1. A semiconductor memory having a plurality of normal memory blocks and a redundant memory block, comprising:
a redundant replacement memory that stores identification information for a normal memory block that is a replacement target;
a select signal generation unit that generates a block select signal on the basis of the redundant replacement memory identification information in response to a memory reset signal inputted to a reset terminal; and
a memory block selection unit that selects the redundant memory block and enables inputoutput access thereto in place of the replacement-target normal memory block on the basis of the block select signal,
wherein the memory block selection unit selects the redundant memory block in place of any normal memory block in response to a redundant select signal which is inputted to the reset terminal and differs from the memory reset signal.
2. The semiconductor memory according to claim 1,
wherein, when the redundant replacement memory is in an initial state, the redundant replacement memory does not store the identification information;
the select signal generation unit generates the block select signal that does not direct replacement with the redundant memory block; and
the memory block selection unit selects the redundant memory block in response to the redundant select signal inputted to the reset terminal instead of selecting the redundant memory block on the basis of the block select signal that does not direct the replacement.
3. The semiconductor memory according to claim 1, wherein the select signal generation unit generates, in response to the redundant select signal in addition to the memory reset signal, a block select signal on the basis of the redundant replacement memory identification information.
4. The semiconductor memory according to claim 1, wherein the select signal generation unit latches the redundant replacement memory identification information in response to the memory reset signal.
5. The semiconductor memory according to claim 1, wherein the memory block selection unit comprises:
a plurality of selectors, provided corresponding with the normal memory blocks respectively, that select either the inputoutput of the corresponding normal memory block, or the inputoutput of the normal memory block adjacent to the corresponding normal memory block or the redundant memory block,
wherein, in response to the block select signal, the memory block selection unit selects the inputoutput of the redundant memory block without selecting the inputoutput of the replacement-target normal memory block.
6. The semiconductor memory according to claim 5, wherein the memory block selection unit further comprises:
a plurality of NOR gates that correspond with the normal memory blocks respectively,
wherein the block select signal is inputted to the corresponding NOR gate together with the output of the previous-stage NOR gate and the output of the NOR gate is supplied as a select signal to the corresponding selector; and
the redundant select signal is inputted to any of the plurality of NOR gates.
7. The semiconductor memory according to claim 6, wherein the memory reset signal is one pulse signal and the redundant select signal is a signal that retains the high level after the rising edge thereof.
8. The semiconductor memory according to claim 1, wherein the select signal generation unit generates a plurality of normal block select signals that select the normal memory blocks and a redundant block select signal that selects the redundant memory block;
when the redundant replacement memory is in the initial state, the select signal generation unit causes the plurality of normal block select signals a selective state and causes the redundant block select signal a nonselective state; and
in response to the redundant select signal, any normal block select signal is caused to be the nonselective state and the redundant block select signal is caused to be the selective state.
9. An integrated circuit device with a built-in memory module, the memory module comprising:
a memory core that includes a plurality of normal memory blocks and a redundant memory block;
a redundant replacement memory that stores identification information for a normal memory block that is a replacement target;
a select signal generation unit that generates a block select signal on the basis of redundant replacement memory identification information in response to a memory reset signal inputted to a reset terminal; and
a memory block selection unit that selects the redundant memory block and enables inputoutput access thereto in place of the replacement-target normal memory block on the basis of the block select signal,
wherein the memory block selection unit selects the redundant memory block in place of any normal memory block in response to a redundant select signal which is inputted to the reset terminal and differs from the memory reset signal.
10. The integrated circuit device according to claim 9, wherein the reset terminal of the memory module is connected to an external terminal.
11. The integrated circuit device according to claim 9, further comprising:
a reset circuit that generates the memory reset signal,
wherein the memory reset signal that is generated by the reset circuit, and a memory reset signal and redundant select signal from an external terminal are selectively supplied to the reset terminal of the memory module.
12. The integrated circuit device according to claim 9, wherein the select signal generation unit latches the redundant replacement memory identification information in response to the memory reset signal.
