Amino compounds for treatment of immune and inflammatory disorders

1. A compound of Formula:

or a pharmaceutically acceptable salt thereof, wherein

A is A1;

B is B1 or B4;

L is L1;

L3 is L4 or L5;

A1 is

B1 is selected from the group consisting of a monocyclic or bicyclic carbocyclic; a monocyclic or bicyclic carbocyclic-oxy group; a monocyclic, bicyclic, or tricyclic heterocyclic group having 1, 2, 3, or 4 heteroatoms independently selected from N, O, and S and from 4 to 7 ring atoms per ring; —(C 0 -C 4 alkyl)(aryl); —(C 0 -C 4 alkyl)(heteroaryl); and —(C 0 -C 4 alkyl)(biphenyl), each of which B1 is unsubstituted or substituted with one or more substituents independently selected from the group consisting of R 33 and R 34 , and 0 or 1 substituents selected from the group consisting of R 35 and R 36 ;

B4 is selected from the group consisting of:

(i) a 4-membered carbocyclic fused to a 5- or 6-membered heteroaryl having 1, 2, or 3 heteroatoms independently selected from N, O, and S;

(ii) a 4-membered carbocyclic fused to a 6-membered aryl ring; and

(iii) (cycloalkyl)-(aryl), (cycloalkyl)-(heteroaryl), (cycloalkyl)-(heterocycle), (alkyl)-alkenyl, or cycloalkyl-alkenyl;

wherein B4 can be substituted 1, 2, 3 or 4 times with the substituents independently selected from the group consisting of R 33 , R 34 , R 35 R 36 and R 48 ;

L1 is a bond or is selected from the group consisting of formulas

L4 is —C(O)—;

L5 is —C(S)—, —P(O)OH—, —S(O)—, —S(O) 2 — or —C(R 52 ) 2 —;

X 11 is N or CR 11 ;

X 12 is CR 12 ;

X 13 is CR 13 ;

X 14 is N or CR 14 ;

R 6 is selected from the group consisting of hydrogen, -JCHO, -JC(O)NH 2 , -JC 2 -C 6 alkanoyl, -JC(O)NH(CH 3 ), -J-COOH, -JP(O)(OR 9 ) 2 , -JOC(O)R 9 , -JC(O)OR 9 , -JC(O)N(CH 2 CH 2 R 9 )(R 10 ), -JNR 9 C(O)R 10 , -JSO 2 NH 2 , -JS(O)NH 2 , -JC(CH 2 ) 2 F, -JCH(CF 3 )NH 2 , -JC(O)C 0 -C 2 alkyl(C 3 -C 7 cycloalkyl), -JNR 9 (C 2 -C 6 alkanoyl), -JNR 9 C(O)NR 9 R 10 , -JSO 2 (C 1 -C 6 alkyl), -JSO 2 (C 1 -C 6 haloalkyl), -JSO 2 NR 7 R 7 , -JSO═NH(C 1 -C 6 alkyl), -J-nitro, -J-halogen, -J-hydroxyl, -J-phenyl, a 5- to 6-membered heteroaryl, -J-cyano, -J-cyanoimino, -J-amino, -J-imino, —C 1 -C 6 alkyl, —C 0 -C 4 alkyl(C 3 -C 7 heterocycloalkyl), —C 0 -C 4 alkyl(C 3 -C 7 cycloalkyl),

each R 6 other than hydrogen, nitro, halogen, cyano, cyanoimino, or —CHO is unsubstituted or substituted with one or more substituents selected from the group consisting of amino, imino, halogen, hydroxyl, cyano, cyanoimino, C 1 -C 2 alkyl, C 1 -C 2 alkoxy, —C 0 -C 2 alkyl(mono- and di-C 1 -C 4 alkylamino), C 1 -C 2 haloalkyl, and C 1 -C 2 haloalkoxy;

R 7 is hydrogen, C 1 -C 6 alkyl, or —C 0 -C 4 alkyl(C 3 -C 7 cycloalkyl);

