1. A compound having the structure of Formula I
wherein n=0-2 and wherein when n=1, X is selected from CH2, O, NRA, CO, and C\u2550NORA and wherein when n=2, X=CH2
Y is O, S, NORA, or NRA
wherein RA is selected from H, alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, \u2014C(\u2550O)RB, \u2014C(\u2550O)ORB, \u2014C(\u2550O)NRBRC, \u2014C(\u2550NRB)RC, \u2014NRBRC, heterocycloalkyl, aryl or polyaromatic, heteroaryl, arylalkyl and alkylaryl
wherein each of said RB and RC is independently H, alkyl, or heteroalkyl,
U and V are each independently selected from C\u2550O, and O\u2550S\u2550O and wherein when U is C\u2550O, V is not C\u2550O,
R1, R2, R3, and R4 are each independently selected from H, alkyl, heteroalkyl, cycloalkyl, arylcycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocycloalkyl, and each of said NR1R2 and NR3R4 can independently combine to form a heterocycloalkyl,
R5 and R6 are each independently selected from H, OH, SH, alkoxy, thioalkoxy, alkyl, halogen, CN, CF3, NO2, COORD,
CONRDRE, NRDRE, NRDCORE, NRDSO2RE, and NRFCONRDRE;
wherein RD, RE and RF are independently H, alkyl, heteroalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, or heterocycloalkyl;
provided that is X is O, Y is O and U and V are both O\u2550S\u2550O, then
NR1R2 and NR3R4 are not identical then R1 and R3 are each independently selected from H and lower alkyl, and wherein R2 and R4 are each independently selected from lower alkoxy(loweralkyl), di(lower)alkylamino(lower)alkyl, halobenzyl, morpholino(lower)alkyl, or NR1R2 and NR3R4 are independently piperidino, morpholino, piperazino, N-phenylpiperazino, ethylamino, or substituted glycine
and wherein if X is (CH2)2, Y is O or NOH, and U and V are each O\u2550S\u2550O then none of R1, R2, R3, and R4 is methyl,
and wherein if n=0, Y is O or NOH, and U and V are each 0=8=0, then NR1R2 and NR3R4 are not identical and R1, R2, R3, and R4 are each independently selected from C1-C5 alkyl, C10 alkyl, C16 alkyl, C17 alkyl, phenyl, benzyl, naphthalenyl, piperizino, pyridinyl, pyrazolyl, benzimidazolyl, triazolyl; or NR1R2 and NR3R4 are independently piperidino, morpholino, or piperazino,
and wherein if X is CO, Y is O, and U and V are each O\u2550S\u2550O then NR1R2 and NR3R4 are not identical, and wherein R1, R2, R3, and R4 are each independently selected from methyl, ethyl, hydroxy-C1-C3-alkyl, SH, RO, COOH, SO, NH2, and phenyl or wherein one or both of non-identical NR1R2 and NR3R4 is unsubstituted piperidino, N-methylpiperazino or N-methylhomopiperazino,
and wherein when X is C\u2550O or C\u2550NOH, Y is O or NOH, and U and V are each O\u2550S\u2550O and one of R1 or R2 and one of R3 or R4 is phenyl then the other of R1 or R2 and R3 or R4 is not H or alkyl,
including all pharmaceutically acceptable salts, esters, amides, stereoisomers, geometric isomers, solvates or prodrugs thereof.
2. The compound of claim 1, wherein U and V are each O\u2550S\u2550O.
3. The compound of claim 1, wherein U and V are each O\u2550S\u2550O, X is CH2 and n=1 or 2 and Y is O or S.
4. The compound of claim 1, wherein U and V are each O\u2550S\u2550O, X is CH2 and n=1 or 2 and Y is NORA, or NRA.
5. The compound of claim 1, wherein U and V are each O\u2550S\u2550O, X is O, and Y is O or S.
6. The compound of claim 1, wherein U and V are each O\u2550S\u2550O, X is O, and Y is NORA, or NRA.
7. The compound of claim 1, wherein U and V are each O\u2550S\u2550O, X is NRA, and Y is O or S.
8. The compound of claim 1, wherein U and V are each O\u2550S\u2550O, X is NRA, and Y is NORA, or NRA.
9. The compound of claim 1, wherein U and V are each O\u2550S\u2550O, X is CO and Y=O.
10. The compound of claim 1 having formula II
wherein R7 and R8 are independently selected from H and SO2NR3R4 and one of R7 or R8 is hydrogen and the other substituents have the meanings as defined in claim 1.
