1. A cryptographic device comprising:
a tamper detection circuit having a physical security boundary;
a volatile memory device located within the physical security boundary;
a battery, external to the physical security boundary, coupled to a power input of the memory device for providing power to the memory device under normal operating conditions;
a capacitor, located within the physical security boundary, having a first node coupled to the power input of the memory device and a second node coupled to ground, the capacitor storing charge from the battery under normal operating conditions, the capacitor, when the battery is shorted, providing the stored charge to the memory device to allow the memory device to perform a clearing operation; and
a discharge prevention means, located within the physical security boundary, having a first node coupled to the first node of the capacitor and a second node coupled to the battery, the discharge prevention means preventing the stored charge from the capacitor from discharging through the battery when the battery is shorted.
2. The cryptographic device of claim 1, wherein the memory device comprises a plurality of memory devices.
3. The cryptographic device of claim 1, further comprising:
a latch having an input coupled to the tamper detection circuit and an output coupled to a clear input of the memory device, the latch, in response to receiving a signal from the tamper detection circuit indicating a tamper activity, causing a clear signal to be input to the clear input of the memory device, the memory device, in response to the clear signal from the latch, performing the clearing operation.
4. The cryptographic device of claim 1, wherein the discharge prevention means comprises a diode.
5. A mail processing system for processing mail pieces comprising:
a control unit for controlling operation of the mail processing system;
a printing device for printing information on mail pieces; and
a cryptographic device for generating indicium to be printed on mail pieces, the cryptographic device comprising
a tamper detection circuit having a physical security boundary;
a volatile memory device located within the physical security boundary;
a battery, external to the physical security boundary, coupled to a power input of the memory device for providing power to the memory device under normal operating conditions;
a capacitor, located within the physical security boundary, having a first node coupled to the power input of the memory device and a second node coupled to ground, the capacitor storing charge from the battery under normal operating conditions, the capacitor, when the battery is shorted, providing the stored charge to the memory device to allow the memory device to perform a clearing operation; and
a discharge prevention means, located within the physical security boundary, having a first node coupled to the first node of the capacitor and a second node coupled to the battery, the discharge prevention means preventing the stored charge from the capacitor from discharging through the battery when the battery is shorted.
6. The mail processing system of claim 5, wherein the discharge prevention means comprises a diode.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
We claim:
1. A compound of formula (1):
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wherein X1 is CH or N;
wherein R1, R2, R3, and R4 are each independently hydrogen, lower alkyl, halogen, hydroxy, alkyloxy, aryl, aryloxy, heteroaryl, trifluoromethoxy, cyano, nitro, thio, alkylthio or a bone targeting moiety, wherein said bone targeting moiety is selected from:
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wherein each occurrence of M is independently CV2, NV, Oor S, wherein each occurrence of V is independently hydrogen, OH, halogen, or aliphatic; each occurrence of Y is independently a covalent bond, O, S or N(RJ)2, wherein RJ, for each occurrence, is independently hydrogen, aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl; each occurrence of x is independently 0-6, and for compounds i-vi, xi, and xvii, x may preferably be 1-6; wherein L is (CH2)nHe, wherein He is absent or is NR, wherein R is hydrogen or lower alkyl, O or S, and n is 0-5, except when He is absent, n is 1-5; wherein L2 is N or CRK, wherein RK is hydrogen, aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl; and wherein each occurrence of R5 is independently hydrogen or lower alkyl, with the proviso that if either of R2 or R4 are bone targeting moieties, He, for the bone targeting moiety at R2 or R4, is NR, wherein R is hydrogen or lower alkyl, O, or S; wherein R13 represents 0-3 substituents selected from hydrogen, halogen, lower alkyl, lower alkenyl, aryl, heteroaryl, carbonyl, thiocarbonyl, ketone, aldehyde, amino, acylamino, amido, amidino, cyano, nitro, azido, sulfonyl, sulfoxido, sulfate, sulfonate, sulfamoyl, sulfonamido, phosphoryl, phosphorothioate, phosphonate, phosphinate, (CH2)n-alkyl-, (CH2)n-alkenyl-, (CH2)nalkynyl-, (CH2)naryl-, (CH2)naralkyl-, (CH2)nOH, (CH2)nO-lower alkyl-, (CH2)n)-lower alkenyl, O(CH2)nR, (CH2)nS-lower alkyl, (CH2)nS-lower alkenyl, S(CH2)nR, (CH2)nNR2, (CH2)nNR-lower alkyl, (CH2)nNR-lower alkenyl, NR(CH2)nR, or protected forms of the above, and wherein n is 1-10;
wherein Hc is:
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wherein R6, R7, R9, R10, R11, and R12 are each independently selected from the group consisting of bone targeting moiety as described above, hydrogen, lower alkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl; or wherein R6 and R7 taken together, or any one of R11 and R12, R10 and R11, and R9 and R10 taken together, comprise a substituted or unsubstituted aryl, heteroryl, or cycloalkyl moiety, wherein said substituted or unsubstituted aryl, heteroaryl, or cycloalkyl moiety is a single ring or is polycyclic; and wherein wherein X2 comprises NR8 or S, wherein R8 is hydrogen, lower alkyl, substituted or unsubstitued aryl, or substituted or unsubstituted heteroaryl; and
whereby at least one of R1-R4 or R6, R7, R9-R12 are substituted with a bone targeting moiety as described above.
