Author: claimsbot

1. A method of treating or preventing cancer in a subject comprising administration to the subject of a PDE-5 inhibitor compound.
2. The method of claim 1, further comprising administration to the subject of an additional anticancer agent.
3. The method of claim 2, wherein the additional anticancer agent is an immunotherapeutic agent.
4. The method of claim 3, wherein the additional anticancer agent is a vaccine.
5. The method of claim 1, wherein the subject is identified as in need of treatment of cancer with a PDE-5 inhibitor compound.
6. The method of claim 1, wherein the PDE-5 inhibitor compound is selected from sildenafil, vardenafil or tadalafil.
7. A method of modulating myeloid suppressor cells (MSCs) immune suppression in a subject comprising administration to the subject of a PDE-5 inhibitor compound.
8. The method of claim 7, wherein the modulating is down-modulation.
9.-16. (canceled)
17. A method of treating or preventing disease in a subject comprising administration to the subject of a PDE-5 inhibitor compound.
18. The method of claim 17, wherein the disease is a disease mediated by myeloid suppressor cells (MSCs).
19. The method of claim 18, wherein the disease is cancer, chronic infection, chronic inflammation, hematopoietic reconstitution following chemotherapy.
20. The method of claim 1, further comprising the step of assessing MSC levels in the subject.
21. The method of claim 1, further comprising the step of assessing MSC levels in the subject before and after administration.
22.-32. (canceled)

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 communication terminal, comprising:
first and second transmitters, which are coupled to produce respective first and second Radio Frequency (RF) signals that are phase-shifted with respect to one another by a beamforming phase offset, and to transmit the RF signals toward a remote communication terminal; and
a reception subsystem, comprising:
first and second receivers, which are respectively coupled to receive third and fourth RF signals from the remote communication terminal; and
a phase correction unit, which is coupled to produce, responsively to the third and fourth RF signals, a phase correction for correcting an error component in the beamforming phase offset.
2. The terminal according to claim 1, wherein the first and second receivers are respectively coupled to down-convert the third and fourth RF signals to produce first and second received signals, and wherein the phase correction unit is coupled to measure a phase shift between the first and second received signals and to compute the phase correction responsively to the measured phase shift.
3. The terminal according to claim 2, wherein the phase correction unit comprises a Differential Phase-Locked Loop (DPLL), which is coupled to measure the phase shift.
4. The terminal according to claim 2, wherein the phase correction unit is coupled to produce first and second baseband signals that include the phase correction, and wherein the first and second transmitters are respectively coupled to process the first and second baseband signals so as to produce the first and second RF signals.
5. The terminal according to claim 1, wherein the phase correction unit is coupled to determine a phase shift between the third and fourth RF signals, and to produce the phase correction proportionally to the measured phase shift.
6. The terminal according to claim 1, and comprising first and second Local Oscillator (LO) generation units, which are coupled to produce respective first and second LO signals that are unsynchronized with one another, wherein the first and second transmitters are respectively coupled to produce the first and second RF signals using the first and second unsynchronized LO signals.
7. The terminal according to claim 6, wherein the first and second receivers are coupled to process the third and fourth RF signals using respectively the first and second unsynchronized LO signals.
8. The terminal according to claim 1, and comprising first and second Local Oscillator (LO) generation units, which are coupled to produce respective first and second LO signals that are locked to a common reference clock signal, wherein the first and second transmitters are respectively coupled to produce the first and second RF signals using the first and second LO signals.
9. The terminal according to claim 8, wherein the first and second receivers are coupled to process the third and fourth RF signals using respectively the first and second LO signals.
10. A communication system, comprising:
transmission baseband circuitry, which is coupled to produce first and second baseband signals with a relative beamforming phase therebetween, the first baseband signal comprising a first sequence of first pilot symbols, and the second baseband signal comprising a second sequence of second pilot signals, such that each first pilot signal is transmitted concurrently with a corresponding second pilot signal, wherein each of the first and second sequences comprises at least first and second interleaved sub-sequences, such that each of the first pilot symbols in the first sub-sequence has a first phase offset relative to the corresponding second pilot signal, and each of the first pilot symbols in the second sub-sequence has a second phase offset, which is different from the first phase offset, relative to the corresponding second pilot signal; and
first and second transmitters, which are respectively coupled to process the first and second baseband signals so as to produce and transmit first and second Radio Frequency (RF) signals.
11. The system according to claim 10, and comprising:
first and second receivers, which are respectively coupled to receive first and second combinations of the first and second transmitted RF signals and to produce respective first and second received signals; and
reception baseband circuitry, which is coupled to combine the first and second received signals to produce a composite signal, to measure respective first and second magnitudes of the pilot symbols belonging to the first and second sub-sequences in the composite signal, to process the first and second magnitudes so as to compute the relative beamforming phase, and to provide the beamforming phase to the transmission baseband circuitry.
12. The system according to claim 11, wherein the reception baseband circuitry is coupled to combine the first and second received signals by applying Maximum Ratio Combining (MRC).
13. The system according to claim 10, wherein the first phase offset comprises \u03c6 degrees, wherein the second phase offset comprises \u2212\u03c6 degrees, and wherein each of the first and second sequences further comprises a third sub-sequence, such that each of the first pilot symbols in the third sub-sequence has no phase offset with respect to the corresponding second pilot signal.
14. A communication terminal, comprising:
first and second receivers, which are respectively coupled to receive first and second combinations of first and second Radio Frequency (RF) signals transmitted from respective first and second transmitters, and to process the first and second combinations to produce respective first and second received signals,
wherein the RF signals have a relative beamforming phase therebetween, the first RF signal comprising a first sequence of first pilot symbols, and the second RF signal comprising a second sequence of second pilot signals, such that each first pilot signal is transmitted concurrently with a corresponding second pilot signal, wherein each of the first and second sequences comprises at least first and second interleaved sub-sequences, such that each of the first pilot symbols in the first sub-sequence has a first phase offset relative to the corresponding second pilot signal, and each of the first pilot symbols in the second sub-sequence has a second phase offset, which is different from the first phase offset, relative to the corresponding second pilot signal; and
a modem, which is coupled to combine the first and second received signals to produce a composite signal, to measure respective first and second magnitudes of the pilot symbols belonging to the first and second sub-sequences in the composite signal, to process the first and second magnitudes so as to compute the relative beamforming phase, and to provide the beamforming phase to the first and second transmitters.
