What is claimed is:
1. A method of inhibiting MetAP2 in mammals, comprising administering to a mammal in need of such inhibition, an effective amount of a compound of formula (IA) or a pharmaceutically acceptable salt or solvate thereof:
6
wherein:
Q is a 5- or 6-membered monocyclic ring containing up to two heteroatoms selected from N, O, or S, or an 8- to 11-membered fused bicyclic ring containing up to four heteroatoms selected from N, O, or S;
R1 and R2 are independently selected from H, Ph-C0-6alkyl-, Het-C0-6alkyl-, C1-6alkyl-, C1-6alkoxy-, C1-6mercaptyl-, Ph-C0-6alkoxy-, Het-C0-6alkoxy-, HO, R4R5N-, Het-SC0-6alkyl-, Ph-SC0-6alkyl-, HO(CH2)1-6, R4R5N(CH2)2-6, R4R5N(CH2)2-6O, R6CO2(CH2)0-6, R6CO2(CH2)2-6O, R6SO2(CH2)1-6, CF3, OCF3, or halogen, and Ph or Het are substituted with up to five of C2-6alkyl-, C1-6alkoxy-, R4R5N(CH2)1-6, R4R5N(CH2)2-6O, CO2R6, CF3 or, halogen;
R3 is H, halogen, or R3 and Q together form a fused bicyclic or tricyclic saturated or unsaturated fused ring system wherein R3 is C, or CC; and
R4, R5, and R6 are independently selected from H, C2-6alkyl-, C3-6alkenyl-, C3-6alkynyl-, Ph-C0-6alkyl-, Het-C0-6alkyl-, or C3-7cycloalkyl-C0-6alkyl-.
2. The method of claim 1, wherein the compound of formula (IA) is selected from:
3-(1H-1,2,3-triazol-4-yl)-phenol;
4-(4-n-butylphenyl)-1H-1,2,3-triazole;
N-(3-1H-1,2,3-triazol-4-ylphenyl)benzamide;
3-(1H-1,2,3-triazol-4-yl)-phenylamine;
N-(3-1H-1,2,3-triazol-4-ylphenyl)acetamide;
4-(4-trifouoromethylphenyl)-1H-1,2,3-triazole;
4-(3-trifouoromethylphenyl)-1H-1,2,3-triazole;
4-(4-n-propylphenyl)-1H-1,2,3-triazole;
4-(4-methoxyphenyl)-1H-1,2,3-triazole;
2-(1H-1,2,3-triazol-4-yl)-pyridine;
4-(1H-1,2,3-triazol-4-yl)-phenylamine;
1-(1H-1,2,3-triazol-4-yl)cyclohexanol;
4-(thiophen-2-yl)-1H-1,2,3-triazole;
4-(2-methylphenyl)-1H-1,2,3-triazole;
4-(1,3-dimethylphenyl)-1H-1,2,3-triazole;
4-(1-biphenyl-2-yl)-1H-1,2,3-triazole;
4-(2-benzyloxy-phenyl)-1H-1,2,3-triazole;
2-(1H-1,2,3-triazol-4-yl)-6-methylpyridine;
3-(1H-1,2,3-triazol-4-yl)-pyridine;
4-(1H-1,2,3-triazol-4-yl)-pyridine;
4-(2-methoxyphenyl)-1H-1,2,3-triazole;
4-(2-bromophenyl)-1H-1,2,3-triazole;
4-benzo1,3dioxol-5-yl-1H-1,2,3-triazole;
4-benzo1,3dioxol-4-yl-1H-1,2,3-triazole;
4-(2-4-chloro-phenylsulfanyl-phenyl)-1H-1,2,3-triazole;
(3-phenyl-propyl)-(3-1H-1,2,3-triazol-4-ylphenyl)amine; phenethyl-(3-1H-1,2,3-triazol-4-ylphenyl)amine;
napthalene-1-ylmethyl-(3-1H-1,2,3-triazol-4-ylphenyl)amine;
napthalene-2-ylmethyl-(3-1H-1,2,3-triazol-4-ylphenyl)amine;
4-(1H-1,2,3-triazol-4-yl)-phenol;
2,6-dibromo-5-(1H-1,2,3-triazol-4-yl)-phenol;
1H-naptho1,2-d-1,2,3-triazole;
2,8-dihydro-indeno1,2-d-1,2,3-triazole;
4-phenyl-1H-1,2,3-triazole; and
5,5a,6,8-tetrahydro-4H-acenaphtho4,5-d-1,2,3-triazole;
or a pharmaceutically acceptable salt or solvate thereof.
