,1-dimethyl-2-morpholin-4-ylethyl)amino]methyl}-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-{[(2-piperazin-l-ylethyl)amino]methyl}-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-4-({[(1-ethylpyrrolidin-2-yl)methyl]amino}methyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-4-({[2-(dimethylamino)propyl]amino}methyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-{[(2-methyl-2-morpholin-4-ylpropyl)amino]methyl}-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-{[(2-methyl-2-piperidin-1-ylpropyl)amino]methyl}-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-{[(piperidin-2-ylmethyl)amino]methyl}-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-4-({[2-(1,1-dioxidothiomorpholin-4-yl(ethyl]-amino}-methyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-[(piperidin-3-ylamino)methyl]-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-{[(pyrrolidin-3-ylmethyl)amino]methyl}-1,2,5-oxadiazole-3-carboximidamide;

N-({4-[(E/Z)-[(3-chloro-4-fluorophenyl)amino](hydroxyimino)methyl]-1,2,5-oxadiazol-3-yl}-methyl)-2-methylpropanamide;

N-({4-[(E/Z)-[(3-chloro-4-fluorophenyl)amino](hydroxyimino)methyl]-1,2,5-oxadiazol-3-yl}-methyl)-2,2-dimethylpropanamide;

N-({4-[(E/Z)-[(3-chloro-4-fluorophenyl)amino](hydroxyimino)methyl]-1,2,5-oxadiazol-3-yl}-methyl)-2-phenylacetamide;

N-({4-[(E/Z)-[(3-chloro-4-fluorophenyl)amino](hydroxyimino)methyl]-1,2,5-oxadiazol-3-yl}-methyl)-3-phenylpropanamide;

N-({4-[(E/Z)-[(3-chloro-4-fluorophenyl)amino](hydroxyimino)methyl]-1,2,5-oxadiazol-3-yl}-methyl)-1,3-thiazole-5-carboxamide;

N-({4-[(E/Z)-[(3-chloro-4-fluorophenyl)amino](hydroxyimino)methyl]-1,2,5-oxadiazol-3-yl}-methyl)cyclopentanecarboxamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-{[(methylsulfonyl)amino]methyl}-1,2,5-oxadiazole-3-carboximidamide;

4-({[(benzylamino)carbonyl]amino}methyl)-N-(3-chloro-4-fluorophenyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-[({[(2-phenylethyl)-amino]carbonyl}-amino)methyl]-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-({[(isopropylamino)-carb onyl]amino}-methyl)-1,2,5-oxadiazole-3-carboximidamide;

N-({4-[(E/Z)-[(3-chloro-4-fluorophenyl)amino](hydroxyimino)methyl]-1,2,5-oxadiazol-3-yl}-methyl)morpholine-4-carboxamide;

N-(3-chloro-4-fluorophenyl)-4-({[(dimethylamino)carbonyl]amino }methyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-({4-[(E/Z)-[(3-chloro-4-fluorophenyl)amino](hydroxyimino)methyl]-1,2,5-oxadiazol-3-yl}methyl) acetamide;

methyl ({4-[(E/Z)-[(3-chloro-4-fluorophenyl)amino](hydroxyimino)methyl]-1,2,5-oxadiazol-3-yl}methyl)carbamate;

isobutyl({4-[(E/Z)-[(3-chloro-4-fluorophenyl)amino](hydroxyimino)methyl]-1,2,5-oxadiazol-3-yl}methyl)carbamate;

benzyl({4-[(E/Z)-[(3-chloro-4-fluorophenyl)amino](hydroxyimino)methyl]-1,2,5-oxadiazol-3-yl}methyl)carbamate;