15. A method for communication, comprising:
producing first and second Radio Frequency (RF) signals that are phase-shifted with respect to one another by a beamforming phase offset;
transmitting the first and second RF signals toward a remote communication terminal;
receiving third and fourth RF signals from the remote communication terminal; and
processing the third and fourth RF signals so as to produce a phase correction for correcting an error component in the beamforming phase offset.
16. The method according to claim 15, wherein processing the third and fourth RF signals comprises down-converting the third and fourth RF signals to produce respective first and second received signals, measuring a phase shift between the first and second received signals and computing the phase correction responsively to the measured phase shift.
17. The method according to claim 16, wherein measuring the phase shift comprises applying a Differential Phase-Locked Loop (DPLL).
18. The method according to claim 16, wherein computing the phase correction comprises producing first and second baseband signals that include the phase correction, and wherein producing the first and second RF signals comprises up-converting the respective first and second baseband signals so as to produce the first and second RF signals.
19. The method according to claim 15, wherein processing the third and fourth RF signals comprises determining a phase shift between the third and fourth RF signals, and producing the phase correction proportionally to the measured phase shift.
20. The method according to claim 15, wherein producing first and second RF signals comprises producing the first and second RF signals using respective first and second Local Oscillator (LO) signals that are unsynchronized with one another.
21. The method according to claim 20, wherein processing the third and fourth RF signals comprises down-converting the third and fourth RF signals using respectively the first and second unsynchronized LO signals.
22. The method according to claim 15, wherein producing first and second RF signals comprises producing the first and second RF signals using respective first and second Local Oscillator (LO) signals that are locked to a common reference clock signal.
23. The method according to claim 22, wherein processing the third and fourth RF signals comprises down-converting the third and fourth RF signals using respectively the first and second LO signals.
24. A method for communication, comprising:
producing first and second baseband signals with a relative beamforming phase therebetween, the first baseband signal comprising a first sequence of first pilot symbols, and the second baseband signal comprising a second sequence of second pilot signals, such that each first pilot signal is transmitted concurrently with a corresponding second pilot signal, wherein each of the first and second sequences comprises at least first and second interleaved sub-sequences, such that each of the first pilot symbols in the first sub-sequence has a first phase offset relative to the corresponding second pilot signal, and each of the first pilot symbols in the second sub-sequence has a second phase offset, which is different from the first phase offset, relative to the corresponding second pilot signal;
processing the first and second baseband signals so as to produce and transmit first and second Radio Frequency (RF) signals;
receiving first and second combinations of the first and second transmitted RF signals so as to produce respective first and second received signals;
combining the first and second received signals to produce a composite signal, and measuring respective first and second magnitudes of the pilot symbols belonging to the first and second sub-sequences in the composite signal; and
processing the first and second magnitudes so as to compute the relative beamforming phase.
25. The method according to claim 24, wherein combining the first and second received signals comprises applying Maximum Ratio Combining (MRC).
26. The method according to claim 24, wherein the first phase offset comprises \u03c6 degrees, wherein the second phase offset comprises \u2212\u03c6 degrees, and wherein each of the first and second sequences further comprises a third sub-sequence, such that each of the first pilot symbols in the third sub-sequence has no phase offset with respect to the corresponding second pilot signal.
27. A method for communication, comprising:
receiving first and second combinations of first and second Radio Frequency (RF) signals transmitted from respective first and second transmitters, and processing the first and second combinations to produce respective first and second received signals, wherein the RF signals have a relative beamforming phase therebetween, the first RF signal comprising a first sequence of first pilot symbols, and the second RF signal comprising a second sequence of second pilot signals, such that each first pilot signal is transmitted concurrently with a corresponding second pilot signal, wherein each of the first and second sequences comprises at least first and second interleaved sub-sequences, such that each of the first pilot symbols in the first sub-sequence has a first phase offset relative to the corresponding second pilot signal, and each of the first pilot symbols in the second sub-sequence has a second phase offset, which is different from the first phase offset, relative to the corresponding second pilot signal;
combining the first and second received signals to produce a composite signal, and measuring respective first and second magnitudes of the pilot symbols belonging to the first and second sub-sequences in the composite signal; and
processing the first and second magnitudes so as to compute the relative beamforming phase.

1. A shopping cart for interaction with inventory, comprising:
a holder for receiving at least one acquired item from a plurality of inventory items having inventory RFID tags, the at least one acquired item having been read by an RFID reader; and
a list-making component for creating and maintaining an interim list of the at least one acquired item and for providing a final list for reconciliation, the interim list associating the at least one acquired item with a personal item having a personal RFID tag, the personal RFID tag being read by the RFID reader.
2. The shopping cart of claim 1, wherein the RFID reader is coupled to the holder.
3. The shopping cart of claim 1, wherein the RFID reader is coupled to the list-making component.
4. The shopping cart of claim 1, wherein the RFID reader is coupled to a cell phone.
5. The shopping cart of claim 1, further comprising:
an exit for receiving the final list and receiving an indication of agreement.
6. The shopping cart of claim 1, wherein the holder is virtual and represented on a web page and the list-making component is associated with the web page.
7. The shopping cart of claim 1, wherein the holder is physical and coupled to the list-making component.
8. The shopping cart of claim 1, further comprising a plurality of exits in communication with the list-making component that allow passage upon a valid sale.
9. The shopping cart of claim 8, wherein the exits do not allow passage upon an invalid sale.
10. The shopping cart of claim 8, wherein the exits set an alarm upon an invalid sale.
11. The shopping cart of claim 1, wherein the at least one acquired item is read by the RFID reader when the at least one acquired item is placed in the holder.

