Substituted N′-hydroxycarbamimidoyl-1,2,5-oxadiazole compounds as indoleamine 2,3-dioxygenase IDO inhibitors

1. A compound of formula (I), or a pharmaceutically acceptable salt thereof:

wherein:

m is 0, 1, 2, 3 or 4; is 1, 2, or 3; p is 0, 1, 2 or 3;

W is selected from (a) —CR a R b — and (b) —NR a —; wherein each R a and R b is independently selected from the group consisting of (a) hydrogen, (b) halogen and (c) C 1-6 alkyl, optionally substituted with —OH or halogen;

R is selected from the group consisting of:

(a) hydrogen;

(b) C 1-6 alkyl, optionally substituted with one to three substituents independently selected from the group consisting of (i) —OH, (ii) halogen, and (iii) —NH 2 ;

(c) C 3-6 cycloalkyl, optionally substituted with one to three substituents independently selected from the group consisting of (i) —OH and (ii) —C 1-6 alkyl, optionally substituted with —OH;

(d) —(C═O)—(NH) q —R c , wherein q is 0 or 1; and R c is selected from the group consisting of:

(i) hydrogen,

(ii) —C 1-6 alkyl, optionally substituted with one to three substituents independently selected from the group consisting of (1) halogen, (2) —OH, (3) —O-methyl, (4) —C 3-6 cycloalkyl, (5) —CN, (6) —S(O) 2 -C 1-6 alkyl and (7) heterocyclyl,

(iii) —O-C 1-6 alkyl,

(iv) —OH,

(v) —C 3-6 cycloalkyl, optionally substituted with —OH or —C 1-6 alkyl, and

(vi) a 4-, 5- or 6-membered heterocyclyl, optionally substituted with one to four substituents independently selected from the group consisting of (1) halogen, (2) C 1-6 alkyl and (3) —OH;

(e) —S(O) 2 —NR d R e ; each of R d and R e is independently hydrogen or C 1-6 alkyl;

(f) —S(O) 2 —C 1-6 alkyl;

(g) C 4-5 cycloalkenyl, optionally substituted with one to four substituents independently selected from the group consisting of (i) oxo, (ii) —C 1-6 alkyl and (iii) —NH—C 1-6 alkyl; and

(h) a 4-, 5- or 6-membered heterocyclyl, optionally substituted with one to four substituents independently selected from the group consisting of (i) halogen, (ii) C 1-6 alkyl, (iii) oxo and (iv) —C(O)—C 1-6 alkyl, optionally substituted with —OH;

each occurrence of R 1 is independently selected from the group consisting of (a) hydrogen, (b) halogen, (c) —CN, (d) C 1-6 alkyl, optionally substituted with 1 to 3 halogens, and (e) —O—C 1-6 alkyl, optionally substituted with one to three halogens;

each occurrence of R 2 is independently selected from the group consisting of (a) hydrogen, (b) halogen, (c) —OH and (d) C 1-6 alkyl, optionally substituted with —OH;

or, alternatively, two R 2 groups together with the carbon to which they are attached form a C 3-6 cycloalkyl or 4-, 5-, or 6-membered heterocycle;

or, alternatively, R 2 and R a of W together with the carbon and/or nitrogen atoms to which they are attached form a 4-, 5- or 6-membered carbocycle or heterocycle;

each occurrence of R 3 is independently selected from the group consisting of (a) hydrogen, (b) halogen, (c) C 1-6 alkyl and (d) —O—C 1-6 alkyl; and

R 4 is selected from the group consisting of (a) hydrogen and (b) C 1-6 alkyl.

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

wherein m is 1 or 2; n is 1 or 2; and p is 0, 1 or 2;

W is selected from (a) —CR a R b —and (b) —NR a —; wherein each occurrence of R a and R b is independently selected from the group consisting of (a) hydrogen and (b) C 1-6 alkyl, optionally substituted with —OH;

R is selected from the group consisting of:

(a) hydrogen;

(b) C 1-6 alkyl, optionally substituted with one to three substituents independently selected from the group consisting of (i) —OH and (ii) halogen;

(c) C 3-6 cycloalkyl, optionally substituted with —OH;

(d) —(C═O)—(NH) q —R c , wherein q is 0 or 1; and R c is selected from the group consisting of:

(i) hydrogen,

(ii) —C 1-6 alkyl, optionally substituted with one to three substituents independently selected from the group consisting of (1) halogen, (2) —OH, (3) —O—methyl and (4) —C 3-6 cycloalkyl,

(iii) —O—C 1-6 alkyl, and

(iv) a 5- or 6-membered heterocyclyl, optionally substituted with one to four substituents independently selected from the group consisting of (1) halogen, (2) C 1-6 alkyl and (3) —OH;