N-(3-chloro-4-fluorophenyl)-4-{[(ethylsulfonyl)amino]methyl}-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-(5-{[({4-[(E/Z)-[(3-chloro-4-fluorophenyl)amino](hydroxyimino)methyl]-1,2,5-oxadiazol-3-yl}methyl)amino]sulfonyl}-4-methyl-1,3-thiazol-2-yl)acetamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-{[({5-[1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl]-2-thienyl}sulfonyl)amino]methyl}-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-({[(1-methyl-1H-imidazol-4-yl)sulfonyl]amino}-methyl)-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-4-({[(2,4-dimethyl-1,3-thiazol-5-yl)sulfonyl]amino}methyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-4-({[(3,5-dimethylisoxazol-4-yl)sulfonyl]amino}methyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-({[(1,3,5-trimethyl-1H-pyrazol-4-yl)sulfonyl]amino}-methyl)-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-4-({[(1,2-dimethyl-1H-imidazol-4-yl)sulfonyl]amino}methyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-{[(propylsulfonyl)amino]methyl}-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-4-{[(cyclopropylsulfonyl)amino]methyl }-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-{[(3-methylisothiazol-5-yl)amino]methyl}-1,2,5-oxadiazole-3-carboximidamide;

ethyl 3-4-[(Z)-[(3-chloro-4-fluorophenyl)amino](hydroxyimino)methyl]-1,2,5-oxadiazol-3-ylpropanoate;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-(3-morpholin-4-ylpropyl)-1,2,5-oxadiazole-3-carboximidamide;

4-[(aminosulfonyl)amino]methyl-N-(3-chloro-4-fluorophenyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-4-([(E/Z)-(cyanoimino)(methylamino)methyl]aminomethyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-([(methylamino)-sulfonyl]aminomethyl)-1,2,5-oxadiazole-3-carboximidamide;

4-[(aminocarbonyl)amino]methyl-N-(3-chloro-4-fluorophenyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

4-([(tert-butylamino)carbonyl]aminomethyl)-N-(3-chloro-4-fluorophenyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-([(3-morpholin-4-ylpropyl)sulfonyl]aminomethyl)-1,2,5-oxadiazole-3-carboximidamide trifluoroacetate;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-[(piperidin-4-ylsulfonyl)amino]methyl-1,2,5-oxadiazole-3-carboximidamide trifluoroacetate;

4-[([1-(aminosulfonyl)piperidin-4-yl]sulfonylamino)methyl]-N-(3-chloro-4-fluorophenyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

4-([(1-acetylpiperidin-4-yl)sulfonyl]aminomethyl)-N-(3-chloro-4-fluorophenyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-[5-(morpholin-4-ylmethyl)-2H-tetrazol-2-yl]methyl-1,2,5-oxadiazole-3-carboximidamide trifluoroacetate;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-[5-(morpholin-4-ylmethyl)-1H-tetrazol-1-yl]methyl-1,2,5-oxadiazole-3-carboximidamide trifluoroacetate;

4-[(5-amino-1,3,4-thiadiazol-2-yl)thio]methyl-N-(3-chloro-4-fluorophenyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

4-[(5-amino-4H-1,2,4-triazol-3-yl)thio]methyl-N-(3-chloro-4-fluorophenyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

4-[(5-amino-4H-1,2,4-triazol-3-yl)sulfonyl]methyl-N-(3-chloro-4-fluorophenyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-4-[({(E/Z)-(cyanoimino)[(4-methoxybenzyl)amino]methyl}amino)-methyl]-N-hydroxy-1,2,5-oxadiazole-3-carboximidamide trifluoroacetate;

4-[({(E/Z)-[(aminocarbonyl)imino][(4-methoxybenzyl)amino]methyl}amino)methyl]-N-(3-chloro-4-fluorophenyl)-N-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

4-({[(E/Z)-amino(nitroimino)methyl]amino}methyl)-N-(3-chloro-4-fluorophenyl)-N-hydroxy-1,2,5-oxadiazole-3-carboximidamide trifluoroacetate;

4-({[amino(imino)methyl]amino}methyl)-N-(3-chloro-4-fluorophenyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-(4H-1,2,4-triazol-4-ylmethyl)-1,2,5-oxadiazole-3-carboximidamide;

4-[2-(5-amino-1H-tetrazol-1-yl)ethyl]-N-(3-chloro-4-fluorophenyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

