1. A compound of the formula (II):
each R1 is hydroxy, alkoxy, or aryloxy, or each R1 is an oxygen atom and together with the boron, to which they are each bound, form a 5-7 membered ring, wherein the ring atoms are carbon, nitrogen, or oxygen;
each R2 is independently hydrogen, alkyl, alkenyl, aryl, aralkyl, aralkenyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, heteroaryl, or heteroaralkyl, or two R2 groups, which are bound to the same nitrogen atom, form together with that nitrogen atom, a 5-7 membered monocyclic heterocyclic ring system; wherein any R2 carbon atom is optionally substituted with J;
J is alkyl, aryl, aralkyl, alkoxy, aryloxy, aralkoxy, cycloalkyl, cycloalkoxy, heterocyclyl, heterocyclyloxy, heterocyclylalkyl, keto, hydroxy, amino, alkylamino, alkanoylamino, aroylamino, aralkanoylamino, carboxy, carboxyalkyl, carboxamidoalkyl, halo, cyano, nitro, formyl, acyl, sulfonyl, or sulfonamido and is optionally substituted with 1-3 J1 groups;
J1 is alkyl, aryl, aralkyl, alkoxy, aryloxy, heterocyclyl, heterocyclyloxy, keto, hydroxy, amino, alkanoylamino, aroylamino, carboxy, carboxyalkyl, carboxamidoalkyl, halo, cyano, nitro, formyl, sulfonyl, or sulfonamido;
L is alkyl, alkenyl, or alkynyl, wherein any hydrogen is optionally substituted with halogen, and wherein any hydrogen or halogen atom bound to any terminal carbon atom is optionally substituted with sulfhydryl or hydroxy;
A1 is
R4 is alkyl, cycloalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, heteroaralkyl, carboxyalkyl, or carboxamidoalkyl, and is optionally substituted with 1-3 J groups;
R5 and R6 are independently hydrogen, alkyl, alkenyl, aryl, aralkyl, aralkenyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroaralkyl, and is optionally substituted with 1-3 J groups;
X is a bond, \u2014C(H)(R7)\u2014, \u2014O\u2014, \u2014S\u2014, or \u2014N(R8)\u2014;
R7 is hydrogen, alkyl, alkenyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroaralkyl, and is optionally substituted with 1-3 J groups;
R8 is hydrogen, alkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, heteroaralkyl, aralkanoyl, heterocyclanoyl, heteroaralkanoyl, \u2014C(O)R14, \u2014SO2R14, or carboxamido, and is optionally substituted with 1-3 J groups; or R8 and Z, together with the atoms to which they are bound, form a nitrogen containing mono- or bicyclic ring system optionally substituted with 1-3 J groups;
R14 is alkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroaralkyl;
Y is a bond, \u2014CH2\u2014, \u2014C(O)\u2014, \u2014C(O)C(O)\u2014, \u2014S(O)\u2014, \u2014S(O)2\u2014, or \u2014S(O)(NR7)\u2014, wherein R7 is as defined above;
Z is alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, heteroaralkyl, \u2014OR2, or \u2014N(R2)2, wherein any carbon atom is optionally substituted with J, wherein R2 is as defined above;
A2 is a bond or
R9 is alkyl, cycloalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, heteroaralkyl, carboxyalkyl, or carboxamidoalkyl, and is optionally substituted with 1-3 J groups;
M is alkyl, cycloalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroaralkyl, optionally substituted by 1-3 J groups, wherein any alkyl carbon atom may be replaced by a heteroatom;
V is a bond, \u2014CH2\u2014, \u2014C(H)(R11)-, O\u2014, \u2014S\u2014, or \u2014N(R11)\u2014;
R11 is hydrogen or C1\u22123 alkyl;
K is a bond, \u2014O\u2014, \u2014S\u2014, \u2014C(O)\u2014, \u2014S(O)\u2014, \u2014S(O)2\u2014, or \u2014S(O)(NR11)\u2014, wherein R11 is as defined above;
T is \u2014R12, -alkyl-R12, -alkenyl-R12, -alkynyl-R12, \u2014OR12, \u2014N(R12)2, C(O)R12, \u2014C(\u2550NOalkyl)R12, or
R12 is hydrogen, aryl, heteroaryl, cycloalkyl, heterocyclyl, cycloalkylidenyl, or heterocycloalkylidenyl, and is optionally substituted with 1-3 J groups, or a first R12 and a second R12, together with the nitrogen to which they are bound, form a mono- or bicyclic ring system optionally substituted by 1-3 J groups;
R10 is alkyl, cycloalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, heteroaralkyl, carboxyalkyl, or carboxamidoalkyl, and is optionally substituted with 1-3 J groups;
R15 is alkyl, cycloalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, heteroaralkyl, carboxyalkyl, or carboxamidoalkyl, and is optionally substituted with 1-3 J groups; and
R16 is hydrogen, alkyl, aryl, heteroaryl, cycloalkyl, or heterocyclyl; provided that when
A2 is
and K is \u2014C(O)\u2014, then V is not \u2014N(R11)\u2014.