(e) —S(O) 2 —NH 2;

(f) —S(O) 2 —C 1-6 alkyl; and

(g) a 4-, 5- or 6-membered heterocyclyl, optionally substituted with one to four substituents independently selected from the group consisting of (i) halogen, (ii) C 1-6 alkyl, (iii) oxo and (iv) —C(O)—C 1-6 alkyl, optionally substituted with —OH;

each occurrence of R 1 is independently selected from the group consisting of (a) hydrogen, (b) halogen, and (c) —CN;

each occurrence of R 2 is independently selected from the group consisting of (a) hydrogen and (b) —OH;

or alternatively, two R 2 groups together with the carbon to which they are attached form a C 3-6 cycloalkyl or a 4-, 5-, or 6-membered heterocycle;

or alternatively, R 2 and R a of W together with the carbon and/or nitrogen atoms to which they are attached form a 4-, 5- or 6-membered carbocycle or heterocycle;

each occurrence of R 3 is independently selected from the group consisting of (a) hydrogen and (b) C 1-6 alkyl; and

R 4 is selected from the group consisting of (a) hydrogen and (b) C 1-6 alkyl.

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

R is selected from the group consisting of:

(a) hydrogen;

(b) C 1-6 alkyl, optionally substituted with one to three —OH;

(c) C 3-6 cycloalkyl, optionally substituted with —OH;

(d) —(C═O)—(NH) q —R c , wherein q is 0 or 1; and R c is selected from the group consisting of:

(i) hydrogen,

(ii) —C 1-6 alkyl, optionally substituted with one to three —OH,

(iii) —O—C 1-6 alkyl, and

(iv) a 5- or 6-membered heterocyclyl, optionally substituted with one to four substituents independently selected from the group consisting of (1) halogen, (2) C 1-6 alkyl and (3) —OH;

(e) —S(O) 2 —NH 2 ;

(f) —S(O) 2 —C 1-4 alkyl; and

(g) a 5- or 6-membered heterocyclyl, optionally substituted with one to four substituents independently selected from the group consisting of (i) halogen, (ii) C 1-6 alkyl and (iii) oxo; and

each occurrence of R a and R b is independently selected from the group consisting of (a) hydrogen and (b) C 1-4 alkyl, optionally substituted with —OH.

4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R is a 5- or 6-membered heterocyclyl selected from the group consisting of pyridinyl, pyrimidinyl, piperidinyl, pyrrolidinyl, triazolyl and thiazolyl;

wherein the 5- or 6-membered heterocyclyl is optionally substituted with one to four substituents independently selected from the group consisting of (i) C 1-6 alkyl and (ii) oxo.

5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each occurrence of R 1 is independently selected from the group consisting of (a) hydrogen and (b) halogen.

6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each occurrence of R 2 is independently selected from the group consisting of (a) hydrogen and (b) —OH.

7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each occurrence of R 3 is independently selected from the group consisting of (a) hydrogen and (b) C 1-4 alkyl.

8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein m is 1 or 2; n is 1; and p is 0, 1 or 2;

W is selected from (a) —CR a R b —and (b) —NR a —; wherein each occurrence of R a and R b is independently selected from the group consisting of (i) hydrogen and (ii) C 1-4 alkyl;

R is selected from the group consisting of:

(a) hydrogen;

(b) C 1-6 alkyl, optionally substituted with one to three —OH;

(c) C 3-6 cycloalkyl, optionally substituted with —OH;

(d) —(C═O)—(NH) q —R c , wherein q is 0 or 1; and R c is selected from the group consisting of:

(i) hydrogen,

(ii) —C 1-6 alkyl, optionally substituted with one to three —OH,

(iii) —O—C 1-6 alkyl, and

(iv) a 5- or 6-membered heterocyclyl selected from the group consisting of pyridinyl, pyrimidinyl, piperidinyl, triazolyl and thiazolyl;

(e) —S(O) 2 —NH 2 ;

(f) —S(O) 2 —C 1-4 alkyl; and

(g) a 5- or 6-membered heterocyclyl selected from the group consisting of pyridinyl, pyrimidinyl, piperidinyl, pyrrolidinyl, triazolyl and thiazolyl;

each occurrence of R 1 is independently selected from the group consisting of (a) hydrogen and (b) halogen;

each occurrence of R 2 is independently selected from the group consisting of (a) hydrogen and (b) —OH;

or alternatively, two R 2 groups together with the carbon to which they are attached form a C 3-6 cycloalkyl or 4-, 5-, or 6-membered heterocycle;

or alternatively, R 2 and R a of W together with the carbon and/or nitrogen atoms to which they are attached form a 4-, 5- or 6-membered carbocycle or heterocycle;

each occurrence of R 3 is hydrogen; and

R 4 is selected from the group consisting of (a) hydrogen and (b) C 1-4 alkyl.

