1. A compound having a structure of formula (I) or a pharmaceutically acceptable salt thereof:
wherein
L is selected from C\u2550O, C\u2550S, and SO2;
X is selected from O, S, NH, and N\u2014C1-6alkyl;
Z is absent, C1-6alkyl, or C1-6alkoxy;
R1, R2, and R3 are each independently selected from hydrogen, C1-6alkyl, C1-6alkenyl, C1-6 alkynyl, C1-6hydroxyalkyl, C1-6alkoxyalkyl, aryl, C1-6 aralkyl, heteroaryl, heterocyclyl, C1-6heterocycloalkyl, C1-6heteroaralkyl, carbocyclyl, and C1-6carbocyclolalkyl;
R4 is selected from hydrogen, C1-6aralkyl, and C1-6alkyl;
R5 is heteroaryl; and
R6 and R7 are independently selected from hydrogen, C1-6alkyl, and C1-6aralkyl.
2. A compound of claim 1, wherein Z is absent.
3. A compound of claim 1 or 2, wherein R4, R6, and R7 are independently selected from hydrogen and methyl.
4. A compound of claim 1 or 2, wherein L is C\u2550O.
5. A compound of claim 1 or 2, wherein L is SO2.
6. A compound of any one of claims 1 to 5, wherein R1, R2, and R3 are independently selected from hydrogen, C1-6alkyl, C1-6alkenyl, C1-6alkynyl, C1-6hydroxyalkyl, C1-6alkoxyalkyl, C1-6aralkyl, C1-6heterocycloalkyl, C1-6heteroaralkyl, and C1-6carbocyclolalkyl.
7. A compound of claim 6, wherein any of R1, R2, and R3 are independently C1-6alkyl.
8. A compound of claim 7, wherein any of R1, R2, and R3 are independently selected from methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, and isobutyl.
9. A compound of claim 6 wherein any of R1, R2, and R3 are independently propargyl.
10. A compound of claim 6, wherein any of R1, R2, and R3 are independently C1-6hydroxyalkyl.
11. A compound of claim 10, wherein any of R1, R2, and R3 are independently selected from hydroxymethyl and hydroxyethyl.
12. A compound of claim 6, wherein any of R1, R2, and R3 are independently C1-6alkoxyalkyl.
13. A compound of claim 12, wherein any of R1, R2, and R3 are independently selected from methoxymethyl and methoxyethyl.
14. A compound of claim 6, wherein any of R1, R2, and R3 are independently C1-6heteroaralkyl.
15. A compound of claim 14, wherein any of R1, R2, and R3 are independently selected from imidazolylmethyl, pyrazolylmethyl, and thiazolylmethyl, and pyridylmethyl.
16. A compound of claim 6, wherein any of R1, R2, and R3 are independently cyclohexylmethyl.
17. A compound of any one of claims 1 to 16, wherein R1, R2, and R3 are all different.
18. A compound of any one of claims 1 to 5, wherein at least one of R1 and R2 is selected from C1-6hydroxyalkyl and C1-6alkoxyalkyl.
19. A compound of claim 18, wherein at least one of R1 and R2 is C1-6alkoxyalkyl.
20. A compound of claim 19, wherein at least one of R1 and R2 is selected from methoxymethyl and methoxyethyl.
21. A compound of any one of claims 1 to 5 or 18 to 20, wherein R3 is selected from C1-6alkyl and C1-6aralkyl.
22. A compound of claim 21, wherein R3 is C1-6alkyl.
23. A compound of claim 22, wherein R3 is selected from methyl, ethyl, isopropyl, sec-butyl, and isobutyl.
24. A compound of claim 23, wherein R3 is isobutyl.
25. A compound of claim 21, wherein R3 is C1-6aralkyl.
26. A compound of claim 25, wherein R3 is phenylmethyl.
27. A compound of any one of claims 1 to 26, wherein R5 is 5- or 6-membered heteroaryl.
28. A compound of claim 27, wherein R5 is selected from isoxazole, isothiazole, furan, thiophene, oxazole, thiazole, pyrazole, or imidazole.
29. A compound of claim 28, wherein R5 is selected from isoxazole, furan, or thiophene.
30. A compound of claim 29, wherein R5 is furan or thiophene.
31. A compound of claim 30, wherein R5 is unsubstituted furan-3-yl or thien-2-yl.
32. A compound of claim 29, wherein R5 is isoxazol-3-yl or isoxazol-5-yl.
33. A compound of claim 32, wherein R3 is isoxazol-3-yl that has a substituent at the 5-position.
34. A compound of claim 32, wherein R3 is isoxazol-5-yl that has a substituent at the 3-position.
35. A compound of claim 33 or 34, wherein the substituent is selected from C1-6alkyl, C1-6alkoxy, C1-6alkoxyalkyl, C1-6hydroxyalkyl, carboxylic acid, aminocarboxylate, C1-6alkylaminocarboxylate, (C1-6alkyl)2aminocarboxylate, C1-6alkylcarboxylate, C1-6heteroaralkyl, C1-6aralkyl, C1-6heterocycloalkyl, and C1-6carbocycloalkyl.