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 formula (I):
wherein,
R1 and R2 are independently selected from the group consisting of H, C1-6 alkyl, C2-6 alkenyl, C3-7 cycloalkyl and benzyl, or alternatively R1 and R2 taken together with the nitrogen atom to which they are attached form a saturated or partially unsaturated 4- to 7-membered heterocyclyl optionally having one carbon replaced with >O, >S, \u2550N\u2014, >NH or >N(C1-4 alkyl), wherein the heterocyclyl is optionally substituted with 1-3 independently selected C1-6 alkyl substituents;
R3 is H or C1-6 alkyl, optionally substituted with NH2;
n is 2, 3, 4 or 5;
m is 0 or 1;
Y1 is a covalent bond, C1-4 alkane-diyl, or cis or trans C2-4 alkene-diyl, optionally substituted with 1 or 2 independently selected C1-4 alkyl substituents;
R4 is H, C1-4 alkyl or phenyl;
R5 is selected from the group consisting of C1-6 alkyl, C2-6 alkenyl, C3-7 cycloalkyl, phenyl, thienyl, benzhydryl and \u2014Y3-Ra, where Y3 is C1-3 alkane-diyl or C2-3 alkene-diyl, and Ra is selected from the group consisting of C3-7 cycloalkyl, phenyl, naphthyl, biphenyl, benzylsulfanyl, benzyloxy, thienyl, furyl, thiazolyl, oxazolyl, imidazolyl, 1H-indol-2-yl, 1H-indol-3-yl and pyridyl;
or alternatively R4 and R5 taken together with the carbon atom to which they are attached form a saturated or partially unsaturated 3- to 7-membered monocyclic carbocyclyl, optionally benzofused;
where R5 is substituted at any stable position except Y3 with 0, 1 or 2 substituents independently selected from the group consisting of hydroxy, sulfanyl, halo, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, C1-4 alkylsulfanyl, carboxy, amino and carbamoyl, and Y3 is substituted with 0, 1 or 2 substituents independently selected from the group consisting of fluoro, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy and amino; or alternatively R4 and R5 taken together is substituted with 0, 1 or 2 substituents independently selected from the group consisting of hydroxy, halo, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy and amino;
R6 is H or C1-4 alkyl;
X is selected from the group consisting of >C\u2550O, >C\u2550S, >C\u2550N\u2014CN and >C\u2550CHNO2;
Y2 is a covalent bond or methylene;
R7 is H, halo or C1-4 alkyl;
R8 is selected from the group consisting of H, phenyl, \u2014O-phenyl, \u2014O-tetrahydronaphthyl, \u2014SO0-2-phenyl, thienyl and pyridyl;
or alternatively R7 and R8 taken together with the phenyl to which they are attached form fluorenyl or tetrahydronaphthyl;
where R8, or R7 and R8 taken together, is substituted with 0, 1 or 2 substituents independently selected from the group consisting of hydroxy, cyano, nitro, amino, dimethylamino, halo, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, \u2014(CO)\u2014C1-4 alkyl and \u2014(SO2)\u2014C1-4 alkyl;
and stereoisomers, solvates, pharmaceutically acceptable salts and polymorphs, thereof.
2. The compound of claim 1 wherein R1 and R2 are independently selected from the group consisting of H, methyl, ethyl, propyl, i-propyl, ethenyl, allyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and benzyl.
3. The compound of claim 1 wherein, optionally substituted, R1 and R2 taken together with the nitrogen atom to which they are attached is selected from the group consisting of 2-pyrrolin-1-yl, 3-pyrrolin-1-yl, pyrrolidin-1-yl, 2-imidazolin-1-yl, imidazolidin-1-yl, 2-pyrazolin-1-yl, pyrazolidin-1-yl, piperidin-1-yl, morpholin-4-yl, thiomorpholin-4-yl and piperazin-1-yl.
4. The compound of claim 1 wherein, optionally substituted, R3 is independently selected from the group consisting of H, methyl, ethyl and propyl.
5. The compound of claim 1 wherein n is 2 or 3.
6. The compound of claim 1 wherein m is 1.
7. The compound of claim 1 wherein, optionally substituted, Y1 is independently selected from the group consisting of a covalent bond, methdiyl, eth-1,2-diyl, prop-1,3-diyl, but-1,4-diyl, cis-ethen-1,2-diyl and trans-ethen-1,2-diyl.
8. The compound of claim 1 wherein R4 is independently selected from the group consisting of H, methyl, ethyl, propyl and phenyl.
9. The compound of claim 1 wherein, optionally substituted, R5 is independently selected from the group consisting of methyl, ethyl, propyl, i-propyl, butyl, t-butyl, i-butyl, ethenyl, allyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, thienyl, benzhydryl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, benzyl, naphthylmethyl, biphenylmethyl, benzylsulfanylmethyl, benzyloxymethyl, thienylmethyl, furylmethyl, thiazolylmethyl, oxazolylmethyl, imidazolylmethyl, 1H-indol-2-ylmethyl, 1H-indol-3-ylmethyl, pyridylmethyl and phenylethyl.
10. The compound of claim 1 wherein R4 and R5 taken together with the carbon atom to which they are attached is selected from the group consisting of cyclobutan-1,1-diyl, cyclopentan-1,1-diyl, cyclohexan-1,1-diyl and indan-2,2-diyl.
11. The compound of claim 1 wherein R6 is selected from the group consisting of H, methyl, ethyl and propyl.
12. The compound of claim 1 wherein Y2 is a covalent bond.
13. The compound of claim 1 wherein X is >C\u2550O.
14. The compound of claim 1 wherein X is >C\u2550S.
15. The compound of claim 1 wherein X is >C\u2550N\u2014CN.
16. The compound of claim 1 wherein X is >C\u2550CHNO2.
17. The compound of claim 1 wherein R7 is selected from the group consisting of H, bromo, chloro, fluoro, iodo, methyl, ethyl, propyl, and t-butyl.
18. The compound of claim 1 wherein, optionally substituted, R is selected from the group consisting of phenyl and \u2014O-phenyl.
19. The compound of claim 1 wherein, optionally substituted, R7 and R8 taken together with the phenyl to which they are attached is fluorenyl.
