1. A compound of general formula (A):
wherein:
\u2014X is
\u2014Y is C(\u2550O)R2 or CN;
\u2014Z is R1\u2014C\u2261C\u2014 or
R1 and R1a represents a radical C1-18alkyl, C2-18alkenyl, C3-10cycloalkyl, C3-10cycloalkyl-C1-6alkylene, C3-10cycloalkenyl, C6-20aryl, C5-14aryl-C1-6 alkylene, C3-10heterocyclyl, C3-10heterocyclyl-C1-6alkylene, C5-20heteroaryl or C5-20heteroaryl-C1-6alkylene, said radicals being optionally substituted with one or more R4;
R2 represents \u2014NH2, \u2014NHR5, an hydroxyl or a C1-6alkoxy group;
R3a, R3b, R3c and R3d represent independently from each others a hydrogen atom, a C2-18alkenyl, C6-20aryl or \u2014C(O)R5;
R4 represents an halogen atom, an hydroxyl, \u2014NH2, \u2014NHR5, \u2014NO2, \u2014CN, \u2014CF3, \u2014C(O)R5, a radical C1-4alkyl, C1-6alkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-20 aryl, C5-20heteroaryl or C5-14aryl-C1-6alkylene;
R5 represents C1-18alkyl, C2-18 alkenyl, C2-18 alkynyl, C5-18aryl, C3-10heterocyclyl, C5-20 heteroaryl, C5-14aryl-C1-6alkylene, C5-14aryl-C2-18alkenylene, C5-14aryl-C2-18alkynylene, C5-20 heteroaryl-C1-6alkylene, C5-20heteroaryl-C2-18 alkenylene, C5-20heteroaryl-C2-18 alkynylene, C3-10heterocyclyl-C1-6alkylene, C3-10 heterocyclyl-C2-18alkenylene or C3-10heterocyclyl-C2-18 alkynylene;
in the form of a free base or of an addition salt with an acid , as well as in the form of an hydrate or of a solvate.
2. The compound of formula (A) according to claim 1, which is a compound of formula (I), (I\u2032) or (I\u2033) :
wherein Y, R1, R1a, R2, R3a, R3b, R3c and R3d are as defined in claim 1.
3. The compound of general formula (I):
wherein R1, R2, R3a, R3b, R3c are as defined in claim 1.
4. The compound according to claim 3, wherein R1 represents a radical C6-20aryl group, said radical being substituted with one or more group R4; and R4 represents an halogen atom, a \u2014CF3 group, a C1-6 alkoxy or else a C1-14 alkyl group; the other groups being as defined in claim 1.
5. The compound according to claim 3, represented by formula (II):
wherein R1, R2, R3a, R3b and R3c are as defined in claim 3.
6. The compound according to claim 5, wherein in the compound of formula (II):
R1 represents a radical C6-20 aryl, said radical being substituted with one or more R4;
R4 represents a \u2014CF3 or a C1-14alkyl group;
R2 represents \u2014NH2 or a C1-C6alkoxy group;
R3a, R3b and R3c represent independently from each others a hydrogen atom, or a \u2014C(O)R5; R5 being a C1-C6alkyl group.
7. The compound according to claim 6, wherein R1 is substituted with one R4 and R4 is in para position.
8. The compound according to claim 3, represented by a compound of formula (III):
wherein R1 is optionally substituted with one or more R4, R1 and R4 being as defined in claim 3.
9. The compound according to claim 3, represented by a compound of formula (IV):
wherein R1 is optionally substituted with one or more R4, R1 and R4 being as defined in claim 3.
10. The compound according to claim 9, wherein:
R1 represents a radical C1-18alkyl, a C6-20aryl, C3-10cycloalkyl or a C3-10cycloalkenyl, said radicals being optionally substituted with one or more R4.
11. The compound according to claim 9, wherein when R1 represents a C6-20 aryl, R1 is substituted with one R4; R4 representing an halogen atom, a \u2014CF3, a C1-14alkyl group or a C1-6 alkoxy group.
12. The compound according to claim 3, wherein the compound of formula (I) is selected from the group consisting of:
Methyl 5-(4-trifluoromethylphenylethynyl)-1-(2,3,5-tri-O-acetyl-\u03b2-D-ribofuranosyl)-1H-1,2,4triazole-3-carboxylate;
Methyl 5-(Cyclohexenylethynyl)-1-(2,3,5-tri-O-acetyl-\u03b2-D-ribofuranosyl)-1H-1,2,4triazole-3-carboxylate;
5-(4-trifluoromethylphenylethynyl)-1-(2,3,5-tri-Hydroxy-\u03b2-D-ribofuranosyl)-1H-1,2,4triazole-3-carboxylic acid amide;
3-(4-pentylphenylethynyl)-1-(2,3,5-tri-Hydroxy-\u03b2-D-ribofuranosyl)-1H-1,2,4triazole-5-carboxylic acid amide.