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 compound of the formula
or a pharmaceutically acceptable salt thereof; wherein
Ar1 is
where G is O, N, or S, and R6 is nitro, cyano, \u2014PO4, \u2014CHO, or \u2014COOH;
X1 is CR1 or N;
X2 is CR2 or N;
X3 is CR3 or N;
X4 is CR4 or N;
wherein
is not unsubstituted or substituted phenyl, unsubstituted pyridyl, or unsubstituted pyridizine, or 2-methylbenzodthiazole, and no more than 2 of X1-X4 are N;
R1 to R4 are independently chosen from hydrogen, halogen, hydroxyl, cyano, nitro, C1-C4alkyl, C1-C4alkoxy, mono- and di-(C1-C4)alkylamino, C1-C2haloalkyl, and C1-C2haloalkoxy; and
One of the following three conditions may be present:
R1 and R2 may be taken together to form a 6-membered carbocyclic ring, or a 5- or 6-membered heterocyclic ring containing 1 or 2 heteroatoms independently chosen from N, O, and S, which carbocyclic or heterocyclic R1R2 ring is substituted with 0 or 1 or more substituents independently chosen from halogen, hydroxyl, amino, cyano, nitro, C1-C4alkyl, C1-C4alkoxy, mono- and di-(C1-C4)alkylamino, C1-C2haloalkyl, and C1-C2haloalkoxy;
R2 and R3 may be taken together to form a 6-membered carbocyclic ring, or a 5- or 6-membered heterocyclic ring containing 1 or 2 heteroatoms independently chosen from N, O, and S, which carbocyclic or heterocyclic R2R3 ring is substituted with 0 or 1 or more substituents independently chosen from halogen, hydroxyl, amino, cyano, nitro, C1-C4alkyl, C1-C4alkoxy, mono- and di-(C1-C4)alkylamino, C1-C2haloalkyl, and C1-C2haloalkoxy;
R3 and R4 may be taken together to form a 6-membered carbocyclic ring, or a 5- or 6-membered heterocyclic ring containing 1 or 2 heteroatoms independently chosen from N, O, and S, which carbocyclic or heterocyclic R3R4 ring is substituted with 0 or 1 or more substituents independently chosen from halogen, hydroxyl, amino, cyano, nitro, C1-C4alkyl, C1-C4alkoxy, mono- and di-(C1-C4)alkylamino, C1-C2haloalkyl, and C1-C2haloalkoxy; and
R5 is hydrogen, halogen, hydroxyl, amino, cyano, nitro, C1-C4alkyl, C1-C4alkoxy, mono- or di-(C1-C4)alkylamino, C1-C2haloalkyl, or C1-C2haloalkoxy.
2. A compound or salt of claim 1, where Ar1 is
where R6 is nitro and G is oxygen.
3. A compound or salt of claim 1, wherein
R1 to R4 are independently chosen from hydrogen, halogen, hydroxyl, nitro, C1-C2alkyl, C1-C2alkoxy, mono- or di-(C1-C2)alkylamino, trifluoromethyl, and trifluoromethoxy; and
one of the following two conditions is present:
R2 and R3 are taken together to form a 6-membered aromatic ring or 6-membered heteroaromatic ring containing one or two nitrogen atoms, which 6-membered R2R3 ring is substituted with 0 or 1 or more substituents independently chosen from halogen, hydroxyl, nitro, C1-C2alkyl, C1-C2alkoxy, mono- and di-(C1-C2)alkylamino, trifluoromethyl, and trifluoromethoxy;
R3 and R4 are taken together to form a 6-membered aromatic ring or 6-membered heteroaromatic ring containing one or two nitrogen atoms, which 6-membered R3R4 ring is substituted with 0 or 1 or more substituents independently chosen from halogen, hydroxyl, nitro, C1-C2alkyl, C1-C2alkoxy, mono- and di-(C1-C2)alkylamino, trifluoromethyl, and trifluoromethoxy; and
R5 is hydrogen or hydroxyl.
4. A compound or salt of claim 3, wherein
X1 is CR1, X4 is CR4; R5 is hydroxyl; and
X2 is CR2; X3 is CR3 and R2 and R3 are taken together to form a 6-membered aromatic ring, which 6-membered R2R3 ring is substituted with 0 or 1 or more substituents independently chosen from halogen, hydroxyl, nitro, C1-C2alkyl, C1-C2alkoxy, mono- and di-(C1-C2)alkylamino, trifluoromethyl, and trifluoromethoxy.
5. A compound or salt of claim 3, wherein
X1 is N; X2 is CR2; R5 is hydroxyl; and
X3 is CR3; X4 is CR4; and X3 and X4 are taken together to form a 6-membered aromatic ring, which 6-membered R3R4 ring is substituted with 0 or 1 or more substituents independently chosen from halogen, hydroxyl, nitro, C1-C2alkyl, C1-C2alkoxy, mono- and di-(C1-C2)alkylamino, trifluoromethyl, and trifluoromethoxy.