3. The method of claim 1, wherein the compound of formula (IA) is selected from:
4-(3-iodophenyl)-1H-1,2,3-triazole;
4-(2-fluorophenyl)-1H-1,2,3-triazole;
4-(2-chlorophenyl)-1H-1,2,3-triazole;
4-(3-methylphenyl)-1H-1,2,3-triazole;
4-(4-chlorophenyl)-1H-1,2,3-triazole;
4-(4-ethylphenyl)-1H-1,2,3-triazole;
4-(4-methylphenyl)-1H-1,2,3-triazole;
2-(1H-1,2,3-triazol-4-yl)-5-methylpyridine;
2-(1H-1,2,3-triazol-4-yl)-4-methyl-pyridine;
4-(thiophen-3-yl)-1H-1,2,3-triazole;
4-(4-bromophenyl)-1H-1,2,3-triazole;
4-(1,3-dichlorophenyl)-1H-1,2,3-triazole;
2-(1H-1,2,3-triazol-4-yl)-benzofuran;
furan-2-ylmethyl-(3-1H-1,2,3-triazol-4-ylphenyl)amine;
furan-3-ylmethyl-(3-1H-1,2,3-triazol-4-ylphenyl)amine;
benzyl-(3-1H-1,2,3-triazol-4-ylphenyl)amine;
4-(4-fluorophenyl)-1H-1,2,3-triazole;
2-bromo-5-(1H-1,2,3-triazol-4-yl)-phenol;
2,4-dibromo-5-(1H-1,2,3-triazol-4-yl)-phenol; and
2-(5-bromo-1H-1,2,3-triazol-4-yl)-4-methyl-pyridine; or a pharmaceutically acceptable salt or solvate thereof.
4. A method for treating a disease mediated by MetAP2 in mammals, comprising administering to a mammal in need of such treatment, an effective amount of a compound of formula (IA) or a pharmaceutically acceptable salt thereof:
7
wherein:
Q is a 5- or 6-membered monocyclic ring containing up to two heteroatoms selected from N, O, or S, or an 8- to 11-membered fused bicyclic ring containing up to four heteroatoms selected from N, O, or S;
R1 and R2 are independently selected from H, Ph-C0-6alkyl-, Het-C0-6 alkyl-, C1-6alkyl-, C1-6alkoxy-, C1-6mercaptyl-, Ph-C0-6alkoxy-, Het-C0-6alkoxy-, HO, R4R5N, Het-SC0-6alkyl-, Ph-SC0-6alkyl-, HO(CH2)1-6, R4R5N(CH2)2-6, R4R5N(CH2)2-6O, R6CO2(CH2)0-6, R6CO2(CH2)2-6O, R6SO2(CH2)1-6, CF3, OCF3, or halogen, and Ph or Het are substituted with up to five of C2-6alkyl-, C1-6alkoxy-, R4R5N(CH2)1-6, R4R5N(CH2)2-6O, CO2R6, CF3 or, halogen;
R3 is H, halogen, or R3 and Q together form a fused bicyclic or tricyclic saturated or unsaturated fused ring system wherein R3 is C, or CC; and
R4, R5, and R6 are independently selected from H, C2-6alkyl-, C3-6alkenyl-, C3-6alkynyl-, Ph-C0-6alkyl-, Het-C0-6alkyl-, or C3-7cycloalkyl-C0-6alkyl-.