4-[2-(5-amino-2H-tetrazol-2-yl)ethyl]-N-(3-chloro-4-fluorophenyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-[2-(1H-imidazol-1-yl)ethyl]-1,2,5-oxadiazole-3-carboximidamide trifluoroacetate;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-(2-morpholin-4-ylethyl)-1,2,5-oxadiazole-3-carboximidamide trifluoroacetate;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-[2-(4-methylpiperazin-1-yl)ethyl]-1,2,5-oxadiazole-3-carboximidamide bis(trifluoroacetate);

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-[2-(4H-1,2,4-triazol-4-yl)ethyl]-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-[2-(1H-1,2,4-triazol-1-yl)ethyl]-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-[2-(1H-tetrazol-1-yl(ethyl]-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-[2-(2H-tetrazol-2-yl(ethyl]-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-4-[2-(dimethylamino)ethyl]-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide trifluoroacetate;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-(2-thiomorpholin-4-ylethyl)-1,2,5-oxadiazole-3-carboximidamide trifluoroacetate;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-(2-pyrrolidin-1-ylethyl)-1,2,5-oxadiazole-3-carboximidamide trifluoroacetate;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-{2-[isopropyl(methyl)amino]ethyl}-1,2,5-oxadiazole-3-carboximidamide trifluoroacetate;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-{2-[(methylsulfonyl)amino]ethyl}-1,2,5-oxadiazole-3-carboximidamide;

4-{2-[(aminosulfonyl)amino]ethyl}-N-(3-chloro-4-fluorophenyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

4-{[(aminosulfonyl)amino]methyl}-N-(3-bromo-4-fluorophenyl)-N-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

4-{[(aminosulfonyl)amino]methyl}-N-hydroxy-N-[3-(trifluoromethyl)phenyl]-1,2,5-oxadiazole-3-carboximidamide;

N-({4-[(E/Z)-[(3-chloro-4-fluorophenyl)amino](hydroxyimino)methyl]-1,2,5-oxadiazol-3-yl}-methyl)-N′-cyanomorpholine-4-carboximidamide;

N-(3-chloro-4-fluorophenyl)-4-[({(E/Z)-(cyanoimino)[(2-morpholin-4-ylethyl)amino]methyl}-amino)methyl]-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

4-[({(E/Z)-[(aminocarbonyl)imino][(2-morpholin-4-ylethyl)amino]methyl}amino)methyl]-N-(3-chloro-4-fluorophenyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-4-{[((E/Z)-(cyanoimino){[2- (dimethylamino) ethyl]amino}methyl)-amino]methyl}-N-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-4-{[((E/Z)-(cyanoimino){[2-(1H-imidazol-5-yl)ethyl]amino}-methyl)amino]methyl}-N-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

4-{[((E/Z)-[(aminocarbonyl)imino]{[2-(1H-imidazol-5-yl)ethyl]amino}methyl)amino]methyl}-N-(3-chloro-4-fluorophenyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-4-[({(E/Z)-(cyanoimino)[(2-hydroxy-1-methylethyl)amino]methyl}-amino)methyl]-N-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-4-({[(E/Z)-(cyanoimino)(isopropylamino)methyl]amino}methyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide trifluoroacetate;

N-(3-chloro-4-fluorophenyl) -4-[({(E/Z)-(cyanoimino)[(2-methoxy-1-methylethyl)amino]-methyl}amino)methyl]-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide trifluoroacetate;

N-(3-chloro-4-fluorophenyl)-4-[({(E/Z)-(cyanoimino)[(2-methoxyl(ethyl)amino]methyl}amino)-methyl]-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide trifluoroacetate;

N-(3-chloro-4-fluorophenyl)-4-({[(E/Z)-(cyanoimino)(tetrahydro-2H-pyran-4-ylamino)methyl]-amino}methyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide trifluoroacetate;

