Author: claimsbot

1. A method for driving a motor-driven mechanical system using a calculated mechanical system specific resonant frequency, comprising:
applying a test drive signal to a motor of a mechanical system to cause oscillatory behavior in the mechanical system;
capturing a back channel electrical signal induced by the motor from the oscillatory behavior;
calculating a resonant frequency of the mechanical system from the captured electrical signal; and
storing the calculated resonant frequency in a register, the resonant frequency to be used in a run time mode.
2. The method of claim 1, further comprising:
applying a drive signal to the motor of the mechanical system in the run time mode, the drive signal having substantially zero energy at the calculated resonant frequency.
3. The method of claim 1, wherein the motor is a lens driver motor.
4. A drive signal generator, comprising:
a test signal generator having an output for connection to a motor of a mechanical system;
a back channel sensor to capture an electrical signal induced by the motor from oscillatory behavior in the mechanical system;
a processor to calculate a resonant frequency of the mechanical system from the captured electrical signal; and
a register to store the calculated resonant frequency.
5. The drive signal generator of claim 4, wherein the accumulator generates a drive signal in a run time operation mode, the drive signal having substantially zero energy at the stored resonant frequency.
6. The drive signal generator of claim 4, further comprising a digital to analog converter to generate an analog representation of the test drive signal.
7. A system comprising;
a mechanical structure having a drive motor;
a drive signal generator coupled to the drive motor, comprising:
an initialization circuit, operable in an initialization mode to generate a test drive signal to cause oscillatory behavior in the mechanical structure;
a back channel sensor to capture an electrical signal induced by the motor from the oscillatory behavior;
a processing unit to calculate a resonant frequency of the mechanical structure from the captured electrical signal; and
a drive circuit, operable in a run time mode, including a register to store the calculated resonant frequency.
8. The system of claim 7, wherein the drive circuit is further operable to generate a drive signal in the run time mode, the drive signal having substantially zero energy at the stored resonant frequency.
9. The system of claim 7, wherein the drive signal generator further comprising a digital to analog converter to generate an analog representation of the test drive signal.
10. A system comprising:
a mechanical structure having a drive motor; and
a back channel detection system, comprising:
an initialization circuit, operable in an initialization mode to applying a test drive signal to the drive motor;
a back channel sensor to monitor a signal line from the drive motor for an electrical signal induced by the drive motor due to movement of the mechanical structure;
a processing unit to calculate a characteristic value of the mechanical structure from the monitored back channel electrical signal; and
a drive circuit, operable in a run time mode, including a register to store the calculated characteristic value.
11. A method for driving a motor-driven mechanical system, comprising:
applying a drive signal to a motor of a mechanical system to cause oscillatory behavior in the mechanical system;
capturing a magnitude estimate of the oscillatory behavior;
adjusting a resonant frequency of the mechanical system based on the magnitude estimate; and
storing the adjusted resonant frequency in a register.
12. The method of claim 11 wherein the drive signal is a test drive signal.
13. The method of claim 11 wherein the drive signal is a normal operation drive signal.
14. A drive signal generator, comprising:
a driver circuit to generate a drive signal to be applied to a motor;
a feedback circuit to capture oscillations caused by the motor due to movement of a mechanical system;
a processor to adjust a resonant frequency according to the captured oscillations; and
a register to store the resonant frequency.

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 I:
37
wherein:
A and A are independently the same or different group of the formula II:
38
wherein:
Ris H, CH3, C(CH3)2, ORa, N(Ra)2, N(Ra)ORa or -DP
R is H or CH3; Ra is H, C1-C3 alkyl;
D is a bond, C1-3 alkylene, C(O), S(O) or S(O)2;
P is an optionally substituted, mono or bicyclic carbo- or heterocycle;
R is H, any of the sidechains found in the natural amino acids, carboxacetamide, or a group (CH2)nDP;
M is a bond or C(O)N(R)-;
Q is absent, a bond, CH(OH) or CH2;
or R together with Q, M and R define an optionally substituted 5 or 6 membered carbo- or heterocyclic ring which is optionally fused with a further 5 or 6 membered carbo- or heterocyclic ring;
with the proviso that R is ORa, N(Ra)2, N(Ra)ORa or -DP, if M is a bond and Q is absent;
X is H, OH, OCH3;
Y is H, OH, OCH3, but X and Y are not both H;
Z and Z are independently (CH2)mP where P is as defined above;
n and m are independently 0, 1 or 2;
and pharmaceutically acceptable salts and prodrugs thereof.