5. The method of claim 4, wherein the compound of formula (IA) is selected from:
3-(1H-1,2,3-triazol-4-yl)-phenol;
4-(4-n-butylphenyl)-1H-1,2,3-triazole;
N-(3-1H-1,2,3-triazol-4-ylphenyl)benzamide;
3-(1H-1,2,3-triazol-4-yl)-phenylamine;
N-(3-1H-1,2,3-triazol-4-ylphenyl)acetamide;
4-(4-trifouoromethylphenyl)-1H-1,2,3-triazole;
4-(3-trifouoromethylphenyl)-1H-1,2,3-triazole;
4-(4-n-propylphenyl)-1H-1,2,3-triazole;
4-(4-methoxyphenyl)-1H-1,2,3-triazole;
2-(1H-1,2,3-triazol-4-yl)-pyridine;
4-(1H-1,2,3-triazol-4-yl)-phenylamine;
1-(1H-1,2,3-triazol-4-yl)cyclohexanol;
4-(thiophen-2-yl)-1H-1,2,3-triazole;
4-(2-methylphenyl)-1H-1,2,3-triazole;
4-(1,3-dimethylphenyl)-1H-1,2,3-triazole;
4-(1-biphenyl-2-yl)-1H-1,2,3-triazole;
4-(2-benzyloxy-phenyl)-1H-1,2,3-triazole;
2-(1H-1,2,3-triazol-4-yl)-6-methylpyridine;
3-(1H-1,2,3-triazol-4-yl)-pyridine;
4-(1H-1,2,3-triazol-4-yl)-pyridine;
4-(2-methoxyphenyl)-1H-1,2,3-triazole;
4-(2-bromophenyl)-1H-1,2,3-triazole;
4-benzo1,3dioxol-5-yl-1H-1,2,3-triazole;
4-benzo1,3dioxol-4-yl-1H-1,2,3-triazole;
4-(2-4-chloro-phenylsulfanyl-phenyl)-1H-1,2,3-triazole;
(3-phenyl-propyl)-(3-1H-1,2,3-triazol-4-ylphenyl)amine;
phenethyl-(3-1H-1,2,3-triazol-4-ylphenyl)amine;
napthalene-1-ylmethyl-(3-1H-1,2,3-triazol-4-ylphenyl)amine;
napthalene-2-ylmethyl-(3-1H-1,2,3-triazol-4-ylphenyl)amine;
4-(1H-1,2,3-triazol-4-yl)-phenol;
2,6-dibromo-5-(1H-1,2,3-triazol-4-yl)-phenol;
1H-naptho1,2-d-1,2,3-triazole;
2,8-dihydro-indeno1,2-d-1,2,3-triazole;
4-phenyl-1H-1,2,3-triazole; and
5,5a,6,8-tetrahydro-4H-acenaphtho4,5-d-1,2,3-triazole;
or a pharmaceutically acceptable salt or solvate thereof.
6. The method of claim 4, wherein the compound of formula (IA) is selected from:
4-(3-iodophenyl)-1H-1,2,3-triazole;
4-(2-fluorophenyl)-1H-1,2,3-triazole;
4-(2-chlorophenyl)-1H-1,2,3-triazole;
4-(3-methylphenyl)-1H-1,2,3-triazole;
4-(4-chlorophenyl)-1H-1,2,3-triazole;
4-(4-ethylphenyl)-1H-1,2,3-triazole;
4-(4-methylphenyl)-1H-1,2,3-triazole;
2-(1H-1,2,3-triazol-4-yl)-5-methylpyridine;
2-(1H-1,2,3-triazol-4-yl)-4-methyl-pyridine;
4-(thiophen-3-yl)-1H-1,2,3-triazole;
4-(4-bromophenyl)-1H-1,2,3-triazole;
4-(1,3-dichlorophenyl)-1H-1,2,3-triazole;
2-(1H-1,2,3-triazol-4-yl)-benzofuran;
furan-2-ylmethyl-(3-1H-1,2,3-triazol-4-ylphenyl)amine;
furan-3-ylmethyl-(3-1H-1,2,3-triazol-4-ylphenyl)amine;
benzyl-(3-1H-1,2,3-triazol-4-ylphenyl)amine;
4-(4-fluorophenyl)-1H-1,2,3-triazole;
2-bromo-5-(1H-1,2,3-triazol-4-yl)-phenol;
2,4-dibromo-5-(1H-1,2,3-triazol-4-yl)-phenol; and
2-(5-bromo-1H-1,2,3-triazol-4-yl)-4-methyl-pyridine; or a pharmaceutically acceptable salt or solvate thereof.