N-(3-chloro-4-fluorophenyl)-4-{[((E/Z)-(cyanoimino){[(1-ethylpyrrolidin-2-yl)methyl]amino}-methyl)amino]methyl}-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide bis (trifluoroacetate);

4-({[(E/Z)-amino(cyanoimino)methyl]amino}methyl)-N-(3-chloro-4-fluorophenyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide trifluoroacetate;

N-(3-chloro-4-fluorophenyl)-4-[({(E/Z)-(cyanoimino)[(2-hydroxyl(ethyl)amino]methyl}amino)-methyl]-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide trifluoroacetate;

N-(3-chloro-4-fluorophenyl)-4-({[(E/Z)-(cyanoimino) (dimethylamino)methyl]amino}methyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-4-({[(E/Z)-(cyanoimino)(ethylamino)methyl]amino}methyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-(3-bromo-4-fluorophenyl)-4-({[(E/Z)-(cyanoimino)(ethylamino)methyl]amino}methyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

4-({[(E/Z)-(cyanoimino)(dimethylamino)methyl]amino}methyl)-N′-hydroxy-N-[3-(trifluoro-methyl)phenyl]-1,2,5-oxadiazole-3-carboximidamide;

4-({[(E/Z)-(cyanoimino)(ethylamino)methyl]amino}methyl)-N′-hydroxy-N-[3-(trifluoromethyl)-phenyl]-1,2,5-oxadiazole-3-carboximidamide;

N-(3-bromo-4-fluorophenyl)-4-({[(E/Z)-(cyanoimino)(dimethylamino)methyl]amino}methyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

4-({[(E/Z)-(cyanoimino)(methylamino)methyl]amino}methyl)-N′-hydroxy-N-[3-(trifluoro-methyl)phenyl]-1,2,5-oxadiazole-3-carboximidamide trifluoroacetate;

N-(3-bromo-4-fluorophenyl)-4-({[(E/Z)-(cyanoimino)(methylamino)methyl]amino}methyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

4-({[(E/Z)-amino(cyanoimino)methyl]amino}methyl)-N-(3-bromo-4-fluorophenyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

4-({[(E/Z)-amino(cyanoimino)methyl]amino}methyl)-N′-hydroxy-N-[3-(trifluoromethyl)phenyl]-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-({[(isopropylamino)sulfonyl]amino}methyl)-1,2,5-oxadiazole-3-carboximidamide;

N-(3-bromo-4-fluorophenyl)-N′-hydroxy-4-({[(methylamino)sulfonyl]amino}methyl)-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-4-({[(ethylamino)sulfonyl]amino}methyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-4-({[(dimethylamino)sulfonyl]amino}methyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-[3-(difluoromethyl)phenyl]-N′-hydroxy-4-(1H-tetrazol-1-ylmethyl)-1,2,5-oxadiazole-3-carboximidamide;

N-[3-(difluoromethyl)phenyl]-N′-hydroxy-4-(2H-tetrazol-2-ylmethyl)-1,2,5-oxadiazole-3-carboximidamide;

N-hydroxy-4-(4H-1,2,4-triazol-4-ylmethyl)-N-[3-(trifluoromethyl)phenyl]-1,2,5-oxadiazole-3-carboximidamide;

N-(3-bromo-4-fluorophenyl)-N′-hydroxy-4-(4H-1,2,4-triazol-4-ylmethyl)-1,2,5-oxadiazole-3-carboximidamide;

4-[(5-amino-1H-tetrazol-1-yl)methyl]-N-(3-bromo-4-fluorophenyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

4-[(5-amino-2H-tetrazol-2-yl)methyl]-N-(3-bromo-4-fluorophenyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-({4-[(Z)-[(3-chloro-4-fluorophenyl)amino](hydroxyimino)methyl]-1,2,5-oxadiazol-3-yl}-methyl)-1H-imidazole-2-carboxamide trifluoroacetate;

N-({4-[(Z)-[(3-chloro-4-fluorophenyl)amino](hydroxyimino)methyl]-1,2,5-oxadiazol-3-yl}-methyl)-1H-pyrazole-4-carboxamide trifluoroacetate;