2. The compound of claim 1, wherein R4 and R5 taken together comprise a substituted or unsubstituted aryl, heteroryl, or cycloalkyl moiety, and wherein said aryl, heteroaryl, or cycloalkyl moiety is a substituted single or polycyclic ring.
3. The compound of claim 2, wherein said substituted single or polycyclic ring is substituted with methyl or alkoxy.
4. The compound of claim 1, wherein a bone targeting moiety comprises formula (II)
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wherein n is 0-5; wherein L is (CH2)pHe, wherein He is absent or is NR, wherein R is hydrogen or lower alkyl, O or S, and p is 0-5, except when He is absent, p is 1-5, with the proviso that if either of R2 or R4 are bone targeting moieties, He, for the bone targeting moiety at R2 or R4, is NR, wherein R is hydrogen or lower alkyl, O or S; wherein Y is (CH2)n, wherein n is 1-3, or NH; and wherein Z is PO3(R14)2, SO3R14, or CO2R14, wherein each occurrence of R14 is independently hydrogen or lower alkyl.
5. The compound of claim 4, wherein R1, R3 and R4 are each hydrogen; wherein R2 is a bone targeting moiety, wherein for L, n is 0 and He is either NR, wherein R is hydrogen or lower alkyl, or O; wherein X2 is NH, wherein Hc is
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and R6 and R7 taken together comprise a pyridyl group; wherein Y is CH2 or NH; and wherein Z is PO3R14, wherein R14 is hydrogen or lower alkyl.
6. The compound of claim 4, wherein R1 and R3 are each hydrogen; wherein R4 is alkoxy; wherein R2 is the bone targeting group; wherein for L n is 0 and Hc is NR, wherein R is hydrogen or lower alkyl, or O; wherein X1 is CH; wherein X2 is NH; wherein Hc is
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and R6 and R7 taken together comprise a pyridyl group; wherein Y is CH2 or NH; and wherein Z is PO3R14, and R14 is hydrogen or lower alkyl.
7. The compound of claim 4, wherein R1 and R3 are each independently a lower alkyl or hydrogen; wherein R4 is hydrogen; wherein R2 is the bone targeting moiety; wherein for L, n is 0 and He is NH or O; wherein X1 is N; wherein X2 is NH; wherein Hc is
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wherein R6 and R7 taken together comprise a substituted or unsubstituted phenyl group; wherein Y is CH2 or NH; and wherein Z is PO3R14, and R14 is hydrogen or lower alkyl.
8. The compound of claim 7, wherein R6 and R7 taken together comprise a substituted phenyl group, wherein said phenyl group is substituted with an electron donating moiety.
9. A pharmaceutical composition comprising:
a compound of any one of claims 1, 2, 3, 4, 5, 6, 7 or 8; and
a pharmaceutically acceptable carrier or excipient.
10. A method for the prevention or treatment of a disease or secondary condition associated with overactivity of osteoclasts in a subject which method comprises the administration of an effective non-toxic amount of a selective inhibitor of mammalian osteoclasts to a subject in need thereof.
11. The method of claim 10, wherein said method comprises the administration of any one of claims 1, 2, 3, 4, 5 , 6, 7, or 8 to a subject in need thereof.
12. The method of claim 10, wherein said disease or secondary condition is selected from the group consisting of osteoporosis, Paget’s Disease, hypercalcemia, rheumatoid arthritis, metastatic bone destruction, cancer, and immune disorder.