2. A compound according to claim 1, wherein A andor A are a group of the formula IIa:
39
wherein
n is 0, 1 or 2;
R is methyl or methyloxy; and
R is hydrogen, methyl, ethyl, isopropyl, cycloalkyl such as cyclopropyl, cyclobutyl or cyclohexyl, cycloalkenyl, benzyl, carboxacetamide or 4-imidazolylmethy or a side chain found in the natural amino acids.
3. A compound according to claim 2 wherein n is 0 and R is methyl.
4. A compound according to claim 1, wherein A andor A are a group of the formula IIb:
40
wherein
R is as defined in claim 2 and
R is hydrogen or methyl.
5. A compound according to claim 1, wherein A andor A are a group of the formula IIc:
41
wherein
Q is a bond, methylene or C(OH),
R is an optionally substituted carbo- or heterocyclic group; and
R and R are as defined in claim 2.
6. A compound according to claim 3, 4 or 5 wherein R is the side chain of leucine, isoleucine, asparagine, histidine or proline and most preferably valine.
7. A compound according to claim 1, wherein A andor A are a group of the formula III:
42
where
R is H or CH3,
R1 is H, NR4R4, C(O)R3, CR3R4 or a monocyclic, optionally substituted, carbo- or heterocycle;
R2 is OH, or together with R1 is O, or if R1 is NR4R4, then R2 may be H;
R3 is H, halo, C1-C3 alkyl, OR5, NR4R4;
R4 is H, C1-C3 alkyl;
R5 is H or a pharmaceutically acceptable ester;
R6 is OH, NH2, carbamoyl or carboxy;
R7 is hydrogen, C1-C4 straight or branched alkyl or together with the adjacent carbon atoms forms a fused phenyl or pyrimidine.
8. A compound according to claim 7, wherein the moiety of formula III has the structure:
43
9. A compound according to claim 1, wherein both A and A are identical.
10. A compound according to claim 1, wherein Z andor Z is benzyl unsubstituted or substituted with one to three substituents selected from halo, methoxy, hydroxy, amino, cyano, hydroxymethyl, aminomethyl, morpholinethoxy, alkylsulfonyl, carbamoyl, benzyloxy phenyl (itself substituted as defined herein) or a 5 or 6 membered heterocycle containing one or two hetero atoms such as thiophene, pyrimidine, N-morpholine, N-piperidine, N-piperazine, N-methyl-N-piperazine, N-pyrrolidone, N-pyrrolidine and the like, optionally substituted as defined herein.
11. A compound according to claim 10 wherein Z andor Z is benzyl, 2-fluorobenzyl, 2-methylbenzyl, 2,4-difluorobenzyl, 4-fluorobenzyl, 4-bromobenzyl, 4-phenylbenzyl, 4-thiophenylbenzyl, 4-(4-nitrophenyl)benzyl, 4-thienylbenzyl, 4-thiazolylbenzyl or 4-(pyridyl)benzyl.
12. A compound according to claim 1, wherein Y is H andor X is OH.
13. A compound accoridng to claim 1, having the 2R, 3R, 4R, 5R configuration.
14. A pharmaceutical composition comprising a compound according to any one of claims 1-5 and 7-13 and a pharmaceutically acceptable carrier or diluent therefor.
15. A method for inhibiting the replication of HIV comprising administering an effective amount of a compound as defined in any one of claims 1-5 and 7-13 to a subject afflicted with said condition.