20. The compound of claim 1 selected from the group consisting of:
(S)-2-(N\u2032-Biphenyl-4-yl-N\u2033-cyano-guanidino)-3-phenyl-N-(3-pyrrolidin-1-yl-propyl)-propionamide;
(S)-2-{N\u2032-4-(4-Fluoro-phenoxy)-phenyl-N\u2033-cyano-guanidino}-3-phenyl-N-(3-pyrrolidin-1-yl-propyl)-propionamide;
(R)-3-(N\u2032-Biphenyl-4-yl-N\u2033-cyano-guanidino)-3-phenyl-N-(2-pyrrolidin-1-yl-ethyl)-propionamide;
3-{N\u2032-4-(3,4-Dichloro-phenoxy)-phenyl-N\u2033-cyano-guanidino}-3-phenyl-N-(2-pyrrolidin-1-yl-ethyl)-propionamide;
3-{N\u2032-4-(4-Chloro-phenoxy)-phenyl-N\u2033-cyano-guanidino}-3-phenyl-N-(2-pyrrolidin-1-yl-ethyl)-propionamide;
3-N\u2032-Methyl-N\u2033-(4-p-tolyloxy-phenyl)-guanidino-3-phenyl-N-(2-pyrrolidin-1-yl-ethyl)-propionamide;
(S)-2-{N\u2032-4-(4-Chloro-phenoxy)-phenyl-N\u2033-cyano-guanidino}-3-phenyl-N-(3-pyrrolidin-1-yl-propyl)-propionamide;
3-{N\u2032-4-(4-Fluoro-phenoxy)-phenyl-N\u2033-cyano-guanidino}-3-phenyl-N-(2-pyrrolidin-1-yl-ethyl)-propionamide;
(S)-2-{N\u2032-4-(4-Chloro-phenoxy)-phenyl-N\u2033-cyano-guanidino}-N-(2-diisopropylamino-ethyl)-3-phenyl-propionamide;
(R)-2-{N\u2032-4-(4-Chloro-phenoxy)-phenyl-N\u2033-cyano-guanidino}-3-phenyl-N-(2-pyrrolidin-1-yl-ethyl)-propionamide;
(R)-4-{N\u2032-4-(4-Chloro-phenoxy)-phenyl-N\u2033-cyano-guanidino}-5-phenyl-pentanoic acid (2-pyrrolidin-1-yl-ethyl)-amide;
(R)-4-(N\u2032-Biphenyl-4-yl-N\u2033-cyano-guanidino)-5-phenyl-pentanoic acid (2-isopropylamino-ethyl)-amide;
3-(N\u2032-Biphenyl-4-yl-N\u2033-cyano-guanidino)-N-(2-diisopropylamino-ethyl)-3-phenyl-propionamide;
3-N\u2032-(9H-Fluoren-2-yl)-N\u2033-cyano-guanidino-3-phenyl-N-(2-pyrrolidin-1-yl-ethyl)-propionamide;
(R)-4-(N\u2032-Biphenyl-4-yl-N\u2033-cyano-guanidino)-5-phenyl-pentanoic acid (2-pyrrolidin-1-yl-ethyl)-amide;
(S)-2-{N\u2032-4-(4-Chloro-phenoxy)-phenyl-N\u2033-cyano-guanidino}-3-phenyl-N-(2-pyrrolidin-1-yl-ethyl)-propionamide;
(R)-4-(N\u2032-Biphenyl-4-yl-N\u2033-cyano-guanidino)-5-phenyl-pentanoic acid (2-diethylamino-ethyl)-amide;
(R)-4-(N\u2032-Biphenyl-4-yl-N\u2033-cyano-guanidino)-5-phenyl-pentanoic acid (2-dimethylamino-ethyl)-amide;
(R)-4-{N\u2032-4-(4-Fluoro-phenoxy)-phenyl-N\u2033-cyano-guanidino}-5-phenyl-pentanoic acid (2-pyrrolidin-1-yl-ethyl)-amide;
(R)-4-{N\u2032-4-(3,4-Dichloro-phenoxy)-phenyl-N\u2033-cyano-guanidino}-5-phenyl-pentanoic acid (2-pyrrolidin-1-yl-ethyl)-amide;
(R)-4-N\u2032-Cyano-N\u2033-(4-p-tolyloxy-phenyl)-guanidino-5-phenyl-pentanoic acid (2-pyrrolidin-1-yl-ethyl)-amide;
3-(N\u2032-Biphenyl-4-yl-N\u2033-cyano-guanidino)-3-phenyl-N-(2-pyrrolidin-1-yl-ethyl)-propionamide;
(S)-3-{N\u2032-4-(4-Chloro-phenoxy)-phenyl-N\u2033-cyano-guanidino}-4-phenyl-N-(2-pyrrolidin-1-yl-ethyl)-butyramide;
(S)-2-{N\u2032-4-(4-Chloro-phenoxy)-phenyl-N\u2033-cyano-guanidino}-N-(2-dimethylamino-ethyl)-3-phenyl-propionamide;
(S)-3-(N\u2032-Biphenyl-4-yl-N\u2033-cyano-guanidino)-5-methyl-hexanoic acid (2-pyrrolidin-1-yl-ethyl)-amide;
(S)-3-(N\u2032-Biphenyl-4-yl-N\u2033-cyano-guanidino)-4-phenyl-N-(2-pyrrolidin-1-yl-ethyl)-butyramide;
(S)-4-(N\u2032-Biphenyl-4-yl-N\u2033-cyano-guanidino)-5-phenyl-pentanoic acid (2-pyrrolidin-1-yl-ethyl)-amide;
3-N\u2032-Cyano-N\u2033-(4-phenoxy-phenyl)-guanidino-3-phenyl-N-(2-pyrrolidin-1-yl-ethyl)-propionamide;
(R)-4-N\u2032-Cyano-N\u2033-(4-phenoxy-phenyl)-guanidino-5-phenyl-pentanoic acid (2-pyrrolidin-1-yl-ethyl)-amide; and
(R)-2-(N\u2032-Biphenyl-4-yl-N\u2033-cyano-guanidino)-3-phenyl-N-(3-pyrrolidin-1-yl-propyl)-propionamide;
and stereoisomers, solvates, pharmaceutically acceptable salts and polymorphs, thereof.
