Triazolone compounds and uses thereof

1. A compound of Formula I

or a pharmaceutical acceptable salt thereof wherein:

A1 is phenyl or a 6-membered heteroaromatic ring having 1, 2 or 3 N in the heteroaromatic ring;

A2 is selected from A2a or A2b

wherein A2a is phenyl or a 6 membered heteroaromatic ring having 1, 2 or 3 N in the heteroaromatic ring, and

A2b is a 5 membered heteroaromatic ring having 1, 2 or 3 heteroatoms independently selected from O, S and N;

X is selected from the group consisting of —(CH 2 ) 2 —, —(CH 2 ) 3 —, —(CH 2 ) 4 — and —(CH 2 ) m —O—(CH 2 ) n —, optionally mono- or di-substituted with halogen, wherein m and n are independently 0, 1, 2, 3 or 4, with the proviso that m+n is 2, 3 or 4;

Y is O;

R 1 and R 2 are each independently selected from the group consisting of:

(a) hydrogen,

(b) halogen,

(c) CN,

(d) CF 3 ,

(e) —C 1-6 alkyl,

(f) —C 1-6 alkyl-C(═O)OH,

(g) —O—(R 7 ),

(h) —S(═O) o R 7 ,

(i) —N(R 7 )(R 8 ),

(j) —N(R 7 )—C(═O)—(R 8 ),

(k) —N(R 7 )—C(═O)—O—(R 8 ),

(l) —N(R 7 )S(═O) 2 (R 8 ),

(m) —C 3-6 cycloalkyl,

(n) —C(═O)(R 7 ),

(o) aryl,

(p) heteroaryl,

(q) —OC(═O)N(R 7 )(R 8 ),

(r) —S(═O) 2 N(R 7 )(R 8 ),

(s) —C(═O)N(R 7 )(R 8 ), and

(t) —C(R 7 )(R 8 )OH,

wherein the alkyl portion of choices (e) and (f), and the cycloalkyl portion of choice (m) are optionally substituted with halogen, and

wherein the aryl of choice (o) and the heteroaryl of choice (p) are optionally mono- or di-substituted with substituents selected from halogen, nitro, C 1-6 alkyl, C 1-6 alkoxy, halo C 1-6 alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkoxy, —NH(C 1-6 alkyl), —NH(C 3-6 cycloalkyl), —N(C 1-6 alkyl) 2 , —N(C 3-6 cycloalkyl) 2 , —S(═O) o C 1-6 alkyl, —S(═O) o C 3-6 cycloalkyl, and CN; each o is independently 0, 1 or 2;

R 3 is selected from the group consisting of:

(a) hydrogen,

(b) halogen,

(c) CN,

(d) CF 3 ,

(e) —C 1-6 alkyl,

(f) —C 1-6 alkyl-C(═O)OH,

(g) —O—(R 7 ),

(h) —S(═O) o R 7 ,

(i) —N(R 7 )(R 8 ),

(j) —N(R 7 )—C(═O)—(R 8 ),

(k) —N(R 7 )—C(═O)—O—(R 8 ),

(l) —N(R 7 )S(═O) 2 (R 8 ),

(m) —C 3-6 cycloalkyl,

(n) —C(═O)(R 7 ),

(o) aryl,

(p) heteroaryl,

(q) —OC(═O)N(R 7 )(R 8 ),

(r) —S(═O) 2 N(R 7 )(R 8 ),

(s) —C(═O)N(R 7 )(R 8 ),

(t) —C(R 7 )(R 8 )OH,

(u) —NHC(═O)—N(R 7 )(R 8 ),

(v) —C 3-6 cycloalkyl-COOH,

(w) heterocycle, and

(x) 1-6 alkylC(═O)—N(R 7 )(R 8 ),

wherein the alkyl portion of choices (e), (f) and (x), and the cycloalkyl portion of choices (m) and (v) are optionally substituted with halogen or hydroxyl, and

wherein the aryl of choice (o), the heteroaryl of choice (p), and the heterocycle of choice (w) are optionally mono- or di-substituted with substituents selected from halogen, nitro, C 1-6 alkyl, C 1-6 alkoxy, halo C 1-6 alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkoxy, —NH(C 1-6 alkyl), —NH(C 3-6 cycloalkyl), —N(C 1-6 alkyl) 2 , —N(C 3-6 cycloalkyl) 2 , —S(═O) o C 1-6 alkyl, —S(═O) o C 3-6 cycloalkyl, hydroxyl and CN;

