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US 2006/0135767 A1Published application
Dipeptidyl peptidase inhibitors
AssigneeTakeda Pharmaceutical Company Limited
InventorsJun Feng, Stephen Gwaltney, Jeffrey Stafford, Michael Wallace, Zhiyuan Zhang
Life of this patent
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Abstract
Compounds, pharmaceuticals, kits and methods are provided for use with DPP-IV and other S9 proteases that comprise a member selected from the group consisting of: wherein E is CH or N, Q is selected from the group consisting of CO, CS, SO, SO2, or C═NR4, and L, X, Z, R2 and R3 are as defined herein.
Claims86
A compound comprising a member selected from the group consisting of:
- wherein
- E is CH or N;
- Q is selected from the group consisting of CO, CS, SO, SO2, or C═NR4;
- M is a moiety providing 1-6 atom separation between R19 and the ring to which M is attached;
- R2 and R3 are each independently selected from the group consisting of hydrogen, halo, perhalo(C1-10)alkyl, amino, cyano, nitro, thio, (C1-10)alkyl, alkenyl, alkynyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, aryl(C1-10)alkyl, heteroaryl (C1-5)alkyl, (C9-12)bicycloaryl, hetero(C8-12)bicycloaryl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, sulfonyl (C1-3)alkyl, sulfinyl (C1-3)alkyl, imino (C1-3)alkyl, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, carbonyl group, imine group, sulfonyl group and sulfinyl group, each substituted or unsubstituted, or R2 and R3 are absent, or R2 and R3 are taken together to form a ring;
- R4 is selected from the group consisting of hydrogen, (C1-10)alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aryl(C1-10)alkyl, heteroaryl(C1-10)alkyl, (C9-12)bicycloaryl, hetero(C8-12)bicycloaryl, each substituted or unsubstituted;
- R19 comprises a basic nitrogen atom that is capable of interacting with a carboxylic acid side chain of an active site residue of a protein;
- L is a linker providing 0-6 atom separation between X and the ring to which L is attached;
- and
- X is selected from the group consisting of (C1-10)alkyl, (C3-12)cycloalkyl, hetero(C3-12)cycloalkyl, aryl(C1-10)alkyl, heteroaryl(C1-5)alkyl, (C9-12)bicycloaryl, hetero(C4-12)bicycloaryl, carbonyl (C1-3)alkyl, thiocarbonyl (C1-3)alkyl, sulfonyl (C1-3)alkyl, sulfinyl (C1-3)alkyl, imino (C1-3)alkyl, amino, aryl, heteroaryl, hydroxy, alkoxy, aryloxy, heteroaryloxy, alkenyl, alkynyl, carbonyl group, cyano, imino group, sulfonyl group and sulfinyl group, each substituted or unsubstituted.
7 more elements
A compound selected from the group consisting of:
- 6-(2-Aminomethyl-benzyl)-5-(3-amino-piperidin-1-yl)-6H-pyrazolo[1,5-c]pyrimidin-7-one;
- 6-(2-Aminomethyl-benzyl)-7-(3-amino-piperidin-1-yl)-6H-imidazo[1,5-c]pyrimidin-5-one;
- 7-(2-Aminomethyl-benzyl)-8-(3-amino-piperidin-1-yl)-4,7-dihydro-pyrazino[1,2-c]pyrimidin-6-one;
- 7-(2-Aminomethyl-benzyl)-8-(3-amino-piperidin-1-yl)-4,7-dihydro-pyrimido[1,6-a]pyrimidin-6-one;
- 1-[5-(2-Aminomethyl-benzyl)-4,5-dihydro-pyrazolo[1,5-a]pyrazin-6-yl]-piperidin-3-ylamine;
- 2-(2-Aminomethyl-benzyl)-3-(3-amino-piperidin-1-yl)-4a,5,6,7-tetrahydro-2H-pyrrolo[1,2-c]pyrimidin-1-one;
- 3-(2-Aminomethyl-benzyl)-2-(3-amino-piperidin-1-yl)-3H-imidazo[1,2-a][1,3,5]triazin-4-one;
- 3-(2-Aminomethyl-benzyl)-2-(3-amino-piperidin-1-yl)-3,6-dihydro-pyrimido[1,6-a][1,3,5]triazin-4-one;