2. The compound according to claim 1, wherein R5 and R6 are hydrogen.
3. The compound according to claim 2, wherein A2 is:
and R9 is alkyl.
4. The compound according to claim 3, wherein R9 is isopropyl.
5. The compound according to claim 4, wherein L is alkyl, alkenyl, or alkynyl, wherein any hydrogen is optionally substituted with halogen, and wherein any hydrogen or halogen atom bound to any terminal carbon atom is optionally substituted with sulfhydryl or hydroxy.
6. The compound according to claim 5, wherein L is trihalomethyl, sulfhydryl, or alkyl substituted with trihalomethyl, sulfhydryl, or hydroxy.
7. The compound according to claim 6, wherein:
X is \u2014O\u2014 or \u2014N(H)\u2014; and
Y is \u2014CH2\u2014, \u2014C(O)\u2014, or \u2014S(O)2\u2014.
8. The compound according to claim 7, wherein:
V is \u2014N(H)\u2014 and
K is \u2014C(O)\u2014 or \u2014S(O)2\u2014.
9. The compound according to claim 1, wherein
R5 and R6 are hydrogen;
A2 is a bond or
and R9 is isopropyl;
L is ethyl;
X is \u2014O\u2014 or \u2014N(H)\u2014;
Y is \u2014CH2\u2014, \u2014C(O)\u2014, or \u2014S(O)2\u2014;
V is \u2014N(H)\u2014; and
K is \u2014S(O)2\u2014.
10. The compound according to claim 9, wherein M is isopropyl.
11. The compound according to claim 10, wherein Z is aryl or heteroaryl.
12. The compound according to claim 11, wherein T is aryl or heteroaryl.
13. The compound according to claim 12, wherein T is pyrazine.
14. The compound according to claim 9, wherein X is \u2014O\u2014 and Y is \u2014CH2\u2014.
15. The compound according to claim 14, wherein Z is aryl or heteroaryl.
16. The compound according to claim 15, wherein Z is aryl.
17. The compound according to claim 16, wherein M is isopropyl.
18. The compound according to claim 9, wherein T is \u2014R12, \u2014OR12, \u2014N(R12)2, or
19. The compound according to claim 18, wherein M is alkyl, heteroaralkyl, aryl, cycloalkylalkyl, aralkyl, or aralkyl wherein one of the alkyl carbon atoms is replaced by O or S.
20. The compound according to claim 19, wherein M is propyl, methyl, pyridylmethyl, benzyl, naphthylmethyl, phenyl, imidazolylmethyl, thiophenylmethyl, cyclohexylmethyl, phenethyl, benzylthiomethyl, or benzyloxyethyl.
21. The compound according to claim 20, wherein T is aryl or heteroaryl.
22. The compound according to claim 21, wherein T is pyrazine.
23. The compound according to claim 2, wherein
A2 is a bond;
L is ethyl;
X is \u2014O\u2014;
Y is \u2014CH2\u2014;
V is \u2014N(H)\u2014; and
K is \u2014C(O)\u2014 or \u2014S(O)2\u2014.