6. A compound or salt of claim 3, wherein
X1 is CR1; X2 is N; R5 hydroxyl; and
X3 is CR3; X4 is CR4; and X3 and X4 are taken together to form a 6-membered aromatic ring, which 6-membered R3R4 ring is substituted with 0 or 1 or more substituents independently chosen from halogen, hydroxyl, nitro, C1-C2alkyl, C1-C2alkoxy, mono- and di-(C1-C2)alkylamino, trifluoromethyl, and trifluoromethoxy.
7. A compound of claim 1 or salt thereof, wherein the compound has the formula
8-9. (canceled)
10. A method of inhibiting p97 andor inducing ER stress in a subject, comprising providing a therapeutically effective amount of a hydrazone or diacylhydrazone p97 ATPase inhibitor to the subject, wherein the ATP inhibitor is a compound or pharmaceutically acceptable salt thereof of the formula
where
dashed lines indicate a single or double covalent bond;
A is hydrogen or oxo (\u2550O);
Ar1 is furanyl, thienyl, pyridyl, or phenyl, each of which is optionally substituted with one or more substituents independently chosen from halogen, hydroxyl, amino, cyano, nitro, \u2014CHO, \u2014COOH, \u2014PO4, C1-C4alkyl, C1-C4alkoxy, C2-C4alkanoyl, C1-C4alkylester, mono- and di-(C1-C4)alkylamino, C1-C2haloalkyl, and C1-C2haloalkoxy;
m is 1, 2, 3, 4, or 5;
X1 is CRS or N;
X2 is CR2 or N;
X3 is CR3 or N;
X4 is CR4 or N;
wherein no more than 2 of X1-X4 are N;
R1 to R4 are independently chosen from hydrogen, halogen, hydroxyl, amino, cyano, nitro, C1-C4alkyl, C1-C4alkoxy, mono- and di-(C1-C4)alkylamino, C1-C2haloalkyl, and C1-C2haloalkoxy;
One of the following conditions may be present:
R2 and R3 may be taken together to form a 6-membered carbocyclic ring, or a 5- or 6-membered heterocyclic ring containing 1 or 2 heteroatoms independently chosen from N, O, and S, which carbocyclic or heterocyclic R2R3 ring is substituted with 0 or 1 or more substituents independently chosen from halogen, hydroxyl, amino, cyano, nitro, C1-C4alkyl, C1-C4alkoxy, mono- and di-(C1-C4)alkylamino, C1-C2haloalkyl, and C1-C2haloalkoxy;
R3 and R4 may be taken together to form a 6-membered carbocyclic ring, or a 5- or 6-membered heterocyclic ring containing 1 or 2 heteroatoms independently chosen from N, O, and S, which carbocyclic or heterocyclic R3R4 ring is substituted with 0 or 1 or more substituents independently chosen from halogen, hydroxyl, amino, cyano, nitro, C1-C4alkyl, C1-C4alkoxy, mono- and di-(C1-C4)alkylamino, C1-C2haloalkyl, and C1-C2haloalkoxy; and
R5 is hydrogen, halogen, hydroxyl, amino, cyano, nitro, C1-C4alkyl, C1-C4alkoxy, mono- or di-(C1-C4)alkylamino, C1-C2haloalkyl, or C1-C2haloalkoxy.
11. A method of inhibiting p97 andor inducing ER stress in a subject comprising providing a therapeutically effective amount of a compound or pharmaceutically acceptable salt thereof of the formula
where
Ar1 is furanyl, thienyl, pyridyl, or phenyl, each of which is optionally substituted with one or more substituents independently chosen from halogen, hydroxyl, amino, cyano, nitro, \u2014CHO, \u2014COOH, \u2014PO4, C1-C4alkyl, C1-C4alkoxy, C2-C4alkanoyl, C1-C4alkylester, mono- and di-(C1-C4)alkylamino, C1-C2haloalkyl, and C1-C2haloalkoxy;
n is a bond or n is a 1 to 4 carbon alkylene or alkenylene linker;
X1 is CR1 or N;
X2 is CR2 or N;
X3 is CR3 or N;
X4 is CR4 or N;
wherein no more than 2 of X1-X4 are N;
R1 to R4 are independently chosen from hydrogen, halogen, hydroxyl, amino, cyano, nitro, C1-C4alkyl, C1-C4alkoxy, mono- and di-(C1-C4)alkylamino, C1-C2haloalkyl, and C1-C2haloalkoxy;
One of the following two conditions may be present:
R2 and R3 may be taken together to form a 6-membered carbocyclic ring, or a 5- or 6-membered heterocyclic ring containing 1 or 2 heteroatoms independently chosen from N, O, and S, which carbocyclic or heterocyclic R2R3 ring is substituted with 0 or 1 or more substituents independently chosen from halogen, hydroxyl, amino, cyano, nitro, C1-C4alkyl, C1-C4alkoxy, mono- and di-(C1-C4)alkylamino, C1-C2haloalkyl, and C1-C2haloalkoxy;
R3 and R4 may be taken together to form a 6-membered carbocyclic ring, or a 5- or 6-membered heterocyclic ring containing 1 or 2 heteroatoms independently chosen from N, O, and S, which carbocyclic or heterocyclic R3R4 ring is substituted with 0 or 1 or more substituents independently chosen from halogen, hydroxyl, amino, cyano, nitro, C1-C4alkyl, C1-C4alkoxy, mono- and di-(C1-C4)alkylamino, C1-C2haloalkyl, and C1-C2haloalkoxy; and
R5 is hydrogen, halogen, hydroxyl, amino, cyano, nitro, C1-C4alkyl, C1-C4alkoxy, mono- or di-(C1-C4)alkylamino, C1-C2haloalkyl, or C1-C2haloalkoxy.