N-({4-[(Z)-[(3-chloro-4-fluorophenyl)amino](hydroxyimino)methyl]-1,2,5-oxadiazol-3-yl}-methyl)-4-methyl-1,2,3-thiadiazole-5-carboxamide;

N-({4-[(Z)-[(3-chloro-4-fluorophenyl)amino](hydroxyimino)methyl]-1,2,5-oxadiazol-3-yl}-methyl)-1H-imidazole-4-carboxamide trifluoroacetate;

N-({4-[(Z)-[(3-chloro-4-fluorophenyl)amino](hydroxyimino)methyl]-1,2,5-oxadiazol-3-yl}-methyl)-1,2,3-thiadiazole-4-carboxamide;

5-amino-N-({4-[(Z)-[(3-chloro-4-fluorophenyl)amino](hydroxyimino)methyl]-1,2,5-oxadiazol-3-yl}methyl)-1,3,4-thiadiazole-2-carboxamide;

5-amino-N-({4-[(Z)-[(3-chloro-4-fluorophenyl)amino](hydroxyimino)methyl]-1,2,5-oxadiazol-3-yl}methyl)-1H-pyrazole-4-carboxamide;

4-(aminomethyl)-N-(3-bromo-4-fluorophenyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide trifluoroacetate;

N-(3-bromo-4-fluorophenyl)-N′-hydroxy-4-{[(methylsulfonyl)amino]methyl}-1,2,5-oxadiazole-3-carboximidamide;

4-(aminomethyl)-N′-hydroxy-N-[3-(trifluoromethyl)phenyl]-1,2,5-oxadiazole-3-carboximidamide trifluoroacetate;

N-hydroxy-4-{[(methylsulfonyl)amino]methyl}-N-[3-(trifluoromethyl)phenyl]-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-({[(2,2,2-trifluoroethyl)sulfonyl]amino}methyl)-1,2,5-oxadiazole-3-carboximidamide;

N-(3-bromo-4-fluorophenyl)-N′-hydroxy-4-(1H-tetrazol-1-ylmethyl)-1,2,5-oxadiazole-3-carboximidamide;

[1-({4-[(Z)-[(3-chloro-4-fluorophenyl)amino](hydroxyimino)methyl]-1,2,5-oxadiazol-3-yl}-methyl)-1H-tetrazol-5-yl]acetic acid;

N-(3-chloro-4-fluorophenyl)-4-({[(2,4-dioxo-1,2,3 ,4-tetrahydropyrimidin-5-yl)sulfonyl]amino}-methyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-4-({[(1,3-dimethyl-2,4-dioxo-1,2,3 ,4-tetrahydropyrimidin-5-yl)-sulfonyl]amino}methyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-[3-(1H-tetrazol-1-yl)propyl]-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-[3-(2H-tetrazol-2-yl)propyl]-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-[3-(4H-1,2,4-triazol-4-yl)propyl]-1,2,5-oxadiazole-3-carboximidamide;

4-{3-[(aminosulfonyl)amino]propyl}-N-(3-chloro-4-fluorophenyl)-N-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl) -4-(3-{[(E/Z)-(cyanoimino)(methylamino)methyl]amino}propyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide trifluoroacetate;

4-[(3-amino-4H-1,2,4-triazol-4-yl)methyl]-N-(3-chloro-4-fluorophenyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

4-[(5-amino-1H-1,2,4-triazol-1-yl)methyl]-N-(3-chloro-4-fluorophenyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-(3-chloro-4-fluorophenyl)-N′-hydroxy-4-[(1,3,4-thiadiazol-2-ylamino)methyl]-1,2,5-oxadiazole-3-carboximidamide trifluoroacetate;

N-[3-(difluoromethyl)phenyl]-N-hydroxy-4-({[(methylamino)sulfonyl]amino}methyl)-1,2,5-oxadiazole-3-carboximidamide;

4-[(5-amino-1H-tetrazol-1-yl)methyl]-N′-[3-(difluoromethyl)phenyl]-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