9. The compound of claim 1 having formula (Ia), or a pharmaceutically acceptable salt thereof:

wherein: m is 1, 2, or 3; n is 1 or 2; p is 0 or 1;

R is selected from the group consisting of:

(a) C 1-6 alkyl, optionally substituted with one to three substituents independently selected from the group consisting of (i) —OH and (ii) halogen,

(b) C 3-6 cycloalkyl, optionally substituted with —OH,

(c) —(C═O)—(NH) q —R c , wherein q is 0 or 1; and R c is selected from the group consisting of:

(i) hydrogen,

(ii) —C 1-6 alkyl, optionally substituted with one to three substituents independently selected from the group consisting of (1) halogen, (2) —OH and (3) heterocyclyl,

(iii) —O—C 1-6 alkyl,

(iv) —C 3-6 cycloalkyl, optionally substituted with —OH, and

(v) a 5- or 6-membered heterocyclyl, optionally substituted with one to four substituents independently selected from the group consisting of (1) halogen, (2) C 16 alkyl and (3) —OH;

(d) —S(O) 2 —NR d R e ; each of R d and R e W is independently hydrogen or C 1-6 alkyl;

(e) —S(O) 2 —C 1-6 alkyl; and

(f) a 5- or 6-membered heterocyclyl, optionally substituted with one to four substituents independently selected from the group consisting of (i) halogen and (ii) C 1-6 alkyl;

R a is selected from the group consisting of (a) hydrogen and (b) C 1-6 alkyl, optionally substituted with —OH,

each occurrence of R 1 is independently selected from the group consisting of (a) hydrogen, (b) halogen and (c) C 1-6 alkyl;

each occurrence of R 2 is independently selected from the group consisting of (a) hydrogen, (b) —OH and (c) C 1-6 alkyl, optionally substituted with —OH; and

each occurrence of R 3 is independently selected from the group consisting of (a) hydrogen and (b) C 1-6 alkyl.

10. The compound of claim 9 , or a pharmaceutically acceptable salt thereof,

wherein: m is 1 or 2; n is 1; p is 0 or 1;

R is selected from the group consisting of:

(a) C 1-6 alkyl, optionally substituted with one to three substituents independently selected from the group consisting of (i) —OH and (ii) halogen,

(b) —(C═O)—(NH) q —R c , wherein q is 0 or 1; and R c is selected from the group consisting of:

(i) hydrogen,

(ii) —C 1-6 alkyl, optionally substituted with one to three substituents independently selected from the group consisting of (1) halogen and (2) —OH,

(iii) —C 3-6 cycloalkyl, optionally substituted with —OH, and

(iv) a 5- or 6-membered heterocyclyl, optionally substituted with one to four substituents independently selected from the group consisting of (1) halogen, (2) C 1-6 alkyl and (3) —OH;

(c) —S(O) 2 —NH 2 ;

(d) —S(O) 2 —C 1-6 alkyl; and

(e) a 5- or 6-membered heterocyclyl selected from pyridinyl, pyrimidinyl, piperidinyl, triazolyl, and thiazolyl;

R a is selected from the group consisting of (a) hydrogen and (b) C 1-4 alkyl, optionally substituted with —OH;

each occurrence of R 1 is independently selected from the group consisting of (a) hydrogen, (b) halogen and (c) C 1-4 alkyl;

each occurrence of R 2 is independently selected from the group consisting of (a) hydrogen, (b) —OH and (c) C 1-4 alkyl, optionally substituted with —OH; and

each occurrence of R 3 is independently selected from the group consisting of (a) hydrogen and (b) C 1-4 alkyl.

11. The compound of claim 9 having formula (Ib), or a pharmaceutically acceptable salt thereof,

wherein: m is 1 or 2;

R is selected from the group consisting of:

(a) —(C═O)—(NH) q —R c , wherein q is 0 or 1; and R c is selected from the group consisting of:

(i) hydrogen,

(ii) —C 1-4 alkyl, optionally substituted with one to two —OH,

(iii) —C 3-6 cycloalkyl, optionally substituted with —OH; and

(b) —S(O) 2 —NH 2 ; and

(c) —S(O) 2 —C 1-4 alkyl;

each occurrence of R 1 is independently selected from the group consisting of (a) hydrogen and (b) halogen; and

each occurrence of R 2 is independently selected from the group consisting of (a) hydrogen and (b) —OH.