R 8 and R 8′ are independently selected from the group consisting of hydrogen, halogen, hydroxyl, C 1 -C 6 alkyl, —C 0 -C 4 alkyl(C 3 -C 7 cycloalkyl), C 1 -C 6 alkoxy, and (C 1 -C 4 alkylamino)C 0 -C 2 alkyl; or R 8 and R 8′ are taken together to form an oxo group; or R 8 and R 8′ can be taken together with the carbon that they are bonded to form a 3-membered carbocyclic ring;

R 9 and R 10 are independently selected at each occurrence from the group consisting of hydrogen, C 1 -C 6 alkyl, (C 3 -C 7 cycloalkyl)C 0 -C 4 alkyl, —C 0 -C 4 alkyl(C 3 -C 7 cycloalkyl), and —O—C 0 -C 4 alkyl(C 3 -C 7 cycloalkyl);

R 11 and R 14 are independently selected at each occurrence from the group consisting of hydrogen, halogen, hydroxyl, nitro, cyano, —O(PO)(OR 9 ) 2 , —(PO)(OR 9 ) 2 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 2 -C 6 alkenyl(aryl), C 2 -C 6 alkenyl(cycloalkyl), C 2 -C 6 alkenyl(heterocycle), C 2 -C 6 alkenyl(heteroaryl), C 2 -C 6 alkynyl, C 2 -C 6 alkynyl(aryl), C 2 -C 6 alkynyl(cycloalkyl), C 2 -C 6 alkynyl(heterocycle), C 2 -C 6 alkynyl(heteroaryl), C 2 -C 6 alkanoyl, C 1 -C 6 alkoxy, C 1 -C 6 thioalkyl, —C 0 -C 4 alkyl(mono- and di-C 1 -C 6 alkylamino), —C 0 -C 4 alkyl(C 3 -C 7 cycloalkyl), —C 0 -C 4 alkoxy(C 3 -C 7 cycloalkyl), C 1 -C 2 haloalkyl, and C 1 -C 2 haloalkoxy;

one of R 12 and R 13 is chosen from R 31 and the other of R 12 and R 13 is chosen from R 32 or both R 12 and R 13 are each independently selected from a R 32 ;

R 17 is hydrogen, C 1 -C 6 alkyl, or —C 0 -C 2 alkyl(C 3 -C 7 cycloalkyl);

R 18 and R 18′ are independently selected from the group consisting of hydrogen, halogen, hydroxymethyl, and methyl;

m is 0, 1, 2, or 3;

R 21 and R 22 are independently selected at each occurrence from the group consisting of hydrogen, hydroxyl, cyano, amino, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, (C 3 -C 7 cycloalkyl)C 0 -C 4 alkyl, (phenyl)C 0 -C 4 alkyl, —C 1 -C 4 alkylOC(O)OC 1 -C 6 alkyl, —C 1 -C 4 alkylOC(O)C 1 -C 6 alkyl, —C 1 -C 4 alkylC(O)OC 1 -C 6 alkyl, (4- to 7-membered heterocycloalkyl)C 0 -C 4 alkyl having 1, 2, or 3 heteroatoms independently selected from N, O, and S, and (5- or 6-membered unsaturated or aromatic heterocycle)C 0 -C 4 alkyl having 1, 2, or 3 heteroatoms independently selected from N, O, and S;

R 23 is independently selected at each occurrence from the group consisting of C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, (aryl)C 0 -C 4 alkyl, (C 3 -C 7 cycloalkyl)C 0 -C 4 alkyl, (phenyl)C 0 -C 4 alkyl, (4- to 7-membered heterocycloalkyl)C 0 -C 4 alkyl having 1, 2, or 3 heteroatoms independently selected from N, O, and S, and (5- or 6-membered unsaturated or aromatic heterocycle)C 0 -C 4 alkyl having 1, 2, or 3 heteroatoms independently selected from N, O, and S;

R 31 is selected from the group consisting of hydrogen, halogen, hydroxyl, nitro, cyano, amino,