R 4 and R 4′ are each independently selected from the group consisting of:

(a) hydrogen,

(b) —N(R 7 )(R 8 ),

(c) —N(R 7 )S(═O) 2 R 8 ,

(d) —N(R 7 )—C(═O)R 8 ,

(e) —N(R 7 )C(═O)OR 8 ,

(f) —S(═O) o R 7 ,

(g) —S(═O) 2 N(R 7 )(R 8 ),

(h) —C(═O)R 7 ,

(i) —C(═O)N(R 7 )(R 8 ),

(j) —OC(═O)N(R 7 )(R 8 ),

(k) —O—R 7 ,

(l) —C(R 7 )(R 8 )OH,

(m) —C 1-4 alkyl-C(═O)NHS(═O) 2 R 7 ,

(n) —C 1-4 alkyl-S(═O) 2 NHC(═O)R 7 ,

(o) —C 1-4 alkyl-C(═O)—N(R 7 )(R 8 ),

(p) —C 1-4 alkyl-N(R 7 )C(═O)(R 8 ),

(q) —C 1-4 alkyl-N(R 7 )S(═O) 2 (R 8 ),

(r) —C 1-4 alkyl-S(═O) 2 N(R 7 )(R 8 ),

(s) —C 1-4 alkyl-N(R 7 )C(═O)O(R 8 )

(t) —C 1-4 alkyl-O—C(═O)N(R 7 )(R 8 )

(u) —C 1-4 alkyl-C(═O)(R 7 ),

(v) —C 1-4 alkyl-C(R 7 )(R 8 )OH,

(w) —C 1-4 alkyl-O(R 7 ),

(x) —C 1-6 alkyl-C(═O)OH,

(y) —C 2-6 alkenyl-C(═O)OH,

(z) —C 3-6 cycloalkyl-C(═O)OH,

(aa) —C 3-6 cycloalkyl-C(═O)NHS(═O) 2 R 7 ,

(bb) —C 3-6 cycloalkyl-S(═O) 2 NHC(═O)R 7 ,

(cc) —C 3-6 cycloalkyl-C(═O)—N(R 7 )(R 8 ),

(dd) —C 3-6 cycloalkyl-N(R 7 )C(═O)(R 8 ),

(ee) —C 3-6 cycloalkyl-N(R 7 )S(═O) 2 (R 8 ),

(ff) —C 3-6 cycloalkyl-S(═O) 2 N(R 7 )(R 8 ),

(gg) —C 3-6 cycloalkyl-N(R 7 )C(═O)O(R 8 ),

(hh) —C 3-6 cycloalkyl-O—C(═O)N(R 7 )(R 8 ),

(ii) —C 3-6 cycloalkyl-C(═O)(R 7 ),

(jj) —C 3-6 cycloalkyl-C(R 7 )(R 8 )OH,

(kk) —C 3-6 cycloalkyl-O(R 7 ),

(ll) —C(═O)OH,

(mm) aryl,

(nn) heteroaryl,

(oo) —C(═O)N(R 7 )S(═O) 2 (R 8 ),

(pp) —S(═O) 2 N(R 7 )C(═O)(R 8 ),

(qq) —NHS(═O) 2 N(R 7 )(R 8 ),

(rr) —NHC(═O)N(R 7 )(R 8 ),

(ss) —CH(OH)—C(═O)—N(R 7 )(R 8 ),

(tt) —C(═O)—C(═O)—N(R 7 )(R 8 ),

(uu) —C 3-6 cycloalkyl,

(vv) —CF 3 ,

(ww) —C 1-6 alkyl N(R 7 )(R 8 ),

(xx) -heterocycle,

(yy) —C 1-6 alkyl,

(zz) halogen, and

(aaa) —O—C 1-6 alkyl-N(R 7 )(R 8 ),

wherein the alkyl portion of choices (m), (n), (o), (p), (q), (r), (s), (t), (u), (v), (w), (x), (ww), (yy) and (aaa), the alkenyl portion of choice (y), and the cycloalkyl portion of choices (z), (aa), (bb), (cc), (dd), (ee), (ff), (gg), (hh), (ii), (jj), (kk) and (uu), are optionally mono- or di-substituted with halogen, CN, aryl, C 1-6 alkyl, halo C 1-6 alkyl, C 3-6 cycloalkyl, C 1-6 alkoxy, or C 3-6 cycloalkoxy, and