12. The compound of claim 11 , or a pharmaceutically acceptable salt thereof, wherein: m is 2;

R is selected from the group consisting of: (a) —S(O) 2 —NH 2 , (b) —S(O) 2 —CH 3 , (c) —S(O) 2 —CH 2 CH 3 and (d) —S(O) 2 —CH 2 CH 2 CH 3

R 1 is selected from the group consisting of (a) hydrogen, (b) —F and (c) —Cl; and

each occurrence of R 2 is hydrogen.

13. The compound of claim 1 having formula (Ic), or a pharmaceutically acceptable salt thereof:

wherein: n is 1 or 2; p is 0 or 1; q is 0, 1 or 2; r is 1 or 2; t is 0, 1 or 2;

W is N or CR a ; provided when W is N, p is 0;

R is selected from the group consisting of:

(a) hydrogen,

(b) —(C═O)—R c , wherein R c is selected from the group consisting of:

(i) hydrogen,

(ii) —C 1-6 alkyl, optionally substituted with one to three substituents independently selected from the group consisting of (1) halogen and (2) —OH,

(iii) —O—C 1-6 alkyl, and

(iv) a 5- or 6-membered heterocyclyl, optionally substituted with one to four substituents independently selected from the group consisting of (1) halogen, (2) C 1-6 alkyl and (3) —OH;

(c) —S(O) 2 —NR d R e ; each of R d and R e is independently hydrogen or C 1-6 alkyl; and

(d) —S(O) 2 —C 1-6 alkyl;

each occurrence of R a and R b is independently selected from the group consisting of (a) hydrogen and (b) C 1-6 alkyl, optionally substituted with —OH;

each occurrence of R 1 is independently selected from the group consisting of (a) hydrogen and (b) halogen;

each occurrence of R 2 is independently selected from the group consisting of (a) hydrogen and (b) —OH; and

each occurrence of R 3 is independently selected from the group consisting of (a) hydrogen and (b) C 1-6 alkyl.

14. The compound of claim 13 , or a pharmaceutically acceptable salt thereof:

wherein: n is 1 or 2; p is 0 or 1; q is 0; r is 1 or 2; t is 0, 1 or 2;

W is N or CR a ; provided when W is N, p is 0;

R is selected from the group consisting of:

(a) hydrogen,

(b) —(C═O)—R c , wherein R c is selected from the group consisting of:

(i) hydrogen,

(ii) —C 1-6 alkyl, optionally substituted with one to three substituents independently selected from the group consisting of (1) halogen and (2) —OH,

(iii) —O—-C 1-6 alkyl, and

(iv) a 5- or 6-membered heterocyclyl selected from pyridinyl, pyrimidinyl, piperidinyl, pyrrolidinyl, triazolyl and thiazolyl;

(c) —S(O) 2 —NH 2 ; and

(d) —S(O) 2 —C 1-4 alkyl;

each occurrence of R a and R b is hydrogen;

each occurrence of R 1 is independently selected from the group consisting of (a) hydrogen and (b) halogen;

each occurrence of R 2 is independently selected from the group consisting of (a) hydrogen and (b) —OH; and

each occurrence of R 3 is hydrogen.

15. The compound of claim 13 having formula (Id), or a pharmaceutically acceptable salt thereof,

wherein: r is 1 or 2; t is 1 or 2;

R is selected from the group consisting of:

(a) hydrogen;

(b) —(C═O)—R c , wherein R c is selected from the group consisting of:

(i) hydrogen,

(ii) —C 1-6 alkyl, optionally substituted with one to three substituents independently selected from the group consisting of (1) halogen and (2) —OH,

(iii) —O—C 1-6 alkyl, and

(iv) a 5- or 6-membered heterocyclyl selected from pyridinyl, pyrimidinyl, piperidinyl, pyrrolidinyl, triazolyl and thiazolyl;

(c) —S(O) 2 —NH 2; and

(d) —S(O) 2 —C 1-4 alkyl;

each occurrence of R a and R b is independently selected from the group consisting of (a) hydrogen and (b) C 1-4 alkyl;

each occurrence of R 1 is independently selected from the group consisting of (a) hydrogen and (b) halogen; and

each occurrence of R 2 is independently selected from the group consisting of (a) hydrogen and (b) —OH.