13. The compound of formule (I\u2032) according to claim 2, represented by formula (II\u2032)
wherein Y, R1, and R3d are as defined in claim 1.
14. The compound of formula (II’) according to claim 13, wherein:
R1 represents a radical C6-20 aryl in particular a phenyl group, said radical being substituted with one or more R4,
R4 represents a halogen atom, notably Br, or \u2014CF3;
Y represents CN or C(\u2550O)R2;
R2 represents \u2014NH2 or a C1-C6alkoxy group;
R3d represents a hydrogen atom or a \u2014C(O)R5; R5 being a C5-14aryl group.
15. The compound of formula (II\u2032) according to claim 14, which is selected from the group consisting of:
1-((2-hydroxyethoxy)methyl)-5-(2-(4-bromophenyl)ethynyl)-1H-1,2,4-triazole-3-carboxamide;
1-(2-(benzoyloxy)ethoxy)methyl-5-(2-(4-trifluoromethylphenyl)ethynyl)-1H-1,2,4-triazole-3-carboxamide; and
1-(2-(benzoyloxy)ethoxy)methyl-5-(2-(4-trifluoromethylphenyl)ethynyl)-1H-1,2,4-triazole-3-nitrile.
16. The compound of formula (I\u2033) according to claim 2, represented by formula (II\u2033):
wherein R1a, R2 and R3d are as defined in claim 1.
17. The compound of formula (II\u2033) according to claim 16, wherein:
R1a represents a radical C1-18alkyl, or C5-14aryl-C1-6alkylene;
R2 represents \u2014NH2 or a C1-C6alkoxy group;
R3d represents a hydrogen atom or a \u2014C(O)R5; R5 being a C1-18 alkyl group.
18. The compound of formula (II\u2033) according to claim 17, which is selected from the group consisting of:
1-((2-hydroxyethoxy)methyl)-5-(1-dodecyl-1H-1,2,3-triazol-4-yl)-1H-1,2,4-triazole-3-carboxamide;
Methyl 1-((2-acetoxyethoxy)methyl)-5-(1-((pyren-3-yl)methyl)-1H-1,2,3-triazol-4-yl)-1H-1,2,4-triazole-3-carboxylate;
1-((2-hydroxyethoxy)methyl)-5-(1-((pyren-3-yl)methyl)-1H-1,2,3-triazol-4-yl)-1H-1,2,4-triazole-3-carboxamide;
1-((2-hydroxyethoxy)methyl)-3-(1-((pyren-3-yl)methyl)-1H-1,2,3-triazol-4-yl)-1H-1,2,4-triazole-5-carboxamide;
1-((2-hydroxyethoxy)methyl)-5-(1-(naphthalen-1-yl)-1H-1,2,3-triazol-4-yl)-1H-1,2,4-triazole-3-carboxamide; and
Methyl 1-((2-acetoxyethoxy)methyl)-5-(1-(pyren-3-yl)-1H-1,2,3-triazol-4-yl)-1H-1,2,4-triazole-3-carboxylate.
19. A Process for the preparation of a compound of formula (I), according claim 3 wherein:
a compound of formula (VI) :
wherein R2, R3a, R3b and R3c are as described for the compounds of formula (I), is reacted with a compound of formula (V):
R1\u2261\u2003\u2003(V)
wherein R1 is as described for the compound of formula (I) according to Pd-catalyzed Sonogashira coupling reaction under microwave irradiation.
20. A medicament comprising a compound of formula (A) according to claim 1 or an addition salt of said compound to a pharmaceutically acceptable salt, or a hydrate or solvate of said compound.
21. A pharmaceutical composition, comprising at least one compound of formula (A) according to claim 1 or an addition salt of said compound to a pharmaceutically acceptable salt, or a hydrate or solvate of said compound and at least one pharmaceutically acceptable excipient.
22. (canceled)
23. (canceled)
24. A method of treating or preventing cancers comprising:
administering the compound according to claim 1 to a mammal in need of treatment andor prevention of cancers.
25. The method according to claim 24, wherein the cancers comprise pancreatic cancer.
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 comprising:
receiving, by a processor of a wearable computing device, an indication that the wearable computing device is not being worn by a user of the wearable computing device; and
responsive to receiving the indication that the wearable computing device is not being worn by the user:
changing, by the processor, an access mode of a computing environment of the wearable computing device from a first increased access mode to a first reduced access mode; and
transmitting, by the processor of the wearable computing device, to a mobile computing device, an instruction to change an access mode of a computing environment of the mobile computing device from a second increased access mode to a second reduced access mode.
2. The method of claim 1, wherein:
the processor receives the indication that the wearable computing device is not being worn by the user from a sensor, and
the sensor comprises at least one of a proximity sensor, an infrared sensor, a camera, a physical contact on a connecting structure of the wearable computing device, an electrical contact on a connecting structure of the wearable computing device, and a pressure sensor.