21. The compound of claim 1 selected from the group consisting of:
1-(R)-1-Benzyl-4-(2-pyrrolidin-1-yl-ethylamino)-butyl-3-biphenyl-4-yl-urea;
(S)-2-{3-4-(4-Chloro-phenoxy)-phenyl-ureido}-N-(2-diisopropylamino-ethyl)-3-phenyl-propionamide;
(S)-2-{3-4-(4-Chloro-phenoxy)-phenyl-ureido}-N-(2-dimethylamino-ethyl)-3-phenyl-propionamide;
(R)-3-(3-Biphenyl-4-yl-ureido)-N-(2-pyrrolidin-1-yl-ethyl)-3-p-tolyl-propionamide;
(S)-N-(2-Diisopropylamino-ethyl)-2-3-(4-phenoxy-phenyl)-ureido-3-phenyl-propionamide;
(E)-(S)-4-{3-4-(4-Fluoro-phenoxy)-phenyl-ureido}-5-phenyl-pent-2-enoic acid (2-pyrrolidin-1-yl-ethyl)-amide;
(S)-2-(3-Biphenyl-4-yl-ureido)-3-phenyl-N-(3-pyrrolidin-1-yl-propyl)-propionamide;
(S)-2-(3-Biphenyl-4-yl-ureido)-N-(3-diethylamino-propyl)-3-phenyl-propionamide;
(S)-2-(3-Biphenyl-4-yl-ureido)-N-(2-isopropylamino-ethyl)-3-phenyl-propionamide;
(R)-3-(3-Biphenyl-4-yl-ureido)-4-methyl-pentanoic acid (2-pyrrolidin-1-yl-ethyl)-amide;
(S)-2-{3-4-(4-Chloro-phenoxy)-phenyl-ureido}-N-(2-methylamino-ethyl)-3-phenyl-propionamide;
(S)-2-(3-Biphenyl-4-yl-ureido)-N-(3-pyrrolidin-1-yl-propyl)-3-thiophen-2-yl-propionamide;
(E)-(S)-4-3-(4-Phenoxy-phenyl)-ureido-5-phenyl-pent-2-enoic acid (2-methylamino-ethyl)-amide;
(E)-(S)-4-(3-Biphenyl-4-yl-ureido)-5-phenyl-pent-2-enoic acid (2-diethylamino-ethyl)-amide;
(E)-(S)-4-(3-Biphenyl-4-yl-ureido)-5-phenyl-pent-2-enoic acid (2-isopropylamino-ethyl)-amide;
(E)-(S)-4-3-(4-Phenoxy-phenyl)-ureido-5-phenyl-pent-2-enoic acid (2-ethylamino-ethyl)-amide;
3-(3-Biphenyl-4-yl-ureido)-3-phenyl-N-(2-pyrrolidin-1-yl-ethyl)-propionamide;
3-(3-Biphenyl-4-yl-ureido)-3-(4-methoxy-phenyl)-N-(2-pyrrolidin-1-yl-ethyl)-propionamide;
(E)-(S)-4-(3-Biphenyl-4-yl-ureido)-5-(3-chloro-phenyl)-pent-2-enoic acid (2-pyrrolidin-1-yl-ethyl)-amide;
(R)-4-(3-Biphenyl-4-yl-ureido)-5-phenyl-pentanoic acid (2-isopropylamino-ethyl)-amide;
(S)-2-{2-4-(4-Chloro-phenoxy)-phenylamino-acetylamino}-3-phenyl-N-(2-pyrrolidin-1-yl-ethyl)-propionamide;
(S)-3-{2-4-(4-Chloro-phenoxy)-phenylamino-acetylamino}-4-phenyl-N-(2-pyrrolidin-1-yl-ethyl)-butyramide;
3-(3-Biphenyl-4-yl-ureido)-N-(2-isopropylamino-ethyl)-3-phenyl-propionamide;
(S)-2-(3-Biphenyl-4-yl-ureido)-N-(2-diisopropylamino-ethyl)-3-phenyl-propionamide;
(E)-(S)-4-(3-Biphenyl-4-yl-ureido)-5-phenyl-pent-2-enoic acid (2-propylamino-ethyl)-amide;
(S)-2-{3-4-(4-Fluoro-phenoxy)-phenyl-ureido}-3-phenyl-N-(2-pyrrolidin-1-yl-ethyl)-propionamide;
(S)-2-{3-4-(4-Methoxy-phenoxy)-phenyl-ureido}-3-phenyl-N-(2-pyrrolidin-1-yl-ethyl)-propionamide;
2-(3-Biphenyl-4-yl-ureido)-N-(2-dimethylamino-ethyl)-N-methyl-3-phenyl-propionamide;
(R)-2-(3-Biphenyl-4-yl-1-methyl-ureido)-N-(2-dimethylamino-ethyl)-3-phenyl-propionamide;
(S)-2-(3-Biphenyl-4-yl-1-methyl-ureido)-3-phenyl-N-(2-pyrrolidin-1-yl-ethyl)-propionamide;
(S)-3-Phenyl-N-(2-pyrrolidin-1-yl-ethyl)-2-{3-4-(5,6,7,8-tetrahydro-naphthalen-2-yloxy)-phenyl-ureido}-propionamide;
(S)-N-(2-Diisopropylamino-ethyl)-3-phenyl-2-3-(4-thiophen-2-yl-phenyl)-ureido-propionamide;
(S)-2-3-(4-Iodo-phenyl)-ureido-3-phenyl-N-(2-pyrrolidin-1-yl-ethyl)-propionamide;
(S)-3-Biphenyl-4-yl-2-(3-biphenyl-4-yl-ureido)-N-(3-pyrrolidin-1-yl-propyl)-propionamide;
2-3-(4-Phenoxy-phenyl)-ureido-2-propyl-pentanoic acid (2-pyrrolidin-1-yl-ethyl)-amide;
(S)-N-(2-Amino-ethyl)-2-(3-biphenyl-4-yl-ureido)-3-cyclohexyl-propionamide;
(S)-2-(3-Biphenyl-4-yl-ureido)-3-phenyl-N-(2-piperazin-1-yl-ethyl)-propionamide;
(S)-N,N-Bis-(3-amino-propyl)-2-(3-biphenyl-4-yl-ureido)-3-phenyl-propionamide;
1-3-(4-Phenoxy-phenyl)-ureido-cyclopentanecarboxylic acid (2-pyrrolidin-1-yl-ethyl)-amide;
(S)-2-3-(9H-Fluoren-2-yl)-ureido-3-phenyl-N-(3-pyrrolidin-1-yl-propyl)-propionamide;
(S)-2-3-(4-Phenoxy-phenyl)-ureido-N-(2-pyrrolidin-1-yl-ethyl)-3-thiazol-4-yl-propionamide;
(S)-3,3-Dimethyl-2-3-(4-phenoxy-phenyl)-ureido-N-(3-pyrrolidin-1-yl-propyl)-butyramide;
