Dipeptidyl peptidase inhibitors for the treatment or prevention of diabetes
AssigneeMerck & Co., Inc.
InventorsWallace T Ashton, Charles G Caldwell, Hyun O Ok, Emma R Parmee, Ann E Weber
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Abstract
The present invention is directed to compounds which are inhibitors of the dipeptidyl peptidase-IV enzyme (“DP-IV inhibitors”) and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved.
Claims40
A compound of the formula I:
- 158
- wherein:
- X is selected from —S—, —S(O)—, —S(O)2—, —CH2—, —CHF—, and —CF2—;
- Y is selected from CH—(C0-4alkyl-R2) and N—R3;
- m is an integer selected from 0, 1 and 2, and n is an integer selected from 0, 1 and 2, with the proviso that the sum of m+n is 1 or 2;
- R1 is selected from hydrogen and —CN;
- R2 is selected from the group consisting of:
- (1) —NR4—CO—NR5R6,
- (2) —NR4—CO2R6,
- (3) —NR4—COR6,
- (4) —NR5R6,
- (5) —NH2,
- (6) —NR4—S(O)2—R6,
- (7) —S(O)2—NR5R6,
- (8) —CO—NR5R6,
- (9) —O—CO—NR5R6,
- (10) —OH,
- (11) —O—R6,
- (12) —R6, and
- (13) hydrogen, with the proviso that R2 is hydrogen only if X is —CHF— or —CF2—;
- R3 is selected from the group consisting of:
- (1) —CO—NR5R6,
- (2) —CO2R6,
- (3) —COR6,
- (4) —S(O)2—R6,
- (5) —R6, and
- (6) hydrogen, with the proviso that R3 is hydrogen only if X is —CHF— or —CF2—;
- R4 and R5 are independently selected from hydrogen and C1-6alkyl;
- R6 is independently selected from:
- (1) C1-10alkyl, which is unsubstituted or substituted, where the substituents are independently selected from:
- (a) hydroxy,
- (b) —O—C1-6alkyl,
- (c) halogen,
- (d) phenyloxy, and
- (e) —CN;
- (2) phenyl, phenyloxy, C1-6alkyl-phenyl, naphthyl, C1-6alkyl-naphthyl, biphenyl, C1-6alkyl-biphenyl, wherein the phenyl, naphthyl, or biphenyl, is unsubstituted or substituted, where the substituents are independently selected from:
- (a) halogen,
- (b) —OCF3,
- (c) —CF3,
- (d) —CHF2,
- (e) —CH2F,
- (f) C1-10alkyl,
- (g) —O—C1-6alkyl,
- (h) —O-phenyl, wherein the phenyl is unsubstituted or substituted, where the substituents are independently selected from:
- (i) halogen,
- (ii) —OCF3,
- (iii) —CF3,
- (iv) C1-6alkyl, and
- (v) —O—C1-6alkyl,
- (i) —CN,
- (j) hydroxy,
- (k) —NR8R9, wherein R8 and R9 are independently selected from hydrogen and C1-6alkyl, or R8 and R9 are joined together with the nitrogen to form a 5-6 membered ring,
- (I) —NR4—CO—NR8R9,
- (m) —NR4—S(O)2—C1-6alkyl,
- (n) —CO—NR8R9,
- (o) —CO2—C1-6alkyl,
- (p) —O—CO—NR8R9, and
- (q) heterocycle, wherein the heterocycle is unsubstituted or substituted, where the substituents are independently selected from:
- (i) halogen,
- (ii) oxo,
- (iii) C1-10alkyl-(C3-6cycloalkyl),
- (iv) C1-10alkyl, which is unsubstituted or substituted with up to 5 halogen,
- (v) —O—C1-6alkyl, which is unsubstituted or substituted with up to 5 halogen,
- (vi) C0-6alkyl-phenyl, wherein the phenyl is unsubstituted or substituted, where the substituents are independently selected from:
- (I) halogen,
- (II) —OCF3,
- (III) —CF3,
- (IV) C1-6alkyl, and
- (V) —O—C1-6alkyl,
- (vii) pyridyl, and
- (viii) —CO—C1-6alkyl;
- (3) heterocycle, and C1-6alkyl-heterocycle, wherein the heterocycle is unsubstituted or substituted, where the substituents are independently selected from:
- (a) halogen,
- (b) oxo,
- (c) C1-6alkyl-(C3-6cycloalkyl),
- (d) C1-10alkyl, which is unsubstituted or substituted with up to 5 halogen,
- (e) —O—C1-6alkyl, which is unsubstituted or substituted with up to 5 halogen,
- (f) C0-6alkyl-phenyl, wherein the phenyl is unsubstituted or substituted, where the substituents are independently selected from:
- (i) halogen,
- (ii) —OCF3,
- (iii) —CF3,
- (iv) C1-6alkyl, and
- (v) —O—C1-6alkyl,
- (g) pyridyl, and
- (h) —CO—C1-6alkyl;
- and pharmaceutically acceptable salts thereof and individual diastereomers thereof.
A compound as recited in any one of Examples 1-128, and pharmaceutically acceptable salts thereof and individual diastereomers thereof.
Dependencies are inferred from the claim text.