wherein the aryl of choice (mm), the heteroaryl of choice (nn), and the heterocycle of choice (xx) are optionally mono- or di-substituted with substituents selected from halogen, nitro, C 1-6 alkyl, C 1-6 alkoxy, halo C 1-6 alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkoxy, —NH(C 1-6 alkyl), —NH(C 3-6 cycloalkyl), —N(C 1-6 alkyl) 2 , —N(C 3-6 cycloalkyl) 2 , —S(═O) o C 1-6 alkyl, —S(═O) o C 3-6 cycloalkyl, hydroxyl and CN, or

wherein R 3 and R 4 or R 4 and R 4′ are joined together to form a 5- or 6-membered heterocyclic ring, said ring having one heteroatom selected from O and N, wherein said ring is optionally substituted with —C(═O)OH, or —C 1-6 alkyl-C(═O)OH, with the proviso that at least one of R 3 , R 4 and R 4′ is other than hydrogen;

R 5 is selected from the group consisting of:

(a) hydrogen,

(b) —C 1-6 alkyl,

(c) —C 1-4 alkyl(R 7 ),

(d) aryl,

(e) heteroaryl,

(f) —C 3-6 cycloalkyl,

(g) —C 3-6 cycloalkyl(R 7 ),

(h) —C 3-6 cycloalkyl-O(R 7 ),

(i) —C 1-4 alkyl-C 3-6 cycloalkyl,

(j) C 1-6 alkoxy, and

(k) C 3-6 cycloalkoxy,

wherein the alkyl portion of choices (b), (c), (i) and (j), the cycloalkyl portion of choices (f), (g), (h), (i) and (k) are optionally substituted with halogen or C 1-4 alkyl, and

wherein the aryl of choice (d) and the heteroaryl of choice (e), are optionally mono- or di-substituted with substituents selected from halogen, nitro, C 1-6 alkyl, CF 3 , C 1-6 alkoxy, halo C 1-6 alkyl, aryl, heteroaryl, C 3-6 cycloalkyl, C 3-6 cycloalkoxy, and CN;

R 6 is selected from the group consisting of:

(a) hydrogen,

(b) —C 1-6 alkyl,

(c) —C 1-6 alkylaryl,

(d) —C 1-6 alkylheteroaryl,

(e) —S(═O) o C 1-6 alkyl(R 7 ),

(f) —C(═O)C 1-6 alkyl(R 7 ),

(g) —C 3-6 cycloalkyl,

(h) aryl,

(i) hetereoaryl,

(j) —C(═O)C 3-6 cycloalkyl(R 7 ),

(k) —S(═O) o C 3-6 cycloalkyl(R 7 ), and

(l) —C 1-6 alkyl(R 7 ),

wherein the alkyl portion of choices (b), (c), (d), (e), (f), and (l) and the cycloalkyl portion of choices (g), (j), and (k), are optionally substituted with halogen or C 1-4 alkyl, and

wherein the aryl portion of choices (c) and (h), and the heteroaryl portion of choices (d) and (i), are optionally mono- or di-substituted with substituents selected from halogen, nitro, —CF 3 , C 1-6 alkyl, C 1-6 alkoxy, halo C 1-6 alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkoxy, aryl, heteroaryl, heterocycle optionally substituted with halogen, —NH(C 1-6 alkyl), —NH(C 3-6 cycloalkyl), —N(C 1-6 alkyl) 2 , —N(C 3-6 cycloalkyl) 2 , —S(═O) o C 1-6 alkyl, S(═O) o C 3-6 cycloalkyl, and CN;

R 7 and R 8 are each independently selected from the following:

(a) hydrogen,

(b) —C 1-6 alkyl,

(c) —C 3-6 cycloalkyl,

(d) -aryl,

(e) -heteroaryl,

(f) —C 1-6 alkylaryl,

(g) —C 1-6 alkylheteroaryl,

(h) —C(═O)C 1-6 alkyl,

(i) —S(═O) o -aryl,

(j) —C 1-6 alkyl-C 3-6 cycloalkyl, and

(k) CF 3 ,

wherein the alkyl of choices (b), (f), (g), (h), and (j), and the cycloalkyl of choices (c) and (j), are each optionally mono-, di- or tri-substituted with halogen, and

wherein the aryl portion of choices (d), (f) and (i), and the heteroaryl portion of choices (e) and (g), are each optionally mono- or di-substituted with substituents selected from halogen, —C(═O)OH, —CF 3 , —NHC(═O)CH 3 , nitro, C 1-6 alkyl, C 1-6 alkoxy, halo C 1-6 alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkoxy, —NH(C 1-3 alkyl), —NH(C 3-6 cycloalkyl), —N(C 1-3 alkyl) 2 , —N(C 3-6 cycloalkyl) 2 , —S(═O) o C 1-4 alkyl, S(═O) o C 3-6 cycloalkyl, aryl, heteroaryl, hydroxyl, and CN;