16. A method for the preparation of a compound of the formula I where X, Y, Z and Z are as defined in claim 1 and each of A and A are independently:
a group of the formula II or a conventional protease P-2P-2 filling group, the method comprising:
i) O-alkylation of an L-mannaric-1,4:6,3-di-lactone to form the Z and Z groups,
ii) opening of the lactone with similar or different primary or secondary amines to form the respective A and A groups; and
iii) optional conversion of the C-3 and C-4 to the appropriate X and Y groups.

1-22. (canceled)
23. A compound of the Formula I:
wherein:
R1 is (C6-C14) aryl, or -(5-14 membered) heteroaryl, wherein said aryl and heteroaryl are each optionally substituted with one or more (C0-C4 alkylene)-R13;
R2 and R3 are independently selected from the group consisting of: \u2014H, a straight or branched C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C8 cycloalkyl, C6-C14 aryl and (5-14 membered) heteroaryl, wherein said alkyl, alkenyl and alkynyl are each optionally substituted with one or more substituents selected from the group consisting of \u2014F, \u2014Cl, \u2014Br, \u2014OH, C1-C4 alkoxy, and \u2014S\u2014(C1-C4)alkyl, and wherein said aryl and heteroaryl are each optionally substituted with one or more (C0-C4 alkylene)-R13; or R2 and R3 taken together form a C3-C8 cycloalkyl;
R4 is C6-C14 aryl or (5-14 membered) heteroaryl substituted with one or more (C0-C4 alkylene)-R13;
R5 and R6 are independently selected from the group consisting of: \u2014H, \u2014F, \u2014Cl, \u2014Br, \u2014CN, \u2014CHO, \u2014NO2, \u2014C(\u2550O)NR9R10, \u2014C(\u2550O)OR10, \u2014NR9R10, \u2014NR9C(\u2550O)R10, \u2014NR9C(\u2550O)OR1, and NR9C(\u2550O)NR9R10;
or R5 and R6 are independently a straight or branched C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, (C0-C6 alkylene)-(C3-C12 cycloalkyl), or (C0-C6 alkylene)-(C3-C12 heterocycloalkyl), wherein said alkyl, alkenyl, alkynyl, alkylene, cycloalkyl and heteroalkyl are each optionally substituted with one or more (C0-C6 alkylene)-R7; or R5 and R6 are independently (C0-C6 alkylene)-(C6-C14 aryl) or (C0-C6 alkylene)-(5-14 membered heteroaryl), wherein said aryl and heteroaryl are each optionally substituted with one or more R7 and wherein said alkylene is optionally substituted with one or more (C0-C6 alkylene)-R8; or R5 and R6, when attached to the adjacent carbon atoms of the thiazole ring, together form a (4-8 membered) cycloalkyl, (4-8 membered)-heterocycloalkyl, or C6-C10 aryl wherein said cycloalkyl and heteroalkyl are each substituted with one or more (C0-C6 alkylene)-R8, (C0-C6 alkylene)-(C6-C14 aryl), and (C0-C6-alkylene)-(5-14 membered heteroaryl), wherein said aryl or heteroaryl are each optionally substituted with one or more R7;
Z is a bond or a straight or branched C1-C6 alkylene, wherein each hydrogen atom of said alkylene is optionally independently replaced with a fluorine;
X is O or S;