11. The compound of claim 10, wherein R1, R2, R3, and R4 are each independently selected from H, alkyl, cycloalkyl, alkenyl, and alkynyl.
12. The compound of claim 10, wherein RA is hydrogen and R1, R2, R3, and R4 are each independently selected from H, alkyl, cycloalkyl, alkenyl, and alkynyl.
13. The compound of claim 10, wherein NR1R2 and NR3R4 are each independently a 6- to 15-membered heterocycloalkyl.
14. The compound of claim 1, wherein U and V are each O\u2550S\u2550O, X is CO and Y is NORA or NRA.
15. The compound of claim 1, wherein U and V are each O\u2550S\u2550O, X is C\u2550NORA and Y is O.
16. The compound of claim 1, wherein U and V are each O\u2550S\u2550O, X is C\u2550NORA and Y is NORA.
17. The compound of claim 1 having formula III
wherein R7 and R8 are independently selected from H and SO2NR3R4, wherein one of R7 and R8 is hydrogen and the other substituents have the meanings as defined in claim 1.
18. The compound of claim 17, wherein R1, R2, R3, and R4 are each independently selected from H, alkyl, cycloalkyl, alkenyl, or alkynyl.
19. A composition comprising a therapeutically effective amount of the compound of claim 1 in a pharmaceutically acceptable carrier.
20. A method of preventing, treating or ameliorating cancer or tumor metastasis in a mammal comprising administering to said mammal an effective amount of a compound of claim 1.
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 pulsed laser array system comprising:
a beam generating sub-system for generating a reference beam and a pulsed signal beam that are frequency locked together, said beam generating sub-system providing optical leakage between the signal beam pulses for phase determination;
a beam splitter for splitting the pulsed signal beam into a plurality of split pulsed signal beams for a plurality of fibers;
a phase adjusting array including a plurality of phase adjusters, each phase adjuster receiving a split pulsed signal beam and a phase adjusting signal, each phase adjuster adjusting the phase of the split pulsed signal beam so that each split pulsed signal beam is in phase with the reference beam;
an amplifier chain including at least one amplifier for amplifying each split pulsed signal beam;
a beam coupler receiving the amplified split pulsed signal beams and the reference beam and coupling a portion of the amplified split pulsed signal beams with the reference beam;
a detector array receiving the combined reference beam and the amplified split pulsed signal beams, and converting the combined reference beam and split pulsed amplified signal beams to an electrical signal; and
a phase sensing circuit responsive to the electrical signal from the detector array, said phase sensing circuit measuring the difference in phase of the optical leakage between the pulses in the split pulsed signal beams and the reference beam, and providing the phase adjusting signal to the phase adjusters for adjusting the phase of the split pulsed signal beams to be in phase with the reference beam.
2. The system according to claim 1 further comprising a pulse clipper circuit, said pulse clipper circuit being responsive to the electrical signal from the detector array and clipping the pulses in the split pulsed signal beams so that only the optical leakage and the reference beam is provided to the phase sensing circuit.
3. The system according to claim 1 wherein the beam generating sub-system includes a frequency shifter that shifts the frequency of the reference beam.
4. The system according to claim 1 wherein the beam generating sub-system includes a continuous wave master oscillator for generating a signal beam and the reference beam, and an amplitude modulator for converting the signal beam into the pulsed signal beam.
5. The system according to claim 1 wherein the beam generating sub-system includes a Q-switched laser, an injection seed oscillator and a cavity locker, said Q-switched laser generating the pulsed signal beam, said seed oscillator generating the reference beam and an injection seed beam and said cavity locker locking the frequency of the pulsed signal beam from the Q-switched laser to the frequency of the seed beam.
6. The system according to claim 1 wherein the beam generating sub-system includes a continuous wave master oscillator, an amplitude modulator, a reference oscillator, a mixer and a frequency locker, said master oscillator generating a signal beam, said reference oscillator generating the reference beam, said mixer mixing the reference beam and the signal beam, said frequency locker locking the frequency of the signal beam to the frequency of the reference beam and said amplitude modulator converting the signal beam to the pulsed signal beam.