R 9 and R 10 are each independently selected from the following

(a) hydrogen,

(b) —C 1-6 alkyl,

(c) —C 3-6 cycloalkyl,

(d) halogen,

(e) —OC 3-6 cycloalkyl,

(f) CF 3 , and

(g) C 1-6 alkoxy,

wherein the alkyl portion of choice (b) and the cycloalkyl portion of choices (c) and (e), are each optionally mono-, di- or tri- substituted with halogen.

2. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein:

X is —CH 2 CH 2 CH 2 — or —CF 2 CH 2 CH 2 —.

3. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein:

A2 is A2a and A2a is a substituted phenyl, substituted pyrimidine, substituted pyrazine, or substituted pyridine.

4. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein:

R 1 and R 2 are each independently selected from the group consisting of:

(a) hydrogen,

(b) halogen,

(c) CN,

(d) CF 3 ,

(e) —C 1-6 alkyl,

(f) —O—(R 7 ),

(g) —C 3-6 cycloalkyl, and

(h) —N(R 7 )(R 8 ),

wherein the alkyl portion of choice (e) and the cycloalkyl portion of choice (g) are optionally substituted with halogen.

5. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein:

R 1 and R 2 are each hydrogen.

6. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein:

R 3 is selected from the group consisting of:

(a) hydrogen,

(b) —O—(R 7 ),

(c) —N(R 7 )S(═O) 2 (R 8 ), and

(d) —C 1-6 alkyl,

wherein the alkyl portion of choice (d) is optionally substituted with halogen or hydroxyl.

7. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein:

R 4 and R 4′ are each independently selected from the group consisting of:

(a) hydrogen,

(b) —N(R 7 )S(═O) 2 R 8 ,

(c) —N(R 7 )—C(═O)R 8 ,

(d) —S(═O) o R 7 ,

(e) —S(═O) 2 N(R 7 )(R 8 ),

(f) —C(═O)N(R 7 )(R 8 ),

(g) —O—(R 7 ),

(h) —C(R 7 )(R 8 )OH,

(i) —C 1-4 alkyl-C(═O)NHS(═O) 2 R 7 ,

(j) —C 1-4 alkyl-S(═O) 2 NHC(═O)R 7 ,

(k) —C 1-4 alkyl-C(═O)—N(R 7 )(R 8 ),

(l) —C 1-4 alkyl-N(R 7 )C(═O)(R 8 ),

(m) —C 1-4 alkyl-N(R 7 )S(═O) 2 (R 8 ),

(n) —C 1-4 alkyl-S(═O) 2 N(R 7 )(R 8 ),

(o) —C 1-4 alkyl-C(R 7 )(R 8 )OH,

(p) —C 1-4 alkyl-O(R 7 ),

(q) —C 1-6 alkyl-C(═O)OH,

(r) —C 2-6 alkenyl-C(═O)OH,

(s) —C 3-6 cycloalkyl-C(═O)OH,

(t) —C 3-6 cycloalkyl-C(═O)NHS(═O) 2 R 7 ,

(u) —C 3-6 cycloalkyl-S(═O) 2 NHC(═O)R 7 ,

(v) —C 3-6 cycloalkyl-C(═O)—N(R 7 )(R 8 ),

(w) —C 3-6 cycloalkyl-N(R 7 )S(═O) 2 (R 8 ),

(x) —C 3-6 cycloalkyl-S(═O) 2 N(R 7 )(R 8 ),

(y) —C 3-6 cycloalkyl-N(R 7 )C(═O)O(R 8 ),

(z) —C 3-6 cycloalkyl-C(R 7 )(R 8 )OH,

(aa) —C 3-6 cycloalkyl-O(R 7 ),

(bb) —C(═O)OH,

(cc) aryl,

(dd) heteroaryl,

(ee) —C(═O)N(R 7 )S(═O) 2 (R 8 ),

(ff) —S(═O) 2 N(R 7 )C(═O)(R 8 ),

(gg) —NHS(═O) 2 N(R 7 )(R 8 ),

(hh) —NHC(═O)N(R 7 )(R 8 ),

(ii) C 3-6 cycloalkyl,

(jj) CF 3 ,

(kk) heterocycle,

(ll) —C 1-6 alkyl, and

(mm) halogen,

wherein the alkyl portion of choices (i), (j), (k), (l), (m), (n), (o), (p), (q), and (ll), the alkenyl portion of choice (r), and the cycloalkyl portion of choices (s), (t), (u), (v), (w), (x), (y), (z), and (aa) are optionally mono- or di-substituted with halogen, CN, aryl, C 1-6 alkyl, halo C 1-6 alkyl, C 3-6 cycloalkyl, C 1-6 alkoxy, or C 3-6 cycloalkoxy and,

wherein the aryl of choice (cc), the heteroaryl of choice (dd), and the heterocycle of choice (kk) are optionally mono- or di-substituted with substituents selected from halogen, hydroxyl, nitro, C 1-6 alkyl, C 1-6 alkoxy, halo C 1-6 alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkoxy, —NH(C 1-6 alkyl), —NH(C 3-6 cycloalkyl), —N(C —6 alkyl) 2 , —N(C 3-6 cycloalkyl) 2 , —S(═O) o C —6 alkyl, —S(═O) o C 3-6 cycloalkyl, and CN.

8. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof wherein:

R 4 and R 4′ are each independently selected from the group consisting of:

(a) —C(R 7 )(R 8 )OH,

(b) —N(R 7 )S(═O) 2 R 8 ,

(c) —O—(R 7 ),

(d) —C 1-6 alkyl-C(═O)OH,

(e) —C(═O)OH,

(f) —NHS(═O) 2 N(R 7 )(R 8 ),

(g) —C 3-6 cycloalkyl,

(h) CF 3 ,

(i) heterocycle,

(j) —C 1-6 alkyl, and

(k) halogen,

wherein the alkyl portion of choices (d) and (j), and the cycloalkyl portion of choice (g) are optionally mono- or di-substituted with halogen, CN, aryl, C 1-6 alkyl, halo C 1-6 alkyl, C 3-6 cycloalkyl, C 1-6 alkoxy, or C 3-6 cycloalkoxy, and

wherein the heterocycle of choice (i) is optionally mono- or di-substituted with substituents selected from halogen, hydroxyl, nitro, C 1-6 alkyl, C 1-6 alkoxy, halo C 1-6 alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkoxy, —NH(C 1-6 alkyl), —NH(C 3-6 cycloalkyl), —N(C 1-6 alkyl) 2 , —N(C 3-6 cycloalkyl) 2 , —S(═O) o C 1-6 alkyl, —S(═O) o C 3-6 cycloalkyl, and CN.

9. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein:

R 5 is selected from the group consisting of:

(a) hydrogen,

(b) —C 1-6 alkyl, and

(c) —C 1-4 alkyl(R 7 ),

wherein the alkyl portion of choices (b) and (c) is optionally substituted with halogen or C 1-4 alkyl.

10. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein:

R 6 is selected from the group consisting of:

(a) —C 1-6 alkylaryl,

(b) —C 1-6 alkylheteroaryl, and

(c) —C 1-6 alkyl(R 7 ),

wherein the alkyl portion of choices (a), (b), and (c) is optionally substituted with halogen or C 1-4 alkyl, and

wherein the aryl portion of choice (a), and the heteroaryl portion of choice (b), are optionally mono- or di-substituted with substituents selected from halogen, nitro, CF 3 , C 1-6 alkyl, C 1-6 alkoxy, halo C 1-6 alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkoxy, aryl, heteroaryl, heterocycle optionally substituted with halogen, —NH(C 1-6 alkyl), —NH(C 3-6 cycloalkyl), —N(C 1-6 alkyl) 2 , —N(C 3-6 cycloalkyl) 2 , —S(═O) o C 3-6 cycloalkyl, and CN.

11. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein:

R 9 and R 10 are each independently

(a) hydrogen,

(b) —C 1-6 alkyl,

(c) halogen,

(d) CF 3 , and

(e) C 1-6 alkoxy,

wherein the alkyl of choice (b) is optionally mono-, di- or tri-substituted with halogen.