(S)-2-3-(4-Phenoxy-phenyl)-ureido-3,3-diphenyl-N-(2-pyrrolidin-1-yl-ethyl)-propionamide;
(R)-3-Benzylsulfanyl-2-3-(4-phenoxy-phenyl)-ureido-N-(2-pyrrolidin-1-yl-ethyl)-propionamide;
(S)-2-(3-Biphenyl-4-yl-ureido)-3-pyridin-4-yl-N-(3-pyrrolidin-1-yl-propyl)-propionamide;
(S)-3-Methyl-2-3-(4-phenoxy-phenyl)-ureido-N-(2-pyrrolidin-1-yl-ethyl)-butyramide;
(S)-2-(3-Biphenyl-4-yl-ureido)-2-phenyl-N-(3-pyrrolidin-1-yl-propyl)-acetamide;
(S)-2-(3-Biphenyl-4-yl-ureido)-4-phenyl-N-(3-pyrrolidin-1-yl-propyl)-butyramide;
(S)-3-Naphthalen-2-yl-2-3-(4-phenoxy-phenyl)-ureido-N-(3-pyrrolidin-1-yl-propyl)-propionamide;
2-3-(4-Phenoxy-phenyl)-ureido-2,2-diphenyl-N-(2-pyrrolidin-1-yl-ethyl)-acetamide;
2-(3-Biphenyl-4-yl-ureido)-indan-2-carboxylic acid (2-pyrrolidin-1-yl-ethyl)-amide;
(S)-2-{3-4-(4-Chloro-benzenesulfonyl)-phenyl-ureido}-3-phenyl-N-(2-pyrrolidin-1-yl-ethyl)-propionamide;
(E)-(S)-4-(3-Biphenyl-4-yl-ureido)-5-phenyl-pent-2-enoic acid (3-diethylamino-propyl)-amide;
(R)-4-(3-Biphenyl-4-yl-ureido)-5-phenyl-pentanoic acid (2-propylamino-ethyl)-amide;
(E)-(S)-4-(3-Biphenyl-4-yl-ureido)-5-(4-methoxy-phenyl)-pent-2-enoic acid (2-pyrrolidin-1-yl-ethyl)-amide;
3-(3-Biphenyl-4-yl-ureido)-N-(2-diethylamino-ethyl)-3-phenyl-propionamide;
(S)-3-3-(9H-Fluoren-2-yl)-ureido-5-methyl-hexanoic acid (2-pyrrolidin-1-yl-ethyl)-amide;
N-(2-Amino-ethyl)-2-(3-biphenyl-4-yl-ureido)-3-phenyl-propionamide;
(R)-4-(3-Biphenyl-4-yl-ureido)-5-phenyl-pentanoic acid (2-amino-ethyl)-amide;
(E)-(R)-4-(3-Biphenyl-4-yl-ureido)-5-phenyl-pent-2-enoic acid (2-amino-ethyl)-amide;
2-(3-Biphenyl-4-yl-ureido)-N-(2-morpholin-4-yl-ethyl)-3-phenyl-propionamide;
(S)-4-(3-Biphenyl-4-yl-ureido)-5-phenyl-pentanoic acid (2-amino-ethyl)-amide;
(R)-4-(3-Biphenyl-4-yl-ureido)-5-phenyl-pentanoic acid (3-amino-propyl)-amide;
(S)-N-(2-Amino-ethyl)-3-phenyl-2-(3-phenyl-ureido)-propionamide;
(S)-N-(2-Amino-ethyl)-2-3-(4-phenoxy-phenyl)-ureido-3-phenyl-propionamide;
2-(3-Biphenyl-4-yl-ureido)-3-phenyl-N-(2-pyrrolidin-1-yl-ethyl)-propionamide;
2-(3-Biphenyl-4-yl-ureido)-3-phenyl-N-(2-piperidin-1-yl-ethyl)-propionamide;
(E)-(S)-4-(3-Biphenyl-4-yl-ureido)-5-phenyl-pent-2-enoic acid (2-pyrrolidin-1-yl-ethyl)-amide;
(S)-2-{3-4-(4-Chloro-phenoxy)-phenyl-ureido}-3-phenyl-N-(2-pyrrolidin-1-yl-ethyl)-propionamide;
(R)-4-(3-Biphenyl-4-yl-ureido)-5-phenyl-pentanoic acid (2-pyrrolidin-1-yl-ethyl)-amide;
(E)-(S)-4-3-(4-Phenoxy-phenyl)-ureido-5-phenyl-pent-2-enoic acid (2-pyrrolidin-1-yl-ethyl)-amide;
(S)-2-3-(4-tert-Butyl-phenyl)-ureido-3-phenyl-N-(2-pyrrolidin-1-yl-ethyl)-propionamide;
2-(3-Biphenyl-4-yl-ureido)-N-(2-dimethylamino-ethyl)-3-phenyl-propionamide;
1-(3-Biphenyl-4-yl-ureido)-cyclopentanecarboxylic acid (2-pyrrolidin-1-yl-ethyl)-amide;
(R)-4-3-(4-Phenoxy-phenyl)-ureido-5-phenyl-pentanoic acid (2-pyrrolidin-1-yl-ethyl)-amide;
(S)-2-{3-4-(3,4-Dichloro-phenoxy)-phenyl-ureido}-3-phenyl-N-(2-pyrrolidin-1-yl-ethyl)-propionamide;
(E)-(S)-4-3-(4-Phenoxy-phenyl)-ureido-5-phenyl-pent-2-enoic acid (2-amino-ethyl)-amide;
(R)-4-3-(4-Phenoxy-phenyl)-ureido-5-phenyl-pentanoic acid (2-amino-ethyl)-amide;
(E)-(S)-4-3-(4-Phenoxy-phenyl)-ureido-5-phenyl-pent-2-enoic acid (3-pyrrolidin-1-yl-propyl)-amide;
(E)-(S)-4-(3-Biphenyl-4-yl-ureido)-5-phenyl-pent-2-enoic acid (3-pyrrolidin-1-yl-propyl)-amide;
(S)-2-3-(4-Phenoxy-phenyl)-ureido-3-phenyl-N-(3-pyrrolidin-1-yl-propyl)-propionamide;
(E)-(S)-4-(3-Biphenyl-4-yl-ureido)-5-phenyl-pent-2-enoic acid (2-methylamino-ethyl)-amide;
(E)-(S)-4-(3-Biphenyl-4-yl-ureido)-5-phenyl-pent-2-enoic acid (2-dimethylamino-ethyl)-amide;
(E)-(S)-4-3-(4-Phenoxy-phenyl)-ureido-5-phenyl-pent-2-enoic acid (2-dimethylamino-ethyl)-amide;
(E)-(S)-4-(3-Biphenyl-4-yl-ureido)-5-phenyl-pent-2-enoic acid (3-methylamino-propyl)-amide;
(E)-(S)-4-(3-Biphenyl-4-yl-ureido)-5-phenyl-pent-2-enoic acid (3-dimethylamino-propyl)-amide;