36. A compound of claim 35, wherein the substituent is selected from methyl, ethyl, isopropyl, and cyclopropylmethyl.
37. A compound of claim 35, wherein the substituent is selected from C1-6heteroaralkyl and C1-6heterocycloalkyl.
38. A compound of claim 37, wherein the substituent is 1,2,4-triazol-5-ylmethyl.
39. A compound of claim 37, wherein the substituent is azetidin-1-ylmethyl.
40. A compound of claim 37, wherein the substituent is
wherein W is O, NR, or CH2, and R is H or C1-6alkyl.
41. A compound of claim 40, wherein W is O.
42. A compound of claim 37, wherein the substituent is selected from C1-6alkoxy and C1-6alkoxyalkyl.
43. A compound of claim 42, wherein the substituent is selected from methoxy, ethoxy, methoxymethyl, and methoxyethyl.
44. A compound of claim 37, wherein the substituent is selected from carboxylic acid, aminocarboxylate, C1-6alkylaminocarboxylate, (C1-6alkyl)2aminocarboxylate, or C1-6alkylcarboxylate.
45. A compound of claim 44, wherein the substituent is methyl carboxylate.
46. A compound selected from
47. A pharmaceutical composition comprising a compound of any one of claims 1 to 46 and a pharmaceutically acceptable diluent or carrier.
48. A pharmaceutical composition of claim 47, which is orally bioavailable.
49. A method for the treatment of inflammation, comprising administering a therapeutically effective amount of a pharmaceutical composition of claim 48.
50. A method for inhibiting or reducing HIV infection, comprising administering a therapeutically effective amount of a pharmaceutical composition of claim 48.
51. A method for the treatment of neurodegenerative disease, comprising administering a therapeutically effective amount of a pharmaceutical composition of claim 48.
52. A method for the treatment of muscle-wasting diseases, comprising administering a therapeutically effective amount of a pharmaceutical composition of claim 48.
53. A method for the treatment of cancer, comprising administering a therapeutically effective amount of a pharmaceutical composition of claim 48.
54. A method for the treatment of chronic infectious diseases, comprising administering a therapeutically effective amount of a pharmaceutical composition of claim 48.
55. A method for the treatment of a hyperproliferative condition, comprising administering a therapeutically effective amount of a pharmaceutical composition of claim 48.
56. A method for the treatment of muscle disuse, comprising administering a therapeutically effective amount of a pharmaceutical composition of claim 35.
57. A method for the treatment of immune-related conditions, comprising administering a therapeutically effective amount of a pharmaceutical composition of claim 48.
58. A method for affecting the level of viral gene expression in a subject, comprising administering a therapeutically effective amount of a pharmaceutical composition of claim 48.
59. A method for altering the variety of antigenic peptides produced by the proteasome in an organism, comprising administering therapeutically effective amount of a pharmaceutical composition of claim 48.
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. An alarm system for use with a structure, comprising:
a safety detector to detect a safety condition with respect to the structure;
a transmitter to transmit a communication to a person in a form perceivable by the person;
a memory having a plurality of stored audible communications;
an input device for accepting a user command; and
a processor functionally connected to the safety detector, the transmitter, the memory, and the input device, and in response to a user command received from the input device, the processor accepts a user selection of an audible communication from the plurality of stored audible communications, and, in response to the safety detector detecting the safety condition, the processor causes the transmitter to transmit a first said communication to the person in the form perceivable by the person and to cause the transmitter to perform at least one of transmitting a second said communication to the person in the form perceivable by the person or ceasing transmission of the first said communication, and wherein the selected audible communication is at least one of the first said communication or the second said communication.
2. The alarm system of claim 1 wherein the plurality of stored audible communications comprises a plurality of stored names and wherein, in response to the user command received from the input device, the processor accepts a user selection of a stored name from the plurality of stored names as the selected audible communication.
3. An alarm system for use with a structure, comprising:
a safety detector to detect a safety condition with respect to the structure;
a transmitter to transmit a communication to a person in a form perceivable by the person;
a voice synthesizer to generate a spoken message from a user command;
an input device for accepting the user command;
a memory to store at least one of the command or the generated message; and
a processor functionally connected to the safety detector, the transmitter, the voice synthesizer, the input device, and the memory and in response to a user command received from the input device, the processor causes the memory to store the at least one of the command or the generated message, in response to the safety detector detecting the safety condition, the processor causes the transmitter to transmit a first said communication to the person in the form perceivable by the person and to cause the transmitter to perform at least one of transmitting a second said communication to the person in the form perceivable by the person or ceasing transmission of the first said communication, and wherein the generated message is at least one of the first said communication or the second said communication.
4. The system of claim 3 wherein the user command is a name, the voice synthesizer generates the name as the spoken message, and the transmitter transmits the generated name as at least one of the first said communication or the second said communication.
5. The system of claim 3 wherein the user command is an instruction to the person, the voice synthesizer generates the instruction as the spoken message, and the transmitter transmits the generated instruction as at least one of the first said communication or the second said communication.