16. The compound of claim 13 having formula (Ie), or a pharmaceutically acceptable salt thereof,

wherein: n is 1 or 2; p is 0 or 1; r is 1 or 2; t is 0, 1 or 2;

R is selected from the group consisting of:

(a) hydrogen,

(b) —(C═O)—R c , wherein R c is selected from the group consisting of:

(i) hydrogen,

(ii) —C 1-6 alkyl, optionally substituted with one to three substituents independently selected from the group consisting of (1) halogen and (2) —OH,

(iii) —O—C 1-6 alkyl, and

(iv) a 5- or 6-membered heterocyclyl, optionally substituted with one to four substituents independently selected from the group consisting of (1) halogen, (2) C 1-6 alkyl and (3) —OH;

(c) —S(O) 2 —NR d R e ; each of R d and R e is independently hydrogen or C 1-6 alkyl; and

(d) —S(O) 2 —C 1-6 alkyl;

each occurrence of R a and R b is independently selected from the group consisting of (a) hydrogen and (b) C 1-6 alkyl, optionally substituted with —OH;

each occurrence of R 1 is independently selected from the group consisting of (a) hydrogen and (b) halogen;

each occurrence of R 2 is independently selected from the group consisting of (a) hydrogen and (b) —OH; and

each occurrence of R 3 is independently selected from the group consisting of (a) hydrogen and (b) C 1-6 alkyl.

17. The compound of claim 16 having formula (If), or a pharmaceutically acceptable salt thereof,

wherein: r is 1 or 2; t is 0, 1 or 2;

R is selected from the group consisting of:

(a) hydrogen,

(b) —(C═O)—R c , wherein R c is selected from the group consisting of:

(i) hydrogen,

(ii) —C 1-6 alkyl, optionally substituted with one to three substituents independently selected from the group consisting of (1) halogen and (2) —OH,

(iii) —O—C 1-6 alkyl, and

(iv) a 5- or 6-membered heterocyclyl selected from pyridinyl, pyrimidinyl, piperidinyl, pyrrolidinyl, triazolyl and thiazolyl;

(c) —S(O) 2 —NH 2; and

(d) —S(O) 2 —C 1-6 alkyl;

each occurrence of R a and R b is hydrogen;

each occurrence of R 1 is independently selected from the group consisting of (a) hydrogen and (b) halogen; and

each occurrence of R 2 is hydrogen.

18. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, selected from the group consisting of:

(S)—N—(4—fluorobicyclo[4.2.0]octa—1(6),2,4—trien—7—yl)—N′—hydroxy—4—(2—(sulfamoylamino)ethoxy) —1,2,5—oxadiazole—3—carboximidamide,

(S)—N—(4—fluorobicyclo[4.2.0]octa—1(6),2,4—trien—7—yl)—N′—hydroxy—4—((1—(2—hydroxyacetyl)azetidin —3—yl)oxy)—1,2,5—oxadiazole—3—carboximidamide,

(S)—N—(2—((4—(N—(4—fluorobicyclo[4.2.0]octa—1(6),2,4—trien—7—yl)—N′—hydroxycarbamimidoyl)—1,2,5—oxadiazol—3—yl)oxy)ethyl)acetamide,

(S)—2—((4—(N—(4—fluorobicyclo[4.2.0]octa-1(6),2,4—trien—7—yl)—N′—hydroxycarbamimidoyl)—1,2,5—oxadiazol—3—yl)oxy)—N—(2—hydroxyethyl)acetamide,

N—{2—[(4—{N—[(7 S)—4—fluorobicyclo[4.2.0]octa—1,3,5—trien—7—yl]—N′—hydroxycarbamimidoyl}—1,2,5—oxadiazol—3 —yl)oxy]ethyl}—2—hydroxyacetamide,

N—[(7S)—4—fluorobicyclo[4.2.0]octa—1,3,5—trien—7—yl]—N′—hydroxy—4—{2—[(methylsulfonyl)amino]ethoxy}—1,2,5 —oxadiazole—3 —carboximidamide,

2—[(4—{N—[(7S)—4—fluorobicyclo[4.2.0]octa—1,3,5—trien—7—yl]—N′—hydroxycarbamimidoyl}—1,2,5—oxadiazol—3 —yl)oxy]—N—[(2 S)—1—hydroxypropan—2—yl]acetamide,

2—[(4—{N—[(7S)—4—fluorobicyclo[4.2.0]octa—1,3,5—trien—7—yl]—N′—hydroxycarbamimidoyl}—1,2,5—oxadiazol—3 —yl)oxy]—N—[(2R)—1—hydroxypropan—2—yl]acetamide,

2—[(4—{N—[(7S)—4—fluorobicyclo[4.2.0]octa—1,3,5—trien—7—yl]—N′—hydroxycarbamimidoyl}—1,2,5—oxadiazol—3 —yl)oxy]—N—[(2 S)—2—hydroxypropyl]acetamide,

2—[(4—{N—(7S)—4—fluorobicyclo[4.2.0]octa—1,3,5—trien—7—yl]—N′—hydroxycarbamimidoyl}—1,2,5—oxadiazol—3 —yl)oxy]—N—[(2R)—2—hydroxypropyl]acetamid,