3. The method of claim 1, wherein, prior to receiving the indication that the wearable computing device is not being worn by the user of the wearable computing device, the wearable computing device is operating in the first increased access mode and the mobile computing device is operating in the second increased access mode.
4. The method of claim 3, wherein the wearable computing device remains in the first increased access mode and the mobile computing device remains in the second increased access mode until the processor of the wearable computing receives the indication that the wearable computing device is not being worn by the user of the wearable computing device.
5. The method of claim 1, further comprising:
receiving, by the processor of the wearable computing device, an indication that the wearable computing device is being worn by the user of the wearable computing device
outputting, by the processor of the wearable computing device, a security challenge;
receiving, by the processor of the wearable computing device, an indication of a response to the security challenge; and
changing, based at least in part on the indication that the wearable computing device is being worn and the indication of the response to the security challenge, the access mode of the computing environment of the wearable computing device from the first reduced access mode to the first increased access mode.
6. The method of claim 1, further comprising:
outputting, by the processor, for display by a display device of the wearable computing device, a graphical user interface including one or more user interface elements.
7. A system comprising:
a mobile computing device comprising one or more mobile computing device processors;
a wearable computing device comprising one or more wearable computing device processors and a sensor, wherein the sensor is configured to generate a first indication that the wearable computing device is being worn by a user and a second indication that the wearable computing device is not being worn by the user;
a mobile computing device access mode module operable by the one or more mobile computing device processors to receive the second indication and change, based at least in part on the second indication, an access mode of a computing environment of the mobile computing device from a first increased access mode to a first reduced access mode in which the user is permitted access to a smaller set of functionality provided by the mobile computing device than when operating in the first increased access mode; and
a wearable computing device access mode module operable by the one or more wearable computing device processors to receive the second indication and change, based at least in part on the second indication, an access mode of a computing environment of the wearable computing device from a second increased access mode to a second reduced access mode in which the user is permitted access to a smaller set of functionality provided by the wearable computing device than when operating in the second increased access mode.
8. The system of claim 7, wherein the sensor comprises at least one of a proximity sensor, an infrared sensor, a camera, a physical contact on a connecting structure of the wearable computing device, an electrical contact on a connecting structure of the wearable computing device, and a pressure sensor.
9. The system of claim 7, wherein, prior to receiving the second indication that the wearable computing device is not being worn by the user of the wearable computing device, the wearable computing device is operating in the second increased access mode and the mobile computing device is operating in the first increased access mode.
10. The system of claim 9, wherein the wearable computing device remains in the second increased access mode and the mobile computing device remains in the first increased access mode until after the sensor generates the second indication.
11. The system of claim 7, wherein the wearable computing device access module is further operable by one or more wearable computing device processors to:
receive the first indication;
output, using a user interface module, a security challenge;
receive an indication of a response to the security challenge; and
change, based at least in part on the first indication and an indication of the response to the security challenge, the access mode of the computing environment of the wearable computing device from the second reduced access mode to the second increased access mode.
12. The system of claim 7, wherein the wearable computing device further comprises a user interface module operable to output, for display by a display device of the wearable computing device, a graphical user interface including one or more user interface elements.
13. A computer-readable storage device storing instructions that, when executed, cause at least one processor of a mobile computing device to:
receive an indication that a wearable computing device is not being worn by a user of the wearable computing device; and
responsive to receiving the indication that the wearable computing device is not being worn by the user, change an access mode of a computing environment of the mobile computing device from an increased access mode to a reduced access mode.
14. The computer-readable storage device of claim 13, wherein:
the increased access mode comprises a first increased access mode;
the reduced access mode comprises a first reduced access mode; and
the instructions, when executed, further cause the at least one processor of the mobile computing device to transmit to the wearable computing device an instruction to change an access mode of a computing environment of the wearable computing device from a second increased access mode to a second reduced access mode.
15. The computer-readable storage device of claim 13, wherein:
the indication that the wearable computing device is not being worn by the user is generated by a sensor; and
the sensor comprises at least one of a proximity sensor, an infrared sensor, a camera, a physical contact on a connecting structure of the wearable computing device, an electrical contact on a connecting structure of the wearable computing device, and a pressure sensor.
16. The computer-readable storage device of claim 14, wherein, prior to the at least one processor of the mobile computing device receiving the indication that the wearable computing device is not being worn by the user of the wearable computing device, the wearable computing device is operating in the second increased access mode and the mobile computing device is operating in the first increased access mode.
17. The computer-readable storage device of claim 16, wherein the wearable computing device remains in the second increased access mode and the mobile computing device remains in the first increased access mode until after the at least one processor of the mobile computing device receives the indication that the wearable computing device is not being worn by the user of the wearable computing device.
18. The computer-readable storage device of claim 13, wherein the wearable computing device comprises a user interface module operable to output, for display by a display device of the wearable computing device, a graphical user interface including one or more user interface elements.