(R)-4-(3-Biphenyl-4-yl-ureido)-5-phenyl-pentanoic acid (3-dimethylamino-propyl)-amide;
(Z)-(S)-4-(3-Biphenyl-4-yl-ureido)-5-phenyl-pent-2-enoic acid (2-pyrrolidin-1-yl-ethyl)-amide;
(S)-2-3-(3-Phenoxy-phenyl)-ureido-3-phenyl-N-(3-pyrrolidin-1-yl-propyl)-propionamide;
(S)-2-(3-Biphenyl-4-yl-ureido)-N-(2-diethylamino-ethyl)-3-phenyl-propionamide;
2-(3-Biphenyl-4-yl-ureido)-2-propyl-pentanoic acid (2-pyrrolidin-1-yl-ethyl)-amide;
(R)-4-(3-Biphenyl-4-yl-ureido)-5-phenyl-pentanoic acid (2-methylamino-ethyl)-amide;
(S)-3-(3-Biphenyl-4-yl-ureido)-4-phenyl-N-(2-pyrrolidin-1-yl-ethyl)-butyramide;
(S)-3-3-(4-Phenoxy-phenyl)-ureido-4-phenyl-N-(2-pyrrolidin-1-yl-ethyl)-butyramide;
(S)-3-(3-Biphenyl-4-yl-ureido)-5-methyl-hexanoic acid (2-pyrrolidin-1-yl-ethyl)-amide;
(S)-5-Methyl-3-3-(4-phenoxy-phenyl)-ureido-hexanoic acid (2-pyrrolidin-1-yl-ethyl)-amide;
(S)-2-3-(2-Phenoxy-phenyl)-ureido-3-phenyl-N-(3-pyrrolidin-1-yl-propyl)-propionamide;
(S)-3-(3-Biphenyl-4-yl-ureido)-3-phenyl-N-(2-pyrrolidin-1-yl-ethyl)-propionamide;
(R)-3-(3-Biphenyl-4-yl-ureido)-3-phenyl-N-(2-pyrrolidin-1-yl-ethyl)-propionamide;
N-(2-Amino-ethyl)-3-(3-biphenyl-4-yl-ureido)-3-phenyl-propionamide;
(R)-4-(3-Biphenyl-4-yl-ureido)-5-phenyl-pentanoic acid (2-diethylamino-ethyl)-amide;
3-(3-Biphenyl-4-yl-ureido)-N-(2-dimethylamino-ethyl)-3-phenyl-propionamide;
(E)-(R)-4-(3-Biphenyl-4-yl-ureido)-5-phenyl-pent-2-enoic acid (3-pyrrolidin-1-yl-propyl)-amide;
(S)-N-(2-Dimethylamino-ethyl)-2-3-(4-phenoxy-phenyl)-ureido-3-phenyl-propionamide;
3-(3-Biphenyl-4-yl-ureido)-3-phenyl-N-(3-pyrrolidin-1-yl-propyl)-propionamide;
(S)-3-(3-Biphenyl-4-yl-ureido)-N-(2-dimethylamino-ethyl)-4-phenyl-butyramide;
(S)-N-(2-Dimethylamino-ethyl)-3-3-(4-phenoxy-phenyl)-ureido-4-phenyl-butyramide;
(S)-2-(3-Biphenyl-4-yl-ureido)-N-(2-pyrrolidin-1-yl-ethyl)-3-thiophen-2-yl-propionamide;
(S)-2-(3-Biphenyl-4-yl-ureido)-3-pyridin-3-yl-N-(3-pyrrolidin-1-yl-propyl)-propionamide;
2-(3-Biphenyl-4-yl-ureido)-2,2-diphenyl-N-(2-pyrrolidin-1-yl-ethyl)-acetamide;
3-(3-Biphenyl-4-yl-ureido)-3-(4-chloro-phenyl)-N-(2-pyrrolidin-1-yl-ethyl)-propionamide;
(R)-4-Methyl-3-3-(4-phenoxy-phenyl)-ureido-pentanoic acid (2-pyrrolidin-1-yl-ethyl)-amide;
(R)-3-(3-Biphenyl-4-yl-ureido)-4-methyl-pentanoic acid (2-diisopropylamino-ethyl)-amide;
(R)-4-Methyl-3-3-(4-phenoxy-phenyl)-ureido-pentanoic acid (2-diisopropylamino-ethyl)-amide;
(E)-(R)-4-(3-Biphenyl-4-yl-ureido)-5-phenyl-pent-2-enoic acid (2-diisopropylamino-ethyl)-amide;
(S)-4-(3-Biphenyl-4-yl-ureido)-5-phenyl-pentanoic acid (2-diisopropylamino-ethyl)-amide;
(S)-2-(3-Biphenyl-3-yl-ureido)-3-phenyl-N-(3-pyrrolidin-1-yl-propyl)-propionamide;
(S)-3-(3-Biphenyl-4-yl-ureido)-N-(2-pyrrolidin-1-yl-ethyl)-3-p-tolyl-propionamide;
(E)-(S)-4-(3-Biphenyl-4-yl-ureido)-5-phenyl-pent-2-enoic acid (3-amino-propyl)-amide;
(E)-(R)-4-(3-Biphenyl-4-yl-ureido)-5-phenyl-pent-2-enoic acid (3-amino-propyl)-amide;
1-(S)-1-Benzyl-2-(2-pyrrolidin-1-yl-ethylamino)-ethyl-3-(4-phenoxy-phenyl)-urea; and
1-(S)-1-Benzyl-4-(2-pyrrolidin-1-yl-ethylamino)-butyl-3-biphenyl-4-yl-urea;
and stereoisomers, solvates, pharmaceutically acceptable salts and polymorphs, thereof.
22. The compound of claim 1 selected from the group consisting of:
(S)-2-{3-4-(4-Chloro-phenoxy)-phenyl-thioureido}-3-phenyl-N-(2-pyrrolidin-1-yl-ethyl)-propionamide;
(S)-N-(2-Diisopropylamino-ethyl)-2-{3-4-(4-fluoro-phenoxy)-phenyl-thioureido}-3-phenyl-propionamide;
(R)-4-(3-Biphenyl-4-yl-thioureido)-5-phenyl-pentanoic acid (2-pyrrolidin-1-yl-ethyl)-amide;
(S)-2-(3-Biphenyl-4-yl-thioureido)-3-phenyl-N-(3-pyrrolidin-1-yl-propyl)-propionamide;
(S)-2-{3-4-(4-Chloro-phenoxy)-phenyl-thioureido}-N-(2-diisopropylamino-ethyl)-3-phenyl-propionamide; and
(S)-N-(2-Diisopropylamino-ethyl)-3-phenyl-2-3-(4-p-tolyloxy-phenyl)-thioureido-propionamide;
and stereoisomers, solvates, pharmaceutically acceptable salts and polymorphs, thereof.