—COOH, C 1 -C 2 haloalkyl, C 1 -C 2 haloalkoxy, C 1 -C 6 alkyl, —C 0 -C 4 alkyl(C 3 -C 7 cycloalkyl), C 2 -C 6 alkenyl, C 2 -C 6 alkanoyl, C 1 -C 6 alkoxy, C 2 -C 6 alkenyloxy, —C(O)OR 9 , C 1 -C 6 thioalkyl, —C 0 -C 4 alkylNR 9 R 10 , —C(O)NR 9 R 10 , —SO 2 R 9 , —SO 2 NR 9 R 10 , —OC(O)R 9 , and —C(NR 9 )NR 9 R 10 , each of which R 31 other than hydrogen, halogen, hydroxyl, nitro, cyano, C 1 -C 2 haloalkyl, and C 1 -C 2 haloalkoxy is unsubstituted or substituted with one or more substituents independently selected from the group consisting of halogen, hydroxyl, nitro, cyano, amino, —COOH, —CONH 2 , C 1 -C 2 haloalkyl, and C 1 -C 2 haloalkoxy, and each of which R 31 is also optionally substituted with one substituent selected from the group consisting of phenyl and 4- to 7-membered heterocycle containing 1, 2, or 3 heteroatoms independently selected from N, O, and S; which phenyl or 4- to 7-membered heterocycle is unsubstituted or substituted with one or more substituents independently selected from the group consisting of halogen, hydroxyl, nitro, cyano, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkanoyl, C 1 -C 6 alkoxy, (mono- and di-C 1 -C 6 alkylamino)C 0 -C 4 alkyl, C 1 -C 6 alkylester, C 0 -C 4 alkyl(C 3 -C 7 cycloalkyl), C 1 -C 2 haloalkyl, and C 1 -C 2 haloalkoxy;

R 32 is selected from the group consisting of NR 72 R 73 , NR 9 SOR 73 , and N(SO 2 R 9 )CH 2 C(O)R 74 ;

R 72 is selected at each occurrence from the group consisting of aryl, heteroaryl, heterocycle, alkynyl, hydroxyl, C 1 -C 6 alkoxy, (C 3 -C 7 cycloalkyl)C 0 -C 4 alkyl, (aryl)C 0 -C 4 alkyl, (heterocycle)C 0 -C 4 alkyl, (heteroaryl)C 0 -C 4 alkyl, —C 1 -C 4 alkylOC(O)OC 1 -C 6 alkyl, —C 1 -C 4 alkylOC(O)C 1 -C 6 alkyl, —C 1 -C 4 alkylC(O)OC 1 -C 6 alkyl, —S(O)(O)(alkyl), —S(O)(alkyl), —S(O)(O)(heteroalkyl), —S(O)(heteroalkyl), —S(O)(O)(aryl), —S(O)(aryl), —S(O)(O)(heteroaryl), —S(O)(heteroaryl), (4- to 7-membered heterocycloalkyl)C 0 -C 4 alkyl having 1, 2, or 3 heteroatoms independently selected from N, O, and S, and (5- or 6-membered saturated or partially unsaturated heterocycle)C 0 -C 4 alkyl having 1, 2, or 3 heteroatoms independently selected from N, O, and S;

R 73 is selected at each occurrence from the group consisting of hydrogen, hydroxyl, cyano, amino, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, (C 3 -C 7 cycloalkyl)C 0 -C 4 alkyl, (phenyl)C 0 -C 4 alkyl, —C 1 -C 4 alkylOC(O)OC 1 -C 6 alkyl, —C 1 -C 4 alkylOC(O)C 1 -C 6 alkyl, —C 1 -C 4 alkylC(O)OC 1 -C 6 alkyl, (4- to 7-membered heterocycloalkyl)C 0 -C 4 alkyl having 1, 2, or 3 heteroatoms independently selected from N, O, and S, and (5- or 6-membered unsaturated or aromatic heterocycle)C 0 -C 4 alkyl having 1, 2, or 3 heteroatoms independently selected from N, O, and S;

R 74 is a proline amide;

R 33 is independently selected from the group consisting of halogen, hydroxyl, —COOH, cyano, C 1 -C 6 alkyl, C 2 -C 6 alkanoyl, C 1 -C 6 alkoxy, —C 0 -C 4 alkylNR 9 R 10 , —SO 2 R 9 , C 1 -C 2 haloalkyl, and C 1 -C 2 haloalkoxy;