7. A compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof:
8
wherein:
Q is a 5- or 6-membered monocyclic ring optionally containing up to two heteroatoms selected from N, O, or S, or an 8- to 11-membered fused bicyclic ring optionally containing up to four heteroatoms selected from N, O, or S;
with the proviso that Q is substituted by up to eight of R1; and further, if Q is phenyl (Ph), Q must be substituted by at least one of substituent R2;
R1 is H, Ph-C0-6alkyl-, Het-C0-6 alkyl-, C1-6alkyl-, C1-6alkoxy-, C1-6mercaptyl-, Ph-C0-6alkoxy-, Het-C0-6alkoxy-, HO, R4R5N, Het-SC0-6alkyl-, Ph-SC0-6alkyl-, HO(CH2)1-6, R4R5N(CH2)2-6, R4R5N(CH2)2-6O, R6CO2(CH2)0-6, R6CO2(CH2)1-6O, R6SO2(CH2)1-6, CF3, OCP3, or halogen, and Ph or Het are substituted with up to five of C2-6alkyl-, C1-6alkoxy-, R4R5N(CH2)1-6, R4R5N(CH2)2-6O, CO2R6, CF3 or, halogen;
R2 is Ph-C0-6alkyl-, Het-C0-6 alkyl-, C5-6alkyl-, C2-6alkoxy-, C1-6mercaptyl-, Ph-C0-6alkoxy-, Het-C0-6alkoxy-, HO, R4R5N, Het-SC0-6alkyl-, Ph-SC0-6alkyl-, HO(CH2)1-6, R4R5N(CH2)2-6, R4R5N(CH2)2-6O, R6CO2(CH2)0-6, R6CO2(CH2)1-6O, R6SO2(CH2)1-6, CF3 or OCF3, and Ph or Het are substituted with up to five of C2-6alkyl-, C1-6alkoxy-, R4R5N(CH2)1-6, R4R5N(CH2)2-6O, CO2R6, CF3 or, halogen;
provided that the compound of formula (I) is not (6-(1H-1,2,3-triazol-4-yl)-2-napthalenyl)oxy-acetic acid; (6-(1H-1,2,3-triazol-4-yl)-2-napthalenyl)oxy-acetic acid 1,1-dimethylethyl ester; 4-(1H-1,2,3-triazol-4-yl)-aniline; 2-chloro-4-(1H-1,2,3-triazol-4-yl)-aniline; 1-(4-fluorophenyl)-5-(1H-1,2,3-triazol-4-yl)-1H-indole; 2-(1H-1,2,3-triazol-4-yl)-pyridine; 3-(1H-1,2,3-triazol-4-yl)-pyridine; 4-(1H-1,2,3-triazol-4-yl)-phenol; 4-(2-napthyl)-1H-1,2,3-triazole; 4-3-bromo-4-(trifluoromethoxy)phenyl-1H-1,2,3-triazole; 4-(1H-1,2,3-triazol-4-yl)-morpholine; 5-methyl-2-(1H-1,2,3-triazol-4-yl)-1H-benzimidazole; 1(1H-1,2,3-triazol-4-yl)-1H-benzotriazole; 5-methyl-2-(1H-1,2,3-triazol-4-yl)-1H-benzotriazole; or 3-(1H-1,2,3-triazol-4-yl)-piperidine; and
R4, R5, and R6 are independently selected from H, C2-6alkyl-, C3-6alkenyl-, C3-6alkynyl-, Ph-C0-6alkyl-, Het-C0-6alkyl-, or C3-7cycloalkyl-C0-6alkyl-.
8. A pharmaceutical composition comprising a compound as claimed in claim 7 and a pharmaceutically acceptable carrier.
9. A process for making compounds of formula (IA), said process comprising:
a) carbon homologation of an aldehyde to provide a compound of formula (II)
9
b) followed by azide cycloaddition of the compound of formula (II) to provide the compound of formula (IA), wherein Q, R1, R2 and R3 are defined as in claim 1; or alternatively,
(c) reductive amination to alkylate an aniline of formula (III)
10
to provide a compound of formula (IV)
11
(d) followed by azide cycloaddition of the compound of formula (IV) to provide the compound of formula (IA), wherein Q, R1, R2 and R3 are defined as in claim 1.
10. A compound selected from:
4-ethynyl-benzo1,3dioxole;
1-(4-chloro-phenylsulfanyl)-2-ethynylbenzene;
(3-phenyl-propyl)-(3-ethynylphenyl)amine;
phenethyl-(3-ethynylphenyl)-amine;
furan-2-ylmethyl-(3-ethynylphenyl)-amine;
furan-3-ylmethyl-(3-ethynylphenyl)-amine;
napthalene-1-ylmethyl-(3-ethynylphenyl)-amine; and
napthalene-2-ylmethyl-(3-ethynylphenyl)-amine.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A method of encoding an image, the method comprising:
partitioning the image into a plurality of areas;
allocating the plurality of areas to views of multi-view image sequences; and
encoding the plurality of areas by using a method of encoding the multi-view image sequences, based on a result of the allocating.