R7 is \u2014F, \u2014Cl, \u2014Br, \u2014OH, \u2014CN, \u2014CHO, \u2014NO2, \u2014NR9R10, \u2014NR9C(\u2550O)R10, \u2014NR9C(\u2550O)NR9R10, \u2014NR9C(\u2550O)OR10, \u2014OC(\u2550O)\u2014R9, \u2014OC(\u2550O)NR9R10, \u2014C(\u2550O)NR9R10, \u2014C(\u2550O)OR10, \u2014SO2NR9R10, \u2014C1-C6 alkyl, \u2014C2-C6 alkenyl, \u2014C2-C6 alkynyl-C3-C8cycloalkyl, \u2014C3-C8 heterocycloalkyl, \u2014C1-C6 alkoxy, \u2014(C6-C14) aryloxy, -(5-14 membered) heteroaryloxy, \u2014(C0-C4 alkylene)-(C6-C14) aryl, or \u2014(C0-C4 alkylene)-(5-14 membered) heteroaryl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl and heterocycloalkyl are each optionally substituted with one or more R8, and wherein each hydrogen atom of said alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl and alkoxy is optionally independently replaced with a fluorine;
R8 is \u2014F, \u2014Cl, \u2014Br, \u2014CN, \u2014CHO, \u2014OR9, \u2014OC(\u2550O)\u2014R9, \u2014OC(\u2550O)NR9R10, \u2014NO2, \u2014NR9R10, \u2014NR9C(\u2550O)R10\u2014NR9C(\u2550O)NR9R10, \u2014NR9C(\u2550O)OR10\u2014C(\u2550O)NR9R10, \u2014SO2NR9R10, \u2014C(\u2550O)R10 or \u2014C(\u2550O)OR10;
R9 and R10 are \u2014H, \u2014C1-C6 alkyl, \u2014C2-C6 alkenyl, \u2014C2-C6 alkynyl, \u2014(C0-C4 alkylene)-(C3-C8 cycloalkyl), \u2014(C0-C4alkylene)-(C6-C14 aryl), \u2014(C0-C4 alkylene)-(3-8 membered heterocycloalkyl), or \u2014(C0-C4 alkylene)-(5-14 membered heteroaryl), wherein said alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocycloalkyl, and heteroaryl are each optionally independently substituted with one or more substituents independently selected from the group consisting of \u2014F, \u2014Cl, \u2014Br, \u2014CN, \u2014CHO, \u2014OH, \u2014NO2, \u2014NR11R12, \u2014C(\u2550)ONR11R12, \u2014C(\u2550O)R11, \u2014C(\u2550O)OR12, \u2014SO2NR11R12, \u2014C1-C6 alkyl, \u2014C1-C6 alkoxy, \u2014C1-C6 hydroxyalkyl, \u2014(C0-C4)\u2014(C6-C14) aryl), and \u2014(C0-C4)-(5-14 membered heteroaryl);
or R9 and R10 with nitrogen forms a 4-8 membered heterocycloalkyl moiety, wherein said heterocycloalkyl is optionally substituted with one or more substitutents selected from the group consisting of \u2014F, \u2014Cl, \u2014Br, \u2014CN, \u2014CHO, \u2014OH, \u2014NO2, \u2014NR11R12, \u2014C(\u2550)ONR11R12, \u2014C(\u2550O)R11\u2014C(\u2550O)OR12\u2014SO2NR11R12, \u2014C1-C6 alkyl, \u2014C2-C6 alkenyl, \u2014C2-C6 alkynyl, \u2014C1-C6 alkoxy, \u2014C3-C8 cycloalkyl, C3-C8 heterocycloalkyl, C6-C10 aryl, and 5-14 membered heteroaryl, wherein said alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, heterocycloalkyl, aryl, heteroaryl are each optionally substituted with F, \u2014Cl, \u2014Br, \u2014CN, \u2014OR11, \u2014OC(\u2550O)\u2014R11, \u2014OC(\u2550O)NR11R12, \u2014NO2, \u2014NR11R12, \u2014NR11C(\u2550O)R12\u2014NR11C(\u2550O)NR11R12, \u2014NR11C(\u2550O)OR12, \u2014C(\u2550O)NR11R12, \u2014SO2NR11R12, \u2014C(\u2550O)R11, or \u2014C(\u2550O)OR11;