7. The system according to claim 1 wherein the beam generating sub-system includes a reference oscillator for generating the reference beam, a beam device for generating the pulsed signal beam and a wavelength division multiplexer for combining the pulsed signal beam and the reference beam.
8. The system according to claim 7 wherein the beam device is selected from the group consisting of Q-switched lasers and amplitude modulated master oscillators.
9. The system according to claim 7 further comprising a band pass filter that filters out the pulses after the reference beam is combined with the split pulsed signal beams, but before they are converted to an electrical signal by the detector array.
10. The system according to claim 1 wherein the beam generating sub-system includes a reference oscillator for generating the reference beam, a beam device for generating the pulsed signal beam and a time-gated switch for frequency locking the pulsed signal beam and the reference beam.
11. The system according to claim 1 wherein the detector array is a heterodyne array.
12. The system according to claim 1 wherein the beam pulses have a duration of less than 10 nano-seconds.
13. A pulsed laser array system comprising:
a beam generating sub-system for generating a reference beam and a plurality of split pulsed signal beams that are frequency locked together, wherein optical leakage is provided between the signal beam pulses, said beam generating sub-system including a frequency shifter that shifts the frequency of the reference beam;
a phase adjusting array including a plurality of phase adjusters, each phase adjuster receiving a split pulsed signal beam and a phase adjusting signal, each phase adjuster adjusting the phase of the split pulsed signal beam so that each split pulsed signal beam is in phase with the reference beam;
an amplifier chain including at least one amplifier for amplifying each split pulsed signal beam;
a beam coupler receiving the amplified split pulsed signal beams and the reference beam and coupling a portion of the amplified split pulsed signal beams with the reference beam;
a detector array receiving the combined reference beam and the amplified split pulsed signal beams, and converting the combined reference beam and split pulsed amplified signal beams to an electrical signal;
a pulse clipper circuit being responsive to the electrical signal from the detector array and clipping the pulses in the split pulsed signal beams so that only the optical leakage between the pulses in the split pulsed signal beam and the reference beam remain; and
a phase sensing circuit responsive to the electrical signal from the pulse clipper circuit, said phase sensing circuit measuring the difference in phase of the optical leakage between the pulses of the split pulsed signal beams and the reference beam, and providing the phase adjusting signal to the phase adjusters for adjusting the phase of the split pulsed signal beams to be in phase with the reference beam.
14. The system according to claim 13 wherein the beam generating sub-system includes a continuous wave master oscillator for generating a signal beam and an amplitude modulator for converting the signal beam into the pulsed signal beam.
15. The system according to claim 13 wherein the beam generating sub-system includes a Q-switched laser, an injection seed oscillator and a cavity locker, said Q-switched laser generating the pulsed signal beam, said seed oscillator generating the reference beam and an injection seed beam and said cavity locker locking the frequency of the pulsed signal beam from the Q-switched laser to the frequency of the seed beam.
16. The system according to claim 13 wherein the beam generating sub-system includes a reference oscillator for generating the reference beam, a beam device for generating the pulsed signal beam and a time-gated switch for frequency locking the pulsed signal beam and the reference beam.
17. The system according to claim 16 wherein the beam device is selected from the group consisting of Q-switched lasers and amplitude modulated master oscillators.
18. The system according to claim 13 wherein the detector array is a heterodyne array.
19. The system according to claim 13 wherein the beam pulses have a duration of less than 10 nano-seconds.
20. A pulsed laser array system comprising:
a beam generating sub-system for generating a reference beam and a plurality of split pulsed signal beams that are frequency locked together, wherein optical leakage is provided between the signal beam pulses; and
a phase adjusting array including a plurality of phase adjusters, each phase adjuster receiving a split pulsed signal beam and a phase adjusting signal, each phase adjuster adjusting the phase of the split pulsed signal beam so that each split pulsed signal beam is in phase with the reference beam, wherein the phase adjusting signal is indicative of the difference in phase of the optical leakage between the pulses in the split pulsed signal beams and the reference beam.
21. The system according to claim 20 further comprising a pulse clipper circuit, said pulse clipper circuit clipping the pulses in the split pulsed signal beams so that only the optical leakage and the reference beam remain.
22. The system according to claim 20 wherein the beam generating sub-system includes a frequency shifter that shifts the frequency of the reference beam.
23. The system according to claim 20 wherein the beam pulses have a duration of less than 10 nano-seconds.