R 34 is independently selected from the group consisting of nitro, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 thioalkyl, -JC 3 -C 7 cycloalkyl, —B(OH) 2 , -JC(O)NR 9 R 23 , -JOSO 2 OR 21 , —C(O)(CH 2 ) 1-4 S(O)R 21 , —O(CH 2 ) 1-4 S(O)NR 21 R 22 , -JOP(O)(OR 21 )(OR 22 ), -JP(O)(OR 21 )(OR 22 ), -JOP(O)(OR 21 )R 22 , -JP(O)(OR 21 )R 22 , -JOP(O)R 21 R 22 , -JP(O)R 21 R 22 , -JSP(O)(OR 21 )(OR 22 ), -JSP(O)(OR 21 )(R 22 ), -JSP(O)(R 21 )(R 22 ), -JNR 9 P(O)(NHR 21 )(NHR 22 ), -JNR 9 P(O)(OR 21 )(NHR 22 ), -JNR 9 P(O)(OR 21 )(OR 22 ), -JC(S)R 21 , -JNR 21 SO 2 R 22 , -JNR 9 S(O)NR 10 R 22 , -JNR 9 SO 2 NR 10 R 22 , -JSO 2 NR 9 COR 22 , -JSO 2 NR 9 CONR 21 R 22 , -JNR 21 SO 2 R 22 , -JC(O)NR 21 SO 2 R 22 , -JC(NH 2 )═NR 22 , -JCH(NH 2 )NR 9 S(O) 2 R 22 , -JOC(O)NR 21 R 22 , -JNR 21 C(O)OR 22 , -JNR 21 OC(O)R 22 , —(CH 2 ) 1-4 C(O)NR 21 R 22 , -JNR 9 C(O)R 21 , -JC(O)R 21 , -JNR 9 C(O)NR 10 R 22 , —CCR 21 , —(CH 2 ) 1-4 OC(O)R 21 , and -JC(O)OR 23 ;

R 35 is independently selected from the group consisting of naphthyl, naphthyloxy, indanyl, (4- to 7-membered heterocycloalkyl)C 0 -C 4 alkyl containing 1 or 2 heteroatoms selected from N, O, and S, and bicyclic heterocycle containing 1, 2, or 3 heteroatoms independently selected from N, O, and S, and containing 4- to 7-ring atoms in each ring; each of which R 35 is unsubstituted or substituted with one or more substituents independently chosen from the group consisting of halogen, hydroxyl, nitro, cyano, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkanoyl, C 1 -C 6 alkoxy, (mono- and di-C 1 -C 6 alkylamino)C 0 -C 4 alkyl, C 1 -C 6 alkylester, —C 0 -C 4 alkyl(C 3 -C 7 cycloalkyl), —SO 2 R 9 , C 1 -C 2 haloalkyl, and C 1 -C 2 haloalkoxy;

R 36 is independently selected from the group consisting of tetrazolyl, (phenyl)C 0 -C 2 alkyl, (phenyl)C 1 -C 2 alkoxy, phenoxy, and 5- or 6-membered heteroaryl containing 1, 2, or 3 heteroatoms independently selected from N, O, B, and S, each of which R 36 is unsubstituted or substituted with one or more substituents independently selected from the group consisting of halogen, hydroxyl, nitro, cyano, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkanoyl, C 1 -C 6 alkoxy, (mono- and di-C 1 -C 6 alkylamino)C 0 -C 4 alkyl, C 1 -C 6 alkylester, —C 0 -C 4 alkyl(C 3 -C 7 cycloalkyl), —SO 2 R 9 , —OSi(CH 3 ) 2 C(CH 3 ) 3 , —Si(CH 3 ) 2 C(CH 3 ) 3 , C 1 -C 2 haloalkyl, and C 1 -C 2 haloalkoxy;