4—[2—(carbamoylamino)ethoxy]—N—(4—fluorobicyclo[4.2.0]octa—1,3,5—trien—7—yl)—N′—hydroxy—1,2,5—oxadiazole—3—carboximidamide,

N—(2,3—dihydroxypropyl)—2—({4—[N—(4—fluorobicyclo[4.2.0]octa—1,3,5 —trien—7—yl)—N′—hydroxycarbamimidoyl]—1,2,5 —oxadiazol—3 —yl }oxy)acetamide,

2—[(4—{N—[(1 S)—6—fluoro 13 2,3 —dihydro—1H—inden—1—yl]—N′—hydroxycarbamimidoyl }—1,2,5—oxadiazol—3—yl)oxy]—N—(2—hydroxyethyl)acetamide,

2—({4[N—(4—fluorobicyclo[4.2.0]octa—1,3,5—trien—7—yl)—N′—hydroxycarbamimidoyl]—1,2,5—oxadiazol —3—yl}oxy)—N—(2—hydroxy—2—methylpropyl)acetamide,

4—{2—[carbamoyl(2—hydroxyethyl)amino]ethoxy}—N—(4—fluorobicyclo[4.2.0]octa—1,3,5—trien—7—yl) —N′—hydroxy—1,2,5—oxadiazole—3 —carboximidamide,

N—[(2R)—2,3—dihydroxypropyl]—2—[(4—{N—[(7S)—4—fluorobicyclo[4.2.0]octa—1,3,5—trien—7—yl]—N′—hydroxycarbamimidoyl}—1,2,5—oxadiazol—3—yl)oxy]acetamide,

2—[(4—{N—[7S)—4—fluorobicyclo[4.2.0]octa—1,3,5—trien—7—yl]—N′—hydroxycarbamimidoyl}—1,2,5—oxadiazol—3—yl)oxy]acetamide,

4{(carbamoylamino)propoxy]—N—[(7S)—4—fluorobicyclo[4.2.0]octa—1,3,5—trien—7—yl]—N′—hydroxy —1,2,5—oxadiazole—3 —carboximidamide,

2—({4[N—(4—fluorobicyclo[4.2.0]octa—1,3,5—trien—7—yl)—N′—hydroxycarbamimidoyl]—1,2,5—oxadiazol —3 —yl }oxy)—N—(2—hydroxyethyl)—2—methylpropanamide,

(2R)—N—{2—[(4—{N—[7S)—4—fluorobicyclo[4.2.0] octa—1,3,5—trien—7—yl]—N′—hydroxycarbamimidoyl}—1,2,5 —oxadiazol—3 —yl)oxy]ethyl}—2,3 —dihydroxypropanamide,

4—[(azetidin—3—yl)oxy]—N—[(7S)—4—fluorobicyclo[4.2.0]octa—1,3,5—trien—7—yl]—N′—hydroxy—1,2,5—oxadiazole—3—carboximidamide,

N—{2—[(4—{N—[(7S)—4—fluorobicyclo[4.2.0]octa—1,3,5—trien—7—yl]—N′—hydroxycarbamimidoyl}—1,2,5—oxadiazol—3 —yl)oxy]ethyl}—1H—1,2,4—triazole—3—carboxamide,

2—({44[N—(4—fluorobicyclo[4.2.0]octa—1,3,5—trien—7—yl)—N′—hydroxycarbamimidoyl]—1,2,5—oxadiazol —3—yl}oxy)—N—(2—hydroxyethyl)propanamide,

N—[(1 S)—6—fluoro—2,3—dihydro—1H—inden—1—yl]—N′—hydroxy—4——[2—(sulfamoylamino)ethoxy]—1,2,5—oxadiazole—3—carboximidamide,

N—[(7S)—4—fluorobicyclo[4.2.0]octa—1,3,5—trien—7—yl]—N′—hydroxy—4—{[(3S)—1—(hydroxyacetyl)pyrrolidin—3—yl]oxy}—1,2,5 —oxadiazole—3—carboximidamide,

(2S)—N—{2—[(4—{N—[(7S)—4—fluorobicyclo[4.2.0]octa—1,3,5—trien—7—yl]—N′—hydroxycarbamimidoyl}—1,2,5 —oxadiazol—3—yl)oxy]ethyl}—2,3 —dihydroxypropanamide,

N—[(7S)—4—fluorobicyclo[4.2.0]octa—1,3,5—trien—7—yl]—N′—hydroxy—4—[2-(methylsulfonyl)ethoxy]—1,2,5—oxadiazole—3—carboximidamide,