24. The compound according to claim 23, wherein M is isopropyl.
25. The compound according to claim 24, wherein Z is aryl or heteroaryl.
26. The compound according to claim 25, wherein Z is phenyl.
27. The compound according to claim 26, wherein T is \u2014R12, -alkyl-R12, -alkenyl-R12, \u2014OR12, \u2014N(R12)2, \u2014C(\u2550NOalkyl)R12, or
28. The compound according to claim 1, wherein
A2 is
29. The compound according to claim 28, wherein M is isopropyl and K is \u2014S(O)2\u2014.
30. The compound according to claim 29, wherein T is \u2014R12, -alkyl-R12, -alkenyl-R12, \u2014OR12, \u2014N(R12)2, \u2014C(\u2550NOalkyl)R12, or
31. The compound according to any one of claims 1 and 2-30, wherein W is
32. The compound according to claim 1, wherein the compound is selected from any one of the following compounds:
T
U
143
S(O2)
144
S(O2)
145
C(O)
146
C(O)
147
C(O)
148
C(O)
149
C(O)
150
C(O)
151
C(O)
152
C(O)
153
C(O)
154
C(O)
155
C(O)
156
C(O)
157
C(O)
158
C(O)
159
C(O)
160
C(O)
161
C(O)
162
C(O)
163
C(O)
164
C(O)
165
C(O)
166
C(O)
167
C(O)
168
C(O)
169
C(O)
170
C(O)
171
C(O)
172
C(O)
173
C(O)
174
C(O)
175
C(O)
176
C(O)
177
C(O)
178
C(O)
179
C(O)
180
C(O)
181
C(O)
182
C(O)
183
C(O)
184
C(O)
185
C(O)
186
C(O)
187
C(O)
188
C(O)
189
C(O)
190
C(O)
191
C(O)
192
C(O)
193
C(O)
194
C(O)
195
C(O)
196
C(O)
197
C(O).
33. A pharmaceutically acceptable composition comprising:
a) a compound according to any of claims 1 and 2-30 in an amount effective to inhibit HCV NS3 protease; and
b) a pharmaceutically suitable carrier.
34. A method for inhibiting serine protease activity in a patient comprising the step of administering to said patient a compound according to any one of claims 1 and 2-30 wherein the serine protease is HCV NS3 protease.
35. A method for treating a hepatitis C viral infection in a patient comprising the step of administering to said patient a compound according to any one of claims 1 and 2-30.
36. The method according to claim 35, wherein said compound is administered to said patient and is formulated together with a pharmaceutically suitable carrier into a pharmaceutically acceptable composition.
37. A pharmaceutically acceptable composition comprising:
a) a compound according to claim 31 or 32; and
b) a pharmaceutically suitable carrier.
38. A method for inhibiting serine protease activity in a patient comprising the step of administering to said patient a compound according to claim 31 or 32 wherein the serine protease is HCV NS3 protease.
39. A method for treating a hepatitis C viral infection in a patient comprising the step of administering to said patient a compound according to claim 31 or 32.
40. The method according to claim 39, wherein said compound is administered to said patient and is formulated together with a pharmaceutically suitable carrier into a pharmaceutically acceptable composition.
41. The compound according to claim 1, wherein Z is phenyl, wherein any carbon atom is optionally substituted with J.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1-16. (canceled)
17. A system for raising and lowering an adjustable headrest of a vehicle seat, comprising:
at least one carrier bar for carrying the adjustable headrest, the carrier bar having at least one first notch arranged on a first line and at least one second notch arranged on a second line, the first and second lines being parallel to a longitudinal axis of the carrier bar;
a carrier bar guiding element operably connected to the at least one carrier bar to permit sliding movement of the at least one carrier bar relative to the carrier bar guiding element;
a spring element including at least first and second portions, the first portion being biased toward the first line and configured to engage the at least one first notch to lock a longitudinal movement of the carrier bar in a first direction, and the second portion being biased toward the second line and configured to engage the at least one second notch to lock the longitudinal movement of the carrier bar in a second direction; and
an actuation arm configured to contact at least one of the first portion and the second portion so as to permit the longitudinal movement of the carrier bar in either the first direction or the second direction.