R 48 is independently selected from the group consisting of hydrogen, halogen, hydroxyl, nitro, cyano, amino, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 thioalkyl, C 1 -C 6 alkoxy, -JC 3 -C 7 cycloalkyl, —B(OH) 2 , -JC(O)NR 9 R 23 , -JOSO 2 OR 21 , —C(O)(CH 2 ) 1-4 S(O)R 21 , —O(CH 2 ) 1-4 S(O)NR 21 R 22 , -JOP(O)(OR 21 )(OR 22 ), -JP(O)(OR 21 )(OR 22 ), -JOP(O)(OR 21 )R 22 , -JP(O)(OR 21 )R 22 , -JOP(O)R 21 R 22 , -JP(O)R 21 R 22 , -JSP(O)(OR 21 )(OR 22 ), -JSP(O)(OR 21 )(R 22 ), -JSP(O)(R 21 )(R 22 ), -JNR 9 P(O)(NHR 21 )(NHR 22 ), -JNR 9 P(O)(OR 21 )(NHR 22 ), -JNR 9 P(O)(OR 21 )(OR 22 ), -JC(S)R 21 , -JNR 21 SO 2 R 22 , -JNR 9 S(O)NR 10 R 22 , -JNR 9 SO 2 NR 10 R 22 , -JSO 2 NR 9 COR 22 , -JSO 2 NR 9 CONR 21 R 22 , -JNR 21 SO 2 R 22 , -JC(O)NR 21 SO 2 R 22 , -JC(NH 2 )═NR 22 , -JCH(NH 2 )NR 9 S(O) 2 R 22 , -JOC(O)NR 21 R 22 , -JNR 21 C(O)OR 22 , -JNR 21 OC(O)R 22 , —(CH 2 ) 1-4 C(O)NR 21 R 22 , -JNR 9 C(O)R 21 , -JC(O)R 21 , -JNR 9 C(O)NR 10 R 22 , —CCR 21 , —(CH 2 ) 1-4 OC(O)R 21 , -JC(O)OR 23 ; and SC 1 -C 6 alkyl(O)═NH;

R 52 is independently selected from the group consisting of halo, hydrogen, and C 1 -C 6 alkyl;

J is independently selected at each occurrence from the group consisting of a covalent bond, C 1 -C 4 alkylene, —OC 1 -C 4 alkylene, C 2 -C 4 alkenylene, and C 2 -C 4 alkynylene;

R 37 is hydrogen, C 1 -C 6 alkyl, or —(C 0 -C 2 alkyl)(C 3 -C 6 cycloalkyl); and

R 38 and R 39 are independently selected from the group consisting of hydrogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 hydroxyalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 alkoxy, (C 3 -C 6 cycloalkyl)C 0 -C 4 alkyl-, (aryl)C 0 -C 2 alkyl-, and (heteroaryl)C 0 -C 2 alkyl-.

2. A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

3. The compound of claim 1 , wherein the compound is of formula:

or a pharmaceutically acceptable salt thereof.

4. The compound of claim 1 , wherein the compound is of formula:

or a pharmaceutically acceptable salt thereof.

5. The compound of claim 4 , wherein B is B1.

6. The compound of claim 1 , wherein B1 is selected from the group consisting of:

7. The compound of claim 1 , wherein R 32 is selected from the group consisting of:

8. The compound of claim 1 , wherein B is phenyl or pyridyl substituted with 1, 2, or 3 substituents selected from the group consisting of chloro, bromo, hydroxyl, C 1 -C 2 alkyl, C 1 -C 2 alkoxy, trifluoromethyl, phenyl, and trifluoromethoxy.

9. The compound of claim 1 , wherein B is 2-fluoro-3-chlorophenyl, or 2-fluoro-3-trifluoromethoxyphenyl.

10. The compound of claim 1 , wherein B is pyridyl, optionally substituted with halogen, C 1 -C 2 alkoxy, and trifluoromethyl.

11. The compound of claim 1 , wherein R 6 is selected from the group consisting of —CHO, —C(O)NH 2 , —C(O)NH(CH 3 ), C 2 -C 6 alkanoyl, and hydrogen.

12. The compound of claim 1 , wherein the compound is selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.