12. A compound according to claim 11 , or a pharmaceutically acceptable salt thereof, wherein:

A2 is A2a, and A2a is a substituted phenyl, substituted pyrimidine, substituted pyrazine, or substituted pyridine;

R 1 and R 2 are each independently selected from:

(a) hydrogen,

(b) halogen,

(c) CF 3 ,

(d) C 1-6 alkyl, and

(e) —O—(R 7 ),

wherein the alkyl portion of choice (d) is optionally substituted with halogen;

R 3 is selected from the group consisting of:

(a) hydrogen,

(b) —O—(R 7 ),

(c) —N(R 7 )S(═O) 2 (R 8 ), and

(d) —C 1-6 alkyl,

wherein the alkyl portion of choice (d) is optionally substituted with halogen or hydroxyl;

R 4 and R 4′ are each independently selected from the group consisting of:

(a) —N(R 7 )S(═O) 2 R 8 ,

(b) —O—(R 7 ),

(c) —C(R 7 )(R 8 )OH,

(d) —C 1-6 alkyl-C(═O)OH,

(e) —C(═O)OH,

(f) —NHS(═O) 2 N(R 7 )(R 8 ),

(g) —C 3-6 cycloalkyl,

(h) CF 3 ,

(i) heterocycle,

(j) —C 1-6 alkyl, and

(k) halogen,

R 5 is selected from the group consisting of:

(a) hydrogen,

(b) —C 1-6 alkyl, and

(c) —C 1-4 alkyl(R 7 ),

wherein the alkyl portion of choices (b) and (c) is optionally substituted with halogen or C 1-4 alkyl;

R 6 is selected from the group consisting of:

(a) —C 1-6 alkylaryl,

(b) —C 1-6 alkylheteroaryl, and

(c) —C 1-6 alkyl(R 7 ),

wherein the alkyl portion of choices (a), (b), and (c) is optionally substituted with halogen or C 1-4 alkyl, and

wherein the aryl portion of choice (a), and the heteroaryl portion of choice (b), are optionally mono- or di-substituted with substituents selected from halogen, nitro, CF 3 , C 1-6 alkyl, C 1-6 alkoxy, halo C 1-6 alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkoxy, aryl, heteroaryl, heterocycle optionally substituted with halogen, —NH(C 1-6 alkyl), —NH(C 3-6 cycloalkyl), —N(C 1-6 alkyl) 2 , —N(C 3-6 cycloalkyl) 2 , —S(═O) o C 1-6 alkyl, —S(═O) o C 3-6 cycloalkyl, and CN.

13. A compound according to claim 12 of Formula 1a:

or a pharmaceutically acceptable salt thereof.

14. A compound according to claim 13 of Formula 1b:

or a pharmaceutically acceptable salt thereof.

15. A compound according to claim 1 selected from the group consisting of:

2-(3′-(3-(1-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)propyl)-[1,1′-biphenyl]-3-yl)acetic acid,

2-(3′-(3-(1-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)propyl)-[1,1′-biphenyl]-4-yl)acetic acid,

3′-(3-(1-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)propyl) -[1,1′-biphenyl]-3-carboxylic acid,

3′-(3-(1-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)propyl)-[1,1′-biphenyl]-4-carboxylic acid,

1-(3′-(3-(1-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)propyl)-4-ethoxy-[1,1′-biphenyl]-3-yl)cyclopropanecarboxylic acid,

2-(3′-(3-(1-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)propyl)-4-ethoxy-[1,1′-biphenyl]-3-yl)acetic acid,

1-(3′-(3-(1-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)propyl)-[1,1′-biphenyl]-3-yl)cyclopropanecarboxylic acid,

1-(3′-(3-(1-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)propyl)-[1,1′-biphenyl]-4-yl)cyclopropanecarboxylic acid,

3′-(3-(1-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)propyl)-4-methoxy-[1,1′-biphenyl]-3-carboxylic acid,

3′-(3-(1-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)propyl)-4-ethoxy-[1,1′-biphenyl]-3-carboxylic acid,

2-(3′-(3-(1-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)propyl)-4-propoxy-[1,1′-biphenyl]-3-yl)acetic acid,

N-(6-(3-(3-(1-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)propyl)phenyl)pyridin-3-yl)benzenesulfonamide,

2-(3′-(3-(1-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)propyl)-4-methoxy-[1,1′-biphenyl]-3-yl)acetic acid,