18. The system of claim 17, wherein upon actuation of the actuation arm in the first direction, the first portion of the spring element moves away from the carrier bar so as not to engage the at least one first notch, and thereby allow the longitudinal movement of the carrier bar in the first direction.
19. The system of claim 17, wherein upon actuation of the actuation arm in the second direction, the second portion of the spring element moves away from the carrier bar so as not to engage the at least one second notch in order to allow the longitudinal movement of the carrier bar in the second direction.
20. The system of claim 17, further comprising a button mounted on the carrier bar guiding element such that the button is depressed to enable movement of the actuation arm in the first direction, and the button blocks movement of the actuation arm in the second direction.
21. The system of claim 20, wherein the button is configured to be dismounted from the carrier bar guiding element.
22. The system of claim 21, wherein the button is operably connected to a mounting frame.
23. The system of claim 21, wherein the actuation arm is actuated in the second direction by manual tearing of the actuation arm.
24. The system of claim 21, wherein the headrest is configured to be removed in an upward direction if the button is dismounted and the actuation arm is actuated in the second direction.
25. The system of claim 20, wherein the button is mounted on a mounting frame, the mounting frame blocking the actuation arm from being actuated in the second direction.
26. The system of claim 17, wherein the at least one first notch has an inclined face pointing downwardly such that the first portion of the spring element can slide against the inclined face to lock in place and prevent further lowering of the headrest.
27. The system of claim 17, wherein the at least one second notch has an inclined face pointing upwardly such that the second portion of the spring element can slide against the inclined face to lock in place and prevent further raising of the headrest.
28. The system of claim 17, wherein the at least one carrier bar supports the headrest.
29. The system of claim 28, wherein the at least one carrier bar comprises first and second carrier bars connected inside the headrest.
30. The system of claim 17, wherein the button protrudes from upholstery of a backrest of the vehicle seat.
31. The adjustable headrest of claim 17, wherein the at least one carrier bar is fixed to the headrest of the vehicle seat.
32. An adjustable headrest for a vehicle seat, comprising:
at least one carrier bar for carrying the adjustable headrest, the carrier bar having at least one first notch arranged on a first line and at least one second notch arranged on a second line, the first and second lines being parallel to a longitudinal axis of the carrier bar;
a carrier bar guiding element operably connected to the at least one carrier bar to permit sliding movement of the at least one carrier bar relative to the carrier bar guiding element;
a spring element including at least first and second portions, the first portion being biased toward the first line and configured to engage the at least one first notch to lock a longitudinal movement of the carrier bar in a first direction, and the second portion being biased toward the second line and configured to engage the at least one second notch to lock the longitudinal movement of the carrier bar in a second direction; and
an actuation arm configured to contact at least one of the first portion and the second portion so as to permit the longitudinal movement of the carrier bar in either the first direction or the second direction, wherein upon actuation of the actuation arm in the first direction, the first portion of the spring element moves away from the carrier bar so as not to engage the at least one first notch, and thereby allow the longitudinal movement of the carrier bar in the first direction, and upon actuation of the actuation arm in the second direction, the second portion of the spring element moves away from the carrier bar so as not to engage the at least one second notch in order to allow the longitudinal movement of the carrier bar in the second direction.
33. The adjustable headrest of claim 32, further comprising a button mounted on the carrier bar guiding element such that the button is depressed to enable movement of the actuation arm in the first direction, and the button blocks movement of the actuation arm in the second direction.
34. The adjustable headrest of claim 32, wherein the at least one first notch has an inclined face pointing downwardly such that the first portion of the spring element can slide against the inclined face to lock in place and prevent further lowering of the headrest.
35. The adjustable headrest of claim 32, wherein the at least one second notch has an inclined face pointing upwardly such that the second portion of the spring element can slide against the inclined face to lock in place and prevent further raising of the headrest.
36. The adjustable headrest of claim 32, wherein the at least one carrier bar supports the headrest.