R11 and R12 are hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C8 cycloalkyl, 4-8 membered heterocycloalkyl, C6-C14 aryl or 5-14 membered heteroaryl, wherein said alkyl, alkenyl, alkynyl, aryl and heteroaryl are each optionally independently substituted with from one to three substituents independently selected from the group consisting of \u2014OH, \u2014C1-C6 alkyl, \u2014C2-C6 alkenyl, \u2014C2-C6 alkynyl, \u2014C1-C6 alkoxy, \u2014C2-C6 alkenoxy, \u2014C2-C6 alkynoxy, \u2014C1-C6 hydroxyalkyl, \u2014F, \u2014Cl, \u2014Br, \u2014I, \u2014CN, \u2014NO2, \u2014CF3, \u2014NH2, \u2014NH(C1-C6 alkyl), \u2014N(C1-C6 alkyl)2, \u2014C(\u2550O)NH2, \u2014C(\u2550O)NH(C1-C6 alkyl), \u2014C(\u2550O)N(C1-C6 alkyl)2, \u2014SO2NH2, \u2014SO2NH(C1-C6 alkyl), \u2014SO2N(C1-C6 alkyl)2, \u2014C(\u2550O)H, \u2014C(\u2550O)OH and \u2014C(\u2550O)O(C1-C6 alkyl), wherein said alkyl, alkenyl and alkynyl substituents are each optionally independently further substituted with from one to six fluorine atoms;
or R11 and R12 with nitrogen taken together form a 4-8 membered heterocycloalkyl, wherein said heterocycloalkyl is optionally independently substituted with from one to three substituents independently selected from the group consisting of \u2014OH, \u2014C1-C6 alkyl, \u2014C2-C6 alkenyl, \u2014C2-C6 alkynyl, \u2014C1-C6 alkoxy, \u2014C2-C6 alkenoxy, \u2014C2-C6 alkynoxy, \u2014C1-C6 hydroxyalkyl, \u2014F, \u2014Cl, \u2014Br, \u2014I, \u2014CN, \u2014NO2, \u2014CF3, \u2014NH2, \u2014NH(C1-C6 alkyl), \u2014N(C1-C6 alkyl)2, \u2014C(\u2550O)NH2, \u2014C(\u2550O)NH(C1-C6 alkyl), \u2014C(\u2550O)N(C1-C6 alkyl)2, \u2014SO2NH2, \u2014SO2NH(C1-C6 alkyl), \u2014SO2N(C1-C6 alkyl)2, \u2014C(\u2550O)H, \u2014C(\u2550O)OH and \u2014C(\u2550O)O(C1-C6 alkyl), wherein said alkyl, alkenyl and alkynyl substituents are each optionally independently further substituted with from one to six fluorine atoms; and
R13 is \u2014F, \u2014Cl, \u2014Br, \u2014CN, \u2014CHO, \u2014OH, \u2014NO2, \u2014NR11R12, \u2014C(\u2550)ONR11R12, \u2014C(\u2550O)R11\u2014C(\u2550O)OR12\u2014SO2NR11R12, \u2014C1-C6 alkyl, \u2014C1-C6 alkoxy, \u2014C3-C8 cycloalkyl, 4-8 membered heterocycloalkyl, C6-C10 aryl or 5-14 membered heteroaryl, wherein each hydrogen atom of said alkyl, alkoxy, cycloalkyl and heterocycloalkyl is optionally independently replaced with a fluorine; or
a pharmaceutically acceptable salt thereof.
24. A compound according to claim 23, wherein Z is a bond, or a pharmaceutically acceptable salt thereof.
25. A compound according to claim 23, wherein Z is methylene, or a pharmaceutically acceptable salt thereof.
26. A compound according to claim 23, wherein R2 is hydrogen and R3 is independently selected from the group consisting of \u2014H, a straight or branched C1-C6alkyl, C2-C6alkenyl, C2-C6 alkynyl, C6-C14 aryl and (5-14 membered) heteroaryl, or a pharmaceutically acceptable salt thereof.
27. A compound according to claim 23, wherein X is S or a pharmaceutically acceptable salt thereof.
28. A compound according to claim 27, wherein
or a pharmaceutically acceptable salt thereof.
29. A compound according to claim 27, wherein
or a pharmaceutically acceptable salt thereof.
30. A pharmaceutical composition for treating a disease or condition associated with the modulation of the Notch signaling pathway, comprising a compound according to claim 23, or a pharmaceutically acceptable salt thereof.