- 3-(2-Aminomethyl-benzyl)-2-(3-amino-piperidin-1-yl)-3H-imidazo[2,1-f][1,2,4]triazin-4-one;
- 3-(2-Aminomethyl-benzyl)-2-(3-amino-piperidin-1-yl)-3H-imidazo[5,1-f][1,2,4]triazin-4-one;
- 7-(2-Aminomethyl-benzyl)-6-(3-amino-piperidin-1-yl)-7H-1,4a,7,8a-tetraaza-naphthalen-8-one;
- 2-(2-Aminomethyl-benzyl)-3-(3-amino-piperidin-1-yl)-2H-2,4a,7,8a-tetraaza-naphthalen-1-one;
- 2-(2-Aminomethyl-benzyl)-3-(3-amino-piperidin-1-yl)-2,4a,5,6,7,8-hexahydro-pyrido[1,2-c]pyrimidin-1-one;
- 7-(2-Aminomethyl-benzyl)-8-(3-amino-piperidin-1-yl)-1,2,3,4,7,9a-hexahydro-pyrazino[1,2-c]pyrimidin-6-one;
- 2-(2-Aminomethyl-benzyl)-3-(3-amino-piperidin-1-yl)-5,6,7,8-tetrahydro-2H-2,4a,8a-triaza-naphthalen-1-one;
- 2-(2-Aminomethyl-benzyl)-3-(3-amino-piperidin-1-yl)-7,8-dihydro-2H,6H-pyrazolo[1,2-a][1,2,4]triazin-1-one;
- 3-(2-Aminomethyl-benzyl)-2-(3-amino-piperidin-1-yl)-5,6,8,8a-tetrahydro-3H-7-oxa-1,3,4a-triaza-naphthalen-4-one;
- 3-(2-Aminomethyl-benzyl)-2-(3-amino-piperidin-1-yl)-5,6,8,8a-tetrahydro-3H-7-thia-1,3,4a-triaza-naphthalen-4-one;
- 2-(2-Aminomethyl-benzyl)-3-(3-amino-piperidin-1-yl)-7,8,9,9a-tetrahydro-2H,6H-pyrido[1,2-a]pyrazin-1-one;
- 2-(2-Aminomethyl-benzyl)-3-(3-amino-piperidin-1-yl)-7,8,9,9a-tetrahydro-2H,6H-pyrazino[1,2-a]pyrazin-1-one;
- 6-(2-Aminomethyl-benzyl)-7-(3-amino-piperidin-1-yl)-6H-imidazo[1,2-c]pyrimidin-5-one;
- 2-(2-Aminomethyl-benzyl)-3-(3-amino-piperidin-1-yl)-2,8-dihydro-pyrimido[1,6-c]pyrimidin-1-one;
- 7-(2-Aminomethyl-benzyl)-6-(3-amino-piperidin-1-yl)-7H-imidazo[1,2-a]pyrazin-8-one;
- 7-(2-Aminomethyl-benzyl)-6-(3-amino-piperidin-1-yl)-7H-imidazo[1,5-a]pyrazin-8-one;
- 3-(2-Aminomethyl-benzyl)-2-(3-amino-piperidin-1-yl)-3H-pyrazolo[1,5-a][1,3,5]triazin-4-one;
- 3-(2-Aminomethyl-benzyl)-2-(3-amino-piperidin-1-yl)-3H-imidazo[1,5-a][1,3,5]triazin-4-one;
- 3-(2-Aminomethyl-benzyl)-2-(3-amino-piperidin-1-yl)-3,6-dihydro-pyrazino[1,2-a][1,3,5]triazin-4-one;
- 3-(2-Aminomethyl-benzyl)-2-(3-amino-piperidin-1-yl)-3,6-dihydro-pyrimido[1,2-a][1,3,5]triazin-4-one;
- 5-(2-Aminomethyl-benzyl)-6-(3-amino-piperidin-1-yl)-5H-1,5,7,7a-tetraaza-inden-4-one;
- 3-(2-Aminomethyl-benzyl)-2-(3-amino-piperidin-1-yl)-6,7,8,8a-tetrahydro-3H-pyrrolo[1,2-a][1,3,5]triazin-4-one;
- 2-(2-Aminomethyl-benzyl)-3-(3-amino-piperidin-1-yl)-2H-[1,2,4]triazino[2,1-a][1,2,4]triazin-1-one;
- 6-(2-Aminomethyl-benzyl)-7-(3-amino-piperidin-1-yl)-6H-1,4a,6,8a-tetraaza-naphthalen-5-one;
- 7-(2-Aminomethyl-benzyl)-8-(3-amino-piperidin-1-yl)-3,4,7,9a-tetrahydro-1H-pyrimido[6,1-c][1,4]oxazin-6-one;
- 7-(2-Aminomethyl-benzyl)-8-(3-amino-piperidin-1-yl)-3,4,7,9a-tetrahydro-1H-pyrimido[6,1-c][1,4]thiazin-6-one;
- 3-(2-Aminomethyl-benzyl)-2-(3-amino-piperidin-1-yl)-3,6,7,8,9,9a-hexahydro-pyrido[1,2-a][1,3,5]triazin-4-one;
- 3-(2-Aminomethyl-benzyl)-2-(3-amino-piperidin-1-yl)-3,6,7,8,9,9a-hexahydro-pyrazino[1,2-a][1,3,5]triazin-4-one;
- 2-(2-Aminomethyl-benzyl)-3-(3-amino-piperidin-1-yl)-6,7,8,8a-tetrahydro-2H-pyrrolo[1,2-a]pyrazin-1-one;
- 3-(2-Aminomethyl-benzyl)-2-(3-amino-piperidin-1-yl)4a,5,6,7-tetrahydro-3H-pyrrolo[2,1-f][1,2,4]triazin-4-one;
- 8-(2-Aminomethyl-benzyl)-7-(3-amino-piperidin-1-yl)-1,3,4,9a-tetrahydro-8H-pyrazino[2,1-c][1,4]oxazin-9-one;
- and
- 8-(2-Aminomethyl-benzyl)-7-(3-amino-piperidin-1-yl)-1,3,4,9a-tetrahydro-8H-pyrazino[2,1-c][1,4]thiazin-9-one.
38 more elements
Dependencies are inferred from the claim text.