N—[(7S)—4—fluorobicyclo[4.2.0]octa—1,3,5—trien—7—yl]—N′—hydroxy—4—[2—(4H—1,2,4—triazol—4—yl)ethoxy]—1,2,5—oxadiazole—3—carboximidamide,

N—[(7S)—4—fluorobicyclo[4.2.0]octa—1,3,5—trien—7—yl]—N′—hydroxy—4—(3—sulfamoylpropoxy)—1,2,5—oxadiazole—3—carboximidamide,

N—[(7S)—4—fluorobicyclo[4.2.0]octa—1,3,5—trien—7—yl]—N′—hydroxy—4—{[1—(1H—1,2,4—triazole—3—carbonyl)azetidin—3—yl]oxy}—1,2,5—oxadiazole—3—carboximidamide,

N—[(7S)—4—fluorobicyclo[4.2.0]octa—1,3,5—trien—7—yl]—N′—hydroxy—4—{[(3R)1—sulfamoylpyrrolidin—3—yl]oxy}—1,2,5—oxadiazole—3—carboximidamide,

N—[(7S)—4—fluorobicyclo[4.2.0]octa—1,3,5—trien—7—yl]—N′—hydroxy—4—{[(3S)—1—sulfamoylpyrrolidin—3—yl]oxy}—1,2,5—oxadiazole—3—carboximidamide,

N—{2—[(4—{N—[7S)—4—fluorobicyclo[4.2.0]octa—1,3,5—trien—7—yl]—N′—hydroxycarbamimidoyl}—1,2,5—oxadiazol—3—yl)oxy]ethyl }propanamide,

N—[(7S)—4—fluorobicyclo[4.2.0]octa—1,3,5—trien—7—yl]—N′—hydroxy—4—(2—sulfamoylethoxy)—1,2,5—oxadiazole—3—carboximidamide,

N—{1—[(4—{N—[(7S)—4—fluorobicyclo[4.2.0]—1,3,5—trien—7—yl]—N′—hydroxycarbamimidoyl}—1,2,5—oxadiazol—3—yl)oxy]—2—methylpropan—2—yl}—2—hydroxyacetamide,

N—{cis—3—[(4—{N—[(7S)—4—fluorobicyclo [4.2.0]octa—1,3,5—trien—7—yl]—N′—hydroxycarbamimidoyl}—1,2,5—oxadiazol—3—yl)oxy]cyclobutyl}acetamide,

N—{trans—3—[(4—{N—[(7S)—4—fluorobicyclo[4.2.0]octa—1,3,5—trien—7—yl]—N′—hydroxycarbamimidoyl}—1,2,5—oxadiazol—3—yl)oxy]cyclobutyl }acetamide,

N—{cis—3—[(4—{N—[(7S)—4—fluorobicyclo[4.2.0]octa—1,3,5—trien—7—yl]—N′—hydroxycarbamimidoyl}—1,2,5—oxadiazol—3—yl)oxy]cyclobutyl}—2—hydroxyacetamide,

N—{1—[(4—{N—[(7S)—4—fluorobicyclo[4.2.0]octa—1,3,5—trien—7—yl]—N′—hydroxycarbamimidoyl}—1,2,5—oxadiazol—3—yl)oxy]—3—hydroxypropan—2—yl}acetamide,

N—{(2S)—2—[(4—{N—[(7S)-4—fluorobicyclo[4.2.0]octa—1,3,5—trien—7—yl]—N′—hydroxycarbamimidoyl}—1,2,5—oxadiazol—3—yl)oxy]propyl }acetamide,

methyl {2—[(4—{N—[(7S)—4—fluorobicyclo[4.2.0]octa—1,3,5—trien—7—yl]—N′—hydroxycarbamimidoyl}—1,2,5—oxadiazol—3—yl)oxy]ethyl}carbamate,

4—{[cis—3—(carbamoylamino)cyclobutyl]oxy}—N—[(7S)—4—fluorobicyclo[4.2.0 ]octa—1,3,5—trien—7—yl]—N′—hydroxy—1,2,5—oxadiazole—3—carboximidamide,

N—[(7S)—4—fluorobicyclo[4.2.0]octa—1,3,5—trien—7—yl]—N′—hydroxy—4—{[cis—3—(sulfamoylamino)cyclobutyl]oxy}—1,2,5—oxadiazole—3—carboximidamide,

N—[(7S)—4—fluorobicyclo[4.2.0]octa—1,3,5—trien—7—yl]—N′—hydroxy—4—{2—[(3R)—3—hydroxypyrrolidin—1—yl]—2—oxoethoxy}—1,2,5—oxadiazole—3—carboximidamide,