23. A method for the treatment or prevention of a disease state selected from the group consisting of muscle spasticity, tinnitus, epilepsy and neuropathic pain comprising administering to a mammal in need thereof an effective amount of a compound of formula (I):
wherein,
R1 and R2 are independently selected from the group consisting of H, C1-6 alkyl, C2-6 alkenyl, C3-7 cycloalkyl and benzyl, or alternatively R1 and R2 taken together with the nitrogen atom to which they are attached form a saturated or partially unsaturated 4- to 7-membered heterocyclyl optionally having one carbon replaced with >O, >S, \u2550N\u2014, >NH or >N(C1-4 alkyl), wherein the heterocyclyl is optionally substituted with 1-3 independently selected C1-6 alkyl substituents;
R3 is H or C1-6 alkyl, optionally substituted with NH2;
n is 2, 3, 4 or 5;
m is 0 or 1;
Y1 is a covalent bond, C1-4 alkane-diyl, or cis or trans C2-4 alkene-diyl, optionally substituted with 1 or 2 independently selected C1-4 alkyl substituents;
R4 is H, C1-4 alkyl or phenyl;
R5 is selected from the group consisting of C1-6 alkyl, C2-6 alkenyl, C3-7 cycloalkyl, phenyl, thienyl, benzhydryl and \u2014Y3\u2014Ra, where Y3 is C1-3 alkane-diyl or C2-3 alkene-diyl, and Ra is selected from the group consisting of C3-7 cycloalkyl, phenyl, naphthyl, biphenyl, benzylsulfanyl, benzyloxy, thienyl, furyl, thiazolyl, oxazolyl, imidazolyl, 1H-indol-2-yl, 1H-indol-3-yl and pyridyl;
or alternatively R4 and R5 taken together with the carbon atom to which they are attached form a saturated or partially unsaturated 3- to 7-membered monocyclic carbocyclyl, optionally benzofused;
where R5 is substituted at any stable position except Y3 with 0, 1 or 2 substituents independently selected from the group consisting of hydroxy, sulfanyl, halo, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, C1-4 alkylsulfanyl, carboxy, amino and carbamoyl, and Y3 is substituted with 0, 1 or 2 substituents independently selected from the group consisting of fluoro, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy and amino; or alternatively R4 and R5 taken together is substituted with 0, 1 or 2 substituents independently selected from the group consisting of hydroxy, halo, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy and amino;
R6 is H or C1-4 alkyl;
X is selected from the group consisting of >C\u2550O, >C\u2550S, >C\u2550N\u2014CN and >C\u2550CHNO2;
Y2 is a covalent bond or methylene;
R7 is H, halo or C1-4 alkyl;
R8 is selected from the group consisting of H, phenyl, \u2014O-phenyl, \u2014O-tetrahydronaphthyl, \u2014SO0-2-phenyl, thienyl and pyridyl;
or alternatively R7 and R8 taken together with the phenyl to which they are attached form fluorenyl or tetrahydronaphthyl;
where R8, or R7 and R8 taken together, is substituted with 0, 1 or 2 substituents independently selected from the group consisting of hydroxy, cyano, nitro, amino, dimethylamino, halo, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, \u2014(CO)\u2014C1-4 alkyl and \u2014(SO2)\u2014C1-4 alkyl;
and stereoisomers, solvates, pharmaceutically acceptable salts and polymorphs, thereof.
24. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective dose of a compound of formula (I):
wherein,
R1 and R2 are independently selected from the group consisting of H, C1-6 alkyl, C2-6 alkenyl, C3-7 cycloalkyl and benzyl, or alternatively R1 and R2 taken together with the nitrogen atom to which they are attached form a saturated or partially unsaturated 4- to 7-membered heterocyclyl optionally having one carbon replaced with >O, >S, \u2550N\u2014, >NH or >N(C1-4 alkyl), wherein the heterocyclyl is optionally substituted with 1-3 independently selected C1-6 alkyl substituents;
R3 is H or C1-6 alkyl, optionally substituted with NH2;
n is 2, 3, 4 or 5;
m is 0 or 1;
Y1 is a covalent bond, C1-4 alkane-diyl, or cis or trans C2-4 alkene-diyl, optionally substituted with 1 or 2 independently selected C1-4 alkyl substituents;
R4 is H, C1-4 alkyl or phenyl;
R5 is selected from the group consisting of C1-6 alkyl, C2-6 alkenyl, C3-7 cycloalkyl, phenyl, thienyl, benzhydryl and \u2014Y3\u2014Ra, where Y3 is C1-3 alkane-diyl or C2-3 alkene-diyl, and Ra is selected from the group consisting of C3-7 cycloalkyl, phenyl, naphthyl, biphenyl, benzylsulfanyl, benzyloxy, thienyl, furyl, thiazolyl, oxazolyl, imidazolyl, 1H-indol-2-yl, 1H-indol-3-yl and pyridyl;
or alternatively R4 and R5 taken together with the carbon atom to which they are attached form a saturated or partially unsaturated 3- to 7-membered monocyclic carbocyclyl, optionally benzofused;
where R5 is substituted at any stable position except Y3 with 0, 1 or 2 substituents independently selected from the group consisting of hydroxy, sulfanyl, halo, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, C1-4 alkylsulfanyl, carboxy, amino and carbamoyl, and Y3 is substituted with 0, 1 or 2 substituents independently selected from the group consisting of fluoro, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy and amino; or alternatively R4 and R5 taken together is substituted with 0, 1 or 2 substituents independently selected from the group consisting of hydroxy, halo, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy and amino;
R6 is H or C1-4alkyl;
X is selected from the group consisting of >C\u2550O, >C\u2550S, >C\u2550N\u2014CN and >C\u2550CHNO2;
Y2 is a covalent bond or methylene;
R7 is H, halo or C1-4 alkyl;
R8 is selected from the group consisting of H, phenyl, \u2014O-phenyl, \u2014O-tetrahydronaphthyl, \u2014SO0-2-phenyl, thienyl and pyridyl;
or alternatively R7 and R8 taken together with the phenyl to which they are attached form fluorenyl or tetrahydronaphthyl;
where R8, or R7 and R8 taken together, is substituted with 0, 1 or 2 substituents independently selected from the group consisting of hydroxy, cyano, nitro, amino, dimethylamino, halo, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, \u2014(CO)\u2014C1-4 alkyl and \u2014(SO2)\u2014C1-4 alkyl;
and stereoisomers, solvates, pharmaceutically acceptable salts and polymorphs, thereof.