2. The method of claim 1, wherein the encoding the plurality of areas comprises:
predicting pictures of the plurality of areas by using at least one of intra-prediction, inter-area prediction, and temporal prediction, according to the method of encoding the multi-view image sequences; and
encoding the plurality of areas, based on a result of the predicting.
3. The method of claim 1, wherein the encoding the plurality of areas comprises encoding information indicating that the image is partitioned into the plurality of areas, and the plurality of areas are encoded by using the method of encoding the multi-view image sequences.
4. The method of claim 3, wherein the information is flag information indicating that the image is partitioned into the plurality of areas, and the plurality of areas are encoded by using the method of encoding the multi-view image sequences.
5. The method of claim 1, wherein the image is a still image.
6. An image encoding apparatus comprising:
a partition unit which partitions an image into a plurality of areas, and allocates the plurality of areas to views of multi-view image sequences;
a prediction unit which predicts pictures of the plurality of areas by using at least one of intra-prediction, inter-area prediction, and temporal prediction, according to a method of encoding the multi-view image sequences; and
an encoding unit which encodes the plurality of areas, based on a result of the prediction by the prediction unit.
7. The image encoding apparatus of claim 6, wherein the encoding unit encodes information indicating that the image is partitioned into the plurality of areas, and the plurality of areas are encoded by using the method of encoding the multi-view image sequences.
8. The image encoding apparatus of claim 7, wherein the information is flag information indicating that the image is partitioned into the plurality of areas, and the plurality of areas are encoded by using the method of encoding the multi-view image sequences.
9. The image encoding apparatus of claim 6, wherein the image is a still image.
10. A method of decoding an image, the method comprising:
receiving data of the image, wherein the image has been partitioned into a plurality of areas and the plurality of areas have been encoded by using a method of encoding multi-view image sequences;
decoding the received data;
restoring the plurality of areas, based on the decoded data; and
restoring the image based on the restored plurality of areas.
11. The method of claim 10, wherein the restoring the plurality of areas comprises:
predicting the plurality of areas by using at least one of intra-prediction, inter-area prediction, and temporal prediction; and
restoring the plurality of areas based on a result of the predicting the plurality of areas and the decoded data.
12. The method of claim 10, wherein the data of the image includes information indicating that the image has been partitioned into the plurality of areas, and the plurality of areas have been encoded by using the method of encoding the multi-view image sequences.
13. The method of claim 12, wherein the information is flag information indicating that the image has been partitioned into the plurality of areas, and the plurality of areas have been encoded by using the method of encoding the multi-view image sequences.
14. The method of claim 10, wherein the image is a still image.
15. An image decoding apparatus comprising:
a decoding unit which receives data of an image, wherein the image has been partitioned into a plurality of areas and the plurality of areas have been encoded by using a method of encoding multi-view image sequences, and decoding the received data;
a prediction unit which predicts the plurality of areas by using at least one of intra-prediction, inter-area prediction, and temporal prediction; and
an image restoration unit which restores the plurality of areas and the image based on a result of the prediction by the prediction unit and the decoded data.
16. The image decoding apparatus of claim 15, wherein the data of the image includes information indicating that the image has been partitioned into the plurality of areas, and the plurality of areas have been encoded by using the method of encoding the multi-view image sequences.
17. The image decoding apparatus of claim 16, wherein the information is flag information indicating that the image has been partitioned into the plurality of areas, and the plurality of areas have been encoded by using the method of encoding the multi-view image sequences.
18. The image decoding apparatus of claim 15, wherein the image is a still image.
19. A computer readable recording medium having recorded thereon a program for enabling a computer to execute a method of decoding an image, the method comprising:
receiving data of the image, wherein the image has been partitioned into a plurality of areas and the plurality of areas have been encoded by using a method of encoding multi-view image sequences;
decoding the received data;
restoring the plurality of areas, based on the decoded data; and
restoring the image based on the restored plurality of areas.