N—[(7S)—4—fluorobicyclo[4.2.0]octa—1,3,5—trien—7—yl]—N′—hydroxy—4—{2—[(3S)—3—hydroxypyrrolidin—1—yl]—2—oxoethoxy}1,2,5—oxadiazole—3—carboximidamide,

N—{(2S)—2—[(4—{N—[(7S)—4—fluorobicyclo[4.2.0]octa—1,3,5—trien—7—yl]—N′—hydroxycarbamimidoyl}—1,2,5—oxadiazol—3—yl)oxy]propyl}—2—hydroxyacetamide,

N—[(7S)—4—fluorobicyclo[4.2.0]octa—1,3,5—trien—7—yl]—N′—hydroxy—4—{[1—(1—hydroxycyclopropane—1—carbonyl)azetidin—3—yl]oxy}—1,2,5—oxadiazole—3—carboximidamide,

N—[(7S)—4—fluorobicyclo[4.2.0]octa—1,3,5—trien—7—yl]—N′—hydroxy—4—({1—[(2S)—2—hydroxypropanoyl]azetidin—3—yl}oxy)—1,2,5—oxadiazole—3—carboximidamide,

N—[(7S)—4—fluorobicyclo[4.2.0]octa—1,3,5—trien—7—yl]—N′—hydroxy—4—[(1—sulfamoylpiperidin—4—yl)oxy]—1,2,5—oxadiazole—3—carboximidamide,

N—[(7S)—4—fluorobicyclo[4.2.0]octa—1,3,5—trien—7—yl]—N′—hydroxy—4—{[1—(hydroxyacetyl)piperidin—4—yl]oxy}—1,2,5—oxadiazole—3—carboximidamide,

N—{(2R)—1—[(4—{N—[(7S)—4—fluorobicyclo[4.2.0]octa—1,3,5—trien—7—yl]—N′—hydroxycarbamimidoyl}—1,2,5—oxadiazol—3—yl)oxy]—3—hydroxypropan—2—yl}acetamide,

N—{(2S)—1—[(4—{N—[(7S)—4—fluorobicyclo[4.2.0]octa—1,3,5—trien—7—yl]—N′—hydroxycarbamimidoyl}—1,2,5—oxadiazol—3—yl)oxy]—3—hydroxypropan—2—yl}acetamide,

N—{(2S)—3—[(4—{N—[(7S)—4—fluorobicyclo[4.2.0]octa—1,3,5—trien—7—yl]—N′—hydroxycarbamimidoyl}—1,2,5 —oxadiazol—3—yl)oxy]—2—hydroxypropyl}acetamide,

N—[(7S)—4—fluorobicyclo[4.2.0]octa—1,3,5—trien—7—yl]—N′—hydroxy—4—{[(2S)—1—(hydroxyacetyl)azetidin—2—yl]methoxy}—1,2,5—oxadiazole—3—carboximidamide,

N—{(2S)—2—[(4—{N—[(7S)—4—fluorobicyclo[4.2.0]octa—1,3,5—trien—7—yl]—N′—hydroxycarbamimidoyl}—1,2,5—oxadiazol—3—yl)oxy]—3—hydroxypropyl acetamide,

N—{trans—3—[(4—{N—[(7S)—4—fluorobicyclo[4.2.0]octa—1,3,5—trien—7—yl]—N′—hydroxycarbamimidoyl}—1,2,5—oxadiazol—3—yl)oxy]cyclobutyl}—2—hydroxyacetamide,

4—{[trans—3—(carbamoylamino)cyclobutyl]oxy}—N—[(7S)—4—fluorobicyclo[4.2.0]octa—1,3,5—trien—7—yl]—N′—hydroxy—1,2,5—oxadiazole—3—carboximidamide,

N—[(7S)—4—fluorobicyclo[4.2.0]octa—1,3,5—trien—7—yl]—N′—hydroxy—4—{[(2R)—1—(hydroxyacetyl)pyrrolidin—2—yl]methoxy}—1,2,5—oxadiazole—3—carboximidamide,

N—[(7S)—4—fluorobicyclo[4.2.0]octa—1,3,5—trien—7—yl]—N′—hydroxy—4—{[1—(hydroxyacetyl)azetidin—3—yl]methoxy}—1,2,5—oxadiazole—3—carboximidamide, and

N—[(7S)—4—fluorobicyclo[4.2.0]octa—1,3,5—trien—7—yl]—N′—hydroxy—4—{[(3R)—1—(hydroxyacetyl)pyrrolidin—3—yl]oxy }-1,2,5—oxadiazole—3—carboximidamide.

19. A composition which comprises an inert carrier and a compound of claim 1 or a pharmaceutically acceptable salt thereof.