31. The composition of claim 30, wherein the disease or condition is cancer.
32. A method of treating a disease or condition selected from the group consisting of cancer, arteriosclerosis, diabetic retinopathy, rheumatoid arthritis, psoriasis, inflammatory bowel disease, inflammation, asthma, graft rejection, graft versus host disease, autoimmune disease and transplant rejection, comprising administering to said mammal an amount of a compound according to claim 23 that is effective in modulating Notch signaling pathway to treat such disease or condition.
33. A method according to claim 32, wherein said disease or condition is 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 downhole non-return valve, comprising:
a housing defining a valve inlet and a valve outlet;
a plug moveable between an open position and a fully sealed position; and
a biasing member urging the plug towards the fully sealed position wherein the urging force of the biasing member is sufficient to move the plug to a partially sealed position but is selected to be insufficient to move the plug to a fully sealed position.
2. The non-return valve of claim 1, wherein in the partially sealed position an outlet side of the plug is exposed to well pressure that aids in moving the plug to the fully sealed position
3. The non-return valve of claim 1, further comprising:
a shield to redirect fluid flow from the outlet of the valve.
4. The non-return valve of claim 3, wherein the shield circumferentially surrounds the outlet.
5. The non-return valve of claim 1, wherein the biasing member is a spring.
6. The non-return valve of claim 1, further comprising:
a seal surface at the plug engagable with a seal seat at the housing.
7. The non-return valve of claim 6, wherein the seal surface and seal seat are metal.
8. The non-return valve of claim 1, further comprising:
a first additional seal that engages a housing bore in the partially sealed position.
9. The non-return valve of claim 8, wherein the first additional seal is a wiper seal.
10. The non-return valve of claim 8, further comprising:
a second additional seal that engages the housing bore in the fully sealed position.
11. The non-return valve of claim 10, wherein the second additional seal is a V-packing seal.
12. The non-return valve of claim 1, further comprising:
run-in-configuration retainers that lock the plug in the fully sealed position during shipping, installation into the downhole environment, and initial pressure testing before releasing the plug from the run-in-configuration.
13. The non-return valve of claim 12, wherein the run-in-configuration retainers are releasable at a selected pressure.
14. The non-return valve of claim 12, wherein the run-in-configuration retainers are shear screws.
15. The non-return valve of claim 12, further comprising:
a collar receptive of the run-in-configuration retainers and movable relative to the plug, the collar configured to position the plug in the fully sealed position prior to release of the run-in-configuration retainers and to not restrict travel of the plug after release of the run-in-configuration retainers.
16. A downhole non-return valve, comprising:
a housing defining a valve inlet and valve outlet;
a plug moveable between an open position and a fully closed position; and
a sacrificial member adapted to divert fluid injected through the valve axially along an external surface of the valve housing.
17. A method of injecting fluid into a well bore through a non-return valve, comprising:
injecting fluid into a non-return valve the valve being in a fully sealed configuration;
pressurizing the fluid sufficiently to overcome a closing force comprising a combination of a biasing force and well pressure to open a valve outlet;
injecting fluid through the valve outlet into a well; and
ceasing injection of the fluid thereby permitting the closing force to fully seal the valve outlet.
18. The method of claim 17, further comprising:
partially sealing the plug to a housing bore with an additional first seal with the biasing force prior to fully sealing the valve outlet with the closing force.
19. The method of claim 18, further comprising:
cleaning the housing bore with the first additional seal prior to a second additional seal engaging the housing bore.
20. The method of claim 19, wherein the first additional seal is a wiper seal and the second additional seal is a V-packing seal.
21. The method of claim 17, further comprising:
shielding well bore components from fluid erosion with a sacrificial shield.
22. The method of claim 17, wherein the biasing force is provided by a biasing member.
23. A non-return valve, comprising:
a valve seat;
a valve piston in operable communication with the valve seat;
a first seal disposed at the piston to interact with the valve seat; and
a second seal positioned at the piston to interact with the valve seat temporally after the first seal.