12. The method of claim 11, wherein the compound is a compound of the formula
or a pharmaceutically acceptable salt thereof.
13. The method of claim 12 wherein
Ar1 is a 2-furanyl or phenyl, each of which is substituted with at least one nitro, hydroxyl, amino, \u2014CHO, \u2014COOH, or \u2014PO4 substituent and optionally substituted with one or more substituents independently chosen from cyano, C1-C2alkyl, C1-C2alkoxy, mono- and di-(C1-C2)alkylamino, C1-C2haloalkyl, and C1-C2haloalkoxy.
14. The method of claim 12, wherein the compound is a compound of the formula
or a pharmaceutically acceptable salt thereof, wherein
R6 is nitro, cyano, \u2014CHO, \u2014COOH, or \u2014PO4; and
R7 is 0, 1, or 2 substituents independently chosen from halogen, C1-C2alkyl, and C1-C2alkoxy.
15. The method of claim 14, wherein R6 is nitro and R7 absent.
16. The method claim 10, wherein
is a phenyl, naphthyl, quinolinyl, isoquinolinyl, or pyridyl, in which
R5 is hydrogen, halogen, hydroxyl, amino, cyano, nitro, C1-C4alkyl, C1-C4alkoxy, mono- or di-(C1-C4)alkylamino, C1-C2haloalkyl, or C1-C2haloalkoxy; and
each of which
phenyl, naphthyl, quinolinyl, isoquinolinyl, is substituted with 0, 1, or 2 substituents independently chosen from halogen, hydroxyl, amino, cyano, nitro, C1-C4alkyl, C1-C4alkoxy, mono- and di-(C1-C4)alkylamino, C1-C2haloalkyl, and C1-C2haloalkoxy.
17. The method of claim 16, wherein
R5 is hydrogen or hydroxyl; and
each of which
phenyl, naphthyl, quinolinyl, isoquinolinyl, is substituted with 0, 1, or 2 substituents independently chosen from chloro, bromo, hydroxyl, nitro, methyl, methoxy, and trifluoromethyl.
18. The method of claim 16, wherein
is phenyl, 3-pyridyl, 2-, 3-, or 4-hydroxy phenyl, 3-hydroxy-naphth-2-yl, 1-hydroxy-isoquinolin-3-yl, 4-hydroxy-quinolin-3-yl;
each of which is additionally substituted with 0, 1, or 2 substituents independently chosen from hydroxyl, nitro, chloro, bromo, methyl, methoxy, and trifluoromethyl.
19. The method of claim 16, wherein
is 3-hydroxy-naphth-2-yl.
20. The method of claim 10, wherein Ar1 is nitro-phenyl or nitro-furanyl.
21. The method of claim 10, wherein Ar1 is
and R6 is nitro, cyano, \u2014PO4, \u2014CHO, or \u2014COOH.
22. The method of claim 21, wherein R6 is nitro.
23. The method of claim 11, wherein the a disease or disorder for which p97 inhibition andor ER stress induction is an effective treatment disorder is cancer, cancer prophylaxis in a patient having an increased risk of cancer, tumor, neoplasm, neovascularization, vascularization, cardiovascular disease, intravasation, extravasation, arthritis, infection, Alzheimer’s dementia, blood clot, atherosclerosis, melanoma, a skin disorder, rheumatoid arthritis, diabetic retinopathy, macular edema, macular degeneration, inflammation or autoimmune disease, or viral infection.
24-37. (canceled)