4-[(5-amino-2H-tetrazol-2-yl)methyl]-N-(4-fluoro-3-methylphenyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-[3-(difluoromethyl)phenyl]-N-hydroxy-4-(1H-tetrazol-1-ylmethyl)-1,2,5-oxadiazole-3-carboximidamide;

N-[3-(difluoromethyl)phenyl]-N′-hydroxy-4-(2H-tetrazol-2-ylmethyl)-1,2,5-oxadiazole-3-carboximidamide;

N-[3-(difluoromethyl)phenyl]-N′-hydroxy-4-{[(methylsulfonyl)amino]methyl}-1,2,5-oxadiazole-3-carboximidamide;

4-{[(aminosulfonyl)amino]methyl}-N-[3-(difluoromethyl)phenyl]-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-[3-(difluoromethyl)phenyl]-N′-hydroxy-4-({[(trifluoromethyl)sulfonyl]amino}methyl)-1,2,5-oxadiazole-3-carboximidamide;

4-{[bis(methylsulfonyl)amino]methyl}-N-[3-(difluoromethyl)phenyl]-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

4-[(5-amino-1H-tetrazol-1-yl)methyl]-N-(4-fluoro-3-methylphenyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

4-{[(6-aminohexyl)amino]methyl}-N-(3-chloro-4-fluorophenyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-(4-fluoro-3-methylphenyl)-N′-hydroxy-4-{[(methylsulfonyl)amino]methyl}-1,2,5-oxadiazole-3-carboximidamide;

4-[2-(5-amino-1H-tetrazol-1-yl)ethyl]-N-(3-bromo-4-fluorophenyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide;

N-(3-bromo-4-fluorophenyl)-N′-hydroxy-4-{2-[(methylsulfonyl)amino]ethyl}-1,2,5-oxadiazole-3-carboximidamide;

4-{2-[(aminosulfonyl)amino]ethyl}-N-(3-bromo-4-fluorophenyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide; and pharmaceutically acceptable salts thereof.

12. The method of claim 1 further comprising administering an anti-viral agent, a chemotherapeutic, an immunosuppressant, radiation, an anti-tumor vaccine, an anti-viral vaccine, cytokine therapy, a tyrosine kinase inhibitor, an anti-CTLA-4 antibody, or an anti-PD-1 antibody.

13. The method of claim 1 , wherein the cancer is melanoma.

14. The method of claim 13 further comprising administering a chemotherapeutic, radiation, an anti-tumor vaccine, or cytokine therapy.

15. The method of claim 1 , wherein the cancer is breast cancer.

16. The method of claim 1 , wherein the cancer is ovarian cancer.

17. The method of claim 1 , wherein the method is a method of inhibiting immunosuppression.

Assignments (3)
CORRECTIVE ASSIGNMENT TO CORRECT THE RECEIVING PARTY INFORMATION PREVIOUSLY RECORDED ON REEL 035920 FRAME 0576. ASSIGNOR(S) HEREBY CONFIRMS THE RECEIVING PARTY NAME SHOULD BE RECORDED AS TWO PARTIES. Recorded Jul 2, 2015
From: INCYTE CORPORATION
To: INCYTE HOLDINGS CORPORATION; INCYTE CORPORATION
Reel/Frame 036054/0740 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 16, 2015
From: INCYTE CORPORATION
To: INCYTE HOLDINGS CORPORATION AND INCYTE CORPORATION
Reel/Frame 035920/0576 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 24, 2013
From: COMBS, ANDREW P.; TAKVORIAN, AMY; ZHU, WENYU; SPARKS, RICHARD B.
To: INCYTE CORPORATION
Reel/Frame 030276/0392 →
Continuity (5)
Division 11641284 · Dec 19, 2006
Provisional Application 60751854 · Dec 20, 2005
Provisional Application 60801337 · May 18, 2006
Provisional Application 60857558 · Nov 8, 2006
Related Publication 20130177590A1 · Jul 11, 2013