1-(3′-(3-(1-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)propyl)-4-methyl-[1,1′-biphenyl]-3-yl)cyclopropanecarboxylic acid,

2-(4-(benzyloxy)-3′-(3-(1-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)propyl)-[1,1′-biphenyl]-3-yl)acetic acid,

2-(3′-(3-(1-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)propyl)-4-(cyclopropylmethoxy)-[1,1′-biphenyl]-3-yl)acetic acid,

2-(3′-(3-(1-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)propyl)-4-fluoro-[1,1′-biphenyl]-3-yl)acetic acid,

2-(3′-(3-(1-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)propyl)-6-ethoxy-[1,1′-biphenyl]-3-yl)acetic acid,

3′-(3-(1-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)propyl)-4-propoxy-[1,1′-biphenyl]-3-carboxylic acid,

N-((3′-(3-(1-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)propyl)-[1,1′-biphenyl]-3-yl)methyl)benzenesulfonamide,

3-(3′-(3-(1-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)propyl)-4-methoxy-[1,1′-biphenyl]-3-yl)propanoic acid,

2-(3′-(3-(1-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)-1,1-difluoropropyl)-4-ethoxy-[1,1′-biphenyl]-3-yl)acetic acid,

N-(6-(3-(3-(1-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)-1,1-difluoropropyl)phenyl)pyridin-3-yl)benzenesulfonamide,

2-(5-(6-(3-(1-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)propyl)pyridin-2-yl)-2-methoxyphenyl)acetic acid,

3-(3-(3′-(1H-tetrazol-5-yl)-[1,1′-biphenyl]-3-yl)propyl)-1-(4-(tert-butyl)benzyl)-4-ethyl-1H-1,2,4-triazol-5(4H)-one,

2-(5-(4-(3-(1-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)propyl)pyrimidin-2-yl)-2-ethoxyphenyl)acetic acid,

2-(5-(6-(3-(1-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)propyl)pyrimidin-4-yl)-2-ethoxyphenyl)acetic acid,

(3′-(3-(1-(4-(tert-Butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)propyl)-3-methoxy-[1,1′-biphenyl]-4-yl)acetic acid,

(3′-(3-(1-(4-(tert-Butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)propyl)-3-ethoxy-[1,1′-biphenyl]-4-yl)acetic acid,

(3′-(3-(1-(4-(tert-Butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)propyl)-3-propoxy-[1,1′-biphenyl]-4-yl)acetic acid,

2-(3′-(3-(1-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)propyl)-3-hydroxy-[1,1′-biphenyl]-4-yl)acetic acid,

2-(3′-(3-(1-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)propyl)-4-isopropoxy-[1,1′-biphenyl]-3-yl)acetic acid, and

2-(3′-(3-(1-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)propyl)-4-(2-(dimethylamino)ethoxy)-[1,1′-biphenyl]-3-yl)acetic acid,

or a pharmaceutically acceptable salt thereof.

16. A pharmaceutical composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

17. A method of treating a cancer in a mammal which is negatively impacted by diminution in its metabolism of fatty acid, through the administration of a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof, to the mammal in need thereof, wherein said cancer is selected from prostate, breast, ovarian, liver, kidney, colon, pancreatic, human chronic lymphocytic leukemia and melanoma.

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

3′-(3-(1-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)propyl)-[1,1′-biphenyl]-4-carboxylic acid;

2-(3′-(3-(1-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)propyl)-4-ethoxy-[1,1′-biphenyl]-3-yl)acetic acid;

1-(3′-(3-(1-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)propyl)-[1,1′-biphenyl]-3-yl)cyclopropanecarboxylic acid;

2-(3′-(3-(1-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)propyl)-4-propoxy-[1,1′-biphenyl]-3-yl)acetic acid;

2-(3′-(3-(1-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)propyl)-4-fluoro-[1,1′-biphenyl]-3-yl)acetic acid;

2-(3′-(3-(1-(4-(tert-butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-y 1 )-1,1-difluoropropyl)-4-ethoxy-[1,1′-biphenyl]-3-yl)acetic acid;

(3′-(3-(1-(4-(tert-Butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)propyl)-3-ethoxy-[1,1′-biphenyl]-4-yl)acetic acid;

(3′-(3-(1-(4-(tert-Butyl)benzyl)-4-ethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)propyl)-3-propoxy-[1,1′-biphenyl]-4-yl)acetic acid,

or a pharmaceutically acceptable salt thereof.